RU2811464C2 - New versions of hyaluronidase with improved stability and the pharmaceutical composition containing them - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: following is proposed: a version of hyaluronidase PH20 or a fragment thereof that has hyaluronidase activity including the replacement, deletion or insertion of an amino acid residue in at least one position in the version containing the amino acid sequence SEQ ID NO: 3. Also the following is proposed: a composition for the treatment of cancer containing a version of PH20 or a fragment thereof, a nucleic acid encoding a version of hyaluronidase PH20 or a fragment thereof, a recombinant expression vector containing the said nucleic acid, a host cell transformed by the said vector, and a method of producing the version of hyaluronidase PH20 or its fragment.

EFFECT: PH20 version or a fragment thereof has improved thermostability and human hyaluronidase enzymatic activity.

13 cl, 4 dwg, 8 tbl, 5 ex

Description

Prior Art

Field of technology to which the invention relates

The present invention relates to new variants of human PH20 or fragments thereof having increased enzymatic activity and heat stability compared to human hyaluronidase, which is an enzyme that hydrolyzes hyaluronic acid, and more particularly to variants of PH20 or fragments thereof that include one or more substitutions, deletions and/or insertions of amino acid residues in hyaluronidase variants having the amino acid sequence of SEQ ID NO: 3 and, optionally, in which one or more amino acid residues are deleted from the N-terminus and/or the C-terminus, to a method for their preparation, and to containing their pharmaceutical composition.

Description of the Prior Art

Human skin is composed of epidermis, dermis and subcutaneous fat layer, and there are six types of glycosaminoglycans in the skin. These glycosaminoglycans include hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin and keratin sulfate.

These glycosaminoglycans are composed of repeating disaccharide sugar units. The number of repeating disaccharide sugar units varies among glycosaminoglycans, but ranges from several hundred to several thousand. Among the glycosaminoglycans, hyaluronic acid is present in the skin at more than half the amount found in the body. Hyaluronic acid, synthesized by hyaluronan synthase present in the cell membrane, is present on its own without binding to proteoglycans and is the only glycosaminoglycan that does not have a sulfate group. Other glycosaminoglycans bind to proteoglycans and have a sulfate group. Hyaluronic acid is composed of glucuronic acid and N-acetylglucosamine, alternately linked through β-1,4 and β-1,3 linkages, and is composed of approximately 5000 repeating units of these disaccharides. It is known that about one third (5 g) of hyaluronic acid in the human body is subject to degradation every day.

Hyaluronidases are enzymes that break down hyaluronic acid present in the extracellular matrix. There are six known hyaluronidase genes in humans: Hyal1, Hyal2, Hyal3, Hyal4, HyalPS1 and PH20/SPAM1. Human Hyal1 and Hyal2 are expressed in most tissues. PH20/SPAM1 (hereafter referred to as PH20) is expressed in the sperm plasma membrane and acrosomal membrane. However, HyalPS1 is not expressed because it is a pseudogene. Depending on the method of cleavage of hyaluronic acid, hyaluronidases are divided into three types: enzymes (EC 3.2.1.35), which cleave the β-1,4 bonds between N-acetylglucosamine and glucuronic acid using H2O; enzymes (EC 3.2.1.36) that cleave β-1,3-bonds between N-acetylglucosamine and glucuronic acid with H ₂ O; and bacterial hyaluronidases (EC 4.2.99.1), which cleave β-1,4 bonds without using _H2O .

The catalytic amino acids of Hyal1 are D129 and E131, which hydrolyze hyaluronic acid through substrate catalysis. Hyal1 exhibits optimal activity at an acidic pH of 3 to 4 and has no enzymatic activity at pH 4.5 or higher. Unlike Hyal1, PH20 is active over a wide pH range from 3 to 8.

Arming et al. found that the catalytic amino acids of PH20 are D111 and E113 (Arming et al., 1997). Arming et al. designated Leu as the first amino acid of PH20 from which a signal peptide or the like is removed, and thus the catalytic amino acids of PH20 containing the signal peptide correspond to D146 and E148, respectively.

Hyaluronidase hydrolyzes hyaluronic acid, thereby reducing the viscosity of hyaluronic acid in the extracellular matrix and increasing its permeability into tissue (skin). The subcutaneous area of the skin has a neutral pH of approximately 7.0 to 7.5. Thus, among the different types of hyaluronidases, PH20 is widely used in clinical practice (Bookbinder et al., 2006). In examples in which PH20 is used in clinical practice, PH20 is used as an ocular relaxant and anesthetic additive in ophthalmic surgery, and is also co-administered with an antibody therapeutic agent that is administered subcutaneously (Bookbinder et al., 2006). In addition, based on the property of hyaluronic acid, which is overexpressed in tumor cells, PH20 is used to hydrolyze hyaluronic acid in the extracellular matrix of tumor cells, thereby increasing the access of the antitumor therapeutic agent to tumor cells. In addition, PH20 is also used to speed up the absorption of body fluids and blood that are excessively present in tissues.

Lathrop et al. first identified PH20 in guinea pig sperm and is also known to be expressed in sperm of a variety of species. The human PH20 gene was cloned by Lin et al. and Gmachl et al. Human PH20 has an amino acid sequence of SEQ ID NO: 1, which consists of 509 amino acid residues and shows 60% amino acid identity with the guinea pig PH20 gene. The human PH20 enzyme is encoded by the SPAM1 (sperm adhesion molecule 1) gene, and Ser490 PH20 is present in a glycosylphosphatidylinositol (GPI)-linked form on the surface of the sperm plasma membrane and in the acrosomal membrane. Sperm hydrolyzes hyaluronic acid with PH20 as it enters the oocytes through the hyaluronan-rich cumulus layer of the oocytes. PH20 is present in amounts corresponding to 1% or less of the proteins in spermatozoa and has six N-glycosylation sites (N82, N166, N235, N254, N368 and N393).

Currently, commercially available PH20 is obtained by extraction from the testes of cattle or sheep. Examples of these include Amphadase® (bovine hyaluronidase) and Vitrase® (ovine hyaluronidase).

Bovine testicular hyaluronidase (BTH) is produced by removing the signal peptide and the C-terminal 56 amino acids from wild-type bovine PH20 during post-translational modification. BTH is also a glycoprotein and has a mannose content of 5% and a glucosamine content of 2.2% of the total components, including amino acids. When animal-derived hyaluronidase is reintroduced into the human body at a high dose, a neutralizing antibody may be formed. Because animal-derived hyaluronidase contains other biomaterials in addition to PH20, it may cause an allergic reaction when introduced into the human body (Bookbinder et al., 2006). In particular, the production and use of PH20 extracted from cattle may be limited due to concerns about mad cow disease. To overcome this problem, studies were carried out on recombinant human PH20 protein.

Recombinant human PH20 protein has been reported to be expressed in yeast (P. pastoris), insect DS-2 cells, and animal cells. Recombinant PH20 proteins produced in insect cells and yeast differ from human PH20 in terms of N-glycosylation patterns during post-translational modification.

The hyaluronidases whose protein structures have been identified are Hyal1 (PDB ID: 2PE4) (Chao et al., 2007) and bee venom hyaluronidase (PDB ID: 1FCQ, 1FCU, 1FCV). Hyal1 consists of two domains: a catalytic domain and an EGF-like domain. The catalytic domain has a (β/α) ₈ shape in which the alpha helix and beta strand, which characterize the secondary structure of the protein, are repeated eight times each (Chao et al., 2007). The EGF-like domain is completely conserved in variants in which the Hyal1 C terminus is spliced in a different manner. The amino acid sequences of Hyal1 and PH20 are 35.1% identical, and the structure of the PH20 protein has not yet been revealed.

Recombinant human PH20 protein was developed by Halozyme Therapeutic, Inc. and is sold under the trade name Hylenex® (Bookbinder et al., 2006; Frost, 2007).

When D146 and E148, which are the catalytic amino acids of PH20, were mutated to asparagine (D146N) and glutamine (E148Q), respectively, there was no enzymatic activity (Arming et al., 1997). In addition, when R246 in PH20 was replaced by glycine, the enzymatic activity was reduced by 90%, and when E319 was replaced by glutamine and R322 was replaced by threonine, the enzymatic activity disappeared. A variant in which 36 amino acids were deleted from the C-terminus of PH20 (deletion of amino acids 474-509) showed a 75% reduction in enzymatic activity compared to wild-type PH20. This mutant was not secreted extracellularly but remained in HeLa cells. A mutant in which the C-terminal 134 amino acids were deleted from PH20 had no enzymatic activity and was not secreted extracellularly. According to Frost et al., the C-terminal region 477-483 of PH20 is important for soluble expression (Frost, 2007). The activity of full-length PH20 (1-509) or the PH20 variant having a truncated C-terminus at position 467 was only 10% of that of the PH20 variant having a truncated C-terminus at one of positions 477-483 (Frost, 2007).

Recombinant PH20 is used in medicine as a carrier for subcutaneous delivery of pharmaceuticals, to reduce intraocular pressure in patients with ophthalmic diseases, to delay stenosis after surgery, as a dispersant to enhance the activity of chemotherapeutic agents in diseases such as cancer, as an adjuvant therapeutic agent for surgery, etc.

Particularly in the case of protein drugs, high-dose products with high concentrations ranging from tens of mg to hundreds of mg per ml have recently been developed, and thus the use of recombinant PH20 as a carrier to facilitate subcutaneous delivery of such protein drugs becomes More. Such protein drugs may have problems with low physical stability as a result of increased viscosity and protein aggregation due to their high concentration. In addition, protein aggregation is irreversible and small amounts of proteins begin to aggregate and the aggregates form larger clumps (Schön et al., 2015). That is, recombinant PH20 administered in combination undergoes aggregation, which reduces the stability of protein drugs.

Meanwhile, conventional recombinant PH20 is still insufficient in terms of thermostability and expression level. Consequently, there is a significant industrial need for recombinant hyaluronidase with even more improved biological and physicochemical properties.

Bibliography

Arming, S., Strobl, B., Wechselberger, C., and Kreil, G. (1997). In-vitro mutagenesis of PH-20 hyaluronidase from human sperm. Eur. J. Biochem. 247, 810-814.

Bookbinder, L.H., Hofer, A., Haller, M.F., Zepeda, M.L., Keller, G.A., Lim, J.E., Edgington, T.S., Shepard, H.M., Patton, J.S., and Frost, G.I. (2006). A recombinant human enzyme for enhanced interstitial transport of therapeutics. J. Control. Release 114, 230-241.

Chao, K. L., Muthukumar, L., and Herzberg, O. (2007). Structure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis. Biochemistry 46, 6911-6920.

Frost, G.I. (2007). Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration. Expert Opin. Drug Deliv. 4, 427-440.

Schön, A., Clarkson, B.R., Siles, R., Ross, P., Brown, R.K., Freire, E. (2015) Denatured state aggregation parameters derived from concentration dependence of protein stability. Anal. Chem. 488, 45-50

WO 2020/022791 A (2020. 1. 30.)

The essence of the invention

Thus, the present invention has been made in view of the above problems, and one of the objects of the present invention is to provide a variant of PH20 or a fragment thereof with improved thermostability, enzymatic activity and expression level compared to wild type PH20, preferably mature wild type PH20.

Another object of the present invention is to provide a composition for treating cancer comprising a variant PH20 or a fragment thereof, and a method of treating cancer therewith.

In accordance with one aspect of the present invention, the above and other objects can be achieved by providing a variant of PH20 or a fragment thereof comprising one or more substitutions, deletions and/or insertions of amino acid residues in the hyaluronidase variant having the amino acid sequence of SEQ ID NO: 3, and in in which one or more amino acid residues at the N-terminus or C-terminus are selectively removed.

In accordance with another aspect of the present invention, there is provided a composition for treating cancer comprising a variant PH20 or a fragment thereof, and a method for treating cancer therewith.

Effects of the invention

The PH20 variants or fragments thereof of the present invention have an increased level of protein expression and also have a higher protein aggregation temperature of 4-11.5°C or so when expressed in CHO cells (ExpiCHO), such that they are efficiently produced and characterized higher heat resistance compared to mature wild type PH20.

In addition, according to the results of the substrate-gel assay, which is one of the tests for measuring hyaluronidase activity, the PH20 variants or fragments thereof according to the present invention have improved protein refolding, so they regenerate faster than wild-type mature PH20, and the original enzymatic activity conserved regardless of the position of the C-terminal break.

In addition, the PH20 variants or fragments thereof according to the present invention have low immunogenicity so that they can be reintroduced into the human body.

Brief description of drawings

The above and other objects, features and other advantages of the present invention will be better understood from the following detailed description taken in conjunction with the accompanying drawings, in which:

in fig. 1 shows the results of an SDS-PAGE analysis of various variants based on the PH20 variant having the amino acid sequence SEQ ID NO: 3. The result of the SDS-PAGE analysis shown below for each variant is obtained by purifying a culture solution of animal cells expressing each variant using column chromatography and performing 10% SDS-PAGE analysis on the final purified version;

more specifically, FIG. 1A shows SDS-PAGE results for variants HM98, HM99, HM130, HM143, HM71, HM100, HM131, HM72, HM101 and HM114;

in fig. 1B shows SDS-PAGE results for variants HM63, HM102, HM115, HM64, HM103, HM116, HM125, HM132, HM65, HM133, HM144, HM104 and HM117;

in fig. 1C shows SDS-PAGE results for variants HM66, HM105, HM134, HM76, HM106, HM135, HM136 and HM67;

in fig. 1D shows the SDS-PAGE results for variants HM82, HM83, HM84, HM85, HM86, HM88, HM89, HM107, HM118, HM90, HM91, HM92, HM93, HM94 and HM95;

in fig. 1E shows SDS-PAGE results for variants HM73, HM111, HM121, HM139, HM74, HM112 and HM140;

in fig. 1F shows SDS-PAGE results for variants HM75, HM141, HM145, HM70, HM77, HM142, HM78, HM79, HM96, HM146, HM147, HM149 and HM150;

in fig. Figure 2 shows the expression levels of wild-type mature PH20 and the Hyal2 variant, Hyal3 variant, and Hyal4 variant in which the M345 to I361 region of wild-type mature PH20 has been replaced by the corresponding Hyal2, Hyal3, and Hyal4 sequences, respectively, where the CS lane in SDS-PAGE represents culture medium sample, lane FT represents unbound impurity in the HisTag column, and lane E represents the HisTag column eluate;

in fig. 3 shows the results of an SDS-PAGE analysis of various variants based on the PH20 variant having the amino acid sequence SEQ ID NO: 3. The result of the SDS-PAGE analysis shown below for each variant is obtained by purifying a culture solution of animal cells expressing each variant using column chromatography and performing 10% SDS-PAGE analysis on the final purified version;

in fig. 3A shows SDS-PAGE results for variants HM152, HM153, HM154, HM155, HM156, HM157, HM158, HM159, HM160, HM161, HM162, HM163, HM164, HM165, HM166, HM167 and HM167;

in fig. 3B shows SDS-PAGE results for variants HM170, HM171, HM172, HM173, HM174, HM175, HM176, HM177, HM178, HM179, HM180, HM181, HM182, HM183, HM184, HM185 and HM186;

in fig. 3C shows the SDS-PAGE results for variants HM190, HM191, HM192, HM193, HM194, HM195, HM196, HM197, HM198, HM199, HM203, HM204 and HM205;

in fig. 3D shows SDS-PAGE results for variants HM208, HM210, HM211, HM212, HM213, HM214, HM216, HM217, HM218, HM219 and HM220;

in fig. 3E shows SDS-PAGE results for variants HM231, HM232, HM233, HM234, HM235, HM243, HM245 and HM246;

in fig. 3F shows SDS-PAGE results for variants HM254, HM261, HM262, HM263, HM266, HM268, HM271, HM275, HM276, HM279, HM280, HM287 and HM288; And

in fig. 4 shows SDS-PAGE results confirming the thermostability of wild type PH20 (L36-Y482) and variant PH20 (F38-F468) having the amino acid sequence of SEQ ID NO: 3, where lanes A, B, C and D show the results of SDS-PAGE analysis for parental wild-type PH20 (lanes A and C) and variant PH20 SEQ ID NO: 3 (lanes B and D) in reduced form (lanes A and B) and unreduced form (lanes C and D), and lanes E, F , G, and H show the results of SDS-PAGE analysis relative to wild-type parental PH20 (lanes E and G) and variant PH20 SEQ ID NO: 3 (lanes F and H) in reduced form (lanes E and F) and unreduced form (lanes G and H) after storage for 7 days at 42°C.

Detailed Description of the Invention

Unless otherwise specified, all technical and scientific terms used herein have the same meanings as would be understood by those skilled in the art to which the present invention relates. In general, the nomenclature used herein is well known in the art and is commonly used.

In the present invention, the amino acid residue position of each variant is determined from the amino acid sequence of SEQ ID NO: 1, when described on the basis of wild-type PH20, and the amino acid residue position of each variant. refers to the amino acid sequence of SEQ ID NO: 3, when described based on the PH20 variant having SEQ ID NO: 3.

In previous studies, the present inventors have discovered that a variant of hyaluronidase PH20 that includes one or more amino acid residue substitutions in the region corresponding to the alpha helix region and/or its linker region, preferably the alpha helix 8 region (S347-C381) and/or or a linker region (A333-R346) between alpha-helix 7 and alpha-helix 8, in wild-type PH20 having the amino acid sequence of SEQ ID NO: 1, preferably mature wild-type PH20, and optionally having one or more N-terminal and /or C-terminal amino acid residues selectively cleaved and removed, demonstrates superior potency compared to conventional wild-type PH20 or fragments thereof, and a patent application has been filed regarding this discovery (see WO 2020/022791A).

As used herein, the term “mature wild-type PH20” means a protein consisting of amino acid residues L36 to Y482 or L36 to S490 of SEQ ID NO: 1, lacking M1-T35, which forms the signal peptide, and N483-L509 or A491-L509, which are not associated with essential enzymatic function of PH20, in the amino acid sequence SEQ ID NO: 1 of wild type PH20.

In particular, in previous studies, the present inventors have discovered that when amino acid regions corresponding to T341-I361, which are part of the alpha helix 8 region (S347 - C381) and/or the linker region (A333 - R346) between the alpha helix 7 and alpha-helix 8, in wild-type PH20 having the amino acid sequence of SEQ ID NO: 1 are replaced by amino acid residues corresponding to wild-type Hyal1 having the sequence of SEQ ID NO: 2, expression efficiency and enzymatic activity are improved, and fragments in which removed part of the amino acid sequence at the N-terminus and C-terminus, also exhibit excellent expression efficiency and high enzymatic activity.

Table 1. Amino acid sequence of wild-type PH20 and wild-type Hyal1

Amino acid sequence of wild type PH20 (SEQ ID NO: 1)
MGVLKFKHIFFRSFVKSSGVSQIVFTFLLIPCCLTLNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAG KDFLVETIKLGKLLRPNHLWGYYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGTLSIMRSMKSCLLLDNYMETILNPYIINVTLAAKMCSQVLCQEQGVC IRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAFLKPPMETEEPQIFYNASPSTLSATMFIVSILFLIISSVASL Amino acid sequence of wild type Hyal1 (SEQ ID NO: 2)
MAAHLLPICALFLTLLDMAQGFRGPLLPNRPFTTVWNANTQWCLERHGVDVDVSVFDVVANPGQTFRGPDMTIFYSSQLGTYPYYTPTGEPVFGGLPQNASLIAHLARTFQDILAAIPAPDFSGLAVIDWEAWRPRWAFNWDTKDIYRQRSRALVQAQHPDWPAPQVEAVAQDQFQGAARAWMAGTLQLGRALPRGLWGFY GFPDCYNYDFLSPNYTGQCPSGIRAQNDQLGWLWGQSRALYPSIYMPAVLEGTGKSQMYVQHRVAEAFRVAVAAGDPNLPVLPYVQIFYDTTNHFLPLDELEHSLGESAAQGAAGVVLWVSWENTRTKESCQAIKEYMDTTLGPFILNVTSGALLCSQALCSGHGRCVRRTSHPKALLLLNPASFSIQLTPGGGPLSLRGALSLEDQA QMAVEFKCRCYPGWQAPWCERKSMW

Through ongoing research, the present inventors have discovered that a variant having the sequence SEQ ID NO: 3 constructed by replacing the amino acid region corresponding to T341 with wild type I361 PH20 having the amino acid sequence SEQ ID NO: 1 with the corresponding amino acid sequence of wild type Hyal1 , having the sequence SEQ ID NO: 2, still exhibits superior expression efficiency and high enzymatic activity, as well as a markedly improved protein aggregation temperature (Tagg) compared to wild type PH20, although it includes additional amino acid substitutions, deletions and/or insertions residues, and further optionally includes deletions of one or more amino acid residues at the N-terminus and/or C-terminus. Based on this discovery, the present invention has been completed.

Option that has a sequence of SEQ ID NO: 3 is designed by replacing 15 amino acid residues, namely T341S, L342W, S343E, i344N, M345T, S347T, M348K, K349E, L352Q, L353AA, L354555K, N356E, E359D and i361 T in PH20 wild type having the amino acid sequence SEQ ID NO: 1.

In this regard, a PH20 variant or fragment thereof according to the present invention includes the substitution, deletion and/or insertion of one or more amino acid residues in the PH20 variant having the amino acid sequence of SEQ ID NO: 3, and optionally includes the deletion of one or more amino acid residues at the N-terminus and/or C-terminus.

As described above, the variant having the amino acid sequence of SEQ ID NO: 3 is a variant in which amino acid residues T341 to I361 of wild-type PH20 are replaced by the corresponding amino acid residues of wild-type Hyal1 (see Table 2). A variant having the amino acid sequence SEQ ID NO: 3 or a fragment thereof comprising deletion of amino acid residues at the N-terminus and C-terminus was identified as having activity and stability superior to that of wild-type PH20 in a previous study.

Table 2. Amino acid sequence of the PH20 variant in which amino acid residues at positions T341 to I361 from wild-type PH20 are replaced by the corresponding amino acid residues of Hyla1 (SEQ ID NO: 3)

In particular, the PH20 variant or fragment thereof according to the present invention may include one or more mutations, preferably one or more amino acid residue substitutions, deletions and/or insertions in the amino acid sequence SEQ ID NO: 3, and has a higher protein aggregation temperature (Tagg) , which is an indicator of protein stability than wild-type PH20. Moreover, the PH20 variant of the present invention does not include wild-type PH20 of SEQ ID NO: 1.

As used herein, the term “PH20 variant” is intended to include a variant having not only a mutation of one or more amino acid residues, preferably a substitution, deletion and/or insertion of one or more amino acid residues in the amino acid sequence SEQ ID NO: 3, but also a deletion of one or more amino acid residues at its N-terminus or C-terminus, together with substitution, deletion and/or insertion of amino acid residues, and is used substantially in the same sense as the expression "PH20 variant or fragment thereof".

Preferably, the PH20 variant according to the present invention comprises substitution, insertion and/or deletion of amino acid residues at one or more positions selected from the group consisting of R39, D65-L68, N82, T84, I102-I105, T132-Y134, N166, L179-T182, T185-K187, V241-K244, N266-Q269, P271, V272, K290-P292, Q311-K314, G340-N363, L441, S442, D451-D453, D461, V463 and D461-V463 in the version, having the amino acid sequence SEQ ID NO: 3, and has a higher protein aggregation temperature (Tagg) than wild type PH20.

The PH20 variant of the present invention may include a mutation of 20 or less, preferably 17 or less, more preferably 15 or less amino acid positions in the amino acid sequence of SEQ ID NO: 3, without limitation.

More preferably, the PH20 variant or fragment thereof of the present invention includes at least one amino acid residue substitution selected from the group consisting of R39K, D65A, E66A, P67A, L68A, N82A, T84N, I102A, D103A, S104A, S104N, I105A, I105Q , T132A, T132S, F133A, Y134A, N166A, N166K, L179A, L179S, L179I, L179F, S180T, S180A, L181A, L181M, T182A, T185A, E186A, E186D, K187A, V241A, E2 42A, I243A, K244A, N266A, T267A , Q268A, Q268D, Q268I, Q268N, Q269A, P271A, V272A, K290A, I291A, I291G, I291L, P292A, P292D, Q311A, V312A, L313A, L313P, L313M, K314A, G340Q, S3 41H, S341D, S341T, W342I, W342D , W342H, W342L, E343V, E343S, E343Y, E343Q, N344F, N344I, T345E, T345K, T345S, R346M, R346F, R346L, R346T, R346S, R346A, T347Q, T347E, T347V, T3 47W, T347H, T347S, K348Q, K348F , K348D, K348T, K348E, K348M, E349L, E349W, E349A, S350Q, S350I, S350D, S350T, S350E, S350N, Q352E, Q352G, Q352Y, Q352W, Q352T, A353E, A353Y, A3 53H, A353K, I354E, I354Q, I354S , I354V, I354A, I354N, I354T, I354R, I354W, I354L, K355Q, K355H, K355D, E356M, E356F, E356I, E356L, E356Q, E356V, E356D, Y357W, Y357F, M358V, M3 58R, M358Y, M358L, D359K, D359V , D359Y, D359Q, D359T, D359S, D359E, T360Y, T360R, T360L, T360D, T360S, T361M, T361E, T361H, T361L, T361D, T361I, L362A, N363M, N363E, L441A, S4 42A, D451A, D451S, T452A, T452D , T452H, T452K, T452G, T452P, T452M, T452F, D453A, D461R, D461A, G462A, V463Y and V463A in a variant having the amino acid sequence of SEQ ID NO: 3, but not limited to those.

In the present invention, an expression described by a single letter amino acid residue code together with numbers, such as "S341", means an amino acid residue at a specific position in the amino acid sequence SEQ ID NO: 1 or SEQ ID NO: 3.

For example, "S341" means that the amino acid residue at position 341 in the amino acid sequence of SEQ ID NO: 3 is serine, and "S341H" means that the serine at position 341 of SEQ ID NO: 3 is replaced by histidine.

A PH20 variant or fragment thereof according to the present invention is interpreted to include variants or fragments thereof in which an amino acid residue at a particular amino acid residue position is conservatively substituted.

As used herein, the term “conservative substitution” refers to modifications of a PH20 variant that involve replacing one or more amino acids with other amino acids having similar biochemical properties that do not result in a loss of biological or biochemical function of the PH20 variant.

The term "conservative amino acid substitution" refers to the replacement of an amino acid residue with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been identified and are well known in the field to which the present invention relates. These families include amino acids with basic side chains (e.g., lysine, arginine, and histidine), amino acids with acidic side chains (e.g., aspartic acid and glutamic acid), amino acids with uncharged polar side chains (e.g., asparagine, glutamine, serine, threonine, tyrosine and cysteine), amino acids with non-polar side chains (e.g. glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine and tryptophan), amino acids with beta-branched side chains (e.g. threonine, valine and isoleucine) and amino acids with aromatic side chains (eg tyrosine, phenylalanine, tryptophan and histidine).

The PH20 variant or fragments thereof of the present invention have been found to remain active despite the presence of conservative amino acid substitutions.

In addition, a PH20 variant or fragment thereof according to the present invention is interpreted to include PH20 variants or fragments thereof having substantially the same function and/or effect as the PH20 variants or fragment thereof according to the present invention and having amino acid sequence homology of at least 80% or 85%, preferably at least 90%, more preferably at least 95% and most preferably at least 99% with the PH20 variant or fragment thereof according to the present invention.

The PH20 variants or fragments thereof of the present invention have increased expression levels and rates of protein refolding and thus have higher thermal stability than wild-type mature PH20. In addition, the enzymatic activity of the PH20 variants was higher than or similar to that of mature wild-type PH20, despite increased thermostability.

Meanwhile, although the mature wild-type PH20 variant having a gap at the C-terminus is known to have reduced enzymatic activity, the PH20 variants of the present invention exhibit similar or increased enzymatic activity and expression efficiency, as well as high protein aggregation temperatures (Tagg) from - for faster refolding of the protein and its thermostability, despite the fact that one or more amino acid residues at the C-terminus are cleaved or deleted, and/or from 1 to 7, preferably from 1 to 5 amino acid residues at the N-terminus are cleaved or deleted .

Accordingly, a PH20 variant or fragment thereof according to the present invention is characterized in that it includes one or more amino acid mutations, preferably one or more substitutions, deletions and/or insertions of amino acid residues in the variant having the amino acid sequence of SEQ ID NO: 3 or the like. , and one or more amino acid residues at the N-terminus and/or C-terminus are further removed, without limitation.

In one embodiment, the PH20 variant or fragment thereof according to the present invention may be a variant in which the cleavage occurs before an amino acid residue selected from the group consisting of M1-P42 at the N-terminus, preferably before the amino acid residue L36, N37, F38, R39, A40, P41 or P42 at the N-terminus in the amino acid sequence SEQ ID NO: 3, such that one or more amino acid residues at the N-terminus are deleted, and/or the break occurs after an amino acid residue selected from the group consisting of V455-L509, preferably after an amino acid residue selected from the group consisting of V455-S490, most preferably after the amino acid residue V455, D456, C458, D461, C464, I465, D466, A467, F468, K470, P471, P472, M473, E474, T475, E476, P478, I480, Y482, A484, P486, T488 or S490 at the C-terminus, such that one or more amino acid residues at the C-terminus are deleted.

The expression “the cleavage occurs before an amino acid residue selected from the group consisting of M1-P42 at the N-terminus” means that a portion of the amino acid residues immediately before the selected amino acid residue from M1-P42 at the N-terminus is cleaved and removed. The expression “the nick occurs before M1” means that the nick does not occur at the N-terminus.

For example, the expression “the break occurs before amino acid residue L36, N37, F38, R39, A40, P41, or P42” means that all amino acid residues M1 to T35 immediately before L36, all amino acid residues M1 to L36 immediately before N37, all amino acid residues residues M1 to N37 immediately before F38, all amino acid residues M1 to F38 immediately before R39, all amino acid residues M1 to R39 immediately before A40, all amino acid residues M1 to A40 immediately before P41, or all amino acid residues M1 to P41 immediately before P42 in the amino acid sequence SEQ ID NO: 3 according to the present invention is cleaved off and removed.

In addition, the expression “the break occurs after an amino acid residue selected from the group consisting of V455-L509 at the C-terminus” means that a portion of the amino acid residues immediately before the selected amino acid residue from M1-P42 at the N-terminus is cleaved and removed.

For example, the expression “the break occurs after amino acid residue V455, D456, C458, D461, C464, I465, D466, A467, F468, K470, P471, P472, M473, E474, T475, E476, P478, I480, Y482, A484, P486 , T488 or S490 at the C-terminus" means that the amino acid residue after amino acid residue V455, D456, C458, D461, C464, I465, D466, A467, F468, K470, P471, P472, M473, E474, T475, E476, P478 , I480, Y482, A484, P486, T488 or S490 in the amino acid sequence SEQ ID NO: 3 in accordance with the present invention is cleaved and/or all amino acid residues from the amino acid residue immediately after the selected amino acid residue L509 are removed.

Preferably, the new PH20 variant or fragment thereof according to the present invention is characterized in that it includes the substitution, deletion or insertion of an amino acid residue at one or more positions in the variant having the amino acid sequence of SEQ ID NO: 3, and a truncation before F38 at the N-terminus and a truncation after F468 at the C-terminus.

More preferably, the novel PH20 variant or fragment thereof of the present invention may include an amino acid sequence selected from the group consisting of, but not limited to, the amino acid sequences of SEQ ID NO: 163-316.

The sequences of substituted or removed amino acids in the PH20 variant constructed in a particular embodiment according to the present invention are shown in Table 6.

Moreover, the present invention has attempted to increase the expression of the recombinant PH20 protein by using a different signal peptide from proteins highly expressed in animal cells instead of using the original PH20 signal peptide.

Therefore, in another embodiment, the novel PH20 variant of the present invention may be a variant wherein the N-terminus further includes a human growth hormone signal peptide having the amino acid sequence MATGSRTSLLLAFGLLCLPWLQEGSA SEQ ID NO: 4, a human serum albumin signal peptide having the amino acid sequence MKWVTFISLLFLFSSAYS SEQ ID NO: 5, or a human Hyal1 signal peptide having the amino acid sequence MAAHLLPICALFLTLLDMAQG SEQ ID NO: 6, as shown in Table 3 below, instead of the wild type PH20 signal peptide, which consists of M1-T35, without limitation.

The expression "instead of the wild-type PH20 signal peptide which consists of M1-T35" means the case in which the signal peptide in the amino acid sequence of SEQ ID NO: 3 is partially or completely removed and thus does not perform its function. In addition, the expression is intended to include a case in which part of the N-terminus is further removed, for example, a case in which the break occurs before residue N37, F38, R39, A40, P41 or P42, so that an additional deletion of the N-terminus occurs along with deletion of the wild-type PH20 signal peptide.

Table 3. Sequence of the signal peptide according to the present invention

Amino acid sequence SEQ ID NO. Human growth hormone MATGSRTSLLLAFGLLCLPWLQEGSA 4 Human serum albumin MKWVTFISLLFLFSSAYS 5 Hyal1 person MAAHLLPICALFLTLLDMAQG 6

In another aspect, the present invention is directed to a composition for treating cancer containing a new variant of PH20 or a fragment thereof according to the present invention, and a method of treating cancer therewith.

Cancers or carcinomas that can be treated with the new PH20 variant or a fragment thereof according to the present invention are not particularly limited, but include both solid malignancies and hematologic malignancies. The cancer may be selected from the group consisting of skin cancer, such as melanoma, liver cancer, hepatocellular carcinoma, gastric cancer, breast cancer, lung cancer, ovarian cancer, bronchial cancer, nasopharyngeal cancer, laryngeal cancer, pancreatic cancer, urinary cancer bladder, colorectal cancer, colon cancer, cervical cancer, brain cancer, prostate cancer, bone cancer, thyroid cancer, parathyroid cancer, kidney cancer, esophageal cancer, biliary tract cancer, testicular cancer, rectal cancer, head cancer and neck, ureteral cancer, osteosarcoma, neurocytoma, fibrosarcoma, rhabdomyosarcoma, astrocytoma, neuroblastoma and neuroglioma, without limitation. Preferably, the cancer that can be treated with the composition of the present invention may be selected from the group consisting of, but not limited to, colorectal cancer, breast cancer, lung cancer and kidney cancer.

The composition of the present invention may be a pharmaceutical composition. The pharmaceutical composition may further include a pharmaceutically acceptable composition. The composition may contain one or more components selected from the group consisting of lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum arabic, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, which are commonly used in the preparation of medicinal products, without limitation. In addition, the pharmaceutical composition may further contain one or more substances selected from the group consisting of diluents, fillers, lubricants, wetting agents, sweeteners, aromatic hydrocarbons, emulsifiers, suspensions and preservatives, which are commonly used in the preparation of medicinal products.

The pharmaceutical composition can be administered orally or parenterally. Parenteral administration is carried out by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endothelial administration, topical administration, intranasal administration, intrapulmonary administration, rectal administration, and the like. For oral administration, the active ingredient in the oral composition must be included in a coated dosage form or in a dosage form that can protect the active ingredient from degradation in the stomach, given that peptides and proteins are digested in the stomach. Alternatively, the present composition may be administered through any device by which the active ingredient can be transported to the target cell of interest.

The pharmaceutical composition may be prepared in the form of solutions, suspensions, syrups or emulsions in oils or aqueous vehicles, or in the form of extracts, grains, powders, granules, tablets or capsules, and may further include dispersing or stabilizing agents for the purpose of drug formulation.

In particular, the composition for treating cancer according to the present invention can be used in combination therapy with other anticancer drugs.

The anti-cancer drug that can be used in combination therapy with the novel PH20 variant or a fragment thereof according to the present invention is preferably a chemical anti-cancer drug, an antibody-based anti-cancer drug, a biological anti-cancer drug, RNAi or a cellular therapeutic agent, without limitation. .

Preferably, the anticancer drug that can be used in combination therapy with the novel PH20 variant or fragment thereof according to the present invention is preferably an immuno-oncology agent, and more preferably an immune checkpoint inhibitor, without limitation.

In addition, the present invention is directed to a method of treating cancer using a new variant or fragment of PH20 in combination with other anticancer agents, in particular the anticancer agents described above.

In another aspect, the present invention is directed to a nucleic acid encoding a PH20 variant or fragment thereof.

Nucleic acids used herein may be present in cells, in a cell lysate, or in partially purified or substantially pure form. "Isolated" or "substantially pure" when referring to nucleic acids refers to those nucleic acids that have been purified and thus separated from other cellular components or other contaminants, such as other cellular nucleic acids or proteins, using standard methods, including alkali treatment/SDS treatment, CsCl coupling, column chromatography, agarose gel electrophoresis and others well known in the art. The nucleic acids of the present invention may be DNA or RNA.

In yet another aspect, the present invention is directed to a recombinant expression vector comprising a nucleic acid. To express a PH20 variant or fragment thereof according to the present invention, DNA encoding the PH20 variant or fragment thereof can be obtained by standard molecular biology techniques (e.g., PCR amplification or cDNA cloning using a hybridoma that expresses the PH20 variant), and the DNA can be inserted into expression vector so that it will be “operably linked” to sequences that control transcription and translation.

As used herein, the term "operably linked" is intended to mean that a gene encoding a PH20 variant or a fragment thereof is ligated into a vector such that transcriptional and translational control sequences serve its intended functions of regulating transcription and translation of the gene encoding a PH20 variant or a fragment thereof. fragment. The expression vector and expression control sequences are selected to be compatible with the expression host cell used. The genes encoding PH20 are inserted into the expression vector by standard methods (eg, by ligating complementary restriction enzyme sites on the gene fragment encoding the PH20 variant or fragment thereof and the vector, or by blunt-end ligation if restriction enzyme sites are not present).

In addition, the recombinant expression vectors carry regulatory sequences that control the expression of the gene encoding the PH20 variant or a fragment thereof in a host cell. The term "regulatory sequence" includes promoters, enhancers and other expression control elements (eg, polyadenylation signals) that control the transcription or translation of genes encoding a PH20 variant or fragment thereof. Those skilled in the art will appreciate that the design of an expression vector, including the choice of regulatory sequences, may depend on factors such as the choice of host cell for transformation, the level of protein expression desired, and the like.

In yet another aspect, the present invention is directed to a host cell including a nucleic acid or vector. The host cell of the present invention is preferably selected from the group consisting of, but not limited to, animal cells, plant cells, yeast, E. coli and insect cells.

In particular, the host cell of the present invention includes prokaryotic cells such as E. coli, Bacillus subtilis, Streptomyces sp., Pseudomonas sp., Proteus mirabilis or Staphylococcus sp., fungi such as Aspergillus sp., Yeast such as Pichia pastoris, Saccharomyces cerevisiae, Schizosaccharomyces sp. and Neurospora crassa, and eukaryotic cells such as lower eukaryotic cells, and higher other eukaryotic cells such as insect cells.

In addition, host cells that can be used in the present invention can be obtained from plants or mammals. Preferably, examples of host cells include, but are not limited to, monkey kidney cells (COS7), NSO cells, SP2/0 cells, Chinese hamster ovary (CHO) cells, W138, baby hamster kidney (BHK) cells, MDCK cells, myeloma cells, HuT 78 and HEK293 cells. More preferred is the use of CHO cells.

The nucleic acid or vector is transfected into a host cell. Transfection can be performed using a variety of techniques commonly used to introduce foreign nucleic acid (DNA or RNA) into prokaryotic or eukaryotic cells, such as electrophoresis, calcium phosphate precipitation, DEAE-dextran transfection, or lipofection. Various combinations of recombinant expression vectors and host cells can be used to express the PH20 variant or fragment thereof of the present invention. A preferred expression vector for eukaryotic cells includes gene expression regulatory sequences derived from, but not limited to, SV40, bovine papillomavirus, adenovirus, adeno-associated virus, cytomegalovirus, and retrovirus. Expression vectors that can be used for bacterial hosts include bacterial plasmids such as pET, pRSET, pBluescript, pGEX2T, pUC vectors, col E1, pCR1, pBR322, pMB9 and their derivatives derived from E. coli; a broad host range plasmid such as RP4; phage DNAs represented by various lambda phage derivatives such as λgt10, λgt11 and NM989; and other DNA phages such as M13 and filamentous single-stranded DNA phage. The expression vector available to yeast cells may be a 2 μm plasmid and derivatives thereof. Expression vectors for insect cells include pVL941.

In another aspect, the present invention is directed to a method for producing a PH20 variant or fragment thereof, the method comprising culturing a host cell and expressing the PH20 variant or fragment thereof according to the present invention.

When a recombinant expression vector capable of expressing a PH20 variant or fragment thereof is introduced into mammalian host cells, the PH20 variant or fragment thereof can be obtained by culturing the host cells for a period of time in which the PH20 variant or fragment thereof is expressed. in host cells, it is preferable for such a period of time that the PH20 variant is secreted into the medium during culture of the host cells.

In an alternative embodiment, the expressed PH20 variant or fragment thereof can be isolated and purified from host cells. Isolation or purification of a PH20 variant or fragment thereof can be accomplished by conventional isolation/purification methods (eg, chromatography) that are used for proteins. The chromatography may include a combination of one or more selected from, but not limited to, affinity chromatography, ion exchange chromatography, and hydrophobic interaction chromatography. In addition to chromatography, a combination of filtration, ultrafiltration, salting out, dialysis, etc. may be used.

To confirm the industrial applicability of an enzyme, it is necessary to analyze the catalytic reaction rate of the enzyme. Types of enzymatic reactions include fixed-site enzymatic reaction with fixed reactivity and multi-site enzymatic reaction with varying reactivity. It is known that the catalytic reaction rate of enzymes having an active site with a fixed reactivity, such as hyaluronidase, corresponds to the Michaelis-Menten rate formula.

Michaelis-Menten enzymatic kinetics is based on the assumption that the enzymatic reaction is a two-step reaction system, including a reversible reaction step in which the [ES] enzyme (E)-substrate (S) complex is formed, and an irreversible reaction step in which the ES complex dissociates with the formation of Product (P). In this case, k _f , k _r and k _cat are the reaction rate constants in each direction (Alan Fersht (1977) Enzyme structure and mechanism).

The enzymatic reaction assumes that the process of the enzyme interacting with the substrate to form the ES complex quickly reaches equilibrium, or it can be considered as a pseudo-stationary state, assuming that d[ES]/dt 0 is satisfied by significantly reducing the enzyme concentration by conducting a reaction that maintains a sufficiently high substrate concentration. Because rate equations assuming fast equilibrium or pseudo-steady state are derived in the same way, most experiments assume a pseudo-steady state in which the substrate concentration is initially higher than the enzyme concentration.

Under conditions such as "the amount of enzyme is constant before and after the reaction" and "when a chemical reaction reaches chemical equilibrium, the rate of reaction at which a product is produced is equal to the rate at which the product decomposes again", using this assumption, the rate of reaction of the final product can be expressed by the following Michaelis-Menten velocity formula. In this case, K _M = (k _r + k _cat ) / k _f , and V _max = k _cat [E] ₀ .

The Lineweaver-Burk equation is used to experimentally analyze the rate of an enzymatic reaction using the Michaelis-Menten rate formula. This equation shows the relationship between the reciprocal 1/V of an experimentally measured reaction rate and the reciprocal 1/[S] of a given substrate concentration in the experiment. A statistical test that this equation is a linear equation demonstrates that the enzyme reaction is a reaction that conforms to the Michaelis-Menten rate formula, and K _M and V _max can be calculated using this equation.

Enzymes that catalyze a chemical reaction have a transition state after binding to a substrate at the active site, and the activation energy to achieve a high energy transition state is reduced by multiple bonds to the substrate. The equilibrium constant to achieve this transition state is proportional to k _cat /K _M . Here 1/K _M is an index that combines the degree to which the enzyme-substrate complex is formed by binding of the enzyme to the substrate with the degree to which the enzyme-substrate complex is maintained without degradation, and k _cat is the equilibrium constant at which the product is obtained from the enzyme-substrate complex. Therefore, k _cat /K _M can be said to be an indicator of how much product can be obtained from the substrate and enzyme, that is, the catalytic efficiency of the enzyme.

The availability of hyaluronidase is proportional to its catalytic efficiency. In particular, when the enzyme is administered subcutaneously along with a polymeric pharmacologically active substance, such as a monoclonal antibody, the catalytic efficiency of hyaluronidase plays an important role. In the case where the variant according to the present invention has a higher k _cat /K _M value than the wild type PH20, when hyaluronidase in combination with a polymeric pharmacologically active substance is administered subcutaneously, the hyaluronic acid present therein is quickly degraded and thus can be obtain a superior effect of a rapidly dispersing pharmacologically active substance. In addition, when the variant of the present invention has a higher k _cat value than the wild type PH20, the maximum reaction rate V _max increases at the same enzyme concentration, thereby providing superior effects of decomposing more hyaluronic acid within the same period of time and distributing pharmacologically active substance in a wider area.

Therefore, to confirm the enzymatic properties of the PH20 variant according to the present invention, the enzymatic reaction rate of each variant was analyzed and in Example 4, V _max (maximum enzymatic reaction rate), K _M (substrate concentration assuming 50% V _max ), k _cat (conversion rate substrate) and k _cat /K _M (enzyme catalyst efficiency). The results described above demonstrate that the PH20 variant of the present invention is superior to wild type PH20.

Examples

Hereinafter, the present invention will be described in more detail with reference to examples. However, it will be apparent to those skilled in the art that these examples are presented to illustrate the present invention only and should not be construed as limiting the scope of the present invention.

Example 1: Creating PH20 variants

To construct PH20 variants, cDNA (clone ID: hMU002604) for wild-type PH20 was purchased from the Korean Human Gene Bank. Wild-type PH20 encodes amino acids L36 to S490. The PH20 gene was amplified by polymerase chain reaction (hereinafter referred to as PCR) and inserted into the XhoI and NotI restriction enzyme sites of the pcDNA3.4-TOPO vector. For expression in ExpiCHO cells, human growth hormone, human serum hormone, or human Hyal1 signal peptide was used as the signal peptide instead of the original PH20 signal peptide. For protein purification using a HisTrap column, the His tag DNA sequence was located at the 3′ end of the PH20 cDNA. Amino acid substitutions of PH20 variants were performed using PCR, and amino acid substitutions were confirmed by DNA sequencing.

The list of primers used in cloning PH20 variants is summarized in Table 4 below, and the specific primer sequences are summarized in Table 5 below.

Table 4 List of primers used when cloning PH20 variants according to the present invention

Clone Primer 1 2 3 cB4205 ALB-SP-Xho B4-hy2 SPAM1-6H-not cB4206 ALB-SP-Xho B4-hy3 SPAM1-6H-not cB4207 ALB-SP-Xho B4-hy4 SPAM1-6H-not cB4213-m63 opB4-Xho-hSA op-F468-6H-not - cB4213-m64 opB4-Xho-hSA op-Q347-m64 op-F468-6H-not cB4213-m65 op-Xho-hSA-L op-Q348-m65 op-F468-R cB4213-m66 op-Xho-hSA-L op-Q350-m66 op-F468-R cB4213-m67 opB4-Xho-hSA op-Q355-m67 op-F468-6H-not cB4213-m69 op-Xho-hSA-L op-V358-m69 op-F468-6H-not cB4213-m70 op-Xho-hSA-L op-A362-m70 op-F468-6H-not cB4213-m71 opB4-Xho-hSA op-V343-m71 op-F468-6H-not cB4213-m72 opB4-Xho-hSA op-F344-m72 op-F468-6H-not cB4213-m73 op-Xho-hSA-L op-K359-mega-NL73 op-F468-6H-not cB4213-m74 op-Xho-hSA-L op-Y360-m74 op-F468-6H-not cB4213-m75 opB4-Xho-hSA op-M361-m75 op-F468-6H-not cB4213-m76 opB4-Xho-hSA op-E352-m76 op-F468-6H-not cB4213-m77 opB4-Xho-hSA op-M363-m77 op-F468-6H-not cB4213-m78 opB4-Xho-hSA op-N84-m78 op-F468-6H-not cB4213-m79 opB4-Xho-hSA op-K166-m79 op-F468-6H-not cB4213-m82 op-Xho-hSA-L op-354E-m82 op-F468-6H-not cB4213-m83 op-Xho-hSA-L op-354Q-m83 op-F468-6H-not cB4213-m84 op-Xho-hSA-L op-354S-m84 op-F468-6H-not cB4213-m85 op-Xho-hSA-L op-354V-m85 op-F468-6H-not cB4213-m86 op-Xho-hSA-L op-354A-m86 op-F468-6H-not cB4213-m88 op-Xho-hSA-L op-354N-m88 op-F468-6H-not cB4213-m89 op-Xho-hSA-L op-354T-m89 op-F468-6H-not cB4213-m90 op-Xho-hSA-L op-356M-m90 op-F468-6H-not cB4213-m91 op-Xho-hSA-L op-356F-m91 op-F468-6H-not cB4213-m92 op-Xho-hSA-L op-356I-m92 op-F468-6H-not cB4213-m93 op-Xho-hSA-L op-356L-m93 op-F468-6H-not cB4213-m94 op-Xho-hSA-L op-356Q-m94 op-F468-6H-not cB4213-m95 op-Xho-hSA-L op-356V-m95 op-F468-6H-not cB4213-m96 op-Xho-hSA-L op-343V_364M-m96 op-F468-6H-not cB4213-m97 op-Xho-hSA-L op-340Q-m97 op-F468-6H-not cB4213-m98 op-Xho-hSA-L op-341H-m98 op-F468-6H-not cB4213-m99 op-Xho-hSA-L op-342I-m99 op-F468-6H-not cB4213-m100 op-Xho-hSA-L op-343Y-m100 op-F468-6H-not cB4213-m101 op-Xho-hSA-L op-345E-m101 op-F468-6H-not cB4213-m102 op-Xho-hSA-L op-346F-m102 op-F468-6H-not cB4213-m103 op-Xho-hSA-L op-347E-m103 op-F468-6H-not cB4213-m104 op-Xho-hSA-L op-349L-m104 op-F468-6H-not cB4213-m105 op-Xho-hSA-L op-350I-m105 op-F468-6H-not cB4213-m106 op-Xho-hSA-L op-352G-m106 op-F468-6H-not cB4213-m107 op-Xho-hSA-L op-354R-m107 op-F468-6H-not cB4213-m110 op-Xho-hSA-L op-358R-m110 op-F468-6H-not cB4213-m111 op-Xho-hSA-L op-359V-m111 op-F468-6H-not cB4213-m112 op-Xho-hSA-L op-360R-m112 op-F468-6H-not cB4213-m114 op-Xho-hSA-L op-345K-m114 op-F468-6H-not cB4213-m115 op-Xho-hSA-L op-346L-m115 op-F468-6H-not cB4213-m116 op-Xho-hSA-L op-347V-m116 op-F468-6H-not cB4213-m117 op-Xho-hSA-L op-349W-m117 op-F468-6H-not cB4213-m118 op-Xho-hSA-L op-354W-m118 op-F468-6H-not cB4213-m121 op-Xho-hSA-L op-359Y-m121 op-F468-6H-not cB4213-m125 op-Xho-hSA-L op-347W-m125 op-F468-6H-not cB4213-m126 op-Xho-hSA-L op-357W-m126 op-F468-6H-not cB4213-m130 op-Xho-hSA-L op-342D-m130 op-F468-6H-not cB4213-m131 op-Xho-hSA-L op-343Q-m131 op-F468-6H-not cB4213-m132 op-Xho-hSA-L op-347H-m132 op-F468-6H-not cB4213-m133 op-Xho-hSA-L op-348F-m133 op-F468-6H-not cB4213-m134 op-Xho-hSA-L op-350D-m134 op-F468-6H-not cB4213-m135 op-Xho-hSA-L op-352Y-m135 op-F468-6H-not cB4213-m136 op-Xho-hSA-L op-353E-m136 op-F468-6H-not cB4213-m138 op-Xho-hSA-L op-358Y-m138 op-F468-6H-not cB4213-m139 op-Xho-hSA-L op-359Q-m139 op-F468-6H-not cB4213-m140 op-Xho-hSA-L op-360L-m140 op-F468-6H-not cB4213-m141 op-Xho-hSA-L op-361E-m141 op-F468-6H-not cB4213-m142 op-Xho-hSA-L op-363E-m142 op-F468-6H-not cB4213-m143 op-Xho-hSA-L op-342H-m143 op-F468-6H-not cB4213-m144 op-Xho-hSA-L op-348D-m144 op-F468-6H-not cB4213-m145 op-Xho-hSA-L op-361H-m145 op-F468-6H-not cB4213-m146 opB4-Xho-hSA Op-R39-m146-R op-F468-6H-not cB4213-m147 opB4-Xho-hSA Op-A40-m147-R op-F468-6H-not cB4213-m149 opB4-Xho-hSA op-D456-6H-not - cB4213-m150 op-Xho-hSA-L op-350Q360R-m150 op-F468-6H-not cB4213-m152 opB4-Xho-hSA Op-m152-D65A-R op-F468-6H-not cB4213-m153 opB4-Xho-hSA Op-m153-E66A-R op-F468-6H-not cB4213-m154 opB4-Xho-hSA Op-m154-P67A-R op-F468-6H-not cB4213-m155 opB4-Xho-hSA Op-m155-L68A-R op-F468-6H-not cB4213-m156 op-Xho-hSA-L op-311A-m156 op-F468-6H-not cB4213-m157 op-Xho-hSA-L op-312A-m157 op-F468-6H-not cB4213-m158 op-Xho-hSA-L op-313A-m158 op-F468-6H-not cB4213-m159 op-Xho-hSA-L op-314A-m159 op-F468-6H-not cB4213-m160 op-Xho-hSA-L N266A-m160 op-F468-6H-not cB4213-m161 op-Xho-hSA-L T267A-m161 op-F468-6H-not cB4213-m162 op-Xho-hSA-L Q268A-m162 op-F468-6H-not cB4213-m163 op-Xho-hSA-L Q269A-m163 op-F468-6H-not cB4213-m164 op-Xho-hSA-L P271A-m164 op-F468-6H-not cB4213-m165 op-Xho-hSA-L V272A-m165 op-F468-6H-not cB4213-m166 opB4-Xho-hSA Op-m166-I102A-R op-F468-6H-not cB4213-m167 opB4-Xho-hSA Op-m167-D103A-R op-F468-6H-not cB4213-m168 opB4-Xho-hSA Op-m168-S104A-R op-F468-6H-not cB4213-m169 opB4-Xho-hSA Op-m169-I105A-R op-F468-6H-not cB4213-m170 op-Xho-hSA-L op-m170-T132A-R op-F468-6H-not cB4213-m171 op-Xho-hSA-L op-m171-F133A-R op-F468-6H-not cB4213-m172 op-Xho-hSA-L op-m172-Y134A-R op-F468-6H-not cB4213-m173 op-Xho-hSA-L V241A-m173 op-F468-6H-not cB4213-m174 op-Xho-hSA-L E242A-m174 op-F468-6H-not cB4213-m175 op-Xho-hSA-L I243A-m175 op-F468-6H-not cB4213-m176 op-Xho-hSA-L K244A-m176 op-F468-6H-not cB4213-m177 opB4-Xho-hSA Op-m177-L179A-R op-F468-6H-not cB4213-m178 opB4-Xho-hSA Op-m178-S180A-R op-F468-6H-not cB4213-m179 opB4-Xho-hSA Op-m179-L181A-R op-F468-6H-not cB4213-m180 opB4-Xho-hSA Op-m180-T182A-R op-F468-6H-not cB4213-m181 opB4-Xho-hSA Op-m181-T185A-R op-F468-6H-not cB4213-m182 opB4-Xho-hSA Op-m182-E186A-R op-F468-6H-not cB4213-m183 opB4-Xho-hSA Op-m183-K187A-R op-F468-6H-not cB4213-m184 op-Xho-hSA-L op-K290A-m184 op-F468-6H-not cB4213-m185 op-Xho-hSA-L op-I291A-m185 op-F468-6H-not cB4213-m186 op-Xho-hSA-L op-P292A-m186 op-F468-6H-not cB4213-m190 op-Xho-hSA-L L441A-m190 op-F468-6H-not cB4213-m191 op-Xho-hSA-L S442A-m191 op-F468-6H-not cB4213-m192 opB4-Xho-hSA op-D451A-m192 op-F468-6H-not cB4213-m193 opB4-Xho-hSA op-T452A-m193 op-F468-6H-not cB4213-m194 op-Xho-hSA-L op-D453A-m194 op-F468-6H-not cB4213-m195 op-Xho-hSA-L op-D461A-6H-not op-F468-6H-not cB4213-m196 op-Xho-hSA-L op-G462A-6H-not op-F468-6H-not cB4213-m197 op-Xho-hSA-L op-V463A-6H-not op-F468-6H-not cB4213-m198 op-Xho-hSA-L op-N82A-m198-R op-F468-6H-not cB4213-m199 op-Xho-hSA-L op-N166A-m199-R op-F468-6H-not cB4213-m203 op-Xho-hSA-L Op-S104N-m203-R op-F468-6H-not cB4213-m204 op-Xho-hSA-L Op-I105Q-m204-R op-F468-6H-not cB4213-m205 op-Xho-hSA-L op-Q268D-m205-F op-F468-6H-not cB4213-m208 op-Xho-hSA-L op-Q268I-m208-F op-F468-6H-not cB4213-m210 op-Xho-hSA-L op-291G-m210-F op-F468-6H-not cB4213-m211 op-Xho-hSA-L op-292D-m211-F op-F468-6H-not cB4213-m212 op-Xho-hSA-L op-T452D-m212 op-F468-6H-not cB4213-m213 op-Xho-hSA-L op-T452H-m213 op-F468-6H-not cB4213-m214 op-Xho-hSA-L op-T452K-m214 op-F468-6H-not cB4213-m216 op-Xho-hSA-L Op-T452G-m216 op-F468-6H-not cB4213-m217 op-Xho-hSA-L Op-T452P-m217 op-F468-6H-not cB4213-m218 op-Xho-hSA-L op-T452M-m218 op-F468-6H-not cB4213-m219 op-Xho-hSA-L op-T452F-m219 op-F468-6H-not cB4213-m220 op-Xho-hSA-L op-D461R-6H-not-m220 op-F468-6H-not cB4213-m231 op-Xho-hSA-L op-V463Y-6H-not-m231 - cB4213-m232 op-Xho-hSA-L op-S180T-R-m232 op-F468-6H-not cB4213-m233 op-Xho-hSA-L op-D451S-F-m233 op-F468-6H-not cB4213-m234 op-Xho-hSA-L op-L313P-m234-F op-F468-6H-not cB4213-m235 op-Xho-hSA-L op-L313M-m235-F op-F468-6H-not cB4213-m243 op-Xho-hSA-L op-L179S-m243-R op-F468-6H-not cB4213-m245 op-Xho-hSA-L op-L179I-m245-R op-F468-6H-not cB4213-m246 op-Xho-hSA-L op-L179F-m246-R op-F468-6H-not cB4213-m254 op-Xho-hSA-L FQQ-Mega-m254 op-F468-6H-not cB4213-m261 op-Xho-hSA-L op-Q268N-m259-m op-F468-6H-not cB4213-m262 op-Xho-hSA-L B4-124-R op-F468-6H-not cB4213-m263 op-Xho-hSA-L B4-124-R op-F468-6H-not cB4213-m266 op-Xho-hSA-L op-L181M,E186D-m266 op-F468-6H-not cB4213-m268 opB4-Xho-hSA op-Q268A-m268-m op-F468-6H-not cB4213-m271 opB4-Xho-hSA op-344I,348M-m271 op-F468-6H-not cB4213-m275 op-Xho-hSA-L op-DLSS-m275 op-F468-6H-not cB4213-m276 op-Xho-hSA-L op-DLS-m276 op-F468-6H-not cB4213-m279 opB4-Xho-hSA Op-K348M-m279 op-F468-6H-not cB4213-m280 opB4-Xho-hSA Op-N344I K348M-m280 op-F468-6H-not cB4213-m287 op-Xho-hSA-L Q268A-m162 op-F468-6H-not cB4213-m288 opB4-Xho-hSA Q268A-m162 op-F468-6H-not

Table 5. Primer sequences used for cloning PH20 variants

Primer SEQ ID NO. Nucleotide sequence (5'->3') B4-hy2 7 ATA TGG GGA ACC CTC AGT ATA ACT ACA AGC ACT GAG ACC TGC CAA TAT CTG AAG GAT TAC CTG ACC AGA CTG CTG AAT CCT TAC ATA ATC AAC B4-hy3 8 ATA TGG GGA ACC CTC AGT ATA TCC AGC AGT GAG GAA GAA TGC TGG CAT TTG CAC GAT TAC CTG GTA GAC ACA CTG AAT CCT TAC ATA ATC AAC B4-hy4 9 ATA TGG GGA ACC CTC AGT ATA ACC GCA TCT AAG GCA AAC TGC ACA AAA GTA AAA CAA TTC GTC TCC AGT GAT CTG AAT CCT TAC ATA ATC AAC ALB-SP-Xho 10 GAA TAT CTC GAG GCC ACC ATG AAG TGG GTT ACA SPAM1-6H-not eleven CTA ATT GCG GCC GCT CAT TAG TGG TGA TGG TGA TGA TGG AAG AAA CCA ATT CTG C op-F468-R 12 AAT TAG GCG GCC GCC TAT TAA AAG GCG TCG ATG CAC ACG CCA TC op-F468-6H-not 13 CTC TAA TTG CGG CCG CTC ATT AGT GGT GAT GGT GAT GAT GAA AGG CGT CGA TGC ACA CGC CAT C op-Xho-hSA-L 14 AAT TAG AGC TCG AGG CCA CCA TGA AAT GGG TGA CCT TTA TCT CC opB4-Xho-hSA 15 CAG ATT CTC GAG GCC ACC ATG AAA TGG G op-Q347-m64 16 ATC TGG GGC TCC TGG GAG AAC ACC AGG CAG AAG GAG AGC TGC CAG GCC ATC op-Q348-m65 17 ATC TGG GGC TCC TGG GAG AAC ACC AGG ACC CAG GAG AGC TGC CAG GCC ATC AAG op-Q350-m66 18 AGA ACA CCA GGA CCA AGG AGC AAT GCC AGG CCA TCA AGG AGT AC op-Q355-m67 19 AGG AGA GCT GCC AGG CCA TCC AGG AGT ACA TGG ACA CAA CCC TG op-V358-m69 20 AGC TGC CAG GCC ATC AAG GAG TAC GTG GAC ACA ACC CTG AAC CCT TAT ATC op-A362-m70 21 AGG AGT ACA TGG ACA CAA CCG CGA ACC CTT ATA TCA TCA ATG op-V343-m71 22 ATC GTG ATC TGG GGC TCC TGG GTG AAC ACC AGG ACC AAG GAG AG op-F344-m72 23 ATC TGG GGC TCC TGG GAG TTC ACC AGG ACC AAG GAG AGC TG op-K359-mega-NL73 24 AGC TGC CAG GCC ATC AAG GAG TAC ATG AAA ACA ACC CTG AAC CCT TAT ATC op-Y360-m74 25 ATC AAG GAG TAC ATG GAC TAC ACC CTG AAC CCT TAT ATC ATC op-M361-m75 26 ATC AAG GAG TAC ATG GAC ACA ATG CTG AAC CCT TAT ATC ATC op-E352-m76 27 ACC AGG ACC AAG GAG AGC TGC GAG GCC ATC AAG GAG TAC ATG G op-M363-m77 28 AGT ACA TGG ACA CAA CCC TGA TGC CTT ATA TCA TCA ATG TGA C op-N84-m78 29 TAG AAG ATT GTC ACG CCC TGG CCG TTG GCA TTG ATC CGA GGA GAG C op-K166-m79 thirty TGC ACC AGC TCG ATG GAC CGT TTC TTA TAC ACG TCC TTA GGC TTC op-354E-m82 31 year ACC AAG GAG AGC TGC CAG GCC GAA AAG GAG TAC ATG GAC ACA ACC op-354Q-m83 32 ACC AAG GAG AGC TGC CAG GCC CAA AAG GAG TAC ATG GAC ACA ACC op-354S-m84 33 ACC AAG GAG AGC TGC CAG GCC TCT AAG GAG TAC ATG GAC ACA ACC op-354V-m85 34 ACC AAG GAG AGC TGC CAG GCC GTC AAG GAG TAC ATG GAC ACA ACC op-354A-m86 35 year ACC AAG GAG AGC TGC CAG GCC GCG AAG GAG TAC ATG GAC ACA ACC op-354N-m88 36 ACC AAG GAG AGC TGC CAG GCC AAC AAG GAG TAC ATG GAC ACA ACC op-354T-m89 37 ACC AAG GAG AGC TGC CAG GCC ACC AAG GAG TAC ATG GAC ACA ACC op-356M-m90 38 AAG GAG AGC TGC CAG GCC ATC AAG ATG TAC ATG GAC ACA ACC CTG AAC op-356F-m91 39 AAG GAG AGC TGC CAG GCC ATC AAG TTC TAC ATG GAC ACA ACC CTG AAC op-356I-m92 40 AAG GAG AGC TGC CAG GCC ATC AAG ATA TAC ATG GAC ACA ACC CTG AAC op-356L-m93 41 AAG GAG AGC TGC CAG GCC ATC AAG TTG TAC ATG GAC ACA ACC CTG AAC op-356Q-m94 42 AAG GAG AGC TGC CAG GCC ATC AAG CAG TAC ATG GAC ACA ACC CTG AAC op-356V-m95 43 AAG GAG AGC TGC CAG GCC ATC AAG GTA TAC ATG GAC ACA ACC CTG AAC op-343V_364M-m96 44 ATC GTG ATC TGG GGC TCC TGG GTG AAC ACC AGG ACC AAG GAG AGC TGC CAG GCC ATC AAG GAG TAC ATG GAC ACA ATG CTG AAC CCT TAT ATC ATC op-340Q-m97 45 AGC TAG CGG CAT CGT GAT CTG GCA ATC CTG GGA GAA CAC CAG GAC C op-341H-m98 46 AGC GGC ATC GTG ATC TGG GGC CAC TGG GAG AAC ACC AGG ACC AAG op-342I-m99 47 AGC GGC ATC GTG ATC TGG GGC TCC ATT GAG AAC ACC AGG ACC AAG GAG op-343Y-m100 48 ATC GTG ATC TGG GGC TCC TGG TAT AAC ACC AGG ACC AAG GAG AG op-345E-m101 49 ATC GTG ATC TGG GGC TCC TGG GAG AAC GAA AGG ACC AAG GAG AGC TGC C op-346F-m102 50 ATC TGG GGC TCC TGG GAG AAC ACC TTC ACC AAG GAG AGC TGC CAG GC op-347E-m103 51 ATC TGG GGC TCC TGG GAG AAC ACC AGG GAA AAG GAG AGC TGC CAG GCC ATC op-349L-m104 52 ATC TGG GGC TCC TGG GAG AAC ACC AGG ACC AAG TTG AGC TGC CAG GCC ATC AAG G op-350I-m105 53 AGA ACA CCA GGA CCA AGG AGA TCT GCC AGG CCA TCA AGG AG op-352G-m106 54 ACC AGG ACC AAG GAG AGC TGC GGG GCC ATC AAG GAG TAC ATG GAC op-354R-m107 55 ACC AAG GAG AGC TGC CAG GCC AGA AAG GAG TAC ATG GAC ACA AC op-358R-m110 56 AGC TGC CAG GCC ATC AAG GAG TAC CGG GAC ACA ACC CTG AAC CCT TAT ATC op-359V-m111 57 AGG CCA TCA AGG AGT ACA TGG TCA CAA CCC TGA ACC CTT ATA TC op-360R-m112 58 AGG CCA TCA AGG AGT ACA TGG ACA GAA CCC TGA ACC CTT ATA TCA TC op-345K-m114 59 ATC TGG GGC TCC TGG GAG AAC AAG AGG ACC AAG GAG AGC TGC CAG op-346L-m115 60 ATC TGG GGC TCC TGG GAG AAC ACC CTG ACC AAG GAG AGC TGC CAG GC op-347V-m116 61 ATC TGG GGC TCC TGG GAG AAC ACC AGG GTC AAG GAG AGC TGC CAG GCC ATC op-349W-m117 62 ATC TGG GGC TCC TGG GAG AAC ACC AGG ACC AAG TGG AGC TGC CAG GCC ATC AAG GAG op-354W-m118 63 ACC AAG GAG AGC TGC CAG GCC TGG AAG GAG TAC ATG GAC ACA AC op-359Y-m121 64 AGG CCA TCA AGG AGT ACA TGT ACA CAA CCC TGA ACC CTT ATA TC op-347W-m125 65 ATC TGG GGC TCC TGG GAG AAC ACC AGG TGG AAG GAG AGC TGC CAG GCC ATC op-357W-m126 66 AGC TGC CAG GCC ATC AAG GAG TGG ATG GAC ACA ACC CTG AAC CC op-342D-m130 67 AGC GGC ATC GTG ATC TGG GGC TCC GAC GAG AAC ACC AGG ACC AAG GAG op-343Q-m131 68 ATC GTG ATC TGG GGC TCC TGG CAG AAC ACC AGG ACC AAG GAG AGC op-347H-m132 69 ATC TGG GGC TCC TGG GAG AAC ACC AGG CAC AAG GAG AGC TGC CAG GCC ATC op-348F-m133 70 ATC TGG GGC TCC TGG GAG AAC ACC AGG ACC TTC GAG AGC TGC CAG GCC ATC AAG op-350D-m134 7 AGA ACA CCA GGA CCA AGG AGG ACT GCC AGG CCA TCA AGG AGT AC op-352Y-m135 72 ACC AGG ACC AAG GAG AGC TGC TAC GCC ATC AAG GAG TAC ATG GAC AC op-353E-m136 73 AGG ACC AAG GAG AGC TGC CAG GAA ATC AAG GAG TAC ATG GAC AC op-358Y-m138 74 AGC TGC CAG GCC ATC AAG GAG TAC TAC GAC ACA ACC CTG AAC CCT TAT ATC op-359Q-m139 75 AGG CCA TCA AGG AGT ACA TGC AGA CAA CCC TGA ACC CTT ATA TC op-360L-m140 76 AGG CCA TCA AGG AGT ACA TGG ACC TAA CCC TGA ACC CTT ATA TCA TC op-361E-m141 77 ATC AAG GAG TAC ATG GAC ACA GAG CTG AAC CCT TAT ATC ATC AAT G op-363E-m142 78 AGT ACA TGG ACA CAA CCC TGG AGC CTT ATA TCA TCA ATG TGA C op-342H-m143 79 AGC GGC ATC GTG ATC TGG GGC TCC CAT GAG AAC ACC AGG ACC AAG GAG op-348D-m144 80 ATC TGG GGC TCC TGG GAG AAC ACC AGG ACC GAC GAG AGC TGC CAG GCC ATC AAG op-361H-m145 81 ATC AAG GAG TAC ATG GAC ACA CAC CTG AAC CCT TAT ATC ATC AAT G Op-R39-m146-R 82 TTT GGA ATC ACA GGA GGA GCC CGA GAG TAT GCG GAG CTA AAC AG Op-A40-m147-R 83 TTT GGA ATC ACA GGA GGA GCA GAG TAT GCG GAG CTA AAC AG op-D456-6H-not 84 CTC TAA TTG CGG CCG CCT ATT AGT GGT GAT GGT GAT GAT GGT CCA CGG CAT CTG TGT CCT TC op-350Q360R-m150 85 AGA ACA CCA GGA CCA AGG AGC AGT GCC AGG CCA TCA AGG AGT ACA TGG ACC GAA CCC TGA ACC CTT ATA TCA TC Op-m152-D65A-R 86 TAA AAG AGA ACA GGC TCA TAT CCA GGG GCT CGG CAA ACT TGC CCA GGC AGA ACT C Op-m153-E66A-R 87 TAA AAG AGA ACA GGC TCA TAT CCA GGG GCG CGT CAA ACT TGC CCA GGC AGA AC Op-m154-P67A-R 88 TAA AAG AGA ACA GGC TCA TAT CCA GGG CCT CGT CAA ACT TGC CCA GGC Op-m155-L68A-R 89 TAA AAG AGA ACA GGC TCA TAT CCG CGG GCT CGT CAA ACT TGC CCA G op-311A-m156 90 ACC AGG ATC GTG TTT ACA GAC GCG GTG CTG AAG TTC CTG TCC op-312A-m157 91 AGG ATC GTG TTT ACA GAC CAG GCG CTG AAG TTC CTG TCC CAG op-313A-m158 92 ATC GTG TTT ACA GAC CAG GTG GCG AAG TTC CTG TCC CAG GAT op-314A-m159 93 ATC GTG TTT ACA GAC CAG GTG CTG GCG TTC CTG TCC CAG GAT GAG N266A-m160 94 GCC CTG TAC CCT AGC ATC TAT CTG GCC ACC CAG CAG AGC CCA GTG GC T267A-m161 95 CTG TAC CCT AGC ATC TAT CTG AAC GCC CAG CAG AGC CCA GTG GCC GCT AC Q268A-m162 96 TAC CCT AGC ATC TAT CTG AAC ACC GCG CAG AGC CCA GTG GCC GCT ACA CTG Q269A-m163 97 TAC CCT AGC ATC TAT CTG AAC ACC CAG GCG AGC CCA GTG GCC GCT ACA CTG TAT G P271A-m164 98 AGC ATC TAT CTG AAC ACC CAG CAG AGC GCA GTG GCC GCT ACA CTG TAT GTG AGG V272A-m165 99 TAT CTG AAC ACC CAG CAG AGC CCA GCG GCC GCT ACA CTG TAT GTG AGG Op-m166-I102A-R 100 TGT CAC TCC GGT GAT AGA ATC GGC ATA TGG ATA GTA GCC CAG TCT G Op-m167-D103A-R 101 TCA CTG TCA CTC CGG TGA TAG AAG CGA TAT ATG GAT AGT AGC CCA G Op-m168-S104A-R 102 TCC GTT CAC TGT CAC TCC GGT GAT AGC ATC GAT ATA TGG ATA GTA GCC CAG Op-m169-I105A-R 103 TCC GTT CAC TGT CAC TCC GGT GGC AGA ATC GAT ATA TGG ATA GTA GC op-m170-T132A-R 104 TTG TCC ACT GGC ATG TAG AAG GCG ATG TCC TTC TTA GCC TTA TC op-m171-F133A-R 105 TGC CCA GAT TGT CCA CTG GCA TGT AGG CGG TGA TGT CCT TCT TAG CCT TAT C op-m172-Y134A-R 106 TGC CCA GAT TGT CCA CTG GCA TGG CGA AGG TGA TGT CCT TCT TAG V241A-m173 107 AGA TCG TCG TTC CTC TTG ATC TCC GCA TTG AAA CAG GAG CCG TTG TAG CC E242A-m174 108 GAC AGA TCG TCG TTC CTC TTG ATC GCC ACA TTG AAA CAG GAG CCG TTG TAG CC I243A-m175 109 AGC CAA GAC AGA TCG TCG TTC CTC TTG GCC TCC ACA TTG AAA CAG GAG CCG TTG K244A-m176 110 AGC CAA GAC AGA TCG TCG TTC CTC GCG ATC TCC ACA TTG AAA CAG GAG CCG Op-m177-L179A-R 111 TCT GTG GCC TCG GTC AGG CTC GCC TGC ACG TTC TGC TGC TGC AC Op-m178-S180A-R 112 TTC TCT GTG GCC TCG GTC AGG GCC AGC TGC ACG TTC TGC TGC TG Op-m179-L181A-R 113 TAG CCT TCT CTG TGG CCT CGG TCG CGC TCA GCT GCA CGT TCT GCT G Op-m180-T182A-R 114 TTA GCC TTC TCT GTG GCC TCG GCC AGG CTC AGC TGC ACG TTC TG Op-m181-T185A-R 115 TCG AAC TCC TGC TTA GCC TTC TCT GCG GCC TCG GTC AGG CTC AGC TG Op-m182-E186A-R 116 TCG AAC TCC TGC TTA GCC TTC GCT GTG GCC TCG GTC AGG CTC AG Op-m183-K187A-R 117 TTC TCG AAC TCC TGC TTA GCC GCC TCT GTG GCC TCG GTC AGG C op-K290A-m184 118 AGA GAG GCT ATC CGC GTG TCT GCG ATC CCC GAC GCC AAG TCC CCA C op-I291A-m185 119 AGG CTA TCC GCG TGT CTA AGG CCC CCG ACG CCA AGT CCC CAC TG op-P292A-m186 120 AGG CTA TCC GCG TGT CTA AGA TCG CCG ACG CCA AGT CCC CAC TGC CC L441A-m190 121 AGT TTT ACT GCT CTT GTT ATT CCA CCG CGA GCT GTA AGG AGA AGG CTG ATG S442A-m191 122 ACT GCT CTT GTT ATT CCA CCC TGG CCT GTA AGG AGA AGG CTG ATG TG op-D451A-m192 123 AAG GAG AAG GCT GAT GTG AAG GCC ACA GAT GCC GTG GAC GTG TGC op-T452A-m193 124 AAG GAG AAG GCT GAT GTG AAG GAC GCA GAT GCC GTG GAC GTG TGC ATC op-D453A-m194 125 AAG GCT GAT GTG AAG GAC ACA GCT GCC GTG GAC GTG TGC ATC G op-D461A-6H-not 126 ATA TTC GCG GCC GCC TAT TAG TGG TGA TGG TGA TGA TGA AAG GCG TCG ATG CAC ACG CCA GCA GCG ATG CAC ACG TCC ACG op-G462A-6H-not 127 ATA TTC GCG GCC GCC TAT TAG TGG TGA TGG TGA TGA TGA AAG GCG TCG ATG CAC ACG GCA TCA GCG ATG CAC ACG TCC AC op-V463A-6H-not 128 ATA TTC GCG GCC GCC TAT TAG TGG TGA TGG TGA TGA TGA AAG GCG TCG ATG CAC GCG CCA TCA GCG ATG CAC ACG op-N82A-m198-R 129 TGT CAC GCC CTG GCC GGT GGC AGC GAT CCG AGG AGA GCC GAT AAA AG op-N166A-m199-R 130 TGC ACC AGC TCG ATG GAC CGA GCC TTA TAC ACG TCC TTA GGC TTC Op-S104N-m203-R 131 TTC ACT GTC ACT CCG GTG ATA TTA TCG ATA TAT GGA TAG TAG CC Op-I105Q-m204-R 132 TCC GTT CAC TGT CAC TCC GGT CTG AGA ATC GAT ATA TGG ATA GTA GC op-Q268D-m205-F 133 ACC CTA GCA TCT ATC TGA ACA CCG ATC AGA GCC CAG TGG CCG CTA C op-Q268I-m208-F 134 ACC CTA GCA TCT ATC TGA ACA CCA TCC AGA GCC CAG TGG CCG CTA C op-291G-m210-F 135 AGG CTA TCC GCG TGT CTA AGG GCC CCG ACG CCA AGT CCC CAC op-292D-m211-F 136 ATC CGC GTG TCT AAG ATC GAC GAC GCC AAG TCC CCA CTG C op-T452D-m212 137 AGA AGG CTG ATG TGA AGG ACG ACG ATG CCG TGG ACG TGT G op-T452H-m213 138 AGA AGG CTG ATG TGA AGG ACC ACG ATG CCG TGG ACG TGT G op-T452K-m214 139 AGA AGG CTG ATG TGA AGG ACA AAG ATG CCG TGG ACG TGT G Op-T452G-m216 140 AGA AGG CTG ATG TGA AGG ACG GAG ATG CCG TGG ACG TGT G Op-T452P-m217 141 AGA AGG CTG ATG TGA AGG ACC CAG ATG CCG TGG ACG TGT G op-T452M-m218 142 AGA AGG CTG ATG TGA AGG ACA TGG ATG CCG TGG ACG TGT G op-T452F-m219 143 AGA AGG CTG ATG TGA AGG ACT TCG ATG CCG TGG ACG TGT G op-D461R-6H-not-m220 144 CTC TAA TTG CGG CCG CCT ATT AGT GGT GAT GGT GAT GAT GAA AGG CGT CGA TGC ACA CGC CCC TAG CGA TGC ACA CGT CCA C op-V463Y-6H-not-m231 145 CTC TAA TTG CGG CCG CTC ATT AGT GGT GAT GGT GAT GAT GAA AGG CGT CGA TGC AGT AGC CAT CAG CGA TGC ACA C op-S180T-R-m232 146 TTC TCT GTG GCC TCG GTC AGG GTC AGC TGC ACG TTC TGC TGC TG op-D451S-F-m233 147 AGG AGA AGG CTG ATG TGA AGA GCA CAG ATG CCG TGG ACG TG op-L313P-m234-F 148 ATC GTG TTT ACA GAC CAG GTG CCG AAG TTC CTG TCC CAG GAT GAG op-L313M-m235-F 149 ATC GTG TTT ACA GAC CAG GTG ATG AAG TTC CTG TCC CAG GAT GAG op-L179S-m243-R 150 TCT GTG GCC TCG GTC AGG CTC GAC TGC ACG TTC TGC TGC TGC AC op-L179I-m245-R 151 TCT GTG GCC TCG GTC AGG CTA ATC TGC ACG TTC TGC TGC TGC AC op-L179F-m246-R 152 TCT GTG GCC TCG GTC AGG CTA AAC TGC ACG TTC TGC TGC TGC AC FQQ-Mega-m254 153 ATC GTG ATC TGG GGC TCC TGG GAG TTC ACC AGG ACC CAG GAG AGC TGC CAG GCC ATC CAG GAG TAC ATG GAC ACA ACC CTG AAC op-Q268N-m259-m 154 ACC CTA GCA TCT ATC TGA ACA CCA ACC AGA GCC CAG TGG CCG CTA C B4-124-R 155 GCC CAG GCA GAA CTC GC op-L181M,E186D-m266 156 TCT CGA ACT CCT GCT TAG CCT TAT CTG TGG CCT CGG TCA TGC TCA GCT GCA CGT TCT GCT GC op-Q268A-m268-m 157 ACC CTA GCA TCT ATC TGA ACA CCG CGC AGA GCC CAG TGG CCG CTA C op-344I,348M-m271 158 ATC GTG ATC TGG GGC TCC TGG GAG ATC ACC AGG ACC ATG GAG AGC TGC CAG GCC ATC AAG op-DLSS-m275 159 AGC GGC ATC GTG ATC TGG GGC GAC CTG TCG ATC TCC TCG ACC ATG GAG AGC TGC CAG GCC op-DLS-m276 160 AGC GGC ATC GTG ATC TGG GGC GAC CTG TCG ATC TCC AGG ACC ATG GAG AGC TGC CAG Op-K348M-m279 161 ATC TGG GGC TCC TGG GAG AAC ACC AGG ACC ATG GAG AGC TGC CAG GCC ATC AAG Op-N344I K348M-m280 162 ATC GTG ATC TGG GGC TCC TGG GAG ATC ACC AGG ACC ATG GAG AGC TGC CAG GCC ATC AAG

Following the discovery of a PH20 variant with increased enzymatic activity and thermostability, a cDNA of a PH20 variant without the His tag was also constructed.

The PH20 variant was constructed as follows using the PH20 variant cDNA.

Expression of the variant was performed using the ExpiCHO expression system. When ExpiCHO cell density reached 6 × 10 ⁶ /ml, a plasmid comprising wild-type or variant PH20 cDNA inserted into the pcDNA3.4-TOPO vector was transfected into ExpiCHO cells using ExpiFectamine CHO reagent. ExpiCHO expression medium (100 to 500 ml) was used as a cell culture medium. After transfection, ExpiCHO cells were cultured with shaking at 130 rpm for a total of 6 days, during which cells were cultured at 37°C for 1 day and further cultured at a lower temperature of 32°C for 5 days. After completion of culture, cell supernatant was collected by centrifugation at 10,000 rpm for 30 minutes.

Recombinant wild-type PH20 with a C-terminal His tag and variant PH20 with a C-terminal His tag, produced in ExpiCHO cells, were purified by three-step column chromatography using the AKTA primary system (GE Healthcare Systems) and three-step column chromatography. Column chromatography was performed using HisTrap HP column-Q-Sepharose column-phenyl-HP column and Q-Sepharose column-HisTrap HP column-butyl-HP column, respectively, depending on the variant.

Purification using a HisTrap HP column, a Q-Sepharose column, and a phenyl-HP column was performed as follows. For protein purification using a HisTrap column, buffer A (20 mM sodium phosphate, pH 7.5, 0.5 M NaCl) and buffer B (20 mM sodium phosphate, pH 7.5, 0.5 M NaCl, 0.5 M imidazole). Protein bound to the HisTrap column, and the column was washed with 5 column volumes (CV) of buffer A to remove nonspecifically bound proteins. After confirming that the conductivity was maintained at a constant level, the column was washed with 5 CV of 20% buffer B to elute the protein. The eluted protein was dialyzed with dialysis buffer (20 mM sodium phosphate, pH 7.5, 50 mM NaCl). For protein purification using a Q-Sepharose column, buffer A (20 mM sodium phosphate, pH 7.5) and buffer B (20 mM sodium phosphate, pH 7.5, 0.5 M NaCl) were prepared. The protein was bound to the Q-Sepharose column, and the column was washed with 5 CV of buffer A to remove nonspecifically bound proteins and then washed with 5 CV of buffer B with a concentration gradient from 0 to 100% to elute the protein. For protein purification using a phenyl-HP column, buffer A (20 mM sodium phosphate, pH 7.0, 1.5 M (NH4)2SO4) and buffer B (20 mM sodium phosphate, pH 7.0) were prepared. The protein bound to the phenyl column, and the column was washed with 5 CV of buffer A to remove nonspecifically bound proteins and then washed with 5 CV of buffer B with a concentration gradient from 0 to 100% to elute the protein.

Purification using a Q-Sepharose column, a HisTrap HP column, and a butyl-HP column was performed as follows. For protein purification using a Q-Sepharose column, buffer A (20 mM NaPi, 15 mM NaCl, pH 8.0) and buffer B (20 mM NaPi, 500 mM NaCl, pH 8.0) were prepared. To bring the pH and conductivity of the culture solution to the same values as buffer A, the pH was titrated to 8 using 1 M Tris buffer, and the conductivity was adjusted to 5 mS/cm or less by adding water (PW). The culture solution was then filtered through a membrane with a pore size of 0.22 μm. The protein was bound to the Q-Sepharose column, and the column was washed with 5 CV of buffer A to remove nonspecifically bound proteins and then washed with 5 CV of buffer B to elute the target protein. For protein purification using a HisTrap HP column, buffer A (20 mM NaPi, 500 mM NaCl, pH 7.5) and buffer B (20 mM NaPi, 500 mM NaCl, 500 mM imidazole, pH 7.5) were prepared. The protein sample was bound to the HisTrap HP column, the column was washed with 10 volumes of 7% Buffer B to remove nonspecifically bound proteins, and then the column was washed with 3 volumes of 40% Buffer B to elute the protein. For protein purification using a butyl-HP column, buffer A (20 mM NaPi, 1.5 M ammonium sulfate, pH 7.0) and buffer B (20 mM NaPi, pH 7.0) were prepared. 3 M ammonium sulfate solution and the protein sample to be loaded onto the column were mixed in a 1:1 ratio, and then the resulting mixture was filtered through a membrane having a pore size of 0.22 μm. The protein sample was bound to a butyl-HP column, and the column was washed with 5 volumes of buffer A to remove impurities. The target protein was then eluted with a linear concentration gradient of 0-100% buffer B and dialyzed using dialysis buffer (20 mM NaPi, 100 mM NaCl, pH 7.0). The embodiment of the present invention was purified by the method proposed in the present invention, 10% SDS-PAGE analysis was performed on each purified product, and the results are shown in FIG. 1 and 3.

The enzymatic activities of wild type and variant PH20 PH20 were measured by turbidimetric assay.

Turbidimetric analysis is a method of measuring absorption in the precipitate that is formed when hyaluronic acid is mixed with albumin (BSA). When hyaluronic acid is hydrolyzed by PH20, the absorption of the precipitate formed when mixed with albumin is reduced. Turbidimetric analysis was usually carried out as follows. Hyaluronidase PH20 (Sigma) was diluted to 1, 2, 5, 7.5, 10, 15, 20, 30, 50, and 60 units/ml and prepared in each tube. Purified protein sample was dissolved in enzyme dilution buffer (20 mM TrisHCl, pH 7.0, 77 mM NaCl, 0.01% (w/v) bovine serum albumin), diluted to 100X, 300X, 600X, 1200X and 2400X and prepared in appropriate test tubes. In fresh tubes, a 3 mg/mL hyaluronic acid solution was diluted 10-fold to a concentration of 0.3 mg/mL, so that the volume in each tube was 180 μL. 60 μl of enzyme was added and mixed with a diluted hyaluronic acid solution and left to react at 37°C for 45 minutes. After completion of the reaction, 50 μL of reacted enzyme and 250 μL of acidic albumin solution were added to each well of a 96-well plate and shaken for 10 minutes, and then the absorbance was measured at 600 nm using a spectrophotometer.

Methods for measuring protein thermal stability include a method for measuring aggregation temperature using dynamic light scattering (DLS), a method for measuring melting temperature (Tm) in real-time PCR using Sypro-Orange dye, and a method for measuring enzymatic activity after holding a protein at a given temperature for a given time. etc. In the DLS aggregation temperature measurement method, molecular aggregation is measured using light scattering, and thus the sensitivity is high and the aggregation temperature is generally lower than the melting temperature of the protein. Since each variant is prepared as a solution at the same concentration of 0.2 mg/ml and then measured, the physical properties of each variant can be compared using the resulting value as the aggregation temperature (Philo, J.S. (2009) Cur. Pharm. Biotech. 10, 359- 372).

The amino acid sequences of the PH20 variants constructed by replacing or eliminating amino acids from the PH20 variant having the sequence SEQ ID NO: 3 in the present invention are shown in Table 6 below.

In the present invention, the experiment was carried out with a variant in which six histidines were added at the C-terminus in the sequence shown in Table 6 to purify the protein. This addition to the C-terminus was found to have no effect on enzyme activity or protein stability. The variant according to the present invention was named as a combination of HM and serial number, and the variants according to Example 3 were named "Hyal2 variant", "Hyal3 variant" and "Hyal4 variant".

Table 6. Amino acid sequences of PH20 variants according to the present invention and characteristic features of substitutions/breaks in them

Name SEQ ID NO. Replacement Subsequence Hyal2-option 163 15 amino acid residues S341T, W342L, E343S, N344I, R346T, T347S, K348T, S350T, A353Y, I354L, E356D, M358L, D359T and T360R, T361L are replaced in SEQ ID NO: 3, the gap is made before amino acid residue L36 at the N-terminus PH20, and the break occurs after amino acid residue S490 at the C-terminus of PH20. LNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQD EQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAFLKPPMETEEPQIFYNASPSTLS Hyal3-option 164 17 amino acid residues S341T, W342L, E343S, N344I, T345S, R346S, T347S, K348E, S350E, Q352W, A353H, I354L, K355H, E356D, M358L, D359V and T360D are replaced in SEQ ID NO: 3, the gap is placed before the amino acid o statcom L36 at the N-terminus of PH20, and the break occurs after amino acid residue S490 at the C-terminus of PH20. LNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQD QEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAFLKPPMETEEPQIFYNASPSTLS Hyal4-option 165 17 amino acid residues S341T, W342L, E343S, N344I, R346A, T347S, E349A, S350N, Q352T, A353K, I354V, E356Q, Y357F, M358V, D359S, T360S and T361D are replaced in SEQ ID NO: 3, the gap is placed before the amino acid o statcom L36 at the N-terminus of PH20, and the break occurs after amino acid residue S490 at the C-terminus of PH20. LNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQD EQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAFLKPPMETEEPQIFYNASPSTLS HM63 166 One amino acid residue R346M is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F38 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENT M TKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM64 167 One amino acid residue T347Q is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F38 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTR O KESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM65 168 One amino acid residue K348Q is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRT O ESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM66 169 One amino acid residue S350Q is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKE O CQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM67 170 One amino acid residue K355Q is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAI O EYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM69 171 One amino acid residue M358V is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEY V DTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM70 172 One amino acid residue L362A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTT A NPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM71 173 One amino acid residue E343V is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSW V NTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM72 174 One amino acid residue N344F is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWE F TRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM73 175 One amino acid residue D359K is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYM K TTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM74 176 One amino acid residue T360Y is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMD Y TLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM75 177 One amino acid residue T361M is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDT M LNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM76 178 One amino acid residue Q352E is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESC E AIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM77 179 One amino acid residue N363M is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTL M PYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM78 180 One amino acid residue T84N is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINA N GQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM79 181 One amino acid residue N166K is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYK K RSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM82 182 One amino acid residue I354E is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQA E KEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM83 183 One amino acid residue I354Q is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQA O KEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM84 184 One amino acid residue I354S is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQA S KEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM85 185 One amino acid residue I354V is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQA V KEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM86 186 One amino acid residue I354A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQA A KEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM88 187 One amino acid residue I354N is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQA N KEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM89 188 One amino acid residue I354T is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQA T KEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM90 189 One amino acid residue E356M is replaced from SEQ ID NO: 3, the cleavage occurs before amino acid residue F38 at the N-terminus of PH20, and the cleavage occurs after amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIK M YMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM91 190 One amino acid residue E356F is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIK F YMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM92 191 One amino acid residue E356I is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIK I YMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM93 192 One amino acid residue E356L is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIK L YMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM94 193 One amino acid residue E356Q is replaced from SEQ ID NO: 3, the cleavage occurs before amino acid residue F38 at the N-terminus of PH20, and the cleavage occurs after amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIK O YMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM95 194 One amino acid residue E356V is replaced from SEQ ID NO: 3, the cleavage occurs before amino acid residue F38 at the N-terminus of PH20, and the cleavage occurs after amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIK V YMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM96 195 3 amino acid residues N166K, E343V and T361M are replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYK K RSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSW V NTRTKESCQAIKEYMDT M LNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFT VRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM97 196 One amino acid residue G340Q is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIW O SWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM98 197 One amino acid residue S341H is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWG H WENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM99 198 One amino acid residue W342I is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGS I ENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM100 199 One amino acid residue E343Y is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSW Y NTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM101 200 One amino acid residue T345E is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWEN E RTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM102 201 One amino acid residue R346F is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENT F TKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM103 202 One amino acid residue T347E is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTR E KESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM104 203 One amino acid residue E349L is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTK L SCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM105 204 One amino acid residue S350I is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKE I CQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM106 205 One amino acid residue Q352G is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESC G AIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM107 206 One amino acid residue I354R is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQA R KEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM110 207 One amino acid residue M358R is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEY R DTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM111 208 One amino acid residue D359V is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYM V TTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM112 209 One amino acid residue T360R is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMD R TLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM114 210 One amino acid residue T345K is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWEN K RTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM115 211 One amino acid residue R346L is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENT L TKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM116 212 One amino acid residue T347V is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTR V KESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM117 213 One amino acid residue E349W is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTK W SCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM118 214 One amino acid residue I354W is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQA W KEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM121 215 One amino acid residue D359Y is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYM Y TTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM125 216 One amino acid residue T347W is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTR W KESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM126 217 One amino acid residue Y357W is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKE W MDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM130 218 One amino acid residue W342D is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGS D ENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM131 219 One amino acid residue E343Q is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSW O NTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM132 220 One amino acid residue T347H is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTR H KESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM133 221 One amino acid residue K348F is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRT F ESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM134 222 One amino acid residue S350D is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKE D CQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM135 223 One amino acid residue Q352Y is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESC Y AIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM136 224 One amino acid residue A353E is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQ E IKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM138 225 One amino acid residue M358Y is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEY Y DTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM139 226 One amino acid residue D359Q is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYM O TTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM140 227 One amino acid residue T360L is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMD L TLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM141 228 One amino acid residue T361E is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDT E LNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM142 229 One amino acid residue N363E is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTL E PYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM143 230 One amino acid residue W342H is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGS H ENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM144 231 One amino acid residue K348D is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRT D ESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM145 232 One amino acid residue T361H is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDT H LNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM146 233 No additional substitutions were made; the break was made before amino acid residue R39 at the N-terminus of PH20, and the break was made after amino acid residue F468 at the C-terminus of PH20. RAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM147 234 No additional substitutions were made; the break was made before amino acid residue A40 at the N-terminus of PH20, and the break was made after amino acid residue F468 at the C-terminus of PH20. APPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHHY KKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLED LEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM149 235 No additional substitutions were made; the break was made before amino acid residue F38 at the N-terminus of PH20, and the break was made after amino acid residue D456 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVD HM150 236 2 amino acid residues S350Q and T360R are replaced in SEQ ID NO: 3, the gap is made before the amino acid residue R39 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. RAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKE O CQAIKEYMD R TLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM152 237 One amino acid residue D65A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKF A EPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYN HHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM153 238 One amino acid residue E66A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFD A PLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM154 239 One amino acid residue P67A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDE A LDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYN HHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM155 240 One amino acid residue N344F is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEP A DMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM156 241 One amino acid residue Q311A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTD A VLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM157 242 One amino acid residue V312A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQ A LKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM158 243 One amino acid residue L313A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQV A KFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM159 244 One amino acid residue K314A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVL A FLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM160 245 One amino acid residue N266A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYL A TQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM161 246 One amino acid residue T267A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLN A QQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM162 247 One amino acid residue Q268A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNT A QSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM163 248 One amino acid residue Q269A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQ A SPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM164 249 One amino acid residue P271A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQS A VAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM165 250 One amino acid residue V272A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSP A AATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM166 251 One amino acid residue I102A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPY A DSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM167 252 One amino acid residue D103A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYI A SITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYN HHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM168 253 One amino acid residue S104A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYID A ITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM169 254 One amino acid residue I105A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDS A TGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYN HHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM170 255 One amino acid residue T132A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDI A FYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM171 256 One amino acid residue F133A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDIT A YMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM172 257 One amino acid residue Y134A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITF A MPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM173 258 One amino acid residue V241A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFN A EIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM174 259 One amino acid residue E242A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNV A IKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM175 260 One amino acid residue I243A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVE A KRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM176 261 One amino acid residue K244A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEI A RNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM177 262 One amino acid residue L179A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQ A SLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM178 263 One amino acid residue S180A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQL A LTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM179 264 One amino acid residue L181A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLS A TEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM180 265 One amino acid residue T182A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSL A EATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM181 266 One amino acid residue T185A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEA A EKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM182 267 One amino acid residue E186A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEAT A KAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM183 268 One amino acid residue K187A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATE A AKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM184 269 One amino acid residue K290A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVS A IPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM185 270 One amino acid residue I291A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSK A PDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM186 271 One amino acid residue P292A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKI A DAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM190 272 One amino acid residue L441A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYST A SCKEKADVKDTDAVDVCIADGVCIDAF HM191 273 One amino acid residue S442A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTL A CKEKADVKDTDAVDVCIADGVCIDAF HM192 274 One amino acid residue D451A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVK A TDAVDVCIADGVCIDAF HM193 275 One amino acid residue T452A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKD A DAVDVCIADGVCIDAF HM194 276 One amino acid residue D453A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDT A AVDVCIADGVCIDAF HM195 277 One amino acid residue D461A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIA A GVCIDAF HM196 278 One amino acid residue G462A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIAD A VCIDAF HM197 279 One amino acid residue V463A is replaced in SEQ ID NO: 3, nicked before amino acid residue F38 at the N-terminus of PH20, and nicked after amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADG A CIDAF HM198 280 One amino acid residue N82A is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRI A ATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM199 281 One amino acid residue N166A is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYK A RSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM203 282 One amino acid residue S104N is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYID N ITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM204 283 One amino acid residue I105Q is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDS O TGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYN HHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM205 284 One amino acid residue Q268D is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNT D QSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM208 285 One amino acid residue Q268I is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNT I QSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM210 286 One amino acid residue I291G is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSK G PDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM211 287 One amino acid residue P292D is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKI D DAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM212 288 One amino acid residue T452D is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKD D DAVDVCIADGVCIDAF HM213 289 One amino acid residue T452D is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKD H DAVDVCIADGVCIDAF HM214 290 One amino acid residue T452K is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKD K DAVDVCIADGVCIDAF HM216 291 One amino acid residue T452G is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKD G DAVDVCIADGVCIDAF HM217 292 One amino acid residue T452P is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKD P DAVDVCIADGVCIDAF HM218 293 One amino acid residue T452M is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKD M DAVDVCIADGVCIDAF HM219 294 One amino acid residue T452F is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKD F DAVDVCIADGVCIDAF HM220 295 One amino acid residue D461R is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIA R GVCIDAF HM231 296 One amino acid residue V463Y is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADG Y CIDAF HM232 297 One amino acid residue S180T is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQL T LTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM233 298 One amino acid residue D451S is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVK S TDAVDVCIADGVCIDAF HM234 299 One amino acid residue L313P is replaced in SEQ ID NO: 3, the cleavage is made before the amino acid residue F38 at the N-terminus of PH20, and the cleavage is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQV P KFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM235 300 One amino acid residue L313M is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQV M KFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPT LEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM243 301 One amino acid residue L179S is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQ S SLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM245 302 One amino acid residue L179I is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQ I SLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM246 303 One amino acid residue L179F is replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQ F SLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM254 304 3 amino acid residues N344F, K348Q and K355Q are replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWE F TRT O ESCQAI O EYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVR GKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM261 305 7 amino acid residues T132S, L181A, E186D, Q268N, I291L, V312A and T452D are replaced in SEQ ID NO: 3, the gap is made before the amino acid residue F38 at the N-terminus of PH20, and the gap is made after the amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDI S FYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLS A TEAT D KAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCY NHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNT N QSPVAATLYVRNRVREAIRVSK L PDAKSPLPVFAYTRIVFTDQ A LKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFT VRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKD D DAVDVCIADGVCIDAF HM262 306 No additional substitutions were made; the break was made before amino acid residue N37 at the N-terminus of PH20, and the break was made after amino acid residue F468 at the C-terminus of PH20. NFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM263 307 No additional substitutions were made; the break was made before amino acid residue L36 at the N-terminus of PH20, and the break was made after amino acid residue F468 at the C-terminus of PH20. LNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNH HYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGK PTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM266 308 9 amino acid residues R39K, I105A, T132S, L181M, E186D, I291L, Q268A, V312A and T452D are replaced in SEQ ID NO: 3, the gap is made before amino acid residue F38 at the N-terminus of PH20, and the gap is made after amino acid residue F468 at C- end of PH20. F K APPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDS A TGVTVNGGIPQKISLQDHLDKAKKDI S FYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLS M TEAT D KAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLF PDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNT A QSPVAATLYVRNRVREAIRVSK L PDAKSPLPVFAYTRIVFTDQ A LKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEK GGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKD D DAVDVCIADGVCIDAF HM268 309 7 amino acid residues T132A, L181A, E186A, Q268A, I291L, V312A and T452D are replaced from SEQ ID NO: 3, cleavage occurs before amino acid residue F38 at the N-terminus of PH20, and cleavage occurs after amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDI A FYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLS A TEAT A KAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCY NHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNT A QSPVAATLYVRNRVREAIRVSK L PDAKSPLPVFAYTRIVFTDQ A LKFLSQDELVYTFGETVALGASGIVIWGSWENTRTKESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFT VRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKD D DAVDVCIADGVCIDAF HM271 310 2 amino acid residues N344I and K348M are replaced from SEQ ID NO: 3, cleavage occurs before amino acid residue F38 at the N-terminus of PH20, and cleavage occurs after amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGSWE I TRT M ESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRG KPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM275 311 10 amino acid residues S341D, W342L, E343S, N344I, T345S, R346S, K348M, K355D, D359E and T361I are replaced in SEQ ID NO: 3, the break is made before the amino acid residue F38 at the N-terminus of PH20, and the break is made after the amino acid residue F468 at C-terminal PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDE GVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM276 312 9 amino acid residues S341D, W342L, E343S, N344I, T345S, K348M, K355D, D359E and T361I are replaced in SEQ ID NO: 3, the gap is made before amino acid residue F38 at the N-terminus of PH20, and the gap is made after amino acid residue F468 at C- end of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHH YKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDE GVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAF HM279 313 8 amino acid residues T132S, L181A, E186D, Q268N, I291L, V312A, T452D and K348M are replaced in SEQ ID NO: 3, the break is made before the amino acid residue F38 at the N-terminus of PH20, and the break is made after the amino acid residue F468 at the C-terminus of PH20 . FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDI S FYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLS A TEAT D KAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCY NHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNT N QSPVAATLYVRNRVREAIRVSK L PDAKSPLPVFAYTRIVFTDQ A LKFLSQDELVYTFGETVALGASGIVIWGSWENTRT M ESCQAIKEYMDTTLNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFT VRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKD D DAVDVCIADGVCIDAF HM280 314 9 amino acid residues T132S, L181A, E186D, Q268N, I291L, V312A, T452D, N344I and K348M are replaced in SEQ ID NO: 3, the gap is made before amino acid residue F38 at the N-terminus of PH20, and the gap is made after amino acid residue F468 at C- end of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDI S FYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLS A TEAT D KAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCY A KFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKD D DAVDVCIADGVCIDAF HM287 315 17 amino acid residues T132A, L181A, E186A, Q268A, I291L, V312A, S341D, W342L, E343S, N344I, T345S, R346S, K348M, K355D, D359E, T361I and T452D are replaced in SEQ ID NO: 3, the gap is placed before the amino acid o statcom F38 at the N-terminus of PH20, and the break is made after amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDI A FYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLS A TEAT A KAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCY NHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNT A QSPVAATLYVRNRVREAIRVSK L PDAKSPLPVFAYTRIVFTDQ A LKFLSQD QGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKD D DAVDVCIADGVCIDAF HM288 316 17 amino acid residues T132A, L181A, E186A, Q268A, I291L, V312A, S341D, W342L, E343S, N344I, T345S, K348M, K355D, D359E, T361I and T452D are replaced in SEQ ID NO: 3, the gap is made before amino acid residue F38 at N -end of PH20, and the break is made after amino acid residue F468 at the C-terminus of PH20. FRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDI A FYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLS A TEAT A KAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCY NHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNT A QSPVAATLYVRNRVREAIR QGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKD D DAVDVCIADGVCIDAF

Example 2 Determination of Characteristics of PH20 Variants of the Present Invention

Further study of protein structure and function was carried out by examining variants, including breaks at the N-terminus and C-terminus, based on the amino acid sequence SEQ ID NO: 3. Expression quantification and activity analysis of the resulting variant yielded the aggregation temperature shown in Table 7.

The expression level and specific activity were analyzed by the turbidimetric assay described in Example 1. The results of the assay are shown. In this case, activity in the culture solution exceeding 300 units/ml was designated as “>LOQ”, and activity after purification exceeding 15 units/μg was designated as “>LOQ” based on the limit of quantitation (LOQ) established for each activity in the culture solution and activity after purification. Otherwise, the sign of inequality changed. The expression level and limits of quantitation (LOQ) of the activity assay and test results based thereon are shown in Table 7. The aggregation temperature of wild type PH20 (L36-Y482) SEQ ID NO: 1 is 46.5°C and the aggregation temperature of the variant PH20 (F38-F468) SEQ ID NO: 3 is 51°C.

Table 7. Expression level, specific activity and aggregation temperature of PH20 variants according to the present invention

Options Change Seq ID NO. 3 Expression level
(LOQ:
300 units/ml) Specific activity
(LOQ:
15
units/mcg) Aggregation point
(℃) Amino acid substitution Start End HM63 R346M F38 F468 >LOQ >LOQ 52℃ HM64 T347Q F38 F468 >LOQ >LOQ 50℃ HM65 K348Q F38 F468 >LOQ >LOQ 51℃ HM66 S350Q F38 F468 >LOQ >LOQ 56℃ HM67 K355Q F38 F468 >LOQ >LOQ 50℃ HM69 M358V F38 F468 >LOQ >LOQ 50℃ HM70 L362A F38 F468 >LOQ >LOQ 48℃ HM71 E343V F38 F468 >LOQ >LOQ 50℃ HM72 N344F F38 F468 >LOQ >LOQ 52℃ HM73 D359K F38 F468 >LOQ >LOQ 50℃ HM74 T360Y F38 F468 >LOQ >LOQ 50℃ HM75 T361M F38 F468 >LOQ >LOQ 49℃ HM76 Q352E F38 F468 >LOQ >LOQ 52℃ HM77 N363M F38 F468 >LOQ >LOQ 58℃ HM78 T84N F38 F468 >LOQ >LOQ 48℃ HM79 N166K F38 F468 >LOQ >LOQ 49℃ HM82 I354E F38 F468 >LOQ >LOQ 49℃ HM83 I354Q F38 F468 >LOQ >LOQ 49℃ HM84 I354S F38 F468 >LOQ >LOQ 48℃ HM85 I354V F38 F468 >LOQ >LOQ 51℃ HM86 I354A F38 F468 >LOQ >LOQ 49℃ HM88 I354N F38 F468 >LOQ >LOQ 49℃ HM89 I354T F38 F468 >LOQ >LOQ 49℃ HM90 E356M F38 F468 >LOQ >LOQ 50℃ HM91 E356F F38 F468 >LOQ >LOQ 49℃ HM92 E356I F38 F468 >LOQ >LOQ 49℃ HM93 E356L F38 F468 >LOQ >LOQ 49℃ HM94 E356Q F38 F468 >LOQ >LOQ 50℃ HM95 E356V F38 F468 >LOQ >LOQ 48℃ HM96 N166K, E343V, T361M F38 F468 >LOQ >LOQ 48℃ HM97 G340Q F38 F468 >LOQ >LOQ 50℃ HM98 S341H F38 F468 >LOQ >LOQ 51℃ HM99 W342I F38 F468 >LOQ >LOQ 51℃ HM100 E343Y F38 F468 >LOQ >LOQ 50℃ HM101 T345E F38 F468 >LOQ >LOQ 51℃ HM102 R346F F38 F468 >LOQ >LOQ 51℃ HM103 T347E F38 F468 >LOQ >LOQ 50℃ HM104 E349L F38 F468 >LOQ >LOQ 50℃ HM105 S350I F38 F468 >LOQ >LOQ 50℃ HM106 Q352G F38 F468 >LOQ >LOQ 49℃ HM107 I354R F38 F468 >LOQ >LOQ 48℃ HM110 M358R F38 F468 >LOQ >LOQ 48℃ HM111 D359V F38 F468 >LOQ >LOQ 50℃ HM112 T360R F38 F468 >LOQ >LOQ 52℃ HM114 T345K F38 F468 >LOQ >LOQ 50℃ HM115 R346L F38 F468 >LOQ >LOQ 52℃ HM116 T347V F38 F468 >LOQ >LOQ 49℃ HM117 E349W F38 F468 >LOQ >LOQ 49℃ HM118 I354W F38 F468 >LOQ >LOQ 51℃ HM121 D359Y F38 F468 >LOQ >LOQ 49℃ HM125 T347W F38 F468 >LOQ >LOQ 51℃ HM126 Y357W F38 F468 >LOQ >LOQ 55℃ HM130 W342D F38 F468 >LOQ >LOQ 51℃ HM131 E343Q F38 F468 >LOQ >LOQ 50℃ HM132 T347H F38 F468 >LOQ >LOQ 51℃ HM133 K348F F38 F468 >LOQ >LOQ 49℃ HM134 S350D F38 F468 >LOQ >LOQ 54℃ HM135 Q352Y F38 F468 >LOQ >LOQ 51℃ HM136 A353E F38 F468 >LOQ >LOQ 49℃ HM138 M358Y F38 F468 >LOQ >LOQ 48℃ HM139 D359Q F38 F468 >LOQ >LOQ 50℃ HM140 T360L F38 F468 >LOQ >LOQ 49℃ HM141 T361E F38 F468 >LOQ >LOQ 48℃ HM142 N363E F38 F468 >LOQ >LOQ 50℃ HM143 W342H F38 F468 >LOQ >LOQ 50℃ HM144 K348D F38 F468 >LOQ >LOQ 50℃ HM145 T361H F38 F468 >LOQ >LOQ 49℃ HM146 - R39 F468 >LOQ >LOQ 52℃ HM147 - A40 F468 >LOQ >LOQ 53℃ HM149 - F38 D456 >LOQ >LOQ 54℃ HM150 S350Q, T360R R39 F468 >LOQ >LOQ 50℃ HM152 D65A F38 F468 >LOQ >LOQ 51℃ HM153 E66A F38 F468 >LOQ >LOQ 51℃ HM154 P67A F38 F468 >LOQ >LOQ 50℃ HM155 L68A F38 F468 >LOQ >LOQ 51℃ HM156 Q311A F38 F468 >LOQ >LOQ 50℃ HM157 V312A F38 F468 >LOQ >LOQ 56℃ HM158 L313A F38 F468 >LOQ >LOQ 55℃ HM159 K314A F38 F468 >LOQ >LOQ 49℃ HM160 N266A F38 F468 >LOQ >LOQ 49℃ HM161 T267A F38 F468 >LOQ >LOQ 50℃ HM162 Q268A F38 F468 >LOQ >LOQ 51℃ HM163 Q269A F38 F468 >LOQ >LOQ 51℃ HM164 P271A F38 F468 >LOQ >LOQ 51℃ HM165 V272A F38 F468 >LOQ >LOQ 52℃ HM166 I102A F38 F468 >LOQ >LOQ 49℃ HM167 D103A F38 F468 >LOQ >LOQ 53℃ HM168 S104A F38 F468 >LOQ >LOQ 51℃ HM169 I105A F38 F468 >LOQ >LOQ 51℃ HM170 T132A F38 F468 >LOQ >LOQ 51℃ HM171 F133A F38 F468 >LOQ >LOQ 50℃ HM172 Y134A F38 F468 >LOQ >LOQ 52℃ HM173 V241A F38 F468 >LOQ >LOQ 50℃ HM174 E242A F38 F468 <LOQ >LOQ 55℃ HM175 I243A F38 F468 >LOQ >LOQ 49℃ HM176 K244A F38 F468 >LOQ >LOQ 50℃ HM177 L179A F38 F468 >LOQ >LOQ 54℃ HM178 S180A F38 F468 >LOQ >LOQ 50℃ HM179 L181A F38 F468 >LOQ >LOQ 50℃ HM180 T182A F38 F468 >LOQ >LOQ 50℃ HM181 T185A F38 F468 >LOQ >LOQ 50℃ HM182 E186A F38 F468 >LOQ >LOQ 51℃ HM183 K187A F38 F468 >LOQ >LOQ 50℃ HM184 K290A F38 F468 >LOQ >LOQ 50℃ HM185 I291A F38 F468 >LOQ >LOQ 54℃ HM186 P292A F38 F468 >LOQ >LOQ 52℃ HM190 L441A F38 F468 >LOQ >LOQ 50℃ HM191 S442A F38 F468 >LOQ >LOQ 54℃ HM192 D451A F38 F468 >LOQ >LOQ 54℃ HM193 T452A F38 F468 >LOQ >LOQ 53℃ HM194 D453A F38 F468 >LOQ >LOQ 49℃ HM195 D461A F38 F468 >LOQ >LOQ 49℃ HM196 G462A F38 F468 >LOQ >LOQ 50℃ HM197 V463A F38 F468 >LOQ >LOQ 49℃ HM198 N82A F38 F468 >LOQ >LOQ 49℃ HM199 N166A F38 F468 >LOQ >LOQ 50℃ HM203 S104N F38 F468 >LOQ >LOQ 48℃ HM204 I105Q F38 F468 >LOQ >LOQ 51℃ HM205 Q268D F38 F468 >LOQ >LOQ 55℃ HM208 Q268I F38 F468 <LOQ >LOQ 52℃ HM210 I291G F38 F468 <LOQ >LOQ 55℃ HM211 P292D F38 F468 <LOQ >LOQ 53℃ HM212 T452D F38 F468 >LOQ >LOQ 50℃ HM213 T452H F38 F468 >LOQ >LOQ 50℃ HM214 T452K F38 F468 >LOQ >LOQ 52℃ HM216 T452G F38 F468 >LOQ >LOQ 54℃ HM217 T452P F38 F468 >LOQ >LOQ 52℃ HM218 T452M F38 F468 >LOQ >LOQ 52℃ HM219 T452F F38 F468 >LOQ >LOQ 53℃ HM220 D461R F38 F468 >LOQ >LOQ 48℃ HM231 V463Y F38 F468 >LOQ >LOQ 51℃ HM232 S180T F38 F468 >LOQ >LOQ 51℃ HM233 D451S F38 F468 >LOQ >LOQ 51℃ HM234 L313P F38 F468 >LOQ >LOQ 49℃ HM235 L313M F38 F468 >LOQ >LOQ 52℃ HM243 L179S F38 F468 >LOQ >LOQ 52℃ HM245 L179I F38 F468 >LOQ >LOQ 48℃ HM246 L179F F38 F468 >LOQ >LOQ 55℃ HM254 N344F, K348Q, K355Q F38 F468 >LOQ >LOQ 53℃ HM261 T132S, L181A, E186D, Q268N, I291L, V312A, T452D F38 F468 >LOQ >LOQ 56℃ HM262 - N37 F468 >LOQ >LOQ 50℃ HM263 - L36 F468 >LOQ >LOQ 49℃ HM266 R39K, I105A, T132S, L181M, E186D, Q268A, I291L, V312A, T452D F38 F468 >LOQ >LOQ 57℃ HM268 T132A, L181A, E186A, Q268A, I291L, V312A, T452D F38 F468 >LOQ >LOQ 53℃ HM271 N344I, K348M F38 F468 >LOQ >LOQ 51℃ HM275 S341D, W342L, E343S, N344I, T345S, R346S, K348M, K355D, D359E, T361I F38 F468 >LOQ >LOQ 48℃ HM276 S341D, W342L, E343S, N344I, T345S, K348M, K355D, D359E, T361I F38 F468 >LOQ >LOQ 48℃ HM279 T132S, L181A, E186D, Q268N, I291L, V312A, K348M, T452D F38 F468 >LOQ >LOQ 56℃ HM280 T132S, L181A, E186D, Q268N, I291L, V312A, N344I, K348M, T452D F38 F468 <LOQ >LOQ 59℃ HM287 T132A, L181A, E186A, Q268A, I291L, V312A, S341D, W342L, E343S, N344I, T345S, R346S, K348M, K355D, D359E, T361I, T452D F38 F468 <LOQ >LOQ 48℃ HM288 T132A, L181A, E186A, Q268A, I291L, V312A, S341D, W342L, E343S, N344I, T345S, K348M, K355D, D359E, T361I, T452D F38 F468 <LOQ >LOQ 48℃

As can be seen from Table 7 above, among the variants having the amino acid sequence SEQ ID NO: 3, there are a total of 133 types of variants having a substitution of one amino acid residue, namely HM63, HM64, HM65, HM66, HM67, HM69, HM70, HM71, HM72, HM73, HM74, HM75, HM76, HM77, HM78, HM79, HM82, HM83, HM84, HM85, HM86, HM88, HM89, HM90, HM91, HM92, HM93, HM94, HM95, HM97, HM98, HM99, HM100, HM1 01, HM102, HM103, HM104, HM105, HM106, HM107, HM110, HM111, HM112, HM114, HM115, HM116, HM117, HM118, HM121, HM125, HM126, HM130, HM131, HM132, HM13 3, HM134, HM135, HM136, HM138, HM139, HM140, HM141, HM142, HM143, HM144, HM145, HM152, HM153, HM154, HM155, HM156, HM157, HM158, HM159, HM160, HM161, HM162, HM163, HM164, HM16 5, HM166, HM167, HM168, HM169, HM170, HM171, HM172, HM173, HM174, HM175, HM176, HM177, HM178, HM179, HM180, HM181, HM182, HM183, HM184, HM185, HM186, HM190, HM191, HM192, HM19 3, HM194, HM195, HM196, HM197, HM198, HM199, HM203, HM204, HM205, HM208, HM210, HM211, HM212, HM213, HM214, HM216, HM217, HM218, HM219, HM220, HM231, HM232, HM233, HM234, HM23 5, HM243, HM245 and HM246 were variants , which still retain activity in the purified fraction obtained after purification and have an aggregation temperature of 48 to 58°C and thus exhibit excellent thermal stability. Among them, there are a total of 65 types of options, namely HM63, HM64, HM65, HM66, HM67, HM69, HM70, HM71, HM72, HM73, HM74, HM75, HM76, HM77, HM78, HM79, HM82, HM83, HM84, HM85, HM86 , HM88, HM89, HM90, HM91, HM92, HM93, HM94, HM95, HM98, HM99, HM100, HM101, HM102, HM103, HM104, HM105, HM106, HM107, HM110, HM111, HM112, HM114, HM115, HM116, HM117 , HM118, HM121, HM125, HM126, HM130, HM131, HM132, HM133, HM134, HM135, HM136, HM138, HM139, HM140, HM141, HM142, HM143, HM144 and HM145 are variants that are mutated in one of the replacement sites in the sequence SEQ ID NO: 3 of PH20 and have an aggregation temperature of 48°C to 58°C. There are a total of 68 types of options, namely HM97, HM152, HM153, HM154, HM155, HM156, HM157, HM158, HM159, HM160, HM161, HM162, HM163, HM164, HM165, HM166, HM167, HM168, HM169, HM170, HM171, HM172, HM173, HM174, HM175, HM176, HM177, HM178, HM179, HM180, HM181, HM182, HM183, HM184, HM185, HM186, HM190, HM191, HM192, HM193, HM194, HM19 5, HM196, HM197, HM198, HM199, HM203, HM204, HM205, HM208, HM210, HM211, HM212, HM213, HM214, HM216, HM217, HM218, HM219, HM220, HM231, HM232, HM233, HM234, HM235, HM243, HM24 5 and HM246 are variants that are mutated in one from positions other than the substitution sites in SEQ ID NO: 3 of PH20, and have an aggregation temperature of 48°C to 56°C.

As a result, it can be seen that the variant having a substitution at one position of SEQ ID NO: 3 has a higher aggregation temperature than wild type PH20 (L36-Y482) of SEQ ID NO: 1, regardless of the position of the substitution. However, among them, HM174, HM208, HM210 and HM211 were found to have activity lower than 300 units/ml, which is the LOQ, in the culture solution, but have higher activity than 15 units/µg, which is the LOQ, after cleaning. In this case, it is believed that the characteristics of the variant itself cannot be accurately analyzed when the activity of the variant is measured only in the culture solution.

In addition, as shown in Table 7 above, among the variants having the amino acid sequence SEQ ID NO: 3, HM146, HM147, HM149, HM262 and HM263, the same mutations are retained as the variant having the amino acid sequence SEQ ID NO: 3 , that is, substitutions of amino acid residues, but additionally includes a gap at the N-terminus and the C-terminus, which means that the expression and activity of proteins in variants having the amino acid sequence SEQ ID NO: 3 additional gap at the N-terminus and C-terminus has no influence. These variants have an aggregation temperature of 49°C to 53°C, which is not significantly different from the temperature of the variant SEQ ID NO: 3, which means that the additional gap at the N-terminus and C-terminus also did not affect the physical properties of the variants.

In addition, in the variants having the amino acid sequence of SEQ ID NO: 3, there are a total of 13 types of variants, namely HM96, HM150, HM254, HM261, HM266, HM268, HM271, HM275, HM276, HM279, HM280, HM287 and HM288, which represent are variants that include one or more amino acid substitutions and breaks from those listed in Table 7 above, belong to well expressed proteins, additionally retain enzymatic activity and have an aggregation temperature from 48°C to 59°C. This means that even in the case of such multiple substitutions, the activity and physical properties of the proteins were retained. However, multiple substitutions exhibit unpredictable enzymatic activity and aggregation temperature, which are unpredictable by the combination of characteristics that are obtained in the case of each individual substitution constituting multiple substitutions.

Example 3. Analysis of the activity of variants replaced by the sequences Hyal2, Hyal3 and Hyal4

In order to study how protein stability changes in the amino acid sequence of wild type PH20 with SEQ ID NO: 1, instead of the M345-I361 regions, the amino acid sequences Hyal2 (TTSTETCQYLKDYLTRL), Hyal3 (SSSEEECWHLHDYLVDT) and Hyal4 (TASKANCTKVKQFVSSD) were introduced into the M345-I361 regions, which are the corresponding parts of human hyaluronidases other than Hyal1.

Variants constructed by replacing the M345-I361 regions of wild-type mature PH20 (L36-S490) with the corresponding Hyal2, Hyal3, and Hyal4 sequences are referred to as “Hyal2-variant,” “Hyal3-variant,” and “Hyal4-variant,” respectively.

A Hyal2 variant, a Hyal3 variant and a Hyal4 variant were constructed and the thermal stability of these variants was then analyzed (see FIG. 2). As a result, the aggregation temperature of the Hyal3 variant measured by DLS was 48°C, which is 1.5°C higher than 46.5°C, which is the aggregation temperature of wild-type PH20, meaning that the thermostability was increased.

Additionally, to confirm whether these variants were expressed in ExpiCHO cell culture, the variants were purified by the same method using a HisTrap column, and protein expression levels were compared by SDS-PAGE analysis. The result showed that the expression level of Hyal3 variant was the highest, followed by Hyal2 variant and Hyal4 variant in descending order.

Example 4 Thermal Stability Analysis of Variants of the Present Invention

SDS-PAGE analysis was performed to confirm the thermostability of the variants according to the present invention. Purified wild-type PH20 SEQ ID NO: 1 (L36-Y482) and purified PH20 variant protein of the present invention SEQ ID NO: 3 (F38-F468) were stored at 42°C for 7 days followed by 10% SDS- PAGE under reducing and non-reducing conditions (Figure 4).

As a result, wild type PH20 (L36-Y482) was observed to aggregate (lane G in Fig. 4), whereas the PH20 variant (F38-F468) SEQ ID NO: 3 did not aggregate (lane H in Fig. 4). This difference in aggregation was found to be due to the difference in aggregation temperature between the two proteins. Accordingly, the variant of the present invention is believed to exhibit higher thermal stability and thus is expected to have a wider industrial application due to its high aggregation temperature compared to wild type PH20.

Example 5 Enzyme Kinetics Analysis of Variants of the Present Invention

To analyze the enzymatic kinetics of the variants of the present invention, enzymatic activity was measured by the Morgan-Elson method (Takahashi, T. et al (2003) Anal. Biochem. 322: 257-263). The Morgan-Elson method is a colorimetric method that detects red substances (at 545 nm) resulting from the reaction of the reducing end of N-acetyl-D-glucosamine (GlcNAc) formed by the hydrolysis of hyaluronic acid by hyaluronidase with para-dimethylaminobenzaldehyde (DMAB) , which is Ehrlich's reagent. N-acetyl-D-glucosamine (GlcNAc, Sigma) diluted to 0.25, 0.50, 0.75, 1.00, or 1.25 mM in dilution buffer (0.1 M NaPi, 0.1 M NaCl, 1.5 mM 1,4-lactone sugar acid, pH 5.35) was reduced by treatment with tetraborate in each tube and then DMAB was added to induce a colorimetric reaction. After the reaction, absorbance was measured at 545 nm to create a standard reaction curve for GlcNAc. Hyaluronic acid substrate was diluted to 0.54, 0.65, 0.87, 1.23 or 2.17 µM in dilution buffer solution in each tube and hyaluronidase was added, followed by reaction at 37°C for 5 minutes and followed by heating at 100°C for 5 minutes to stop the enzymatic reaction. The sample obtained from the enzymatic reaction was reconstituted by treatment with tetraborate and DMAB was added to induce a colorimetric reaction. After the reaction, the absorbance was measured at 545 nm and the enzyme activity was measured using the above standard GlcNAc reaction curve. The kinetics of the wild type PH20 enzyme of SEQ ID NO: 1 and the PH20 variant of the present invention were analyzed using this method. As a result, linearity of the Lineweaver-Burk curve was found, which means that the PH20 variant according to the present invention corresponds to the Michaelis-Menten enzyme kinetics equation.

Table 8 shows V _max (maximum enzymatic reaction rate), K _M (50% substrate concentration), k _cat (substrate conversion rate), and k _cat /K _M (enzyme catalyst efficiency) obtained from enzyme kinetics analysis relative to the PH20 of the wild type (L36-Y482) with SEQ ID NO: 1, variant PH20 (F38-F468) with SEQ ID NO: 3, HM261 and HM268. It can be seen that as the K _M value decreases, the ability of the enzyme to bind the substrate increases, and as the k _cat value increases, the rate of substrate conversion by the enzyme increases, so the k _cat /K _M (enzyme catalyst efficiency) of each PH20 variant is higher than the wild type PH20. In addition, the kcat of each of SEQ ID NO: 3, HM261 and HM268 is greater than that of wild-type PH20 of SEQ ID NO: 1, and thus the substrate conversion rate of the enzyme is greater than that of wild-type PH20 of SEQ ID NO: 1. 1, therefore the industrial availability of each PH20 variant is higher than the availability of wild type PH20.

Table 8. Results of enzyme kinetics analysis of PH20 variants according to the present invention

_Vmax
(µM/sec) K _M
(µM) k _cat
(1/sec) k _cat / K _M PH20
SEQ ID NO: 1
(L36-Y482) 4.5±0.5 2.0±0.3 30.6±3.0 15.1±1.1 SEQ ID NO: 3
(F38-F468) 3.7±0.3 1.3±0.0 47.6±3.7 36.8±2.0 HM261 5.2±0.5 1.4±0.2 33.9±3.0 23.7±2.2 HM268 2.9±0.5 0.9±0.2 37.1±6.4 40.0±3.4

--->

LIST OF SEQUENCES

<110> ALTEOGEN, INC.

<120> NEW HYALURONIDASE VARIANTS WITH IMPROVED STABILITY AND

PHARMACEUTICAL COMPOSITION CONTAINING THEM

<130>PP-B2512

<150> KR 10-2020-0009046

<151> 2020-01-23

<160> 316

<170> Patent In version 3.2

<210> 1

<211> 509

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 1

Met Gly Val Leu Lys Phe Lys His Ile Phe Phe Arg Ser Phe Val Lys

1 5 10 15

Ser Ser Gly Val Ser Gln Ile Val Phe Thr Phe Leu Leu Ile Pro Cys

20 25 30

Cys Leu Thr Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro

35 40 45

Phe Leu Trp Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe

50 55 60

Asp Glu Pro Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg

65 70 75 80

Ile Asn Ala Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu

85 90 95

Gly Tyr Tyr Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly

100 105 110

Gly Ile Pro Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys

115 120 125

Lys Asp Ile Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val

130 135 140

Ile Asp Trp Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro

145 150 155 160

Lys Asp Val Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn

165 170 175

Val Gln Leu Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe

180 185 190

Glu Lys Ala Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys

195 200 205

Leu Leu Arg Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys

210 215 220

Tyr Asn His His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn

225 230 235 240

Val Glu Ile Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser

245 250 255

Thr Ala Leu Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val

260 265 270

Ala Ala Thr Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val

275 280 285

Ser Lys Ile Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr

290 295 300

Arg Ile Val Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu

305 310 315 320

Leu Val Tyr Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile

325 330 335

Val Ile Trp Gly Thr Leu Ser Ile Met Arg Ser Met Lys Ser Cys Leu

340 345 350

Leu Leu Asp Asn Tyr Met Glu Thr Ile Leu Asn Pro Tyr Ile Ile Asn

355 360 365

Val Thr Leu Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln

370 375 380

Gly Val Cys Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu

385 390 395 400

Asn Pro Asp Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr

405 410 415

Val Arg Gly Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys

420 425 430

Phe Tyr Cys Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp

435 440 445

Val Lys Asp Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys

450 455 460

Ile Asp Ala Phe Leu Lys Pro Pro Met Glu Thr Glu Glu Pro Gln Ile

465 470 475 480

Phe Tyr Asn Ala Ser Pro Ser Thr Leu Ser Ala Thr Met Phe Ile Val

485 490 495

Ser Ile Leu Phe Leu Ile Ile Ser Ser Val Ala Ser Leu

500 505

<210> 2

<211> 435

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 2

Met Ala Ala His Leu Leu Pro Ile Cys Ala Leu Phe Leu Thr Leu Leu

1 5 10 15

Asp Met Ala Gln Gly Phe Arg Gly Pro Leu Leu Pro Asn Arg Pro Phe

20 25 30

Thr Thr Val Trp Asn Ala Asn Thr Gln Trp Cys Leu Glu Arg His Gly

35 40 45

Val Asp Val Asp Val Ser Val Phe Asp Val Val Ala Asn Pro Gly Gln

50 55 60

Thr Phe Arg Gly Pro Asp Met Thr Ile Phe Tyr Ser Ser Gln Leu Gly

65 70 75 80

Thr Tyr Pro Tyr Tyr Thr Pro Thr Gly Glu Pro Val Phe Gly Gly Leu

85 90 95

Pro Gln Asn Ala Ser Leu Ile Ala His Leu Ala Arg Thr Phe Gln Asp

100 105 110

Ile Leu Ala Ala Ile Pro Ala Pro Asp Phe Ser Gly Leu Ala Val Ile

115 120 125

Asp Trp Glu Ala Trp Arg Pro Arg Trp Ala Phe Asn Trp Asp Thr Lys

130 135 140

Asp Ile Tyr Arg Gln Arg Ser Arg Ala Leu Val Gln Ala Gln His Pro

145 150 155 160

Asp Trp Pro Ala Pro Gln Val Glu Ala Val Ala Gln Asp Gln Phe Gln

165 170 175

Gly Ala Ala Arg Ala Trp Met Ala Gly Thr Leu Gln Leu Gly Arg Ala

180 185 190

Leu Arg Pro Arg Gly Leu Trp Gly Phe Tyr Gly Phe Pro Asp Cys Tyr

195 200 205

Asn Tyr Asp Phe Leu Ser Pro Asn Tyr Thr Gly Gln Cys Pro Ser Gly

210 215 220

Ile Arg Ala Gln Asn Asp Gln Leu Gly Trp Leu Trp Gly Gln Ser Arg

225 230 235 240

Ala Leu Tyr Pro Ser Ile Tyr Met Pro Ala Val Leu Glu Gly Thr Gly

245 250 255

Lys Ser Gln Met Tyr Val Gln His Arg Val Ala Glu Ala Phe Arg Val

260 265 270

Ala Val Ala Ala Gly Asp Pro Asn Leu Pro Val Leu Pro Tyr Val Gln

275 280 285

Ile Phe Tyr Asp Thr Thr Asn His Phe Leu Pro Leu Asp Glu Leu Glu

290 295 300

His Ser Leu Gly Glu Ser Ala Ala Gln Gly Ala Ala Gly Val Val Leu

305 310 315 320

Trp Val Ser Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile

325 330 335

Lys Glu Tyr Met Asp Thr Thr Leu Gly Pro Phe Ile Leu Asn Val Thr

340 345 350

Ser Gly Ala Leu Leu Cys Ser Gln Ala Leu Cys Ser Gly His Gly Arg

355 360 365

Cys Val Arg Arg Thr Ser His Pro Lys Ala Leu Leu Leu Leu Asn Pro

370 375 380

Ala Ser Phe Ser Ile Gln Leu Thr Pro Gly Gly Gly Pro Leu Ser Leu

385 390 395 400

Arg Gly Ala Leu Ser Leu Glu Asp Gln Ala Gln Met Ala Val Glu Phe

405 410 415

Lys Cys Arg Cys Tyr Pro Gly Trp Gln Ala Pro Trp Cys Glu Arg Lys

420 425 430

Ser Met Trp

435

<210> 3

<211> 509

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 3

Met Gly Val Leu Lys Phe Lys His Ile Phe Phe Arg Ser Phe Val Lys

1 5 10 15

Ser Ser Gly Val Ser Gln Ile Val Phe Thr Phe Leu Leu Ile Pro Cys

20 25 30

Cys Leu Thr Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro

35 40 45

Phe Leu Trp Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe

50 55 60

Asp Glu Pro Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg

65 70 75 80

Ile Asn Ala Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu

85 90 95

Gly Tyr Tyr Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly

100 105 110

Gly Ile Pro Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys

115 120 125

Lys Asp Ile Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val

130 135 140

Ile Asp Trp Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro

145 150 155 160

Lys Asp Val Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn

165 170 175

Val Gln Leu Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe

180 185 190

Glu Lys Ala Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys

195 200 205

Leu Leu Arg Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys

210 215 220

Tyr Asn His His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn

225 230 235 240

Val Glu Ile Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser

245 250 255

Thr Ala Leu Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val

260 265 270

Ala Ala Thr Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val

275 280 285

Ser Lys Ile Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr

290 295 300

Arg Ile Val Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu

305 310 315 320

Leu Val Tyr Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile

325 330 335

Val Ile Trp Gly Ser Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln

340 345 350

Ala Ile Lys Glu Tyr Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn

355 360 365

Val Thr Leu Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln

370 375 380

Gly Val Cys Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu

385 390 395 400

Asn Pro Asp Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr

405 410 415

Val Arg Gly Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys

420 425 430

Phe Tyr Cys Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp

435 440 445

Val Lys Asp Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys

450 455 460

Ile Asp Ala Phe Leu Lys Pro Pro Met Glu Thr Glu Glu Pro Gln Ile

465 470 475 480

Phe Tyr Asn Ala Ser Pro Ser Thr Leu Ser Ala Thr Met Phe Ile Val

485 490 495

Ser Ile Leu Phe Leu Ile Ile Ser Ser Val Ala Ser Leu

500 505

<210> 4

<211> 26

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 4

Met Ala Thr Gly Ser Arg Thr Ser Leu Leu Leu Ala Phe Gly Leu Leu

1 5 10 15

Cys Leu Pro Trp Leu Gln Glu Gly Ser Ala

20 25

<210> 5

<211> 18

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 5

Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala

1 5 10 15

Tyr Ser

<210> 6

<211> 21

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 6

Met Ala Ala His Leu Leu Pro Ile Cys Ala Leu Phe Leu Thr Leu Leu

1 5 10 15

Asp Met Ala Gln Gly

20

<210> 7

<211> 93

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 7

atatggggaa ccctcagtat aactacaagc actgagacct gccaatatct gaaggattac

60

ctgaccagac tgctgaatcc ttacataatc aac

93

<210> 8

<211> 93

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 8

atatggggaa ccctcagtat atccagcagt gaggaagaat gctggcattt gcacgattac

60

ctggtagaca cactgaatcc ttacataatc aac

93

<210> 9

<211> 93

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 9

atatggggaa ccctcagtat aaccgcatct aaggcaaact gcacaaaagt aaaacaattc

60

gtctccagtg atctgaatcc ttacataatc aac

93

<210> 10

<211> 33

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 10

gaatatctcg aggccaccat gaagtgggtt aca

33

<210> 11

<211> 55

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 11

ctaattgcgg ccgctcatta gtggtgatgg tgatgatgga agaaaccaat tctgc

55

<210> 12

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 12

aattaggcgg ccgcctatta aaaggcgtcg atgcacacgc catc

44

<210> 13

<211> 64

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 13

ctctaattgc ggccgctcat tagtggtgat ggtgatgatg aaaggcgtcg atgcacacgc

60

catc

64

<210> 14

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 14

aattagagct cgaggccacc atgaaatggg tgacctttat ctcc

44

<210> 15

<211> 28

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 15

cagattctcg aggccaccat gaaatggg

28

<210> 16

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 16

atctggggct cctgggagaa caccaggcag aaggaggct gccaggccat c

51

<210> 17

<211> 54

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 17

atctggggct cctgggagaa caccaggacc caggagagct gccaggccat caag

54

<210> 18

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 18

agaacaccag gaccaaggag caatgccagg ccatcaagga gtac

44

<210> 19

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 19

aggagagctg ccaggccatc caggagtaca tggacacaac cctg

44

<210> 20

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 20

agctgccagg ccatcaagga gtacgtggac acaaccctga acccttatat c

51

<210> 21

<211> 42

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 21

aggagtacat ggacacaacc gcgaaccctt atatcatcaa tg

42

<210> 22

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 22

atcgtgatct ggggctcctg ggtgaacacc aggaccaagg agag

44

<210> 23

<211> 41

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 23

atctggggct cctgggagtt caccaggacc aaggaggct g

41

<210> 24

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 24

agctgccagg ccatcaagga gtacatgaaa acaaccctga acccttatat c

51

<210> 25

<211> 42

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 25

atcaaggagt acatggacta caccctgaac ccttatatca tc

42

<210> 26

<211> 42

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 26

atcaaggagt acatggacac aatgctgaac ccttatatca tc

42

<210> 27

<211> 43

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 27

accaggacca aggagagctg cgaggccatc aaggagtaca tgg

43

<210> 28

<211> 43

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 28

agtacatgga cacaaccctg atgccttata tcatcaatgt gac

43

<210> 29

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 29

tagaagattg tcacgccctg gccgttggca ttgatccgag gagagc

46

<210> 30

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 30

tgcaccagct cgatggaccg tttcttatac acgtccttag gcttc

45

<210> 31

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 31

accaaggaga gctgccaggc cgaaaaggag tacatggaca caacc

45

<210> 32

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 32

accaaggaga gctgccaggc ccaaaaggag tacatggaca caacc

45

<210> 33

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 33

accaaggaga gctgccaggc ctctaaggag tacatggaca caacc

45

<210> 34

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 34

accaaggaga gctgccaggc cgtcaaggag tacatggaca caacc

45

<210> 35

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 35

accaaggaga gctgccaggc cgcgaaggag tacatggaca caacc

45

<210> 36

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 36

accaaggaga gctgccaggc caacaaggag tacatggaca caacc

45

<210> 37

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 37

accaaggaga gctgccaggc caccaaggag tacatggaca caacc

45

<210> 38

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 38

aaggagagct gccaggccat caagatgtac atggacacaa ccctgaac

48

<210> 39

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 39

aaggagagct gccaggccat caagttctac atggacacaa ccctgaac

48

<210> 40

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 40

aaggagagct gccaggccat caagatatac atggacacaa ccctgaac

48

<210> 41

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 41

aaggagagct gccaggccat caagttgtac atggacacaa ccctgaac

48

<210> 42

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 42

aagggagagct gccaggccat caagcagtac atggacacaa ccctgaac

48

<210> 43

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 43

aaggagagct gccaggccat caaggtatac atggacacaa ccctgaac

48

<210> 44

<211> 96

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 44

atcgtgatct ggggctcctg ggtgaacacc aggaccaagg agagctgcca ggccatcaag

60

gagtacatgg acacaatgct gaacccttat atcatc

96

<210> 45

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 45

agctagcggc atcgtgatct ggcaatcctg ggagaacacc aggacc

46

<210> 46

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 46

agcggcatcg tgatctgggg ccactgggag aacaccagga ccaag

45

<210> 47

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 47

agcggcatcg tgatctgggg ctccattgag aacaccagga ccaaggag

48

<210> 48

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 48

atcgtgatct ggggctcctg gtataacacc aggaccaagg agag

44

<210> 49

<211> 49

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 49

atcgtgatct ggggctcctg ggagaacgaa aggaccaagg agagctgcc

49

<210> 50

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 50

atctggggct cctgggagaa caccttcacc aaggaggct gccaggc

47

<210> 51

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 51

atctggggct cctgggagaa caccagggaa aaggaggct gccaggccat c

51

<210> 52

<211> 55

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 52

atctggggct cctgggagaa caccaggacc aagttgagct gccaggccat caagg

55

<210> 53

<211> 41

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 53

agaacaccag gaccaaggag atctgccagg ccatcaagga g

41

<210> 54

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 54

accaggacca aggagagctg cggggccatc aaggagtaca tggac

45

<210> 55

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 55

accaaggaga gctgccaggc cagaaaggag tacatggaca caac

44

<210> 56

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 56

agctgccagg ccatcaagga gtaccgggac acaaccctga acccttatat c

51

<210> 57

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 57

aggccatcaa ggagtacatg gtcacaaccc tgaaccctta tatc

44

<210> 58

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 58

aggccatcaa ggagtacatg gacagaaccc tgaaccctta tatcatc

47

<210> 59

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 59

atctggggct cctgggagaa caagaggacc aaggaggct gccag

45

<210> 60

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 60

atctggggct cctgggagaa caccctgacc aaggagct gccaggc

47

<210> 61

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 61

atctggggct cctgggagaa caccagggtc aaggaggct gccaggccat c

51

<210> 62

<211> 57

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 62

atctggggct cctgggagaa caccaggacc aagtggagct gccaggccat caaggag

57

<210> 63

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 63

accaaggaga gctgccaggc ctggaaggag tacatggaca caac

44

<210> 64

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 64

aggccatcaa ggagtacatg tacacaaccc tgaaccctta tatc

44

<210> 65

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 65

atctggggct cctgggagaa caccaggtgg aaggagct gccaggccat c

51

<210> 66

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 66

agctgccagg ccatcaagga gtggatggac acaaccctga accc

44

<210> 67

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 67

agcggcatcg tgatctgggg ctccgacgag aacaccagga ccaaggag

48

<210> 68

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 68

atcgtgatct ggggctcctg gcagaacacc aggaccaagg agagc

45

<210> 69

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 69

atctggggct cctgggagaa caccaggcac aaggaggct gccaggccat c

51

<210> 70

<211> 54

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 70

atctggggct cctgggagaa caccaggacc ttcgagagct gccaggccat caag

54

<210> 71

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 71

agaacaccag gaccaaggag gactgccagg ccatcaagga gtac

44

<210> 72

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 72

accaggacca aggagagctg ctacgccatc aaggagtaca tggacac

47

<210> 73

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 73

aggaccaagg agagctgcca ggaaatcaag gagtacatgg acac

44

<210> 74

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 74

agctgccagg ccatcaagga gtactacgac acaaccctga acccttatat c

51

<210> 75

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 75

aggccatcaa ggagtacatg cagacaaccc tgaaccctta tatc

44

<210> 76

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 76

aggccatcaa ggagtacatg gacctaaccc tgaaccctta tatcatc

47

<210> 77

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 77

atcaaggagt acatggacac agagctgaac ccttatatca tcaatg

46

<210> 78

<211> 43

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 78

agtacatgga cacaaccctg gagccttata tcatcaatgt gac

43

<210> 79

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 79

agcggcatcg tgatctgggg ctcccatgag aacaccagga ccaaggag

48

<210> 80

<211> 54

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 80

atctggggct cctgggagaa caccaggacc gacgagagct gccaggccat caag

54

<210> 81

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 81

atcaaggagt acatggacac acacctgaac ccttatatca tcaatg

46

<210> 82

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 82

tttggaatca caggaggagc ccgagagtat gcggagctaa acag

44

<210> 83

<211> 41

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 83

tttggaatca caggaggagc agagtatgcg gagctaaaca g

41

<210> 84

<211> 62

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 84

ctctaattgc ggccgcctat tagtggtgat ggtgatgatg gtccacggca tctgtgtcct

60

tc

62

<210> 85

<211> 74

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 85

agaacaccag gaccaaggag cagtgccagg ccatcaagga gtacatggac cgaaccctga

60

acccttatat catc

74

<210> 86

<211> 55

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 86

taaaagagaa caggctcata tccaggggct cggcaaactt gcccaggcag aactc

55

<210> 87

<211> 53

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 87

taaaagagaa caggctcata tccaggggcg cgtcaaactt gcccaggcag aac

53

<210> 88

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 88

taaaagagaa caggctcata tccagggcct cgtcaaactt gcccaggc

48

<210> 89

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 89

taaaagagaa caggctcata tccgcgggct cgtcaaactt gcccag

46

<210> 90

<211> 42

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 90

accaggatcg tgtttacaga cgcggtgctg aagttcctgt cc

42

<210> 91

<211> 42

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 91

aggatcgtgt ttacagacca ggcgctgaag ttcctgtccc ag

42

<210> 92

<211> 42

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 92

atcgtgttta cagaccaggt ggcgaagttc ctgtcccagg at

42

<210> 93

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 93

atcgtgttta cagaccaggt gctggcgttc ctgtcccagg atgag

45

<210> 94

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 94

gccctgtacc ctagcatcta tctggccacc cagcagagcc cagtggc

47

<210> 95

<211> 50

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 95

ctgtacccta gcatctatct gaacgcccag cagagcccag tggccgctac

50

<210> 96

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 96

taccctagca tctatctgaa caccgcgcag agcccagtgg ccgctacact g

51

<210> 97

<211> 55

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 97

taccctagca tctatctgaa cacccaggcg agcccagtgg ccgctacact gtatg

55

<210> 98

<211> 54

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 98

agcatctatc tgaacaccca gcagagcgca gtggccgcta cactgtatgt gagg

54

<210> 99

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 99

tatctgaaca cccagcagag cccagcggcc gctacactgt atgtgagg

48

<210> 100

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 100

tgtcactccg gtgatagaat cggcatatgg atagtagccc agtctg

46

<210> 101

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 101

tcactgtcac tccggtgata gaagcgatat atggatagta gcccag

46

<210> 102

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 102

tccgttcact gtcactccgg tgatagcatc gatatatgga tagtagccca g

51

<210> 103

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 103

tccgttcact gtcactccgg tggcagaatc gatatatgga tagtagc

47

<210> 104

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 104

ttgtccactg gcatgtagaa ggcgatgtcc ttcttagcct tatc

44

<210> 105

<211> 52

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 105

tgcccagatt gtccactggc atgtaggcgg tgatgtcctt cttagcctta tc

52

<210> 106

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 106

tgcccagatt gtccactggc atggcgaagg tgatgtcctt cttag

45

<210> 107

<211> 50

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 107

agatcgtcgt tcctcttgat ctccgcattg aaacaggagc cgttgtagcc

50

<210> 108

<211> 53

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 108

gacagatcgt cgttcctctt gatcgccaca ttgaaacagg agccgttgta gcc

53

<210> 109

<211> 54

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 109

agccaagaca gatcgtcgtt cctcttggcc tccacattga aacaggagcc gttg

54

<210> 110

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 110

agccaagaca gatcgtcgtt cctcgcgatc tccacattga aacaggagcc g

51

<210> 111

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 111

tctgtggcct cggtcaggct cgcctgcacg ttctgctgct gcac

44

<210> 112

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 112

ttctctgtgg cctcggtcag ggccagctgc acgttctgct gctg

44

<210> 113

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 113

tagccttctc tgtggcctcg gtcgcgctca gctgcacgtt ctgctg

46

<210> 114

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 114

ttagccttct ctgtggcctc ggccaggctc agctgcacgt tctg

44

<210> 115

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 115

tcgaactcct gcttagcctt ctctgcggcc tcggtcaggc tcagctg

47

<210> 116

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 116

tcgaactcct gcttagcctt cgctgtggcc tcggtcaggc tcag

44

<210> 117

<211> 43

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 117

ttctcgaact cctgcttagc cgcctctgtg gcctcggtca ggc

43

<210> 118

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 118

agagaggcta tccgcgtgtc tgcgatcccc gacgccaagt ccccac

46

<210> 119

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 119

aggctatccg cgtgtctaag gcccccgacg ccaagtcccc actg

44

<210> 120

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 120

aggctatccg cgtgtctaag atcgccgacg ccaagtcccc actgccc

47

<210> 121

<211> 51

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 121

agttttactg ctcttgttat tccaccgcga gctgtaagga gaaggctgat g

51

<210> 122

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 122

actgctcttg ttattccacc ctggcctgta aggagaaggc tgatgtg

47

<210> 123

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 123

aaggagaagg ctgatgtgaa ggccacagat gccgtggacg tgtgc

45

<210> 124

<211> 48

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 124

aaggagaagg ctgatgtgaa ggacgcagat gccgtggacg tgtgcatc

48

<210> 125

<211> 43

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 125

aaggctgatg tgaaggacac agctgccgtg gacgtgtgca tcg

43

<210> 126

<211> 81

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 126

atattcgcgg ccgcctatta gtggtgatgg tgatgatgaa aggcgtcgat gcacacgcca

60

gcagcgatgc acacgtccac g

81

<210> 127

<211> 80

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 127

atattcgcgg ccgcctatta gtggtgatgg tgatgatgaa aggcgtcgat gcacacggca

60

tcagcgatgc acacgtccac

80

<210> 128

<211> 75

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 128

atattcgcgg ccgcctatta gtggtgatgg tgatgatgaa aggcgtcgat gcacgcgcca

60

tcagcgatgc acacg

75

<210> 129

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 129

tgtcacgccc tggccggtgg cagcgatccg aggagagccg ataaaag

47

<210> 130

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 130

tgcaccagct cgatggaccg agccttatac acgtccttag gcttc

45

<210> 131

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 131

ttcactgtca ctccggtgat attatcgata tatggatagt agcc

44

<210> 132

<211> 47

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 132

tccgttcact gtcactccgg tctgagaatc gatatatgga tagtagc

47

<210> 133

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 133

accctagcat ctatctgaac accgatcaga gcccagtggc cgctac

46

<210> 134

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 134

accctagcat ctatctgaac accatccaga gcccagtggc cgctac

46

<210> 135

<211> 42

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 135

aggctatccg cgtgtctaag ggccccgacg ccaagtcccc ac

42

<210> 136

<211> 40

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 136

atccgcgtgt ctaagatcga cgacgccaag tccccactgc

40

<210> 137

<211> 40

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 137

agaaggctga tgtgaaggac gacgatgccg tggacgtgtg

40

<210> 138

<211> 40

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 138

agaaggctga tgtgaaggac cacgatgccg tggacgtgtg

40

<210> 139

<211> 40

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 139

agaaggctga tgtgaaggac aaagatgccg tggacgtgtg

40

<210> 140

<211> 40

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 140

agaaggctga tgtgaaggac ggagatgccg tggacgtgtg

40

<210> 141

<211> 40

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 141

agaaggctga tgtgaaggac ccagatgccg tggacgtgtg

40

<210> 142

<211> 40

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 142

agaaggctga tgtgaaggac atggatgccg tggacgtgtg

40

<210> 143

<211> 40

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 143

agaaggctga tgtgaaggac ttcgatgccg tggacgtgtg

40

<210> 144

<211> 82

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 144

ctctaattgc ggccgcctat tagtggtgat ggtgatgatg aaaggcgtcg atgcacacgc

60

ccctagcgat gcacacgtcc ac

82

<210> 145

<211> 76

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 145

ctctaattgc ggccgctcat tagtggtgat ggtgatgatg aaaggcgtcg atgcagtagc

60

catcagcgat gcacac

76

<210> 146

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 146

ttctctgtgg cctcggtcag ggtcagctgc acgttctgct gctg

44

<210> 147

<211> 41

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 147

aggagaaggc tgatgtgaag agcacagatg ccgtggacgt g

41

<210> 148

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 148

atcgtgttta cagaccaggt gccgaagttc ctgtcccagg atgag

45

<210> 149

<211> 45

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 149

atcgtgttta cagaccaggt gatgaagttc ctgtcccagg atgag

45

<210> 150

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 150

tctgtggcct cggtcaggct cgactgcacg ttctgctgct gcac

44

<210> 151

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 151

tctgtggcct cggtcaggct aatctgcacg ttctgctgct gcac

44

<210> 152

<211> 44

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 152

tctgtggcct cggtcaggct aaactgcacg ttctgctgct gcac

44

<210> 153

<211> 84

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 153

atcgtgatct ggggctcctg ggagttcacc aggacccagg agagctgcca ggccatccag

60

gagtacatgg acacaaccct gaac

84

<210> 154

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 154

accctagcat ctatctgaac accaaccaga gcccagtggc cgctac

46

<210> 155

<211> 17

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 155

gccaggcag aactcgc

17

<210> 156

<211> 62

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 156

tctcgaactc ctgcttagcc ttatctgtgg cctcggtcat gctcagctgc acgttctgct

60

gc

62

<210> 157

<211> 46

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 157

accctagcat ctatctgaac accgcgcaga gcccagtggc cgctac

46

<210> 158

<211> 60

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 158

atcgtgatct ggggctcctg ggagatcacc aggaccatgg agagctgcca ggccatcaag

60

<210> 159

<211> 60

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 159

agcggcatcg tgatctgggg cgacctgtcg atctcctcga ccatggagag ctgccaggcc

60

<210> 160

<211> 57

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 160

agcggcatcg tgatctgggg cgacctgtcg atctccagga ccatggagag ctgccag

57

<210> 161

<211> 54

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 161

atctggggct cctgggagaa caccaggacc atggagagct gccaggccat caag

54

<210> 162

<211> 60

<212> DNA

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 162

atcgtgatct ggggctcctg ggagatcacc aggaccatgg agagctgcca ggccatcaag

60

<210> 163

<211> 455

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 163

Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp

1 5 10 15

Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro

20 25 30

Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala

35 40 45

Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr

50 55 60

Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro

65 70 75 80

Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile

85 90 95

Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp

100 105 110

Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val

115 120 125

Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu

130 135 140

Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala

145 150 155 160

Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg

165 170 175

Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His

180 185 190

His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile

195 200 205

Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu

210 215 220

Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr

225 230 235 240

Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile

245 250 255

Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val

260 265 270

Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr

275 280 285

Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp

290 295 300

Gly Thr Leu Ser Ile Thr Thr Ser Thr Glu Thr Cys Gln Tyr Leu Lys

305 310 315 320

Asp Tyr Leu Thr Arg Leu Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu

325 330 335

Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys

340 345 350

Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp

355 360 365

Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly

370 375 380

Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys

385 390 395 400

Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp

405 410 415

Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala

420 425 430

Phe Leu Lys Pro Pro Met Glu Thr Glu Glu Pro Gln Ile Phe Tyr Asn

435 440 445

Ala Ser Pro Ser Thr Leu Ser

450 455

<210> 164

<211> 455

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 164

Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp

1 5 10 15

Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro

20 25 30

Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala

35 40 45

Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr

50 55 60

Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro

65 70 75 80

Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile

85 90 95

Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp

100 105 110

Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val

115 120 125

Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu

130 135 140

Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala

145 150 155 160

Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg

165 170 175

Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His

180 185 190

His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile

195 200 205

Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu

210 215 220

Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr

225 230 235 240

Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile

245 250 255

Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val

260 265 270

Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr

275 280 285

Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp

290 295 300

Gly Thr Leu Ser Ile Ser Ser Ser Glu Glu Glu Cys Trp His Leu His

305 310 315 320

Asp Tyr Leu Val Asp Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu

325 330 335

Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys

340 345 350

Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp

355 360 365

Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly

370 375 380

Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys

385 390 395 400

Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp

405 410 415

Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala

420 425 430

Phe Leu Lys Pro Pro Met Glu Thr Glu Glu Pro Gln Ile Phe Tyr Asn

435 440 445

Ala Ser Pro Ser Thr Leu Ser

450 455

<210> 165

<211> 455

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 165

Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp

1 5 10 15

Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro

20 25 30

Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala

35 40 45

Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr

50 55 60

Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro

65 70 75 80

Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile

85 90 95

Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp

100 105 110

Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val

115 120 125

Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu

130 135 140

Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala

145 150 155 160

Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg

165 170 175

Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His

180 185 190

His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile

195 200 205

Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu

210 215 220

Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr

225 230 235 240

Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile

245 250 255

Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val

260 265 270

Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr

275 280 285

Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp

290 295 300

Gly Thr Leu Ser Ile Thr Ala Ser Lys Ala Asn Cys Thr Lys Val Lys

305 310 315 320

Gln Phe Val Ser Ser Asp Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu

325 330 335

Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys

340 345 350

Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp

355 360 365

Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly

370 375 380

Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys

385 390 395 400

Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp

405 410 415

Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala

420 425 430

Phe Leu Lys Pro Pro Met Glu Thr Glu Glu Pro Gln Ile Phe Tyr Asn

435 440 445

Ala Ser Pro Ser Thr Leu Ser

450 455

<210> 166

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 166

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Met Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 167

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 167

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Gln Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 168

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 168

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Gln Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 169

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 169

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Gln Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 170

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 170

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Gln Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 171

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 171

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Val Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 172

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 172

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Ala Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 173

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 173

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Val Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 174

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 174

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Phe Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 175

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 175

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Lys Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 176

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 176

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Tyr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 177

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 177

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Met Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 178

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 178

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Glu Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 179

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 179

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Met Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 180

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 180

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Asn Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 181

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 181

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Lys Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 182

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 182

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Glu Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 183

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 183

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Gln Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 184

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 184

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ser Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 185

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 185

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Val Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 186

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 186

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ala Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 187

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 187

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Asn Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 188

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 188

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Thr Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 189

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 189

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Met Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 190

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 190

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Phe Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 191

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 191

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Ile Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 192

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 192

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Leu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 193

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 193

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Gln Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 194

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 194

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Val Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 195

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 195

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Lys Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Val Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Met Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 196

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 196

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gln Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 197

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 197

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly His

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 198

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 198

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Ile Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 199

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 199

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Tyr Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 200

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 200

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Glu Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 201

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 201

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Phe Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 202

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 202

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Glu Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 203

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 203

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Leu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 204

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 204

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ile Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 205

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 205

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gly Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 206

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 206

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Arg Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 207

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 207

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Arg Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 208

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 208

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Val Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 209

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 209

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Arg Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 210

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 210

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Lys Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 211

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 211

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Leu Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 212

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 212

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Val Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 213

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 213

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Trp Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 214

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 214

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Trp Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 215

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 215

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Tyr Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 216

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 216

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Trp Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 217

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 217

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Trp

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 218

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 218

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Asp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 219

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 219

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Gln Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 220

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 220

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg His Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 221

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 221

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Phe Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 222

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 222

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Asp Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 223

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 223

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Tyr Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 224

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 224

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Glu Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 225

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 225

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Tyr Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 226

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 226

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Gln Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 227

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 227

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Leu Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 228

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 228

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Glu Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 229

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 229

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Glu Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 230

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 230

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

His Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 231

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 231

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Asp Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 232

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 232

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr His Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 233

<211> 430

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 233

Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp Asn

1 5 10 15

Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp Met

20 25 30

Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly Gln

35 40 45

Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr Ile

50 55 60

Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys Ile

65 70 75 80

Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe Tyr

85 90 95

Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu Trp

100 105 110

Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys Asn

115 120 125

Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu Thr

130 135 140

Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys Asp

145 150 155 160

Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn His

165 170 175

Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr Lys

180 185 190

Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg Asn

195 200 205

Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro Ser

210 215 220

Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr Val

225 230 235 240

Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp Ala

245 250 255

Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr Asp

260 265 270

Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe Gly

275 280 285

Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser Trp

290 295 300

Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr Met

305 310 315 320

Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala Lys

325 330 335

Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg Lys

340 345 350

Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe Ala

355 360 365

Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro Thr

370 375 380

Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys Tyr

385 390 395 400

Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp Ala

405 410 415

Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 234

<211> 429

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 234

Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp Asn Ala

1 5 10 15

Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp Met Ser

20 25 30

Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly Gln Gly

35 40 45

Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr Ile Asp

50 55 60

Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys Ile Ser

65 70 75 80

Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe Tyr Met

85 90 95

Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu Trp Arg

100 105 110

Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys Asn Arg

115 120 125

Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu Thr Glu

130 135 140

Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys Asp Phe

145 150 155 160

Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn His Leu

165 170 175

Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr Lys Lys

180 185 190

Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg Asn Asp

195 200 205

Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro Ser Ile

210 215 220

Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr Val Arg

225 230 235 240

Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp Ala Lys

245 250 255

Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr Asp Gln

260 265 270

Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe Gly Glu

275 280 285

Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser Trp Glu

290 295 300

Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr Met Asp

305 310 315 320

Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala Lys Met

325 330 335

Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg Lys Asn

340 345 350

Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe Ala Ile

355 360 365

Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro Thr Leu

370 375 380

Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys Tyr Ser

385 390 395 400

Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp Ala Val

405 410 415

Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425

<210> 235

<211> 419

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 235

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp

<210> 236

<211> 430

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 236

Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp Asn

1 5 10 15

Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp Met

20 25 30

Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly Gln

35 40 45

Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr Ile

50 55 60

Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys Ile

65 70 75 80

Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe Tyr

85 90 95

Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu Trp

100 105 110

Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys Asn

115 120 125

Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu Thr

130 135 140

Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys Asp

145 150 155 160

Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn His

165 170 175

Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr Lys

180 185 190

Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg Asn

195 200 205

Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro Ser

210 215 220

Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr Val

225 230 235 240

Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp Ala

245 250 255

Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr Asp

260 265 270

Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe Gly

275 280 285

Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser Trp

290 295 300

Glu Asn Thr Arg Thr Lys Glu Gln Cys Gln Ala Ile Lys Glu Tyr Met

305 310 315 320

Asp Arg Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala Lys

325 330 335

Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg Lys

340 345 350

Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe Ala

355 360 365

Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro Thr

370 375 380

Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys Tyr

385 390 395 400

Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp Ala

405 410 415

Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 237

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 237

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Ala Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 238

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 238

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Ala Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 239

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 239

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Ala Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 240

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 240

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Ala Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 241

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 241

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Ala Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 242

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 242

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 243

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 243

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Ala Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 244

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 244

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Ala Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 245

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 245

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Ala Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 246

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 246

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Ala Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 247

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 247

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Ala Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 248

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 248

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Ala Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 249

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 249

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Ala Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 250

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 250

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Ala Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 251

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 251

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ala Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 252

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 252

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Ala Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 253

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 253

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ala Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 254

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 254

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ala Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 255

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 255

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ala Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 256

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 256

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Ala

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 257

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 257

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Ala Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 258

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 258

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Ala Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 259

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 259

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Ala Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 260

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 260

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ala Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 261

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 261

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Ala Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 262

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 262

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Ala Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 263

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 263

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ala Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 264

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 264

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 265

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 265

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Ala Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 266

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 266

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Ala Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 267

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 267

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Ala Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 268

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 268

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Ala Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 269

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 269

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Ala Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 270

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 270

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ala Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 271

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 271

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Ala Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 272

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 272

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Ala Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 273

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 273

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ala Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 274

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 274

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Ala Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 275

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 275

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Ala Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 276

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 276

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Ala

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 277

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 277

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Ala Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 278

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 278

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Ala Val Cys Ile Asp Ala Phe

420 425 430

<210> 279

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 279

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Ala Cys Ile Asp Ala Phe

420 425 430

<210> 280

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 280

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Ala Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 281

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 281

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Ala Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 282

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 282

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Asn Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 283

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 283

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Gln Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 284

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 284

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Asp Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 285

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 285

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Ile Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 286

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 286

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Gly Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 287

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 287

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Asp Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 288

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 288

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 289

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 289

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp His Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 290

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 290

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Lys Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 291

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 291

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Gly Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 292

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 292

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Pro Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 293

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 293

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Met Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 294

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 294

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Phe Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 295

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 295

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Arg Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 296

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 296

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Tyr Cys Ile Asp Ala Phe

420 425 430

<210> 297

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 297

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Thr Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 298

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 298

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Ser Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 299

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 299

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Pro Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 300

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 300

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Met Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 301

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 301

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Ser Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 302

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 302

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Ile Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 303

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 303

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Phe Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 304

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 304

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Phe Thr Arg Thr Gln Glu Ser Cys Gln Ala Ile Gln Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 305

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 305

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ser Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala

130 135 140

Thr Glu Ala Thr Asp Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Asn Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 306

<211> 432

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 306

Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala

1 5 10 15

Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu

20 25 30

Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr

35 40 45

Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro

50 55 60

Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln

65 70 75 80

Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr

85 90 95

Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu

100 105 110

Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr

115 120 125

Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser

130 135 140

Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly

145 150 155 160

Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro

165 170 175

Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His

180 185 190

Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys

195 200 205

Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr

210 215 220

Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu

225 230 235 240

Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro

245 250 255

Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe

260 265 270

Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr

275 280 285

Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly

290 295 300

Ser Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu

305 310 315 320

Tyr Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala

325 330 335

Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile

340 345 350

Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn

355 360 365

Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys

370 375 380

Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser

385 390 395 400

Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr

405 410 415

Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 307

<211> 433

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 307

Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp

1 5 10 15

Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro

20 25 30

Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala

35 40 45

Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr

50 55 60

Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro

65 70 75 80

Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile

85 90 95

Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp

100 105 110

Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val

115 120 125

Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu

130 135 140

Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala

145 150 155 160

Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg

165 170 175

Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His

180 185 190

His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile

195 200 205

Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu

210 215 220

Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr

225 230 235 240

Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile

245 250 255

Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val

260 265 270

Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr

275 280 285

Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp

290 295 300

Gly Ser Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys

305 310 315 320

Glu Tyr Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu

325 330 335

Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys

340 345 350

Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp

355 360 365

Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly

370 375 380

Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys

385 390 395 400

Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp

405 410 415

Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala

420 425 430

Phe

<210> 308

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 308

Phe Lys Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ala Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ser Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Met

130 135 140

Thr Glu Ala Thr Asp Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Ala Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 309

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 309

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ala Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala

130 135 140

Thr Glu Ala Thr Ala Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Ala Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 310

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 310

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Ile Thr Arg Thr Met Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 311

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 311

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Asp

290 295 300

Leu Ser Ile Ser Ser Thr Met Glu Ser Cys Gln Ala Ile Asp Glu Tyr

305 310 315 320

Met Glu Thr Ile Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 312

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 312

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu

130 135 140

Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Asp

290 295 300

Leu Ser Ile Ser Arg Thr Met Glu Ser Cys Gln Ala Ile Asp Glu Tyr

305 310 315 320

Met Glu Thr Ile Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 313

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 313

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ser Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala

130 135 140

Thr Glu Ala Thr Asp Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Asn Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Asn Thr Arg Thr Met Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 314

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 314

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ser Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala

130 135 140

Thr Glu Ala Thr Asp Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Asn Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser

290 295 300

Trp Glu Ile Thr Arg Thr Met Glu Ser Cys Gln Ala Ile Lys Glu Tyr

305 310 315 320

Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 315

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 315

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ala Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala

130 135 140

Thr Glu Ala Thr Ala Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Ala Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Asp

290 295 300

Leu Ser Ile Ser Ser Thr Met Glu Ser Cys Gln Ala Ile Asp Glu Tyr

305 310 315 320

Met Glu Thr Ile Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<210> 316

<211> 431

<212>PRT

<213> Artificial Sequence

<220>

<223> Artificial Sequence

<400> 316

Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp

1 5 10 15

Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp

20 25 30

Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly

35 40 45

Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr

50 55 60

Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys

65 70 75 80

Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ala Phe

85 90 95

Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu

100 105 110

Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys

115 120 125

Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala

130 135 140

Thr Glu Ala Thr Ala Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys

145 150 155 160

Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn

165 170 175

His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr

180 185 190

Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg

195 200 205

Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro

210 215 220

Ser Ile Tyr Leu Asn Thr Ala Gln Ser Pro Val Ala Ala Thr Leu Tyr

225 230 235 240

Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp

245 250 255

Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr

260 265 270

Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe

275 280 285

Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Asp

290 295 300

Leu Ser Ile Ser Arg Thr Met Glu Ser Cys Gln Ala Ile Asp Glu Tyr

305 310 315 320

Met Glu Thr Ile Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala

325 330 335

Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg

340 345 350

Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe

355 360 365

Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro

370 375 380

Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys

385 390 395 400

Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp

405 410 415

Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe

420 425 430

<---

Claims (16)

1. A variant of hyaluronidase PH20 or a fragment thereof having hyaluronidase activity, including the substitution, deletion or insertion of an amino acid residue at at least one position in the variant containing the amino acid sequence SEQ ID NO: 3, wherein at least one amino acid residue is deleted by cleavage to an amino acid residue selected from the group consisting of L36, N37, F38, R39, A40, P41 or P42 from the N-terminus, and at least one amino acid residue is deleted by cleavage after the amino acid a residue selected from the group consisting of V455 to S490 from the C-terminus, and where the PH20 variant or fragment thereof includes a substitution of an amino acid residue at at least one position selected from the group consisting of R39, D65 - L68, N82, T84, I102 - I105, T132 - Y134, N166, L179 - T182, T185 - K187 , V241 - K244, N266 - Q269, P271, V272, K290 - P292, Q311 - K314, G340 - S350, Q352 - N363, L441, S442, D451 - D453, D461, V463 and D461 - V463 in a variant containing the amino acid sequence SEQ ID NO: 3, and wherein the variant or fragment has an aggregation temperature of 46.5°C or higher. 2. A variant of hyaluronidase PH20 or a fragment thereof according to claim 1, characterized in that the replacement of the amino acid residue includes at least one selected from the group consisting of R39K, D65A, E66A, P67A, L68A, N82A, T84N, I102A, D103A, S104A, S104N, I105A, I105Q, T132A, T132S, F133A, Y134A, N166A, N166K, L179A, L179S, L179I, L179F, S180T, S180A, L181A, L181M, T182A, T185A, E186 A, E186D, K187A, V241A, E242A, I243A, K244A, N266A, T267A, Q268A, Q268D, Q268I, Q268N, Q269A, P271A, V272A, K290A, I291A, I291G, I291L, P292A, P292D, Q311A, V312A, L313A, L313 P, L313M, K314A, G340Q, S341H, S341D, S341T, W342I, W342D, W342H, W342L, E343V, E343S, E343Y, E343Q, N344F, N344I, T345E, T345K, T345S, R346M, R346F, R346L, R346T, R346S, R346 A, T347Q, T347E, T347V, T347W, T347H, T347S, K348Q, K348F, K348D, K348T, K348E, K348M, E349L, E349W, E349A, S350Q, S350I, S350D, S350T, S350E, S350N, Q352E, Q352G, Q352Y, Q352 W, Q352T, A353E, A353Y, A353H, A353K, I354E, I354Q, I354S, I354V, I354A, I354N, I354T, I354R, I354W, I354L, K355Q, K355H, K355D, E356M, E356F, E356I, E356L, E356Q, E356V, E356 D, Y357W, Y357F, M358V, M358R, M358Y, M358L, D359K, D359V, D359Y, D359Q, D359T, D359S, D359E, T360Y, T360R, T360L, T360D, T360S, T361M, T361E, T361H, T361L, T361D, T361I, L362 A, N363M, N363E, L441A, S442A, D451A, D451S, T452A, T452D, T452H, T452K, T452G, T452P, T452M, T452F, D453A, D461R, D461A, G462A, V463Y and V463A. 3. A variant of hyaluronidase PH20 or a fragment thereof according to claim 1, characterized in that at least one amino acid residue is removed by cleavage after amino acid residue V455, D456, C458, D461, C464, I465, D466, A467, F468, K470, P471 , P472, M473, E474, T475, E476, P478, I480, Y482, A484, P486, T488 or S490 from the C-terminus. 4. A variant of hyaluronidase PH20 or a fragment thereof according to claim 1, characterized in that at least one amino acid residue is removed by cleavage before amino acid residue F38 from the N-terminus and after amino acid residue F468 from the C-terminus. 5. A variant of hyaluronidase PH20 or a fragment thereof according to any one of claims. 1-4, characterized in that the hyaluronidase variant PH20 or a fragment thereof contains an amino acid sequence selected from the group consisting of amino acid sequences SEQ ID NO: 163-316. 6. Composition for the treatment of cancer, including a variant of hyaluronidase PH20 or a fragment thereof according to any one of paragraphs. 1-5 and a pharmaceutically acceptable excipient. 7. The composition according to claim 6, characterized in that the composition is used in combination therapy with another anticancer drug. 8. The composition according to claim 7, characterized in that the anticancer drug is an immuno-oncological agent. 9. The composition according to claim 8, characterized in that the immuno-oncology agent includes an immune checkpoint inhibitor. 10. Nucleic acid encoding a variant of hyaluronidase PH20 or a fragment thereof according to any one of paragraphs. 1-5. 11. Recombinant expression vector containing the nucleic acid according to claim 10. 12. A host cell transformed with the recombinant expression vector according to claim 11 for expressing the PH20 hyaluronidase variant or a fragment thereof according to any one of claims. 1-5. 13. A method for producing a variant of hyaluronidase PH20 or a fragment thereof, including culturing a host cell according to claim 12.