RU2824199C1 - TGFβR2 MOLECULE WITH TRUNCATED EXTRACELLULAR DOMAIN, FUSION PROTEIN OF TGFβR2 MOLECULE WITH TRUNCATED EXTRACELLULAR DOMAIN, AND ANTI-EGFR ANTIBODIES, AND ANTI-TUMOUR USE OF FUSED PROTEIN - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: invention relates to biotechnology, specifically to recombinant molecules of transforming growth factor beta (TGFβR2) and can be used in medicine for treating a tumour associated with EGFR.

EFFECT: invention provides obtaining a TGFβR2 molecule with a truncated extracellular domain, which, when combined with an antibody targeting a cancer cell, is more resistant to protease cleavage compared to the natural form of the TGFβR2 molecule.

12 cl, 35 dwg, 25 tbl, 8 ex

Description

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims the benefit of Chinese Patent Application No. 202010351280.6, filed on April 28, 2021, the entire contents of which are incorporated herein by reference.

AREA OF TECHNOLOGY

The present invention relates to the field of antitumor immunotherapeutic agents. In particular, the present invention relates to a TGFβR2 (immunomodulation factor) molecule with a truncated extracellular domain, a fusion protein containing a TGFβR2 molecule with a truncated extracellular domain and a targeting portion. The present invention includes pharmaceutical compositions and their use as antitumor drugs.

LEVEL OF TECHNOLOGY

Transforming growth factor-β (TGF-β) belongs to the TGF-β superfamily, which regulates cell growth and differentiation, and is a pleiotropic and multifunctional cytokine that regulates cell proliferation, differentiation, and apoptosis through cell surface receptor signaling pathways in an autocrine or paracrine manner. It also plays an important regulatory role in extracellular matrix synthesis, injury repair, immune function, etc. Three isoforms, TGF-β1, TGF-β2, and TGF-β3, are present in mammals, and the most abundant and expressed isoform is TGF-β1. TGF-β initiates classical Smad and non-Smad pathways for downstream signaling by binding to the serine-threonine kinase receptors TGFβR1 and TGFβR2 on the cell membrane surface ^[1] . Under normal homeostasis in vivo, TGF-β regulates signaling of key processes such as growth, regeneration, differentiation, etc. of various tissues. In the immune system, TGF-β induces tolerance and suppresses inflammation. Genetic mutations can alter TGF-β signaling in tumor-initiating cells. In the initial stages of oncogenesis, TGF-β plays a key role in inhibiting cancer by inhibiting cell proliferation and triggering the apoptotic program. However, as the tumor progresses, selective pressure from tumor cells leads to the loss of TGF-β tumor suppressor function through various mechanisms. Acquired inactivating mutations in the TGF-β signaling pathway allow many malignant cells to grow in a TGF-β-enriched environment. Additionally, tumor cells somehow translate the pro-apoptotic capacity of TGF-β into pro-tumor developmental functions such as invasive and migratory capacity and promotion of mesenchymal transition ^[2-4] . TGF-β regulates various types and functions of immune cells. TGF-β controls adaptive immunity by directly stimulating the proliferation of Treg cells, thereby suppressing the production and function of effector T cells and antigen-presenting dendritic cells. TGF-β also inhibits NK cell function and converts macrophages and neutrophils into pro-tumor growth subtypes, promoting the formation of a tumor microenvironment with negative tumor immune regulation ^[4] . TGF-β1 is frequently expressed at higher levels than in normal paraneoplastic tissue in a variety of solid tumors, including EGFR-positive colorectal cancer, non-small cell lung cancer, and squamous cell carcinoma of the head and neck. Clinical data suggest that blockade of the TGF-β pathway alone is not sufficient to fully restore the immune system to suppress tumorigenesis, and therefore antibodies to TGF-β have not yet been developed.

The epidermal growth factor receptor (EGFR) is the expression product of the C-ErbB1 proto-oncogene, and it is a receptor for cell proliferation and epithelial growth factor (EGF) signaling, a member of the human epidermal growth factor receptor (HER) family, and a 170-kDa receptor tyrosine kinase ^[5] . EGFR consists of an extracellular ligand-binding region, a transmembrane region, and an intracellular kinase region. The extracellular domain of EGFR converts from a monomer to a dimer upon ligand binding, activates the intracellular kinase region and several downstream signaling pathways, and plays an important role in cell growth, proliferation, and differentiation ^[6] . High EGFR expression causes enhanced downstream signaling; overexpression of mutant EGFR receptors or ligands results in sustained EGFR activation, increased secretory loop activity, and impaired receptor downregulation, etc., which in turn activates tumor proliferation and differentiation-related genes and plays an important role in tumor formation and progression ^[7] . Overexpression of EGFR is associated with decreased survival in several types of cancer, including head and neck, bladder, ovarian, cervical, and esophageal cancer. Additionally, anti-EGFR drugs have been shown to be effective in the treatment of several types of solid tumors, such as colorectal, head and neck, non-small cell lung cancer (NSCLC), and pancreatic cancer, including overall survival, progression-free survival, and overall response rates. ^[8] Thus, as a clear target associated with tumor proliferation, EGFR-targeting agents have become a first-line treatment option for various malignancies.

Although the signals initiated by TGF-β are distinct from those initiated by the EGF/EGFR pathway, the signaling pathways between them can interact. TGF-β and EGFR signaling pathways have been found to interact and jointly promote tumor progression in various tumor types. TGF-β can induce EGFR trans-activation in a cell type- and context-dependent manner. For example, TGF-β promotes migration and invasion of breast cancer cells (MDA-MB-231, T47D, 4T1) by activating EGFR through the classical Smad and ERK/Sp1 signaling pathways ^[9,10] . In squamous cell carcinoma (A431, SCC13), TGF-β activates the EGFR pathway through _{H2O2 -} dependent mechanisms to increase Erk1/2 phosphorylation levels ^[11] . EGF and its associated downstream signaling pathways can also regulate TGF-β signaling in various cell types. For example, in human primary ovarian cancer cells, EGF desensitizes ovarian cancer cells to the antiproliferative effects of TGF-β by decreasing mRNA expression of the TCF-β-inducible cell cycle regulator p15 ^{INK4B [12]} . Oncogenic Ras in breast and lung epithelial cells reduces the cell growth inhibitory effect of TGF-β by inhibiting TGF-β-mediated signaling through negative regulation of Smad2 and Smad3 ^[13,14] . EGF also positively regulates Smad2 signaling in COS7 cells by increasing Smad2 phosphorylation via the ERK pathway ^[15] .

TGF-β and EGF synergistically promote the malignant phenotype of tumors, and studies in various tissues have shown that EGF in combination with TGF-β enhances epithelial-mesenchymal transition (EMT). For example, EGF and TGF-β1 promote laminin-332 expression, which synergistically promotes EMT in oral epithelial cancer ^[16] . EGF and TGF-β1 promote EMT in intestinal epithelial cells by downregulating E-cadherin via the MAPK pathway but not via PI3K, p38MAPK, JNK, or AP-1 ^[17] . EGF and TGF-β1 induce Slug and Snail expression via Smad and MEK1/2-dependent signaling pathways, downregulate E-cadherin, and promote EMT in ovarian epithelial cells ^[18] . EGF and TGF-β1 activate the ERK1/2 signaling pathway, synergistically enhance Snail protein expression, and promote EMT and migration in human renal proximal tubular epithelial cells (HK-2) ^[19] . EGF enhances TGF-β-induced EMT in lung cancer (H322, H358) and pancreatic cancer (HPAF-II, CAPAN-2) cells by promoting SHP2 binding to GAB1 ^[20] .

Several clinical studies have shown that elevated TGF-β levels are closely associated with the development of drug resistance and poor prognosis. TGF-β1-induced EMT in osteosarcoma cancer stem cells downregulates miR-499a expression, which leads to increased SHKBP1 expression occurring concomitantly with TGFβ-induced switch of EMT-related kinase to AKT-activated EGFR-independent state, thereby downregulating EGFR activity and inducing osteosarcoma resistance to EGFR kinase inhibitors (Fig. 5) ^[21] . Treg cells are one of the major TGF-β producing cells. Increased Treg levels in tumors from cetuximab-treated patients with squamous cell carcinoma of the head and neck are accompanied by increased TGF-β levels, while TGF-β levels in patients with low cetuximab efficacy are even higher ^[22] . Increased TGF-β levels may induce resistance to anti-EGFR antibody therapy by inhibiting the expression of the corresponding molecular effectors of effector cell cytotoxicity, activating the EGFR-independent AKT pathway, and enhancing EMT induction ^[23] . In EGFR-mutant non-small cell lung cancer, the classical TGF-βSmad signaling pathway is involved in the development of PD-L1-induced tumor resistance to EGFR kinase inhibitors ^[24] . In breast cancer tissues, TGF-β expression was positively correlated with EGFR expression, and elevated levels of TGF-β and EGFR were associated with poor prognosis in breast cancer patients ^[9] . Thus, EGFR and TGF-β play relatively independent but closely related roles in this tumor pathway. Additionally, TGF-β is a key molecule in the development of acquired tumor resistance to EGFR-targeted therapies. Animal studies have shown that TGF-β inhibition improves the in vivo antitumor effect of cetuximab on head and neck squamous cell tumor xenografts ^[23] . These data provide a theoretical basis for combined targeting of TGF-β to enhance the therapeutic efficacy of an anti-EGFR antibody against EGFR-positive tumors.

The present invention provides novel fusion proteins containing a truncated TGFβR2 that can specifically target both EGFR and TGF-β, two relatively independent but closely related signaling pathways. They are used to treat solid tumors, including but not limited to gastric cancer.

BRIEF DESCRIPTION

In one aspect, the present invention provides a TGFβR2 molecule with a truncated extracellular domain, which, compared to its natural form,

a) at least amino acid residues at positions 6-16 are removed, and additionally, optionally, amino acid residues at positions 17-17+n are removed, where n is an integer from 1 to 10; preferably, n is 2, 4, 8, 9 or 10; more preferably, n is 9; or

b) based on the deletion of amino acid residues at positions 6-26, in addition, amino acid residues at positions 5, 4-5, 3-5, 2-5, 1, 1-2, 1-3, or 1-4 are deleted; or

c) amino acid residues at positions 7-26 are removed.

In one embodiment, said amino acid sequence comprises any of SEQ ID NOs: 48-62.

In another aspect, the present invention provides a fusion protein comprising the molecules described above.

In one embodiment, said fusion protein comprises

a) the specified TGFβR2 molecule with a shortened extracellular domain and

b) the targeting part.

In one embodiment of said fusion protein, the targeting portion is a cancer cell-specific targeting portion selected from an antibody or an antigen-binding fragment thereof, a functional ligand or an Fc fusion protein thereof, and a receptor protein or an Fc fusion protein thereof.

In one embodiment of said fusion protein, the targeting portion is an anti-EGFR antibody or an antigen-binding fragment thereof.

In one embodiment, the N-terminus of said TGFβR2 molecule with a truncated extracellular domain in said fusion protein is connected to the C-terminus of said heavy chain of the targeting moiety, optionally via a linker.

In one embodiment, said linker is preferably a G ₄ S flexible peptide linker, preferably a (G ₄ S) ₄ peptide linker.

In another aspect, the present invention provides an isolated binding antibody or antigen-binding fragment thereof against EGFR comprising

(a) a heavy chain variable region comprising the heavy chain CDR1, heavy chain CDR2, and heavy chain CDR3 domains comprising SEQ ID NOs: 19, 20, and 21, respectively, and/or

(b) a light chain variable region comprising a light chain CDR1, light chain CDR2, and light chain CDR3 domains comprising SEQ ID NO: 16, 17, and 18, respectively.

In one embodiment, said antibody or antigen-binding fragment thereof comprises

a) a heavy chain variable region comprising a sequence comprising SEQ ID NO: 28 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to that sequence; and/or

(b) a light chain variable region comprising a sequence comprising SEQ ID NO: 29 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to that sequence.

In one embodiment, said antibody further comprises:

a) a heavy chain constant region comprising a sequence comprising SEQ ID NO: 30 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to that sequence; and/or

b) a light chain constant region comprising a sequence comprising SEQ ID NO: 31 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to that sequence.

In one embodiment, the targeting portion of said fusion protein is selected from an anti-EGFR antibody, trastuzumab, bevacizumab, ramucirumab, ipilimumab, or panitumumab.

In one embodiment, said fusion protein comprises

a) a heavy chain amino acid sequence comprising SEQ ID NO: 141 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to that sequence; and

b) a light chain amino acid sequence comprising SEQ ID NO: 23 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to this sequence,

which contain two heavy chains and two light chains; a disulfide bond is formed between its first light chain and its first heavy chain, a disulfide bond is formed between its second light chain and its second heavy chain, and a disulfide bond is formed between its first heavy chain and its second heavy chain.

In one embodiment, said fusion protein has a K _D value in the range of 2.92 pM - 26.3 pM, preferably 7 pM - 9 pM, more preferably 8.77 pM, for binding affinity to human EGFR protein; and

has a K _D value in the range of 23 pM - 288.3 pM, preferably 64 pM - 144 pM, more preferably 96.1 pM in binding affinity to human TGF-β1 protein.

In another aspect, the present invention provides a conjugate comprising a TGFβR2 molecule with a truncated extracellular domain as described herein, a fusion protein as described herein, an antibody or antigen-binding fragment thereof as described herein, and an additional therapeutic agent, wherein preferably said antibody or antigen-binding fragment thereof and said additional therapeutic agent are connected via a linker.

In another aspect, the present invention provides a nucleic acid encoding said TGFβR2 molecule with a truncated extracellular domain described herein, a fusion protein described herein, an antibody or an antigen-binding fragment thereof described herein, which is mRNA and/or DNA.

In one embodiment, said nucleic acid comprises

any of the sequences SEQ ID NO: 32-39;

any of SEQ ID NO: 67-84; or

any of the sequences SEQ ID NO: 148-163, or functional variants thereof.

In another aspect, the present invention provides an expression vector comprising said nucleic acid described herein.

In another aspect, the present invention provides a host cell comprising said nucleic acid described herein or said expression vector described herein.

In another aspect, the present invention provides a method for producing said TGFβR2 molecule with a truncated extracellular domain described herein, a fusion protein described herein, an antibody or an antigen-binding fragment thereof described herein, comprising growing said host cell described herein under conditions suitable for expressing the molecule of the protein described above, and isolating the expressed product from the culture fluid.

In another aspect, the present invention provides a pharmaceutical composition comprising

(a) a TGFβR2 molecule with a truncated extracellular domain as described herein, a fusion protein as described herein, an antibody or antigen-binding fragment thereof as described herein, a conjugate as described herein, a nucleic acid as described herein, or an expression vector as described herein; and

b) a pharmaceutically acceptable carrier; optionally

c) one or more other therapeutic agents.

In another aspect, the present invention provides the use of said TGFβR2 molecule with a truncated extracellular domain described herein, a fusion protein described herein, an antibody or antigen-binding fragment thereof described herein, a conjugate described herein, a nucleic acid described herein, an expression vector described herein, or a pharmaceutical composition described herein for the prevention and treatment of cancer, preferably for the treatment of gastric cancer.

In another aspect, the present invention provides the use of said TGFβR2 molecule with a truncated extracellular domain described herein, a fusion protein described herein, an antibody or antigen-binding fragment thereof described herein, a conjugate described herein, a nucleic acid described herein, an expression vector described herein, or a pharmaceutical composition described herein for the preparation of a medicament for the prevention and treatment of cancer, preferably for the treatment of gastric cancer.

In another aspect, the present invention provides a pharmaceutical combination comprising a TGFβR2 molecule with a truncated extracellular domain as described herein, a fusion protein as described herein, an antibody or antigen-binding fragment thereof as described herein, a conjugate as described herein, a nucleic acid as described herein, an expression vector as described herein, or a pharmaceutical composition as described herein, and one or more additional therapeutic agents.

In another aspect, the present invention provides a kit comprising a TGFβR2 molecule with a truncated extracellular domain as described herein, a fusion protein as described herein, an antibody or antigen-binding fragment thereof as described herein, a conjugate as described herein, a nucleic acid as described herein, an expression vector as described herein, or a pharmaceutical composition as described herein, preferably further comprising a device for administering a drug.

In another aspect, the present invention provides a method for preventing and treating neoplasms, comprising administering to a subject said TGFβR2 molecule with a truncated extracellular domain described herein, a fusion protein described herein, an antibody or antigen-binding fragment thereof described herein, a conjugate described herein, a nucleic acid described herein, an expression vector described herein, or a pharmaceutical composition described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 shows the binding analysis of the mouse EGFR-mhPA8 antibody to the recombinant human EGFR-His protein.

Fig. 2 shows blockade of EGF binding to EGFR by the mouse antibody EGFR-mhPA8.

Fig. 3 shows inhibition of MDA-MB-468 cell proliferation by the mouse EGFR-mhPA8 antibody.

Fig. 4 shows the binding analysis of humanized EGFR-HPA8 antibody to recombinant human EGFR-His protein.

Fig. 5 shows blockade of EGF binding to EGFR by the humanized EGFR-HPA8 antibody.

Fig. 6 shows the inhibition of MDA-MB-468 cell proliferation by humanized EGFR-HPA8 antibody under different ligand conditions.

Fig. 7 shows the inhibition of Fadu cell proliferation by humanized EGFR-HPA8 antibody under different ligand conditions.

Fig. 8 shows the ADCC effect mediated by humanized EGFR-HPA8 antibody.

Fig. 9 shows the effect of EGFR-HPA8 on body weight of mice with subcutaneously xenografted SNU-5 gastric cancer cells.

Fig. 10 shows the effect of EGFR-HPA8 on tumor volume and TGI results in mice with subcutaneously xenografted SNU-5 gastric cancer cells.

Fig. 11 shows the effect of EGFR-HPA8 on body weight in mice bearing subcutaneously xenografted NCI-H1975 non-small cell lung cancer cells.

Fig. 12 shows the effect of EGFR-HPA8 on tumor volume and TGI results in mice bearing subcutaneously xenografted NCI-H1975 non-small cell lung cancer cells.

Fig. 13 shows the schematic structure of the EGFR antibody/TGFβR2 fusion protein.

Fig. 14 shows the detection of degradation of the EGFR antibody/TGFβR2 fusion protein.

Fig. 15 shows the detection of the degradation propensity of the EGFR antibody/TGFβR2 fusion protein.

Fig. 16 shows the detection of the binding ability of different truncated forms of the EGFR antibody/TGFβR2 fusion protein to TGF-β1 and EGFR.

Fig. 17 shows the detection of the ability of the truncated TGFβR2 EGFR antibody/TGFβR2 fusion protein to neutralize TGF-β1.

Fig. 18 shows the detection of the ability of the truncated TGFβR2 EGFR antibody/TGFβR2 fusion protein to neutralize TGF-β3.

Fig. 19 shows the analysis of the ability of fusion protein 6 to bind to TGF-β1 and TGF-β3 proteins, respectively.

Fig. 20 shows an analysis of the ability of fusion protein 6 to block the binding of TGF-β1 protein or TGF-β3 protein to TGFβR2-Fc, respectively.

Fig. 21 shows the binding and competition ability analysis of fusion protein 6.

Fig. 22 shows the affinity analysis of fusion protein 6 for recombinant human EGFR protein.

Fig. 23 shows the affinity analysis of fusion protein 6 for recombinant human TGF-β1 protein.

Fig. 24 shows the neutralizing effect of TGF-β1 by fusion protein 6 on Mv-1-lu cells.

Fig. 25 shows the neutralizing effect of TGF-β1 by fusion protein 6 analyzed using a reporter gene system.

Fig. 26 shows inhibition of MDA-MB-468 cell proliferation by fusion protein 6.

Fig. 27 shows the effect of ADCC mediated by fusion protein 6.

Fig. 28 shows the effect of fusion protein 6 on body weight in mice bearing subcutaneously xenografted NCI-H1975 non-small cell lung cancer cells.

Fig. 29 shows the effect of fusion protein 6 on tumor volume in mice with subcutaneously xenografted NCI-H1975 non-small cell lung cancer cells.

Fig. 30 shows the ultrafiltration stability analysis of fusion protein 6.

Fig. 31 shows the degradation analysis of the X/TGFβR2 fusion protein.

Fig. 32 shows the degradation propensity analysis of the X/TGFβR2 fusion protein.

Fig. 33 shows the analysis of the binding ability of the X/TGFβR2 fusion protein to TGF-β1.

Fig. 34 shows the analysis of the ability of the X/TGFβR2 fusion protein to neutralize TGF-β1 and TGF-β3.

Fig. 35 shows the binding assay of the X/TGFβR2 fusion protein to the target of the X moiety.

DETAILED DESCRIPTION

Definitions

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. For the purposes of this invention, the following terms are further defined.

When used in this specification and the appended claims, the singular forms "one," "another," and "said" include plural designations of the subject matter unless the context clearly indicates otherwise.

The term "truncated" form of a protein molecule means that the modified form lacks one or more amino acid residues compared to the natural form of the protein molecule.

The term "fusion protein" refers to a protein molecule that combines two or more proteins. It is usually produced by expressing a hybrid gene that combines the sequences of two or more genes, which are inserted into an expression vector in a form with the appropriate matching reading frame.

The term "antibody" refers to an immunoglobulin molecule and refers to any form of antibody that exhibits the desired biological activity. It includes, but is not limited to, monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, and polyspecific antibodies (e.g., bispecific antibodies), and even antibody fragments.

The term "variable region" refers to the region in the heavy or light chain of an antibody that is involved in the binding of the antibody to an antigen. The variable regions of the heavy and light chains of a natural antibody (V _H and V _L , respectively) are generally similar in structure and can be further subdivided into highly variable regions (called complementarity determining regions (CDRs)) interspersed with more conserved regions (called framework regions (FRs)).

The complementarity determining region (CDR) and framework region (FR) of a particular antibody can be identified using the Kabat system (Kabat et al.: Sequences of Proteins of Immunological Interest, 5th edition, U.S. Department of Health and Human Services, PHS, NIH, NIH Publication No. 91-3242, 1991).

The term "constant region" refers to those amino acid sequences in the light and heavy chains of an antibody that are not directly involved in binding of the antibody to antigen, but exhibit various effector functions such as antibody-induced cytotoxicity (ADCC).

"An antigen-binding fragment of an antibody" includes a portion of an intact antibody molecule that retains at least some of the binding specificity of the parent antibody, and typically includes at least a portion of the antigen-binding region or variable region (e.g., one or more CDRs) of the parent antibody. Examples of antigen-binding fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2, Fd fragments, Fd' fragments, single-chain antibody molecules (e.g., scFv, di-scFv, or tri-scFv, bipartite antibodies, or scFab), and single-domain antibodies.

The term "conjugate" refers to biologically active protein or peptide molecules that form a covalent or non-covalent bond with another molecule, whether a small molecule or a biomolecule.

The term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous population of antibodies, i.e., a population containing homogeneous antibodies that are identical to each other except for possible mutations (e.g., natural mutations) that may be present in very small amounts. Accordingly, the term "monoclonal" indicates the nature of the antibody in question, rather than a mixture of unrelated antibodies. Unlike polyclonal antibody preparations, which typically include different antibodies against different clusters (epitopes), each monoclonal antibody in a monoclonal antibody preparation is directed against a specific cluster of an antigen. In addition to their specificity, monoclonal antibody preparations have the advantage that they are typically not contaminated with other antibodies. The term "monoclonal" should not be construed as requiring any particular method for producing a particular antibody. The term "monoclonal antibody" specifically includes chimeric antibodies, humanized antibodies, and human antibodies.

An antibody "specifically binds" to a target antigen, such as a tumor-associated antigen protein (herein, EGFR), i.e., binds said antigen with sufficient affinity to allow said antibody to be used as a therapeutic agent targeting a tissue or cell expressing said antigen, and without significant cross-reactivity with other proteins or with proteins other than homologues and variants (e.g., mutant forms, splice variants, or hydrolyzed truncated forms of the protein) of the target antigens mentioned above.

The term "binding affinity" refers to the strength of the sum of non-covalent interactions between the individual binding sites of a molecule and its binding partners. Unless otherwise specified, the term "binding affinity" as used herein refers to the intrinsic binding affinity, which reflects the 1:1 interaction between members of a binding pair (e.g., antibody and antigen). Parameters such as "K _D ", "binding rate constant k _on ", and "dissociation rate constant k _off " are commonly used to describe the affinity between a molecule (e.g., an antibody) and its binding partner (e.g., an antigen), i.e., how tightly a ligand binds to a particular protein. Binding affinity is influenced by non-covalent intermolecular interactions such as hydrogen bonding, electrostatic interactions, and hydrophobic and van der Waals forces between the two molecules. Additionally, the binding affinity between a ligand and its target molecule can be influenced by the presence of other molecules. Affinity can be assayed by conventional methods known in the art, including the ELISA described herein.

The term "targeting moiety" refers to the portion of the fusion protein that functions to specifically bind to a target cell. The term includes antibodies and other natural (e.g., receptors, ligands) or synthetic (e.g., DARPin) molecules that specifically bind to a target cell. As used herein, "specifically binds to a target cell" indicates that the moiety preferentially binds target cells in a complex mixture.

An "isolated" biomolecule is a biomolecule that has been identified and separated from a cell that naturally expresses such molecules. Isolated biomolecules include biomolecules in situ in recombinant cells, as well as biomolecules that are typically obtained through at least one purification step.

The term "receptor" is a biochemical concept referring to a class of molecules that specifically recognize and bind extracellular signals (i.e., the term "ligand") and produce a specific effect within the cell. The effects produced may only last for a short period of time, such as altering cellular metabolism or cell motility. It may also have a long-term effect, such as increasing or decreasing the expression of a gene or genes.

"Antibody-dependent cell-mediated cytotoxicity" or "ADCC" refers to a form of cytotoxicity in which the binding of secreted Ig to Fcγ receptors present on certain cytotoxic cells (e.g., NK cells, neutrophils, and macrophages) allows these cytotoxic effector cells to specifically bind to target cells bearing the antigen and subsequently kill said target cells using, for example, a cytotoxic agent. To assess the ADCC activity of a target antibody, an in vitro ADCC assay can be performed, such as the in vitro ADCC assay documented in U.S. Patent No. 5,500,362 or 5,821,337 or U.S. Patent No. 6,737,056 (Presta) and the methods described in embodiments of the present application. Useful effector cells for such assays include PBMCs and NK cells.

A TGFβR2 molecule with a truncated extracellular domain according to the present invention, fusion proteins comprising a TGFβR2 molecule with a truncated extracellular domain and a targeting portion

There are multiple susceptibility sites between sites 7-15 of the N-terminus of the full-length extracellular domain of TGFβR2. In order to improve the structural stability of the fusion protein, the present inventors modified the N-terminus of the amino acid sequence of the extracellular domain of TGFβR2 by deleting various numbers of amino acids. Fifteen TGFβR2 molecules with a truncated extracellular domain were obtained.

The present inventors used their recently isolated anti-EGFR antibodies EGFR-HPA8, trastuzumab, bevacizumab, ramucirumab, ipilimumab or panitumumab as the targeting portion of the fusion protein and a TGFβR2 protein molecule with a truncated extracellular domain as the immunomodulatory portion of the fusion protein. The TGFβR2 protein molecule with a truncated extracellular domain fused to the C-terminus of the heavy chain of the anti-EGFR antibody was obtained by homologous recombination, i.e., a fusion protein (EGFR/TGFβR2) was obtained containing two chains, i.e., the light chain and the heavy chain of the anti-EGFR antibody, and the extracellular domain of TGFβR2, the structure of which is shown in Fig. 13. In the EGFR antibody/TGFβR2 fusion protein, the C-terminal amino acid of the heavy chain of the anti-EGFR antibody is linked to the extracellular domain of TGFβR2 with different forms of amino acid deletion via a (G ₄ S) ₄ linker (SEQ ID NO: 66). Additionally, the C-terminal lysine residue of the heavy chain of the anti-EGFR antibody was deleted to reduce the risk of proteolysis.

In one preferred embodiment of the present invention, fusion protein 6 retains high binding affinity for human EGFR protein, having a K _D value of 8.77 pM for binding affinity for human EGFR protein, a binding constant value k _{on of} 1.68 E+06 M ^-1 s ^-1 , and a dissociation constant value k _{dis of} 1.47 E-05 s ^-1 . Additionally, fusion protein 6, which contains truncated TGFβR2, has similar affinity for human TGF-β1 protein as fusion protein 1, which contains full-length TGFβR2, with a K _D value of 96.1 pM, a binding constant value k _{on of} 1.53 E+06 M ^-1 s ^-1 , and a dissociation constant value k _{dis of} 1.47 E-04 s ^-1 .

Nucleic acids according to the present invention

The present invention also relates to nucleic acids encoding TGFβR2 molecules with a truncated extracellular domain according to the present invention, molecules including fusion proteins comprising the truncated molecule and the targeting portion, or parts thereof. Some examples of sequences of these nucleic acids are given in the Sequence Listing.

The nucleic acid molecules of the present invention are not limited to the sequences described herein, but also include variants thereof and other corresponding forms of nucleic acids, such as mRNA, DNA, and variants thereof. The variants of the present invention may be described with reference to their physical properties in hybridization. A person skilled in the art will understand that the use of nucleic acid hybridization techniques may be used to identify their complements, as well as their equivalents or congeners.

Recombinant vectors and expression

The present invention also provides recombinant constructs comprising one or more nucleotide sequences according to the present invention. The recombinant constructs according to the present invention can be used in vectors, such as plasmids, phagemids, phages, or viral vectors, and nucleic acid molecules encoding antibodies according to the present invention can be introduced into said vectors.

Said TGFβR2 molecule with a truncated extracellular domain, targeting portions, fusion proteins containing said truncated molecule and targeting portion can be obtained by recombinant expression of a nucleotide sequence encoding said molecule or protein in a host cell. Said molecule or protein can contain more than one amino acid sequence, and in order to express a plurality of amino acid sequences by recombinant methods, one or more recombinant expression vectors containing coding nucleotide sequences can be transfected into said host cell so that said plurality of amino acid sequences are expressed in said host cell. Standard recombinant DNA methodologies are used to produce nucleic acids encoding desired molecules or proteins, incorporate these nucleic acids into recombinant expression vectors, and introduce said vectors into host cells, see, e.g., Sambrook, Fritsch, and Maniatis (eds.), Molecular Cloning; A Laboratory Manual, Second Edition, Cold Spring Harbor, N.Y., (1989), Ausubel, F. M., et al. (eds.) Current Protocols in Molecular Biology, Greene Publishing Associates, (1989), and the methodologies documented in U.S. Patent No. 4,816,397 (Boss et al.).

Examples of prokaryotic host cells include bacteria, and examples of eukaryotic host cells include yeast, insect, or mammalian cells. It should be understood that the design of an expression vector, including the choice of regulatory sequence, is influenced by various factors, such as the choice of host cell, the level of expression of the desired protein, and whether expression is constitutive or inducible.

The extracellular domain truncated TGFβR2 molecules, the targeting portion, and the fusion proteins of the present invention can be isolated and purified from recombinant cell cultures by well-known methods, said well-known methods include, but are not limited to, ammonium sulfate or ethanol precipitation, acid extraction, protein A affinity chromatography, protein G affinity chromatography, anion or cation exchange chromatography, cellulose phosphate chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxyapatite chromatography, lectin chromatography. High performance liquid chromatography ("HPLC") can also be used for purification.

Application

The extracellular domain-truncated TGFβR2 molecules, antibodies and fusion proteins of the present invention can be used to treat cancer, such as gastric cancer.

Pharmaceutical compositions

One or more types of truncated protein(s), fusion proteins, antibodies and antigen-binding fragments, truncated protein-drug conjugates, fusion protein-drug conjugates, conjugates, nucleic acids and carriers according to the present invention can be prepared with at least one other chemical agent to form a pharmaceutical composition containing the preceding active ingredient(s) described above and one or more pharmaceutically acceptable carriers, diluents or excipients; they can optionally also include one or more other therapeutic agents.

Reagent kits

The present invention also relates to pharmaceutical packages and kits comprising one or more containers, wherein said containers contain the pharmaceutical compositions according to the present invention, mentioned above. Associated with such containers, they may be presented in a form established by a government agency regulating the production and use or distribution of a medicinal product or biological product, which reflects approval for their administration to humans by said agency of the state in which said product is manufactured, used or distributed.

Preparation and storage

The pharmaceutical compositions of the present invention can be prepared by methods known in the art, for example, by conventional mixing, dissolving, granulating, grinding, emulsifying, encapsulating, encapsulating or lyophilizing techniques.

Once the pharmaceutical form is prepared, the composition containing the compounds of the present invention formulated in a suitable carrier can be placed in appropriate dispensers and labeled for the treatment of the indicated condition. Such labeling should include the amount, frequency and route of administration of the drug.

Combinations of drugs

The combinations containing the antibodies of the present invention described above are also combined with one or more other therapeutic agents, provided that the resulting combination does not cause an unacceptable adverse effect.

The following embodiments are used to illustrate the present invention as examples and are not intended to limit the present invention.

Examples

Example 1: Screening of mouse antibodies that block EGF binding to EGFR using an antibody phage library

1.1 Immunization of mice and screening of phage antibody library

Mice were immunized with plasmids pCMV3-mFlt3L (G12FE5S01-D, constructed by Sinocelltech Limited, SEQ ID NO: 142) and pCMV3-mCSF2 (G12FE5S02-D, constructed by Sinocelltech Limited, SEQ ID NO: 143) containing the said nucleic acids. The specific method was as follows: mice were immunized with cardiotoxin 10 M intramuscularly two days before the first immunization. The mixture of pCMV3-mFlt3L and pCMV3-mCSF2 at a ratio of 1:1 was administered intramuscularly at 20 g per leg and pGS6-EGFR-TT-WPRE (constructed by Sinocelltech Limited, SEQ ID NO: 144) was administered intramuscularly at 3 days after immunization, and EGFR-overexpressing insect ^cells were intraperitoneally injected at 5×106 for the fourth and fifth immunizations at immunization intervals of 2 weeks, 2 weeks, 2 weeks and 2 weeks sequentially. Starting from the third immunization, blood was collected through the medial canthal plexus of the eye seven days after each immunization. Recombinant human EGFR protein (source: Sino Biological, Inc., Cat. No. 10001-H08B, hereinafter the same) was coated to determine the anti-EGFR titer in mouse serum. The fifth immunization sera reached the criteria of 8000-fold serum titers and OD>1 serum titers, then intraperitoneal booster injection was performed using 5× ¹⁰⁶ MDA-MB468 cells at 20-day intervals, and after 7 days, the mice were sacrificed and the spleen tissues were frozen in liquid nitrogen.

Mouse spleen tissue was extracted with TriPure Isolation Reagent (source: Roche cat. No. 11 667 165 001) for RNA extraction, and cDNA was obtained by reverse transcription using TriPure Isolation Reagent Reverse Transcription Kit (source: Invitrogen cat. No. 18080-051), PCR amplified to obtain the nucleotide sequences encoding the variable regions of the light and heavy chains of mouse antibody, the nucleotide sequence encoding the light and heavy chains of the variable regions of mouse antibody was spliced into the nucleotide sequence encoding scFv by overlap extension PCR splicing, the variable regions of the light and heavy chain were connected by a linker ^[25] :

then ligated into the phage vector pComb3x (source: Sino Biological, Inc.) using restriction endonuclease SfiI (source: Fermentas), and the scFv antibody phage display library for mouse immunization was constructed by electrotransformation of X-Blue competent cells. The ELISA plate was coated with recombinant human EGFR protein, and the phage library enriched for positive anti-EGFR antibodies was obtained by phage antibody panning. Then, the resulting library was mixed with MDA-MB-468 cells (source: Cell Resource Center, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences), and phage libraries enriched with positive antibodies against MDA-MB-468 cells were selected from the above libraries by phage antibody panning (O'Brien, R. M., & Aitken, R. (Eds.), Springer Science & Business Media. 2002; ISBN: 9780896037113). Phage colonies were selected from the enriched library, expressed, binding to recombinant human EGFR protein was detected by ELISA, and clones with high-binding EGFR-mhPA8 scFv antibody with specific binding to recombinant human EGFR were screened and sent to a sequencing company, resulting in the nucleotide sequence of EGFR-mhPA8 scFv antibody (SEQ ID NO: 3).

1.2 Functional analysis of mouse antibodies targeting EGFR

1.2.1 Mouse Antibody Binding and Ligand Competition Functions ELISA was used to determine the binding ability of mouse antibodies to recombinant human EGFR protein. Recombinant human EGFR-His protein (source: Sino Biological, Inc., hereinafter referred to as the same) at different concentrations (1.37 ng/mL, 4.12 ng/mL, 12.35 ng/mL, 37.04 ng/mL, 111.11 ng/mL, 333.33 ng/mL, 1000 ng/mL, and 3000 ng/mL) were added to 96-well plates at 100 μL per well and left overnight at 4°C. The plates were washed the next day and blocked at room temperature for 1 h. EGFR-mhPA8 and H7N9-R1 antibody as a negative control (source: Sinocelltech Limited, hereinafter the same) were added at a concentration of 13.89 nM and incubated for 1 h, after which the plates were washed to remove unbound antibodies. Goat anti-hIgG F(ab)2/HRP secondary antibody (source: Jackson ImmunoResearch, Cat. No. 109-036-006, hereinafter the same) was added and incubated for 1 h, the plates were washed repeatedly and chromogenic substrate solution was added for color development, then OD ₄₅₀ was measured using a microplate reader after the completion of the reaction. Using the concentration of recombinant human EGFR-His protein as the horizontal coordinate and the OD ₄₅₀ value as the vertical coordinate, an S-shaped curve was plotted and the EC ₅₀ of antibody binding to recombinant human EGFR-His protein was analyzed using GraphPad Prism 6.0 software. The results are shown in Fig. 1. The human-mouse chimeric EGFR-mhPA8 antibody could effectively bind recombinant human EGFR-His with an EC ₅₀ of 128.7 ng/ml and R ² = 1.000. The negative control, H7N9-R1, did not bind to recombinant human EGFR-His protein.

In this Example, the ability of EGFR-mhPA8 to block EGFR ligand and receptor binding was further analyzed by FACS. MDA-MB-468 cells at 3× ¹⁰⁵ were added to 10 μl of biotin-labeled EGF-Fc protein at a final concentration of 217.1 nM (source: Sino Biological, Inc.). EGFR-mhPA8 antibodies at final concentrations of 306.74 nM, 102.25 nM, 34.08 nM, and 11.36 nM were added after 30 min of incubation at 2-8°C, and H7N9-R1 was used as a negative control antibody. The mixture was mixed and incubated at 2-8°C for 20 min, and then washed with BSA and centrifuged to remove unbound antibodies and ligands. The secondary antibody Streptavidin-488-FITC (source: Sino Biological, Inc., hereinafter the same) was added and incubated for 1 h at 2-8°C. Washing and centrifugation were repeated to remove unbound secondary antibodies. Finally, 200 μl of BSA was added to the resuspended cells and filtered through a 400 mesh filter into a flow tube for flow detection. The results are shown in Fig. 2, EGFR-mhPA8 can effectively block the binding of EGF-Fc protein to EGFR on MDA-MB-468 cells in a concentration gradient.

1.2.2 Inhibition of MDA-MB-468 cell proliferation by mouse antibodies

MDA-MB-468 breast cancer cells highly express EGFR as well as various autocrine EGFR ligand factors. In this example, the growth inhibitory function of mouse antibodies was determined on MDA-MB-468 cells using the WST-8 assay.

MDA-MB-468 cells were uniformly inoculated into 96-well plates at 5×10³per well. The cells were incubated in a CO2 incubator.₂for 3 h and different concentrations of mouse EGFR-mhPA8 antibodies (66.7 nM, 22.2 nM, 7.4 nM, 2.5 nM, 0.82 nM, 0.27 nM, 0.093 nM, 0.033 nM and 0.013 nM) were added. A negative control group M (containing cells) and a control group B (medium only without cells) were also used. The cells were incubated in a CO incubator.₂at 37°C and 5% CO₂ for 5 days, and then WST-8 was added in an amount of 15 μl per well. After 240 min of incubation, OD was measured.₄₅₀-OD₆₃₀using a microplate reader, and the inhibition rate of the mouse-derived antibody was calculated by subtracting the detected value of the well reading of the control group B. The inhibition rate = (OD of group M - OD of the sample) / (OD of group M) × 100%, and the quantitative efficiency curve was analyzed and plotted using GraphPad Prism software, where the horizontal coordinate was the concentration of the antibody and the vertical coordinate was the inhibition rate. As shown in Fig. 3, EGFR-mhPA8 effectively inhibited the proliferation of MDA-MB-468, and the inhibition rate increased with the increase of the drug concentration in an S-shaped curve. EGFR-mhPA8 inhibited MDA-MB-468 cells with EC₅₀, equal to 2.78 hM and R²=0.991.

Example 2: Humanization of the mouse EGFR-mhPA8 antibody and ex vivo characterization of the humanized antibody

2.1 Humanization and production of mouse mhPA8 antibody

The nucleotide sequence of the EGFR-mhPA8 antibody was determined, yielding the amino acid sequence of the heavy chain (SEQ ID NO: 8) and the variable region of the light chain (SEQ ID NO: 9) of the EGFR-mhPA8 scFv antibody. The amino acid sequence of each of the three CDRs for the light and heavy chains of EGFR-mhPA8 scFv was determined with reference to the approaches of Kabat [26] and the IMGT numbering, see SEQ ID NOs: 10-15. According to the Kabat numbering, except for the N to D mutation at position 52 in LCDR2, the corresponding three CDRs of the aforementioned light and heavy chains were grafted in the subsequent humanization step and retained in the final humanized EGFR-HPA8 scFv antibody.

Humanization of mouse antibodies was performed using the classical CDR grafting method ^[27,28] . Antibodies that have more than 50% amino acid sequence similarity to the variable regions of both the light chain and the heavy chain of a mouse antibody and more than 50% amino acid sequence similarity to the framework regions of the variable regions of the light chain and the heavy chain of a mouse antibody to be modified, respectively, were selected as a template library for humanization. The human antibody with the highest spatial similarity to a given variable region of the antibody to be modified was selected as a template for humanization. Three CDR sequences of the light or heavy chain of a mouse antibody were substituted for the corresponding CDR amino acid sequences in the humanization template and the amino acids NG, NS, NA and NT, which are at high risk of deamidation in the mutated sequence, were mutated to improve the chemical stability and maintain the biological function of the antibody. The affinity of the humanized antibody is determined by ELISA, and humanized antibodies whose affinity is retained are selected. The humanization template used to graft the light chain variable region of EGFR-mhPA8 in this example is IGKV1-NL1*01, which has 68.4% homology with the light chain of EGFR-mhPA8, and the humanization template used to graft the heavy chain variable region is IGHV1-69-2*01, which has 64.9% homology with the heavy chain of EGFR-mhPA8. N52 of the LCDR2 variable region of the humanized EGFR-HPA8 antibody, which is prone to deamidation, is mutated to D.

Since the key site of the framework region of mouse antibody is necessary for maintaining the stability of the CDR spatial structure, the key site should be back mutated to the corresponding amino acids of mouse antibody. According to Kabat numbering, the light chain was back mutated to Q at position 45, to I at position 48, to K at position 74 and to D at position 76, and the heavy chain was back mutated to K at position 38, to I at position 48 and to L at position 70. Humanized EGFR-HPA8 antibody was prepared by humanizing CDR grafting and framework reverse mutations, and the amino acid sequences of its heavy chain and light chain are shown in SEQ ID NOs: 22/23, respectively; the amino acid sequences of its heavy chain and light chain containing the signal peptide are shown in SEQ ID NO: 24/25, respectively, containing the amino acid sequences of the signal peptide sequentially linked to the heavy chain/light chain are shown in (SEQ ID NO: 26/27), the variable region of the heavy chain/light chain of the humanized antibody (SEQ ID NO: 28/29) and the constant region of the humanized antibody, namely the heavy chain constant region/light chain constant region of human IgG1 kappa (SEQ ID NO: 30/31); and the sequences of its humanized CDRs are shown in Table 2.

A nucleotide sequence containing the light chain signal peptide of EGFR-HPA8 antibody (SEQ ID NO: 33) sequentially linked to the light chain nucleotide sequence (SEQ ID NO: 35), the light chain variable region nucleotide sequence of humanized antibody (SEQ ID NO: 37), and the human kappa light chain constant region nucleotide sequence (SEQ ID NO: 39) were amplified by PCR splicing. The above PCR product was inserted into pSTEP2 vector (source: constructed by Sinocelltech Limited, hereinafter the same) by the infusion method (double digestion with HindIII+XbaI), and the correctness of the plasmid sequence was verified by sequencing. The nucleotide sequence of the variable region of the heavy chain of the EGFR-HPA8 antibody (SEQ ID NO: 36) was obtained by synthesizing the whole gene and inserted into the pSTEP2 vector (after double digestion with SeaI + NheI) containing the nucleotide sequence of the heavy chain signal peptide (SEQ ID NO: 34) and the nucleotide sequence of the constant region of the human IgG1 heavy chain (SEQ ID NO: 38) by the infusion method, and the correctness of the sequence of the expression vector of the light and heavy chains of EGFR-HPA8 was verified by sequencing. After isolating the plasmid and transfecting HEK-293 cells (fut8 knockout), these cells were cultured and expressed for 7 days, the cell supernatant was purified using affinity chromatography after centrifugation, and the chromatographic medium was a package of protein A, which interacts with Fc. After equilibrating the protein A chromatography column with 50 mM Tris, 10 mM NaCl, pH 8.0 buffer for 5-10 column volumes, the filtered culture supernatant was added to the chromatography column for binding, and the column was packed with 20 mM Tris, 0.3 M Arg, pH 6.5 buffer for 5-10 column volumes, and then the column was washed with 0.1 M Gly, 10 mM NaCl, pH 3.5 elution buffer, and the collected samples were neutralized with 2 M Tris (pH 8.0), resulting in high purity and high quality ADCC-enhanced EGFR-HPA8 antibody.

Splicing primer sequences for PCR amplification of the light chain of the EGFR-HPA8 antibody containing the signal peptide:

Primer sequences for whole-genome synthesis of the variable region of the heavy chain of the EGFR-HPA8 antibody:

2.2 In vitro characterization of humanized EGFR-HPA8 antibody

2.2.1. Humanized Antibody Specificity and Ligand Competition Analysis

Referring to Example 1.2.1, the binding ability of the human antibody to the recombinant human EGFR protein was detected by ELISA using SCT200 (documented in CN200610012002.8, hereinafter the same), Erbitux (MERCK, 201621, hereinafter the same) and a negative control. As shown in Fig. 4, the EC ₅₀ of the humanized EGFR-HPA8 antibody specific binding to the recombinant human EGFR-His was 116.6 ng/mL, R ² = 1.000; the EC ₅₀ of SCT200 was 166.5 ng/mL, R ² = 1.000; the EC ₅₀ of Erbitux was 253.6 ng/mL, R ² = 1.000; The negative control H7N9-R1 did not bind. These results indicate that EGFR-HPA8 has a better ability to block recombinant human EGFR-his than SCT200 and Erbitux.

Meanwhile, the ability of the humanized EGFR-HPA8 antibody to block the binding of ligand and EGFR receptor was analyzed by FACS with reference to Example 1.2.1 using SCT200, Erbitux and a negative control. The results are shown in Fig. 5, the ability of EGFR-HPA8 to block the binding of EGF-Fc protein to EGFR on MDA-MB-468 cells is stronger than that of SCT200 and Erbitux.

2.2.2. Inhibition of proliferation of various tumor cells by humanized antibodies

2.2.2.1. Ability of humanized antibodies to inhibit proliferation of MDA-MB-468 cells

MDA-MB-468 cells were uniformly inoculated into 96-well plates at 5× ¹⁰³ /well. The cells were incubated in a _CO2 incubator for 3 h, and different concentrations of humanized EGFR-HPA8 antibody (666.7 nM, 222.2 nM, 74.1 nM, 24.7 nM, 8.23 nM, 2.74 nM, 0.91 nM, 0.31 nM, and 0.1 nM) were added, and SCT200 and Erbitux were used as controls. Then, the ligands HB-EGF (source: Sino Biological, Inc., hereinafter the same) were added at a final concentration of 8 ng/mL, BTC-Fc (source: Sino Biological, Inc., hereinafter the same) at a final concentration of 200 ng/mL, or Fc-EREG (source: Sino Biological, Inc., hereinafter the same) at a final concentration of 1 μg/mL, respectively. The cells were incubated in a _CO2 incubator at 37°C and 5% _CO2 for 5 days, and then WST-8 was added at 15 μL per well. After 240 minutes of incubation, _OD450 - _OD630 were measured using a microplate reader, and the increase in the cell inhibition rate of the antibody was calculated. The addition of ligand without antibody was used as group M. The inhibition rate=(OD of group M - OD of sample)/(OD of group M) × 100%, and the quantitative efficiency curve was analyzed and plotted using GraphPad Prism software, the horizontal coordinate was the antibody concentration and the vertical coordinate was the inhibition rate. The results are shown in Fig. 6A and Table 3. EGFR-HPA8 showed better growth inhibition of MDA-MB-468 cells than the control antibodies SCT200 and cetuximab under ligand-free conditions. EGFR-FJPA8 has a similar maximal inhibition rate to SCT200, but has a lower _EC50 of growth inhibition. The results of Example 2.2.1 demonstrate that the ability of EGFR-HPA8 to block EGF-Fc protein binding to EGFR in MDA-MB-468 cells was more potent than that of SCT200 and Erbitux. In this Example, various EGFR ligands were added to the MDA-MB-468 cell growth inhibition assay to further evaluate the ability of EGFR-HPA8 to block EGFR ligand-receptor binding at the cellular functional level. The results are shown in Figs. 6B-6D and Table 3. EGFR-HPA8 inhibited MDA-MB-468 cell proliferation better than SCT200 and cetuximab under the conditions with various ligands.

2.2.2.2. Ability of humanized antibodies to inhibit Fadu cell proliferation

Fadu is a human pharyngeal squamous cell carcinoma cell strain that highly expresses EGFR and also autocrine various EGFR ligand factors. With reference to Example 2.2.2.1, the inhibition of Fadu cell proliferation (source: Cell Resource Center, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences) by EGFR-HPA8 antibody under different ligand conditions was measured using the WST-8 assay. The results are shown in Fig. 7 and Table 4. The ability of EGFR-HPA8 to inhibit Fadu cell growth was similar to SCT200 and better than cetuximab under ligand-free conditions, while the ability of EGFR-HPA8 to inhibit Fadu cell growth was significantly better than SCT200 and cetuximab under different ligand conditions. These results demonstrated that EGFR-HPA8 antibody had superior ability to inhibit ligand binding to EGFR receptor compared with SCT200 and cetuximab.

2.2.3. Action of humanized ADCC antibody

In this Example, a recombinant CD16a reporter gene system is used to determine the effects of ADCC mediated by a humanized EGFR-HPA8 antibody. The recombinant CD16a reporter gene system comprises Jurkat-NFAT-Luc2p-CD16A effector cells and target cells expressing EGFR. When the two cell types are co-cultured and the Fab fragment of the EGFR antibody is added simultaneously, the EGFR antibody binds to EGFR expressed on the surface of the target cells, and its Fc fragment can bind to the effector cell overexpressing the FCy receptor CD16a, thereby activating the Jurkat-NFAT-Luc2p-CD16A effector cells and stimulating NFAT-RE-mediated bioluminescence.

The target A431 cells (source: Cell Resource Center, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences) were uniformly inoculated into 96-well plates at 1× ¹⁰⁴ /well. After overnight incubation, different concentrations of antibodies (2.67 nM, 0.53 nM, 0.11 nM, 0.021 nM, 0.0043 nM, 0.00085 nM, 0.00017 nM, and 0.000034 nM) were added at 40 μl/well, followed by 1× ¹⁰⁵ Jurkat-NFAT-Luc2p-CD16A effector cells (Source: Sinocelltech Limited, hereinafter the same), 40 μl/well, and three replicate wells were used for each assay. Wells with target cells, effector cells, and negative control antibody were also used. Cells were incubated for 4 h in a _CO2 incubator at 37°C and 5% _CO2 , and 5x passive lysis buffer was added, 20 μl per well. Cells were frozen and thawed once, and 20 μl of supernatant from each well was transferred to a 96-well white-bottomed plate, then the plate was shaken and mixed, luminescence was detected using an LB960-Microplate Luminol Detector. Quantitative efficiency curves were analyzed and plotted using GraphPad Prism software, where the horizontal coordinate represented the sample concentration and the vertical coordinate represented the RLU value. Bioluminescence intensity induction multiplier = sample RLU/negative control RLU. The results are shown in Fig. 8, EGFR-HPA8, positive controls Erbitux and SCT200 could mediate the effective ADCC effect on EGFR-expressing A431 tumor cells. Among them, EGFR-HPA8 had an advantage in the half-effective concentration and induction fold with an _EC50 of 0.008 nM and ^R2 = 0.999 in ADCC induction.

2.3 Efficacy of EGFR-HPA-8 against subcutaneously xenografted tumors of the human gastric cancer cell line SNU-5 and the human non-small cell lung cancer cell line NCI-H1975 in mice

Logarithmic-stage SNU-5 cells (ATCC Cell Bank) were washed with PBS and digested with 0.25% trypsin, and the digestion product was collected followed by centrifugation at 800 rpm for 5 min. The cells were resuspended in PBS, and the cell concentration was adjusted to 5.0 × 10 ⁷ cells/mL (with 50% matrix gel). Balb/c-nude mice (Beijing Viton Lever Laboratory Animal Technology Co.) were subcutaneously inoculated with 5.0 × 10 ⁶ SNU-5 cell suspension in the right back, 100 μL per mouse. After the tumor volume reached approximately 170 mm ³ , the mice were randomly divided into seven groups according to tumor volume, with five mice in each group. The drug was administered intraperitoneally (IP) on the day of group assignment and then twice weekly for 7 consecutive doses. The specific dosing regimen is shown in Table 5 below.

Note: The injection volume was calculated based on the body weight of mice at 10 ml/kg.

The tumor growth inhibition value (TGI) was calculated as follows: T/C(%) = T _RTV /C _RTV × 100% (Trtv is the RTV of the treatment group; C _RTV is the RTV of the negative control group), relative tumor volume (RTV) = V _T /V ₀ , V ₀ is the tumor volume measured on day 0 (D ₀ ), namely the day of allocation to groups and the start of dosing, V _T is the tumor volume measured over a certain time. TGI(%) = 1 - T/C(%).

All experimental animals were in good condition and showed some weight gain throughout the course of administration. There was no significant difference in the body weight of mice in each of the drug-treated groups compared to the vehicle-treated control group (P>0.05). The changes in body weight of all animals are shown in Fig. 9 and Table 6.

The tumor volume and TGI results for each group in this study are shown in Table 7 and Fig. 10. After 31 days of dosing, the mean tumor volume in the vehicle group was 559.9±144.9 ^mm3 and in the low dose SCT200 5 mg/kg positive control group was 317.1±197.6 ^mm3 with a TGI value of 44.3%, which was not significantly different from the vehicle group (P=11.28%). The low dose EGFR-HPA8 group 5 mg/kg showed better efficacy in tumor volume of 113.8±74.0 ^mm3 and TGI of 80.0%, which was significant difference compared with the vehicle group (P<0.05), indicating that EGFR-HPA8 showed slightly better tumor inhibitory property than the positive control SCT200 at this dose (P=0.09). The tumor volume of the positive control SCT200 20 mg/kg group was 191.8±189.1 ^mm3 with TGI of 66.5%, which was significantly different from the vehicle group (P<0.05). The tumor volume in the high dose EGFR-HPA8 20 mg/kg group was 175.0±175.0 ^mm3 with TGI value of 68.9%, which was significantly different from that of the vehicle group (P<0.05). The EGFR-HPA8 and positive control SCT200 20 mg/kg groups showed significant tumor inhibition effect, and there was no significant difference in tumor volume between the two treatment groups (P=0.9). In conclusion, EGFR-HPA8 molecules showed significant antitumor efficacy in the human gastric cancer xenograft tumor model SNU-5 at both the dosage levels of 5 mg/kg and 20 mg/kg, and the tumor inhibition effect was slightly better than that of SCT200 at low doses.

EGFR-HPA8 also showed significant inhibitory effect on human non-small cell lung cancer tumor cell line NCI-H1975 in a mouse subcutaneous xenograft model. Balb/c-nude mice were subcutaneously inoculated with NCI-H1975 cells in the right dorsal side (Cell Resource Center, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences), and were divided into groups and administered doses as shown in Table 8.

All experimental animals were in good condition and showed some increase in body weight throughout the course of administration, and there was no significant difference in the body weight of mice in each administration group compared with the control group receiving the vehicle (P>0.05). The changes in body weight of all animals are shown in Fig. 11 and Table 9.

The tumor volume and TGI results for each group in this study are shown in Table 10 and Fig. 12. At 18 days after group allocation and dosing, the SCT200 positive control and high- and low-dose EGFR-HPA8 groups showed significant tumor growth inhibition effects and statistically significant differences in tumor volume between each treatment group and the vehicle group. The mean tumor volume in the vehicle group on day 18 was 1564.3±529.0 ^mm3 . The tumor volumes after SCT200 5 mg/kg and EGFR-HPA8 5 mg/kg treatment were 151.9±99.1 ^mm3 and 86.5±107.5 ^mm3 , with TGI values of 90.4% and 94.5%, respectively. Tumor volumes after treatment with SCT200 20 mg/kg and EGFR-HPA8 20 mg/kg were 289.8±321.4 ^mm3 and 149.3±94.9 ^mm3 , with TGI values of 81.8% and 90.4%, respectively. EGFR-HPA8 at both 5 mg/kg and 20 mg/kg doses showed slightly better antitumor effect than the positive control SCT200, but there was no statistically significant difference. Collectively, these results suggest that EGFR-HPA8 has significant antitumor efficacy in the NCI-H1975 human non-small cell lung cancer xenograft tumor model.

Example 3: Construction and characterization of EGFR antibody/TGFβR2 fusion proteins containing different truncated forms of TGFβR2

3.1 Construction of EGFR antibody/TGFβR2 fusion protein expression vectors with different truncated forms of TGFβR2, protein expression and purification

In this embodiment, an anti-EGFR antibody was used as the targeting portion of the fusion protein and the extracellular domain of TGFβR2 was used as the immunomodulatory portion of the fusion protein. The extracellular domain of TGFβR2 was fused to the C-terminus of the heavy chain of the EGFR antibody by homologous recombination, and the EGFR antibody/TGFβR2 extracellular domain (EGFR/TGFβR2) fusion protein was formed by two chains, a light chain and a heavy chain. The structure of the fusion protein is shown in Fig. 13. The results of mass spectrometry showed the presence of multiple sensitivity sites between sites 7-15 of the N-terminus of the full-length extracellular domain of TGFβR2. In order to improve the structural stability of the protein, the amino acid sequence of the N-terminus of the extracellular domain of TGFβR2 was modified by amino acid deletions in various amounts of amino acids in this Example (SEQ ID NOs: 47-65). In the EGFR antibody/TGFβR2 fusion protein, the amino acid of the C-terminus of the EGFR antibody heavy chain is linked to the extracellular domain of TGFβR2 with different forms of deleted amino acids via a linker (G ₄ S) ₄ (SEQ ID NO: 66). Additionally, the lysine of the C-terminus of the EGFR antibody heavy chain was removed to reduce the risk of proteolysis. The specific protocol for constructing the EGFR antibody/TGFβR2 fusion protein is shown in Table 11.

In the above protocol, the target gene was amplified by PCR or overlap PCR, ligated into the expression vector by infusion, and the plasmids were extracted separately after sequence verification and transiently transferred into HEK-293 cells (fut8 knockout) and cultured until day 7. Centrifugation was performed and the supernatant was collected. The cell supernatant after centrifugation was purified by protein A affinity chromatography to obtain EGFR antibody/TCPβR2 fusion protein with enhanced ADCC.

3.2 Cleavage of EGFR antibody/TGFβR2 fusion proteins containing different truncated forms of TGFβR2

The purity as well as the degradation of the expression products were analyzed by SDS-PAGE under reducing conditions. The various truncated EGFR antibody/TGFβR2 1-16 fusion proteins purified in Example 3.1 were run on SDS-PAGE under reducing conditions. The specific steps of SDS-PAGE under reducing conditions were: (1) SDS-PAGE preparation: 3.9% stacking gel, 13% resolving gel; (2) samples were boiled at 100°C for 2 min, centrifuged, and then 8 μg samples were loaded; (3) constant current 40 mA, electrophoresis time 1 h. The results are shown in Fig. 14. The molecular weight of said light chain of the EGFR antibody/TGFβR2 fusion protein was approximately 25 kDa, the molecular weight of said heavy chain was approximately 66 kDa, and the molecular weight of the truncated versions was in the range of 45-66 kDa. The results showed that obvious cleaved fragments were present in the extracellular domain of TGFβR2, while in various truncated forms of the TGFβR2 fusion proteins, the extracellular domain had significantly fewer bands of its cleavage than in the full-length forms of the TGFβR2 extracellular domain in the fusion protein. Accordingly, the various truncated forms of the TGFβR2 extracellular domain obtained in the present invention significantly increased the stability of the fusion protein comprising the TGF-β receptor and the antibody.

3.3 Degradation tendency of EGFR antibody/TGFβR2 fusion proteins containing various truncated forms of TGFβR2

The 293E cell supernatant, which accelerates the processing of fusion proteins, was additionally used to assess the stability of various truncated forms of the EGFR antibody/TGFβR2 fusion proteins. The 293E cell expression system, which is often used for antibody expression, expresses various host cell proteins (HCPs) and proteases required for cell growth. Thus, antibody stability can be assessed by monitoring the propensity for fusion protein degradation in the 293E cell supernatant.

The purified fusion protein was mixed with the supernatant of 293E cells cultured for 10 days at a volume ratio of 1:0.3, and the final concentration of the fusion protein was approximately 1 mg/mL. The mixed samples were vortexed and mixed well and incubated at 37°C for 48 h. An incubation control without cell supernatant was also used. The purity of the samples and the content of truncated forms were determined by SDS-PAGE, and the purity of the heavy chain of the fusion protein was determined by BandScan software.

The results of the analysis are shown in Fig. 15, and the cleavage percentage in each sample is shown in Table 12. The results showed that the percentage of cleaved forms of TGFβR2 truncated form fusion protein (fusion proteins 2-16) in all control groups was less than 4.0%, which was significantly lower than that of the full-length form of TGFβR2 fusion protein (fusion protein 1), which was 24.8%. After incubation with the same cell supernatant for 48 hours at 37°C, all full-length forms of TGFβR2 fusion protein (fusion protein 1) in the experimental group were sensitive with a percentage of 100%. The truncated forms of TGFβR2 fusion proteins (fusion proteins 2-16) contained varying percentages of cleaved forms, but they were significantly better than the full-length control protein, with fusion protein 2, fusion protein 6, fusion protein 9, fusion protein 10, and fusion protein 13 showing the best performance with percentages of cleaved forms less than 3.0%.

The results shown above indicate that EGFR antibody/TGFβR2 fusion proteins with various truncated forms of TGFβR2 are more resistant to protease degradation than fusion protein 1 with the full-length form of TGFβR2.

3.4 Binding analysis of EGFR antibody/TGFβR2 fusion protein with different truncated forms of TGFβR2 with TGF-β

100 ng/ml TGF-β1 protein and 40 ng/ml EGFR-His protein were coated into 96-well plates at 100 μl per well, respectively, and incubated overnight at 4°C. The plates were washed the next day, blocked at room temperature for 1 h, and 2 μg/ml EGFR antibody/TGFβR2 fusion protein with different truncated forms of TGFβR2 were added at 100 μl per well. The plates were washed after incubation for 1 h to remove unbound antibodies, goat anti-hIgG Fc/HRP secondary antibody was added, incubated, and washed again. Finally, chromogenic substrate solution was added for color development, and the _OD450 value was read with a microplate reader after the reaction was completed. The results are shown in Fig. 16. The binding ability of the EGFR antibody/TGFβR2 fusion protein to different truncated forms of TGFβR2 with TGF-β1 was different, but the binding ability to EGFR was the same.

3.5 TGF-β neutralization assay by EGFR antibody/TGFβR2 fusion protein with different truncated forms of TGFβR2

TGF-β regulates cellular functions by regulating the transcription of several target genes. Plasminogen activator inhibitor 1 (PAI-1) is an important downstream target of the TGF-β1/Smad signaling pathway and activates Smad3 binding to a cis-acting element of the PAI-1 promoter region to regulate PAI-1 expression. An element containing a portion of the PAI-1 promoter region was inserted in a specific form into a luciferase-containing vector and transferred into HepG2 cells. In this reporter gene system, addition of exogenous TGF-β protein initiates expression of the luciferase reporter gene and luminescence in the presence of substrate. When exogenous TGF-β antibody is added, it neutralizes TGF-β protein, blocks TGF-β binding to TGFβR2, inhibits the downstream signaling pathway, and finally inhibits the expression of the luciferase reporter gene. Therefore, the in vitro efficacy of TGF-β neutralizing TGF-β antibody can be determined by detecting the intensity of the light signal.

HepG2-3TP-Luc2p-puro cells (source: Sinocelltech Limited, hereinafter the same) were uniformly plated into 96-well plates at a concentration of 30,000 cells per well. After maintaining the monolayer culture overnight, the culture medium in the 96-well plate was removed and replaced with DMEM medium containing 0.5% FBS and incubated for 6 hours at 37°C in a 5% CO ₂ incubator. The medium in the 96-well plate was removed and 4 ng/ml TGF-β1 protein together with EGFR antibody/TGFβR2 fusion protein were added at a final concentration of 0.02 μg/ml and incubated for 18 hours at 37°C in a 5% CO ₂ incubator. A negative control group M (containing cells and TGF-β1) and a negative control group M' (containing cells without TGF-β1) were used at the same time. Finally, 5× lysis buffer was added and 10 μl of the cell samples were collected to determine the bioluminescence intensity (RLU) value, and the neutralization rate of the EGFR antibody/TGFβR2 fusion protein was calculated. The neutralization rate, % = (RLU value of group M - RLU value of sample) / (OD value of group M - OD value of group M') × 100%. The concentration of antibody was used as the horizontal coordinate, the neutralization rate of antibody was used as the vertical coordinate, and the quantitative efficiency curves were analyzed and plotted using GraphPad Prism software. As shown in Fig. 17, EGFR antibody/TGFβR2 fusion protein 2, fusion protein 6, fusion protein 8, fusion protein 13, fusion protein 14 and fusion protein 16 containing truncated forms of TGFβR2 had some TGF-β1 neutralizing ability, among which fusion protein 2 had similar neutralizing ability with fusion protein 1 containing full-length form of TGFβR2, while fusion protein 5, fusion protein 6 and fusion protein 8 showed better neutralizing ability than fusion protein 1 at the same concentration. Fusion protein 6 showed the strongest TGF-β1 neutralizing ability. The remaining EGFR antibody/TGFβR2 fusion proteins containing truncated forms of TGFβR2 had essentially no or weak neutralizing ability.

TGF-β3 protein has high affinity for TGFβR2 and can activate downstream TGF-β signaling. The TGF-β3 neutralizing ability of the fusion protein (final concentration 20 ng/ml) was analyzed using the reporter gene system in this example. The results are shown in Fig. 18. Fusion protein 2, fusion protein 4, and fusion protein 13 had the same TGF-β3 neutralizing ability as fusion protein 1, while fusion protein 3, fusion protein 5, fusion protein 6, and fusion protein 8 had a better TGF-β3 neutralizing propensity than fusion protein 1. Fusion protein 6 also showed the highest TGF-β3 neutralizing ability.

Based on the above analysis of the composition and neutralization ability of the fusion proteins containing truncated forms of TGFβR2, in the present invention, the fusion protein forms 2~6, 8, 13, 14 and 16 with truncated TGFβR2 are preferred, the fusion protein forms 2, 5, 6 and 8 with truncated TGFβR2 are more preferred, and the fusion protein form 6 with truncated TGFβR2 is most preferred.

Example 4: In vitro biological properties of fusion protein 6, an EGFR antibody/TGFβR2 fusion protein with a truncated form of TGFβR2

4.1 Analysis of the binding capacity of the EGFR antibody/TGFβR2 fusion protein 4.1.1 Properties of the EGFR antibody/TGFβR2 fusion protein for binding and competition with TGF-β

TGF-β1 protein and TGF-β3 protein at a final concentration of 2 μg/ml were added to 96-well plates at 100 μl per well, respectively, and allowed to coat overnight at 4°C. The plates were washed the next day, blocked at room temperature for 1 h, and incubated with different concentrations (1.22 pM, 4.88 pM, 19.53 pM, 78.13 pM, 312.5 pM, 1250 pM, 500 pM, 2000 pM) of EGFR antibody/TGFβR2 fusion protein 6 for 1 h. Afterwards, the plates were washed to remove unbound antibodies and incubated with goat anti-hIgG ₅₀ ² F(ab) ₂ /HRP secondary antibody and washed again, chromogenic substrate solution was added for color development, and the OD ₄₅₀ value was read using a microplate reader after the reaction was completed. The results are shown in Fig. 19. The binding ability of fusion protein 6 to TGF-β1 and TGF-β3 proteins was similar to that of fusion protein 1, with an EC ₅₀ of 91 pM and R ² = 0.998 for binding to TGF-β1 protein and an EC ₅₀ of 102 pM and R ² = 0.998 for binding to TGFβ3 protein.

In this Example, the ability of fusion protein 6 to compete with TGF-β1 protein or TGF-β3 protein for binding to TGFβR2-Fc protein at the protein level was further analyzed.

TGF-β1 protein at a final concentration of 0.2 μg/ml or TGF-β3 protein at a concentration of 0.5 μg/ml was applied to a 96-well plate at 100 μl per well and incubated overnight at 4°C. The plates were washed the next day, blocked at room temperature for 1 hour, and 100 μl of EGFR antibody/TGFβR2 fusion protein at different concentrations (0.05 nM, 0.14 nM, 0.42 nM, 1.25 nM, 3.75 nM, 11.24 nM, 33.71 nM, 101.12 nM) were added with 100 μl of a final concentration of 0.2 μg/ml (competition with TGF-β1) or 1 μg/ml (competition with TGF-β3) of biotin-labeled TGFβR2-Fc protein (protein source: Sino Biological, Inc., and biotin-labeled protein: Sinocelltech Limited, hereinafter the same). Wells with TGFβR2-Fc protein were also used as a positive control. The plate was washed after 1 hour of incubation, and then the plate was washed several times after incubation for 1 hour after adding the secondary detection antibody streptavidin/horseradish peroxidase. Finally, the chromogenic substrate solution was added for color development, and after the reaction was completed, the OD ₄₅₀ value was read by a microplate reader. The PI inhibition competition rate% of the fusion protein was calculated based on the OD ₄₅₀ value, and the PI inhibition rate(%)=(OD ₄₅₀ value of the positive control well - OD ₄₅₀ value of the sample well)/OD ₄₅₀ value of the positive control well × 100%. The results are shown in Fig. 20, and fusion protein 6 had a similar ability to block the binding of TGF-β1 protein or TGF-β3 protein to TGFβR2-Fc as fusion protein 1.

4.1.2. Binding properties of the EGFR antibody/TGFβR2 fusion protein to EGFR

With reference to Example 1.2.1, the binding ability of the fusion protein to the recombinant human EGFR protein was measured by ELISA. As shown in Fig. 21, the binding ability of the fusion protein 6 to EGFR and the ability to compete with EGF in binding to EGFR were similar to that of EGFR-HPA8 when the EC ₅₀ was 133.1 ng/mL and R ² = 1.000.

4.2 Binding affinity analysis of EGFR antibody/TGFβR2 fusion protein

In this Example, the affinity of the EGFR antibody/TGFβR2 fusion protein to bind biotinylated recombinant human EGFR protein and TGF-β1 protein was determined using a biomolecular interaction assay system (model: OctetRED96e, manufacturer: Fortebio) with EGFR-HPA8 and H7N9-R1, respectively, as negative controls. The affinity parameters were obtained by fitting multiple concentration point binding and dissociation curves, and the results are shown in Tables 13 and 14, and the specific kinetic characteristic parameter curves are shown in Figs. 22 and 23.

These results indicate that fusion protein 6 retained high binding affinity for human EGFR protein compared to monoclonal antibody EGFR-HPA8, with a K _D value of 8.77 pM, a binding constant k _on value of 1.68 E+06 M ^-1 s ^-1 , and a dissociation constant k _dis value of 1.47 E-05 s ^-1 . In addition, truncated TGFβR2 fusion protein 6 exhibits similar affinity for human EGFR protein as full-length TGFβR2 fusion protein 1 with a K _D value of 96.1 pM, a binding constant k _on value of 1.53 E+06 M s ^-1 , and a dissociation constant k _dis value of 1.47 E-04 s ^-1 .

The above results show that fusion protein 6 has good affinity for both human EGFR and TGF-β1.

4.3. EGFR antibody/TGFβR2 fusion protein assay for TGF-β neutralization

TGF-β1 can inhibit the proliferation of Mv-1-lu cells, so the ability of EGFR antibody/TGFβR2 fusion protein to neutralize TGF-β1 can be detected by WST-8 assay.

Mv-1-lu cells (source: Cell Resource Center, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences) were uniformly inoculated at 50 μl/well in a 96-well plate at a cell density of 1× ¹⁰³ /well. The cells were incubated in a _CO2 incubator for about 3 h to allow them to adhere to the well walls, and then EGFR antibody/TGFβR2 fusion protein samples at different concentrations (0.0078 nM, 0.0156 nM, 0.0313 nM, 0.0625 nM, 0.125 nM, 0.25 nM, 0.5 nM, 1 nM, 2 nM) diluted in 1640 medium containing 10% FBS were added at 50 μl/well. Finally, TGF-β1 was added at a final concentration of 1 ng/mL at 10 μL per well. Group M was used as a positive control (containing cells and TGF-β1), group M' as a negative control (containing cells without TGF-β1), and group B as a blank control (containing only the culture medium without cells). The cells were incubated in a CO ₂ incubator at 37°C and 5% CO ₂ for 5 days, and then WST-8 was added at 10 μL per well. The samples were left for 180 min and the _OD450 - _OD630 value was measured by a microplate reader, and the neutralization rate of the EGFR antibody/TGFβR2 fusion protein was calculated by subtracting the value of the blank control B. The neutralization rate, %=(OD of group M' - OD of sample)/(OD of group M' - OD of group M) × 100%, and the quantitative efficiency curve was analyzed and plotted by GraphPad Prism software, the horizontal coordinate was the concentration of the antibody and the vertical coordinate was the inhibition rate. As shown in Fig. 24, both fusion protein 6 and the control product H7N9-R1-43-IgG1 (L9) for TGFβR2 (source: Sinocelltech Limited for biotin labeling, hereinafter the same) could effectively neutralize the inhibition of Mv-1-lu proliferation by TGF-β1 in a dose-dependent manner, and the half-effective concentration of fusion protein 6 was lower than that of the control product H7N9-R1-43-IgG1 (L9), indicating a better neutralizing activity of this molecule. EGFR-HPA8 did not neutralize TGF-β1, suggesting that it is the TGFβR2 part of fusion protein 6 that exhibits the neutralizing effect on TGF-β1.

The ability of fusion protein 6 to neutralize TGF-β was further analyzed using the reporter gene system in this Example, with reference to Example 3.5. The results are shown in Fig. 25, and both fusion protein 6 and the control product H7N9-R1-43-IgG1 (L9) for TGFβR2 could effectively neutralize TGF-β1 in a dose-dependent manner, and the maximum neutralization rate of fusion protein 6 (74.8%) was significantly higher than that of the control product H7N9-R1-43-IgG1 (L9) (55.3%), further indicating the excellent neutralizing activity of fusion protein 6.

4.4 Analysis of the activity of the EGFR antibody/TGFβR2 fusion protein in inhibiting cell proliferation

The inhibition of MDA-MB-468 cell growth by the EGFR antibody/TGFβR2 fusion protein was analyzed using the WST-8 method according to Example 1.2.2 to determine the properties of the EGFR portion. As shown in Fig. 26, the ability of fusion protein 6 to inhibit MDA-MB-468 cell proliferation was similar to EGFR-HPA8, and the degree of inhibition increased with increasing drug concentration according to an S-shaped curve. The control product H7N9-R1-43-IgG1 (L9) with TGFβR2 function did not inhibit MDA-MB-468 cell proliferation, indicating that fusion protein 6 inhibited tumor cell proliferation through its EGFR portion.

4.5 Effect of EGFR antibody/TGFβR2 fusion protein on ADCC

The effect on ADCC mediated by EGFR antibody/TGFβR2 fusion protein on EGFR-expressing cells was analyzed with reference to Example 2.2.3. The results are shown in Fig. 27. In the concentration range of 0.00004-3 nM, fusion protein 6 and anti-EGFR antibody EGFR-HPA8 could induce similar ADCC effects on EGFR-expressing A431 tumor cells. The control product H7N9-R1-43-IgG1 (L9) with TGFβR2 function had no effect on ADCC of A431 cells, indicating that it was the EGFR portion of fusion protein 6 that induced ADCC in this experimental system.

Example 5: Pharmacodynamic study of an EGFR antibody/TGFβR2 fusion protein with a truncated form of TGFβR2 (fusion protein 6) in the NCI-H1975 subcutaneous graft tumor model

Balb/c-nu mice were injected subcutaneously with 1× ¹⁰⁶ NCI-H1975 cells in the right side of the chest. When the tumor volume reached approximately 300 ^mm3 , the animals were randomly grouped according to tumor volume with 6 animals in each group and dosed. Dosing was started on the day of group assignment, administered via intraperitoneal injection (LP) twice a week for 10 consecutive doses, and stopped after the last dose to observe tumor recurrence. The specific dosing regimen is shown in Table 15 below.

The animals in each group were in good general condition such as activity and nutrition during the course of administration, and their body weight increased slightly. There was no significant difference in body weight between the dosed group and the vehicle control group after the doses were administered (P>0.05). The change in body weight of all animals are shown in Table 16 and Fig. 28.

The tumor volume measurement results for each group in this study are shown in Table 17 and Fig. 29. After 35 days of treatment in the groups, the mean tumor volume of the vehicle control group was 7150.78±780.4 ^mm3 . Five of the six mice treated with fusion protein 6 showed complete tumor clearance (CR) with a mean tumor volume of 4.55±4.55 ^mm3 and TGI of 99.9%, which was significantly different from that of the vehicle control group (P<0.001). In contrast, only one mouse in the EGFR-HPA8 group showed complete tumor clearance with a mean tumor volume of 79.44±28.65 ^mm3 and TGI of 98.9%. The results showed that fusion protein 6 exerted a significant inhibitory effect on NCI-H1975 non-small cell lung cancer tumors transplanted subcutaneously, and the tumor inhibitory effect was superior to that of EGFR-HPA8 at the same molar dose (P=0.237).

Example 6: Stability analysis of the EGFR antibody/TGFβR2 fusion protein with a truncated form of TGFβR2 (fusion protein 6)

6.1. Ultrafiltration analysis of EGFR antibody/TGFβR2 fusion protein stability

The EGFR antibody/TGFβR2 fusion protein samples were concentrated to approximately 10 mg/mL by ultrafiltration in 100 mM glycine, 10 mM NaCl, 50 mM Tris, pH 7.5. The concentrated samples were tested for purity and stability of the ultrafiltered samples by reducing SDS-PAGE and selective sieve chromatography (SEC-HPLC, Agilent 1260 Liquid Chromatography System, TSK-G3000SWXL column). SEC-HPLC steps: (1) mobile phase: 200 mM NaH ₂ PO ₄ , 100 mM arginine, pH 6.5; (2) loading volume 80 μg; (3) the analysis time was 30 min, the flow rate was 0.5 ml/min, and the column temperature was 25°C; (4) the purity was calculated by the peak area normalization method.

The results of the purity test after concentration of the samples are shown in Fig. 30, and the purity of the samples and the fragment ratio are shown in Table 18. The results showed that the fusion protein 6 with truncated TGFβR2 was less likely to be degraded after concentration and had a higher ultrafiltration rate compared with the fusion protein with full-length TGFβR2.

6.2 Thermal stability analysis of EGFR antibody/TGFβR2 fusion protein

Thermal stability of the samples was measured by differential scanning fluorimetry (DSF) using the UNcle system (Unchained Labs, model: UNCLE-0330). The process steps were: (1) the sample volume was 9 μL; (2) the experimental parameters were set as follows: the temperature range was from 25 °C to 95 °C, and the heating rate was 0.3 °C/min; (3) UNcle Analysis software was used to analyze the data, the average value of the intrinsic fluorescence change curve under UV266 was taken as Tm, and the aggregation onset temperature of the aggregation change curve formed by the static light scattering signal under UV266/Blue473 was taken as Tagg266 and Tagg473.

Table 19 shows the results of thermal stability analysis of fusion protein 6, which showed good thermal stability.

6.3. Analysis of thermo-accelerated stability of the EGFR antibody/TGFβR2 fusion protein

After storing the samples at 45°C for 1 week, the thermoaccelerated stability of the samples was analyzed by SEC-HPLC and SDS-PAGE, and the procedure was the same as in 6.1.

The results of the thermoaccelerated stability analysis of fusion protein 6 are shown in Table 20. After 1 week of storage at 45°C, the SEC purity of fusion protein 6 decreased by 0.7%, but the purity remained high, the aggregate level increased to a lesser extent, and the fragment level did not change, indicating good thermoaccelerated stability.

6.4 Freeze/thaw stability analysis of EGFR antibody/TGFβR2 fusion protein

The samples were stored at -80°C for 3 h and then placed at 45°C for 1 h to thaw, and five repeated freeze-thaw cycles were performed. The freeze-thaw stability of the samples was analyzed by SEC-HPLC, and the procedure was the same as in 6.1.

The freeze/thaw stability results of fusion protein 6 are shown in Table 21. After five consecutive freeze/thaw cycles, the SEC purity of fusion protein 6 did not change significantly, and the levels of aggregates and fragments did not increase significantly, demonstrating good freeze/thaw stability.

6.5. Shaking stability of EGFR antibody/TGFβR2 fusion protein Samples were placed in deepwell plates and vortexed at 800 rpm for 24 hours. Samples were analyzed by SEC-HPLC using the same procedure as in 6.1. The results are shown in Table 22, which show that the SEC purity of the samples for monomers did not change significantly after 24 hours of shaking, and the levels of aggregates and fragments did not change significantly, indicating that fusion protein 6 has good shaking stability.

Example 7: Construction and characterization of fusion proteins of antibodies X directed to solid tumor antigens and TGFβR2, where the TGFβR2 moiety is a truncated form of TGFβR2 (fusion protein 6)

7.1 Construction of antibody X/truncated TGFβR2 fusion protein expression vector, expression and purification

To further evaluate the structural stability and TGF-β1 neutralizing ability of the selected truncated forms of TGFβR2 in Example 3.2, this Example used various solid tumor antigens as the targeting portion of the fusion protein and the extracellular domain of TGFβR2 (full-length and ECD(6-26)-deleted, fusion protein 6) as the immunomodulatory portion of the fusion protein to form an antibody X/TGFβR2 extracellular domain fusion protein (X/TGβPR2 fusion protein). Similar to the above, in the X/TGFβR2 fusion protein, the C-terminal amino acid of the heavy chain of antibody X is linked to the extracellular domain of TGFβR2 via a ( _G4S ) ₄ linker. Additionally, the C-terminal lysine of the heavy chain of antibody X was removed to reduce the risk of proteolytic cleavage. The protocol for constructing the X/TGFβR2 fusion protein is shown in Table 23.

The target gene was amplified by PCR or overlap PCR and ligated into the specified expression vector by infusion. The correct sequence of the recombinant expression vector was confirmed by sequencing, plasmids were extracted, transiently transferred into HEK-293 cells (fut8 knockout), cultured for 7 days, and the supernatant was collected by centrifugation. The resulting cell supernatant was purified by protein A affinity chromatography to purify the fusion protein.

7.2. Degradation of antibody X/truncated TGFβR2 fusion proteins

The purity as well as degradation of the X/TGFβR2 fusion protein were assessed by SDS-PAGE under reducing conditions. The results are shown in Fig. 31. The various expressed samples of the X/TGFβR2 fusion proteins with the selected truncated forms of the TGFβR2 extracellular domain were significantly more stable and had significantly fewer bands of degraded products than the control samples with the full-length TGFβR2 extracellular domain. It should be recognized that the stability of the samples is due to the presence of the truncated forms of the TGFβR2 extracellular domain, regardless of which types of targeting moiety, i.e. antibodies, are used.

7.3. Degradation tendency of the antibody X/truncated TGFβR2 fusion protein

In this Example, the supernatant of 293E cells was used for accelerated processing of the fusion protein, and the stability under degradation conditions of the X/TGFβR2 fusion protein with the selected truncated extracellular domain of TGFβR2 was further determined as in Example 3.3. The results of the sample purity analysis are shown in Fig. 32, and the sample purity and the percentage of cleaved portions are shown in Table 24. The results indicate that the X/TGFβR2 fusion proteins with the preferred truncated form of the extracellular domain of TGFβR2 are more resistant to protease degradation than the fusion protein with the full-length form of TGFβR2.

To evaluate the stability of the X/TGFβR2 fusion proteins with the selected truncated TGFβR2 extracellular domain under defined concentration conditions, their stability during ultrafiltration was analyzed using the method of Example 6.1. The results are shown in Table 25. The X/TGFβR2 fusion protein with the preferred truncated TGFβR2 extracellular domain was less susceptible to degradation. After concentration, the percentage of cleaved portions was less than 4.0% (SDS-PAGE purity), indicating higher stability during ultrafiltration than the X/TGFβR2 fusion protein with the full-length TGFβR2 extracellular domain.

Thus, the excellent stability of the fusion protein containing the preferred truncated extracellular domain of TGFβR2 was further confirmed using fusion proteins with several types of antibodies against solid tumor antigens as the targeting moiety.

Example 8: In vitro biological properties of X/TGFβR2 fusion proteins with solid tumor antigen-targeting antibodies as the targeting moiety and truncated TGFβR2 (fusion protein 6)

8.1 X/TGFβR2 Fusion Protein Binding Assay

The binding ability of the X/TGFβR2 fusion proteins to TGF-β1 was measured by ELISA according to the method of Example 3.4. As shown in Fig. 33, the ability of the X/TGFβR2 fusion proteins with the preferred truncated form of TGFβR2 to block TGF-β1 was slightly lower than that of the X/TGFβR2 fusion protein with the full-length form of TGFβR2.

8.2 Analysis of X/TGFβR2 fusion protein in TGF-β neutralization

The ability of the X/TGFβR2 fusion protein to neutralize TGF-β1 and TGF-β3 was tested with reference to Example 3.5. As shown in Fig. 34, the ability of the X/TGFβR2 fusion protein with the preferred truncated form of TGFβR2 to neutralize both TGF-β1 and TGF-β3 was higher than that of the X/TGFβR2 fusion protein with the full-length form.

8.3. Analysis of X/TGFβR2 fusion protein binding to the target of the X moiety

The antigens ERBB2-his, VEGF165, VEGFR2-His, CTLA4-his, and EGFR-His, which are targeted by the targeting moieties of X, were coated onto 96-well plates at final concentrations of 10 ng/mL, 5 ng/mL, 80 ng/mL, 80 ng/mL, and 40 ng/mL, respectively, at 100 μL per well. The plates were coated overnight at 4°C. The plates were washed the next day, blocked at room temperature for 1 h, and incubated with 100 μL of the X-TGFβR2 fusion protein at a final concentration of 13.89 nM for 1 h. The plates were washed to remove unbound antibodies, incubated with goat anti-hIgG Fc/HRP secondary antibody, and washed again. Finally, chromogenic substrate solution was added for color development, and _OD450 was read using a microplate reader after the reaction was completed. As shown in Fig. 35, the X/TGFβR2 fusion protein with the selected truncated TGFβR2 had similar ability to block the corresponding antigen from the X side of the X/TGFβR2 fusion protein containing the full-length form of TGFβR2.

SEQUENCE LIST

REFERENCE MATERIALS

1. Xie, E, et al. TGF-beta signaling in cancer metastasis. Acta Biochim Biophys Sin (Shanghai), 2018. 50(1): p. 121-132.

2. Colak, S. and P. Ten Dijke. Targeting TGF-beta Signaling in Cancer. Trends Cancer, 2017. 3(1): p. 56-71.

3. Fabregat, I. et al. TGF-beta signaling in cancer treatment. Curr Pharm Des, 2014. 20(17): p. 2934-47.

4. Batlle, E. and J. Massague, Transforming Growth Factor-beta Signaling in Immunity and Cancer. Immunity, 2019. 50(4): p. 924-940.

5. Laskin, J.J. and A.B. Sandler, Epidermal growth factor receptor: a promising target in solid tumors. Cancer treatment reviews, 2004. 30(1): p. 1-17.

6. Hynes, N. et al. The ErbB receptor tyrosine family as signal integrators. Endocrine-related cancer, 2001. 8(3): p. 151-159.

7. Zandi, R. et al. Mechanisms for oncogenic activation of the epidermal growth factor receptor. Cellular signaling, 2007. 19(10): p. 2013-2023.

8. Seshacharyulu, P. et al. Targeting the EGFR signaling pathway in cancer therapy. Expert opinion on therapeutic targets, 2012. 16(1): p. 15-31.

9. Zhao, Y. et al. TGF-β transactivates EGFR and facilitates mammary cancer migration and invasion through canonical Smad3 and ERK/Sp1 signaling pathways. Molecular oncology, 2018.12(3): p. 305-321.

10. Wendt, M.K., J.A. Smith, and W.P. Schiemann, Transforming growth factors-induced epithelial-mesenchymal transition facilitates epidermal growth factor-dependent mammary cancer progression. Oncogene, 2010. 29(49): p. 6485.

11. Lee, E., et al. Transforming growth factorβ1 transactivates EGFR via an H ₂ O ₂ -dependent mechanism in squamous carcinoma cell line. Cancer letters, 2010. 290(1): p. 43-48.

12. Dunfield, L.D. and M.W. Nachtigal, Inhibition of the antiproliferative effect of TGFβ by EGF in primary human ovarian cancer cells. Oncogene, 2003. 22(30): p. 4745.

13. Kretzschmar, M. et al. A mechanism of repression of TGFβ/Smad signaling by oncogenic Ras. Genes & development, 1999. 13(7): p. 804-816.

14. ten Dijke, P., K. Miyazono, and C.-H. Heldin, Signaling inputs converge on nuclear effectors in TGF-β signaling. Trends in biochemical sciences, 2000. 25(2): p. 64-70.

15. Funaba, M., C.M. Zimmerman, and L.S. Mathews, Modulation of Smad2-mediated signaling by extracellular signal-regulated kinase. Journal of Biological Chemistry, 2002. 277(44): p. 41361-41368.

16. Richter, P. et al. EGF/TGFbeta1 co-stimulation of oral squamous cell carcinoma cells causes an epithelial-mesenchymal transition cell phenotype expressing laminin 332. J Oral Pathol Med, 2011. 40(1): p. 46-54.

17. Uttamsingh, S. et al. Synergistic effect between EGF and TGF-beta1 in inducing oncogenic properties of intestinal epithelial cells. Oncogene, 2008. 27(18): p. 2626-34.

18. Xu, Z. et al. TGFbeta and EGF synergistically induce a more invasive phenotype of epithelial ovarian cancer cells. Biochem Biophys Res Commun, 2010. 401(3): p. 376-81.

19. Xiong, J. et al. Epidermal growth factor promotes transforming growth factor-beta 1-induced epithelial-mesenchymal transition in HK-2 cells through a synergistic effect on Snail. Mol Biol Rep, 2014. 41(1): p. 241-50.

20. Buonato, J.M., I.S. Lan, and M.J. Lazzara, EGF augments TGFbeta-induced epithelial-mesenchymal transition by promoting SHP2 binding to GAB1. J Cell Sci, 2015. 128(21): p. 3898-909.

21. Wang, T. et al. The TGFβ-miR-499a-SHKBP1 pathway induces resistance to EGFR inhibitors in osteosarcoma cancer stem cell-like cells. Journal of Experimental & Clinical Cancer Research, 2019. 38(1): p. 226.

22. Jie, H.B. et al. CTLA-4(+) Regulatory T Cells Increased in Cetuximab-Treated Head and Neck Cancer Patients Suppress NK Cell Cytotoxicity and Correlate with Poor Prognois. Cancer Res, 2015. 75(11): p. 2200-10.

23. Bedi, A. et al. Inhibition of TGF-beta enhances the in vivo antitumor efficacy of EGF receptor-targeted therapy. Mol Cancer Ther, 2012. 11(11): p. 2429-39.

24. Zhang, Y. et al. The canonical TGF-beta/Smad signaling pathway is involved in PD-L1-induced primary resistance to EGFR-TKIs in EGFR-mutant non-small-cell lung cancer. Respir Res, 2019. 20(1): p. 164.

25. Jones, S.T. and M.M. Bendig, Rapid PCR-cloning of full-length mouse immunoglobulin variable regions. Biotechnology (N Y), 1991. 9(6): p. 579.

26. Kabat, E.A. and others. Sequences of proteins of immunological interest. 1992: DIANE publishing.

27. Jones, P.T. and others. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature, 1986. 321(6069): p. 522.

28. Verhoeyen, M. and L. Riechmann, Engineering of antibodies. BioEssays, 1988. 8(2 - 3): p. 74-78.

--->

SEQUENCE LIST

<110> SinoCellTech Ltd.

<120> TGFbetaR2 MOLECULE WITH A SHORTENED EXTRACELLULAR DOMAIN, FUSION PROTEIN

TGFbetaR2 MOLECULES WITH A SHORTENED EXTRACELLULAR DOMAIN AND ANTIBODIES AGAINST EGFR, AND

ANTITUMOR USE OF FUSION PROTEIN

<130> PCT69149SXB

<160> 190

<170> PatentIn version 3.3

<210> 1

<211> 645

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 1

Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala

1 5 10 15

Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln

20 25 30

Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe

35 40 45

Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn

50 55 60

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

65 70 75 80

Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val

85 90 95

Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr

100 105 110

Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn

115 120 125

Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu

130 135 140

His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu

145 150 155 160

Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met

165 170 175

Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro

180 185 190

Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln

195 200 205

Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg

210 215 220

Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys

225 230 235 240

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

245 250 255

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

260 265 270

Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly

275 280 285

Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His

290 295 300

Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu

305 310 315 320

Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val

325 330 335

Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn

340 345 350

Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp

355 360 365

Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr

370 375 380

Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu

385 390 395 400

Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp

405 410 415

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

420 425 430

His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu

435 440 445

Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser

450 455 460

Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu

465 470 475 480

Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu

485 490 495

Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro

500 505 510

Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn

515 520 525

Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly

530 535 540

Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro

545 550 555 560

Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro

565 570 575

Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val

580 585 590

Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp

595 600 605

Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys

610 615 620

Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro Thr Asn Gly

625 630 635 640

Pro Lys Ile Pro Ser

645

<210> 2

<211> 54

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 2

tctagtggtg gcggtggttc gggcggtggt ggaggtggta gttctagatc ttcc 54

<210> 3

<211> 732

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 3

gatatccaga tgacccagtc tccagcctcc ctggctgcat ctgtgggaga aactgtcacc 60

atcacatgtc gagcaagtga gaacatttac tacagtttag cttggtatca gcagaaggaa 120

gggaaatctc ctcagctcct gatctatatt acaaacggct tggcagatgg tgtcccatcg 180

aggttcagtg gcagtggatc tgggacacag tattctatga agatcgacag catgcagcct 240

gaagataccg caacttattt ctgtaaacag tcttatgacg ttccgctcac gttcggtgct 300

gggaccaagc tggagatgaa atctagtggt ggcggtggtt cgggcggtgg tggaggtggt 360

agttctagat cttcccaggt gcagctgcag caatctggac ctgatttggt gaagcctggg 420

gcttcagtga ggatatcttg caaggtttct ggctacacct tcacaaccta ctatacacac 480

tgggtgaagc agaggcctgg acggggactt gaatggattg gatggattta tcctggagat 540

gttaatacga agtacaatga gaaattcaag ggcaaggcca cactgactgc agacaaaacc 600

tccagcacag cctacatgca gctcagcagc ctgacctctg aggactctgc ggtctatttc 660

tgtgcaagag aagaccccgg tagtaactac tttgactact ggggccaagg caccactctc 720

acagtctcct ca 732

<210> 4

<211> 357

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 4

caggtgcagc tgcagcaatc tggacctgat ttggtgaagc ctggggcttc agtgaggata 60

tcttgcaagg tttctggcta caccttcaca acctactata cacactgggt gaagcagagg 120

cctggacggg gacttgaatg gattggatgg atttatcctg gagatgttaa tacgaagtac 180

aatgagaaat tcaagggcaa ggccacactg actgcagaca aaacctccag cacagcctac 240

atgcagctca gcagcctgac ctctgaggac tctgcggtct atttctgtgc aagagaagac 300

cccggtagta actactttga ctactggggc caaggcacca ctctcacagt ctcctca 357

<210> 5

<211> 321

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 5

gatatccaga tgacccagtc tccagcctcc ctggctgcat ctgtgggaga aactgtcacc 60

atcacatgtc gagcaagtga gaacatttac tacagtttag cttggtatca gcagaaggaa 120

gggaaatctc ctcagctcct gatctatatt acaaacggct tggcagatgg tgtcccatcg 180

aggttcagtg gcagtggatc tgggacacag tattctatga agatcgacag catgcagcct 240

gaagataccg caacttattt ctgtaaacag tcttatgacg ttccgctcac gttcggtgct 300

gggaccaagc tggagatgaa a 321

<210> 6

<211> 993

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 6

gcaagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 60

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 120

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 180

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 240

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 300

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 360

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 420

gaggtcacgt gcgtggtggt ggacgtgagc cacgaagacc ccgaggtcaa gttcaactgg 480

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 540

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 600

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 660

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 720

ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 780

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 840

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 900

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 960

cagaagagcc tctccctgtc tccgggtaaa tga 993

<210> 7

<211> 324

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 7

cgtacggtgg ctgcaccatc tgtcttcatc ttcccgccat ctgatgagca gttgaaatct 60

ggaactgcct ctgttgtgtg cctgctgaat aacttctatc ccagagaggc caaagtacag 120

tggaaggtgg ataacgccct ccaatcgggt aactcccagg agagtgtcac agagcaggac 180

agcaaggaca gcacctacag cctcagcagc accctgacgc tgagcaaagc agactacgag 240

aaacacaaag tctacgcctg cgaagtcacc catcagggcc tgagctcgcc cgtcacaaag 300

agcttcaaca ggggagagtg ttag 324

<210> 8

<211> 119

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 8

Gln Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala

1 5 10 15

Ser Val Arg Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Thr Tyr

20 25 30

Tyr Thr His Trp Val Lys Gln Arg Pro Gly Arg Gly Leu Glu Trp Ile

35 40 45

Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Thr Ser Ser Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys

85 90 95

Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Thr Leu Thr Val Ser Ser

115

<210> 9

<211> 107

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 9

Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ala Ala Ser Val Gly

1 5 10 15

Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Tyr Ser

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Glu Gly Lys Ser Pro Gln Leu Leu Ile

35 40 45

Tyr Ile Thr Asn Gly Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Gln Tyr Ser Met Lys Ile Asp Ser Met Gln Pro

65 70 75 80

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

85 90 95

Thr Phe Gly Ala Gly Thr Lys Leu Glu Met Lys

100 105

<210> 10

<211> 11

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 10

Arg Ala Ser Glu Asn Ile Tyr Tyr Ser Leu Ala

1 5 10

<210> 11

<211> 7

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 11

Ile Thr Asn Gly Leu Ala Asp

1 5

<210> 12

<211> 9

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 12

Lys Gln Ser Tyr Asp Val Pro Leu Thr

1 5

<210> 13

<211> 10

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 13

Gly Tyr Thr Phe Thr Thr Tyr Tyr Thr His

1 5 10

<210> 14

<211> 17

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 14

Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn Glu Lys Phe Lys

1 5 10 15

Gly

<210> 15

<211> 12

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 15

Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr

1 5 10

<210> 16

<211> 11

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 16

Arg Ala Ser Glu Asn Ile Tyr Tyr Ser Leu Ala

1 5 10

<210> 17

<211> 7

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 17

Ile Thr Asp Gly Leu Ala Asp

1 5

<210> 18

<211> 9

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 18

Lys Gln Ser Tyr Asp Val Pro Leu Thr

1 5

<210> 19

<211> 10

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 19

Gly Tyr Thr Phe Thr Thr Tyr Tyr Thr His

1 5 10

<210> 20

<211> 17

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 20

Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn Glu Lys Phe Lys

1 5 10 15

Gly

<210> 21

<211> 12

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 21

Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr

1 5 10

<210> 22

<211> 449

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 22

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Thr Tyr

20 25 30

Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

Lys

<210> 23

<211> 214

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 23

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Tyr Ser

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Gln Leu Leu Ile

35 40 45

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

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Lys Ile Asp Ser Leu Gln Pro

65 70 75 80

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

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

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

165 170 175

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

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 24

<211> 468

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 24

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Lys

465

<210> 25

<211> 233

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 25

Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly

1 5 10 15

Val His Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala

20 25 30

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile

35 40 45

Tyr Tyr Ser Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Gln

50 55 60

Leu Leu Ile Tyr Ile Thr Asp Gly Leu Ala Asp Gly Val Pro Ser Arg

65 70 75 80

Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Lys Ile Asp Ser

85 90 95

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

100 105 110

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

115 120 125

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

130 135 140

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

145 150 155 160

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

165 170 175

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

180 185 190

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

195 200 205

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

210 215 220

Thr Lys Ser Phe Asn Arg Gly Glu Cys

225 230

<210> 26

<211> 19

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 26

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser

<210> 27

<211> 19

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 27

Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly

1 5 10 15

Val His Ser

<210> 28

<211> 119

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 28

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Thr Tyr

20 25 30

Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 29

<211> 107

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 29

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Tyr Ser

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Gln Leu Leu Ile

35 40 45

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

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Lys Ile Asp Ser Leu Gln Pro

65 70 75 80

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

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 30

<211> 330

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 30

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys

1 5 10 15

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

20 25 30

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

35 40 45

Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser

50 55 60

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr

65 70 75 80

Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys

85 90 95

Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys

100 105 110

Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro

115 120 125

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys

130 135 140

Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp

145 150 155 160

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu

165 170 175

Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu

180 185 190

His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn

195 200 205

Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly

210 215 220

Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu

225 230 235 240

Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr

245 250 255

Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn

260 265 270

Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe

275 280 285

Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn

290 295 300

Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr

305 310 315 320

Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

325 330

<210> 31

<211> 107

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 31

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

1 5 10 15

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

20 25 30

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

35 40 45

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

50 55 60

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

65 70 75 80

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

85 90 95

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

100 105

<210> 32

<211> 1407

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 32

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg taaatga 1407

<210> 33

<211> 702

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 33

atgggctggt cctgtatcat cctgttcctg gtggctacag ccacaggagt gcatagtgac 60

atccagatga cccagagccc atcctccctg tctgcctctg tgggagacag ggtgaccatc 120

acttgtaggg catctgagaa catctactac tccctggctt ggtatcaaca gaagcctggc 180

aaggctccac agctgctgat ttacatcacc gacggactgg ctgatggagt gccaagcagg 240

ttctctggct ctggctctgg cacagactac accctgaaga tcgactccct ccaacctgag 300

gactttgcca cctactactg taagcagtcc tatgatgtgc cactgacctt tggaggaggc 360

accaaggtgg agattaagcg tacggtggct gcaccatctg tcttcatctt cccgccatct 420

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660

agctcgcccg tcacaaagag cttcaacagg ggagagtgtt ga 702

<210> 34

<211> 57

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 34

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagt 57

<210> 35

<211> 57

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 35

atgggctggt cctgtatcat cctgttcctg gtggctacag ccacaggagt gcatagt 57

<210> 36

<211> 357

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 36

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagc 357

<210> 37

<211> 321

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 37

gacatccaga tgacccagag cccatcctcc ctgtctgcct ctgtgggaga cagggtgacc 60

atcacttgta gggcatctga gaacatctac tactccctgg cttggtatca acagaagcct 120

ggcaaggctc cacagctgct gatttacatc accgacggac tggctgatgg agtgccaagc 180

aggttctctg gctctggctc tggcacagac tacaccctga agatcgactc cctccaacct 240

gaggactttg ccacctacta ctgtaagcag tcctatgatg tgccactgac ctttggagga 300

ggcaccaagg tggagattaa g 321

<210> 38

<211> 993

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 38

gcaagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 60

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 120

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 180

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 240

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 300

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 360

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 420

gaggtcacgt gcgtggtggt ggacgtgagc cacgaagacc ccgaggtcaa gttcaactgg 480

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 540

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 600

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 660

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 720

ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 780

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 840

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 900

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 960

cagaagagcc tctccctgtc tccgggtaaa tga 993

<210> 39

<211> 324

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 39

cgtacggtgg ctgcaccatc tgtcttcatc ttcccgccat ctgatgagca gttgaaatct 60

ggaactgcct ctgttgtgtg cctgctgaat aacttctatc ccagagaggc caaagtacag 120

tggaaggtgg ataacgccct ccaatcgggt aactcccagg agagtgtcac agagcaggac 180

agcaaggaca gcacctacag cctcagcagc accctgacgc tgagcaaagc agactacgag 240

aaacacaaag tctacgcctg cgaagtcacc catcagggcc tgagctcgcc cgtcacaaag 300

agcttcaaca ggggagagtg ttga 324

<210> 40

<211> 244

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 40

Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ala Ala Ser Val Gly

1 5 10 15

Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Tyr Ser

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Glu Gly Lys Ser Pro Gln Leu Leu Ile

35 40 45

Tyr Ile Thr Asn Gly Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Gln Tyr Ser Met Lys Ile Asp Ser Met Gln Pro

65 70 75 80

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

85 90 95

Thr Phe Gly Ala Gly Thr Lys Leu Glu Met Lys Ser Ser Gly Gly Gly

100 105 110

Gly Ser Gly Gly Gly Gly Gly Gly Ser Ser Arg Ser Ser Gln Val Gln

115 120 125

Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala Ser Val Arg

130 135 140

Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Thr Tyr Tyr Thr His

145 150 155 160

Trp Val Lys Gln Arg Pro Gly Arg Gly Leu Glu Trp Ile Gly Trp Ile

165 170 175

Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn Glu Lys Phe Lys Gly Lys

180 185 190

Ala Thr Leu Thr Ala Asp Lys Thr Ser Ser Thr Ala Tyr Met Gln Leu

195 200 205

Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys Ala Arg Glu

210 215 220

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

225 230 235 240

Thr Val Ser Ser

<210> 41

<211> 18

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 41

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Gly Ser Ser Arg

1 5 10 15

Ser Ser

<210> 42

<211> 1407

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 42

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtcag 60

gtgcagctgc agcaatctgg acctgatttg gtgaagcctg gggcttcagt gaggatatct 120

tgcaaggttt ctggctacac cttcacaacc tactatacac actgggtgaa gcagaggcct 180

ggacggggac ttgaatggat tggatggatt tatcctggag atgttaatac gaagtacaat 240

gagaaattca agggcaaggc cacactgact gcagacaaaa cctccagcac agcctacatg 300

cagctcagca gcctgacctc tgaggactct gcggtctatt tctgtgcaag agaagacccc 360

ggtagtaact actttgacta ctggggccaa ggcaccactc tcacagtctc ctcagcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg taaatga 1407

<210> 43

<211> 702

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 43

atgggctggt cctgtatcat cctgttcctg gtggctaag ccacaggagt gcatagtgat 60

atccagatga cccagtctcc agcctccctg gctgcatctg tgggagaaac tgtcaccatc 120

acatgtcgag caagtgagaa catttactac agtttagctt ggtatcagca gaaggaaggg 180

aaatctcctc agctcctgat ctatattaca aacggcttgg cagatggtgt cccatcgagg 240

ttcagtggca gtggatctgg gacacagtat tctatgaaga tcgacagcat gcagcctgaa 300

gataccgcaa cttatttctg taaacagtct tatgacgttc cgctcacgtt cggtgctggg 360

accaagctgg agatgaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 420

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 660

agctcgcccg tcacaaagag cttcaacagg gggagagtgtt ag 702

<210> 44

<211> 468

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 44

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Gln Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys

20 25 30

Pro Gly Ala Ser Val Arg Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Arg Pro Gly Arg Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Thr Ser Ser

85 90 95

Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Phe Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Lys

465

<210> 45

<211> 233

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 45

Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly

1 5 10 15

Val His Ser Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ala Ala

20 25 30

Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile

35 40 45

Tyr Tyr Ser Leu Ala Trp Tyr Gln Gln Lys Glu Gly Lys Ser Pro Gln

50 55 60

Leu Leu Ile Tyr Ile Thr Asn Gly Leu Ala Asp Gly Val Pro Ser Arg

65 70 75 80

Phe Ser Gly Ser Gly Ser Gly Thr Gln Tyr Ser Met Lys Ile Asp Ser

85 90 95

Met Gln Pro Glu Asp Thr Ala Thr Tyr Phe Cys Lys Gln Ser Tyr Asp

100 105 110

Val Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Met Lys Arg Thr

115 120 125

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

130 135 140

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

145 150 155 160

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

165 170 175

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

180 185 190

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

195 200 205

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

210 215 220

Thr Lys Ser Phe Asn Arg Gly Glu Cys

225 230

<210> 46

<211> 329

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 46

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys

1 5 10 15

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

20 25 30

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

35 40 45

Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser

50 55 60

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr

65 70 75 80

Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys

85 90 95

Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys

100 105 110

Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro

115 120 125

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys

130 135 140

Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp

145 150 155 160

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu

165 170 175

Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu

180 185 190

His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn

195 200 205

Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly

210 215 220

Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu

225 230 235 240

Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr

245 250 255

Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn

260 265 270

Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe

275 280 285

Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn

290 295 300

Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr

305 310 315 320

Gln Lys Ser Leu Ser Leu Ser Pro Gly

325

<210> 47

<211> 136

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 47

Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr

1 5 10 15

Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp

20 25 30

Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys

35 40 45

Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val

50 55 60

Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp

65 70 75 80

Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro

85 90 95

Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met

100 105 110

Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu

115 120 125

Glu Tyr Asn Thr Ser Asn Pro Asp

130 135

<210> 48

<211> 124

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 48

Ile Pro Pro His Val Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys

1 5 10 15

Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys

20 25 30

Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val

35 40 45

Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr

50 55 60

Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp

65 70 75 80

Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu

85 90 95

Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile

100 105 110

Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

115 120

<210> 49

<211> 122

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 49

Ile Pro Pro His Val Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe

1 5 10 15

Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser

20 25 30

Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val

35 40 45

Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys

50 55 60

His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala

65 70 75 80

Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe

85 90 95

Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe

100 105 110

Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

115 120

<210> 50

<211> 120

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 50

Ile Pro Pro His Val Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp

1 5 10 15

Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys

20 25 30

Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val

35 40 45

Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp

50 55 60

Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro

65 70 75 80

Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met

85 90 95

Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu

100 105 110

Glu Tyr Asn Thr Ser Asn Pro Asp

115 120

<210> 51

<211> 116

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 51

Ile Pro Pro His Val Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser

1 5 10 15

Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser

20 25 30

Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn

35 40 45

Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro

50 55 60

Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met

65 70 75 80

Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser

85 90 95

Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr

100 105 110

Ser Asn Pro Asp

115

<210> 52

<211> 115

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 52

Ile Pro Pro His Val Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr

1 5 10 15

Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile

20 25 30

Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp

35 40 45

Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr

50 55 60

His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys

65 70 75 80

Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser

85 90 95

Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser

100 105 110

Asn Pro Asp

115

<210> 53

<211> 114

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 53

Ile Pro Pro His Val Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys

1 5 10 15

Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys

20 25 30

Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu

35 40 45

Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His

50 55 60

Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu

65 70 75 80

Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp

85 90 95

Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn

100 105 110

Pro Asp

<210> 54

<211> 116

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 54

Ile Pro Pro His Val Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser

1 5 10 15

Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser

20 25 30

Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn

35 40 45

Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro

50 55 60

Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met

65 70 75 80

Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser

85 90 95

Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr

100 105 110

Ser Asn Pro Asp

115

<210> 55

<211> 114

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 55

Ile Pro Pro His Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys

1 5 10 15

Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys

20 25 30

Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu

35 40 45

Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His

50 55 60

Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu

65 70 75 80

Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp

85 90 95

Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn

100 105 110

Pro Asp

<210> 56

<211> 113

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 56

Ile Pro Pro Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp

1 5 10 15

Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu

20 25 30

Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn

35 40 45

Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp

50 55 60

Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys

65 70 75 80

Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu

85 90 95

Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro

100 105 110

Asp

<210> 57

<211> 112

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 57

Ile Pro Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn

1 5 10 15

Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys

20 25 30

Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile

35 40 45

Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe

50 55 60

Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys

65 70 75 80

Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys

85 90 95

Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

100 105 110

<210> 58

<211> 111

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 58

Ile Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln

1 5 10 15

Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro

20 25 30

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

35 40 45

Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile

50 55 60

Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys

65 70 75 80

Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn

85 90 95

Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

100 105 110

<210> 59

<211> 114

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 59

Pro Pro His Val Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys

1 5 10 15

Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys

20 25 30

Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu

35 40 45

Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His

50 55 60

Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu

65 70 75 80

Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp

85 90 95

Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn

100 105 110

Pro Asp

<210> 60

<211> 113

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 60

Pro His Val Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp

1 5 10 15

Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu

20 25 30

Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn

35 40 45

Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp

50 55 60

Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys

65 70 75 80

Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu

85 90 95

Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro

100 105 110

Asp

<210> 61

<211> 112

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 61

His Val Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn

1 5 10 15

Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys

20 25 30

Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile

35 40 45

Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe

50 55 60

Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys

65 70 75 80

Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys

85 90 95

Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

100 105 110

<210> 62

<211> 111

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 62

Val Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln

1 5 10 15

Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro

20 25 30

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

35 40 45

Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile

50 55 60

Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys

65 70 75 80

Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn

85 90 95

Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

100 105 110

<210> 63

<211> 117

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 63

Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe

1 5 10 15

Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr

20 25 30

Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys

35 40 45

Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu

50 55 60

Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile

65 70 75 80

Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys

85 90 95

Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn

100 105 110

Thr Ser Asn Pro Asp

115

<210> 64

<211> 115

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 64

Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr

1 5 10 15

Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile

20 25 30

Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp

35 40 45

Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr

50 55 60

His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys

65 70 75 80

Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser

85 90 95

Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser

100 105 110

Asn Pro Asp

115

<210> 65

<211> 110

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 65

Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys

1 5 10 15

Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln

20 25 30

Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu

35 40 45

Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu

50 55 60

Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro

65 70 75 80

Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp

85 90 95

Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

100 105 110

<210> 66

<211> 20

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 66

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

1 5 10 15

Gly Gly Gly Ser

20

<210> 67

<211> 987

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 67

gcaagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 60

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 120

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 180

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 240

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 300

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 360

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 420

gaggtcacgt gcgtggtggt ggacgtgagc cacgaagacc ccgaggtcaa gttcaactgg 480

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 540

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 600

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 660

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 720

ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 780

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 840

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 900

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 960

cagaagagcc tctccctgtc tccggggt 987

<210> 68

<211> 412

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 68

atcccaccgc acgttcagaa gtcggttaat aacgacatga tagtcactga caacaacggt 60

gcagtcaagt ttccacaact gtgtaaattt tgtgatgtga gattttccac ctgtgacaac 120

cagaaatcct gcatgagcaa ctgcagcatc acctccatct gtgagaagcc acaggaagtc 180

tgtgtggctg tatggagaaa gaatgacgag aacataacac tagagacagt ttgccatgac 240

cccaagctcc cctaccatga ctttattctg gaagatgctg cttctccaaa gtgcattatg 300

aaggaaaaaa aaaagcctgg tgagactttc ttcatgtgtt cctgtagctc tgatgagtgc 360

aatgacaaca tcatcttctc agaagaatat aacaccagca atcctgacta aa 412

<210> 69

<211> 376

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 69

atcccaccgc acgttaacaa cggtgcagtc aagtttccac aactgtgtaa attttgtgat 60

gtgagatttt ccacctgtga caaccagaaa tcctgcatga gcaactgcag catcacctcc 120

atctgtgaga agccacagga agtctgtgtg gctgtatgga gaaagaatga cgagaacata 180

acactagaga cagtttgcca tgaccccaag ctcccctacc atgactttat tctggaagat 240

gctgcttctc caaagtgcat tatgaaggaa aaaaaaaagc ctggtgagac tttcttcatg 300

tgttcctgta gctctgatga gtgcaatgac aacatcatct tctcagaaga atataacacc 360

agcaatcctg actaaa 376

<210> 70

<211> 370

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 70

atcccaccgc acgttggtgc agtcaagttt ccacaactgt gtaaattttg tgatgtgaga 60

ttttccacct gtgacaacca gaaatcctgc atgagcaact gcagcatcac ctccatctgt 120

gagaagccac aggaagtctg tgtggctgta tggagaaaga atgacgagaa cataacacta 180

gagacagttt gccatgaccc caagctcccc taccatgact ttattctgga agatgctgct 240

tctccaaagt gcattatgaa ggaaaaaaaa aagcctggtg agactttctt catgtgttcc 300

tgtagctctg atgagtgcaa tgacaacatc atcttctcag aagaatataa caccagcaat 360

cctgactaaa 370

<210> 71

<211> 364

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 71

atcccaccgc acgttgtcaa gtttccacaa ctgtgtaaat tttgtgatgt gagattttcc 60

acctgtgaca accagaaatc ctgcatgagc aactgcagca tcacctccat ctgtgagaag 120

ccacaggaag tctgtgtggc tgtatggaga aagaatgacg agaacataac actagagaca 180

gtttgccatg accccaagct cccctaccat gactttattc tggaagatgc tgcttctcca 240

aagtgcatta tgaaggaaaa aaaaaagcct ggtgagactt tcttcatgtg ttcctgtagc 300

tctgatgagt gcaatgacaa catcatcttc tcagaagaat ataacaccag caatcctgac 360

taaa 364

<210> 72

<211> 352

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 72

atcccaccgc acgttcaact gtgtaaattt tgtgatgtga gattttccac ctgtgacaac 60

cagaaatcct gcatgagcaa ctgcagcatc acctccatct gtgagaagcc acaggaagtc 120

tgtgtggctg tatggagaaa gaatgacgag aacataacac tagagacagt ttgccatgac 180

cccaagctcc cctaccatga ctttattctg gaagatgctg cttctccaaa gtgcattatg 240

aaggaaaaaa aaaagcctgg tgagactttc ttcatgtgtt cctgtagctc tgatgagtgc 300

aatgacaaca tcatcttctc agaagaatat aacaccagca atcctgacta aa 352

<210> 73

<211> 349

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 73

atcccaccgc acgttctgtg taaattttgt gatgtgagat tttccacctg tgacaaccag 60

aaatcctgca tgagcaactg cagcatcacc tccatctgtg agaagccaca ggaagtctgt 120

gtggctgtat ggagaaagaa tgacgagaac ataacactag agacagtttg ccatgacccc 180

aagctcccct accatgactt tattctggaa gatgctgctt ctccaaagtg cattatgaag 240

gaaaaaaaaa agcctggtga gactttcttc atgtgttcct gtagctctga tgagtgcaat 300

gacaacatca tcttctcaga agaatataac accagcaatc ctgactaaa 349

<210> 74

<211> 346

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 74

atcccaccgc acgtttgtaa attttgtgat gtgagatttt ccacctgtga caaccagaaa 60

tcctgcatga gcaactgcag catcacctcc atctgtgaga agccacagga agtctgtgtg 120

gctgtatgga gaaagaatga cgagaacata acactagaga cagtttgcca tgaccccaag 180

ctcccctacc atgactttat tctggaagat gctgcttctc caaagtgcat tatgaaggaa 240

aaaaaaaagc ctggtgagac tttcttcatg tgttcctgta gctctgatga gtgcaatgac 300

aacatcatct tctcagaaga atataacacc agcaatcctg actaaa 346

<210> 75

<211> 352

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 75

atcccaccgc acgttcagct gtgtaaattt tgtgatgtga gattttccac ctgtgacaac 60

cagaaatcct gcatgagcaa ctgcagcatc acctccatct gtgagaagcc acaggaagtc 120

tgtgtggctg tatggagaaa gaatgacgag aacataacac tagagacagt ttgccatgac 180

cccaagctcc cctaccatga ctttattctg gaagatgctg cttctccaaa gtgcattatg 240

aaggaaaaaa aaaagcctgg tgagactttc ttcatgtgtt cctgtagctc tgatgagtgc 300

aatgacaaca tcatcttctc agaagaatat aacaccagca atcctgacta aa 352

<210> 76

<211> 346

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 76

atcccaccgc acctgtgtaa attttgtgat gtgagatttt ccacctgtga caaccagaaa 60

tcctgcatga gcaactgcag catcacctcc atctgtgaga agccacagga agtctgtgtg 120

gctgtatgga gaaagaatga cgagaacata acactagaga cagtttgcca tgaccccaag 180

ctcccctacc atgactttat tctggaagat gctgcttctc caaagtgcat tatgaaggaa 240

aaaaaaaagc ctggtgagac tttcttcatg tgttcctgta gctctgatga gtgcaatgac 300

aacatcatct tctcagaaga atataacacc agcaatcctg actaaa 346

<210> 77

<211> 343

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 77

atcccaccgc tgtgtaaatt ttgtgatgtg agattttcca cctgtgacaa ccagaaatcc 60

tgcatgagca actgcagcat cacctccatc tgtgagaagc cacaggaagt ctgtgtggct 120

gtatggagaa agaatgacga gaacataaca ctagagacag tttgccatga ccccaagctc 180

ccctaccatg actttattct ggaagatgct gcttctccaa agtgcattat gaaggaaaaa 240

aaaaagcctg gtgagacttt cttcatgtgt tcctgtagct ctgatgagtg caatgacaac 300

atcatcttct cagaagaata taacaccagc aatcctgact aaa 343

<210> 78

<211> 340

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 78

atcccactgt gtaaattttg tgatgtgaga ttttccacct gtgacaacca gaaatcctgc 60

atgagcaact gcagcatcac ctccatctgt gagaagccac aggaagtctg tgtggctgta 120

tggagaaaga atgacgagaa cataacacta gagacagttt gccatgaccc caagctcccc 180

taccatgact ttattctgga agatgctgct tctccaaagt gcattatgaa ggaaaaaaaa 240

aagcctggtg agactttctt catgtgttcc tgtagctctg atgagtgcaa tgacaacatc 300

atcttctcag aagaatataa caccagcaat cctgactaaa 340

<210> 79

<211> 337

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 79

atcctgtgta aattttgtga tgtgagattt tccacctgtg acaaccagaa atcctgcatg 60

agcaactgca gcatcacctc catctgtgag aagccacagg aagtctgtgt ggctgtatgg 120

agaaagaatg acgagaacat aacactagag acagtttgcc atgaccccaa gctcccctac 180

catgacttta ttctggaaga tgctgcttct ccaaagtgca ttatgaagga aaaaaaaaag 240

cctggtgaga ctttcttcat gtgttcctgt agctctgatg agtgcaatga caacatcatc 300

ttctcagaag aatataacac cagcaatcct gactaaa 337

<210> 80

<211> 346

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 80

ccaccgcacg ttctgtgtaa attttgtgat gtgagatttt ccacctgtga caaccagaaa 60

tcctgcatga gcaactgcag catcacctcc atctgtgaga agccacagga agtctgtgtg 120

gctgtatgga gaaagaatga cgagaacata acactagaga cagtttgcca tgaccccaag 180

ctcccctacc atgactttat tctggaagat gctgcttctc caaagtgcat tatgaaggaa 240

aaaaaaaagc ctggtgagac tttcttcatg tgttcctgta gctctgatga gtgcaatgac 300

aacatcatct tctcagaaga atataacacc agcaatcctg actaaa 346

<210> 81

<211> 343

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 81

ccgcacgttc tgtgtaaatt ttgtgatgtg agattttcca cctgtgacaa ccagaaatcc 60

tgcatgagca actgcagcat cacctccatc tgtgagaagc cacaggaagt ctgtgtggct 120

gtatggagaa agaatgacga gaacataaca ctagagacag tttgccatga ccccaagctc 180

ccctaccatg actttattct ggaagatgct gcttctccaa agtgcattat gaaggaaaaa 240

aaaaagcctg gtgagacttt cttcatgtgt tcctgtagct ctgatgagtg caatgacaac 300

atcatcttct cagaagaata taacaccagc aatcctgact aaa 343

<210> 82

<211> 340

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 82

cacgttctgt gtaaattttg tgatgtgaga ttttccacct gtgacaacca gaaatcctgc 60

atgagcaact gcagcatcac ctccatctgt gagaagccac aggaagtctg tgtggctgta 120

tggagaaaga atgacgagaa cataacacta gagacagttt gccatgaccc caagctcccc 180

taccatgact ttattctgga agatgctgct tctccaaagt gcattatgaa ggaaaaaaaa 240

aagcctggtg agactttctt catgtgttcc tgtagctctg atgagtgcaa tgacaacatc 300

atcttctcag aagaatataa caccagcaat cctgactaaa 340

<210> 83

<211> 337

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 83

gttctgtgta aattttgtga tgtgagattt tccacctgtg acaaccagaa atcctgcatg 60

agcaactgca gcatcacctc catctgtgag aagccacagg aagtctgtgt ggctgtatgg 120

agaaagaatg acgagaacat aacactagag acagtttgcc atgaccccaa gctcccctac 180

catgacttta ttctggaaga tgctgcttct ccaaagtgca ttatgaagga aaaaaaaaag 240

cctggtgaga ctttcttcat gtgttcctgt agctctgatg agtgcaatga caacatcatc 300

ttctcagaag aatataacac cagcaatcct gactaaa 337

<210> 84

<211> 355

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 84

ggtgcagtca agtttccaca actgtgtaaa ttttgtgatg tgagattttc cacctgtgac 60

aaccagaaat cctgcatgag caactgcagc atcacctcca tctgtgagaa gccacaggaa 120

gtctgtgtgg ctgtatggag aaagaatgac gagaacataa cactagagac agtttgccat 180

gaccccaagc tcccctacca tgactttatt ctggaagatg ctgcttctcc aaagtgcatt 240

atgaaggaaa aaaaaaagcc tggtgagact ttcttcatgt gttcctgtag ctctgatgag 300

tgcaatgaca acatcatctt ctcagaagaa tataacacca gcaatcctga ctaaa 355

<210> 85

<211> 349

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 85

gtcaagtttc cacaactgtg taaattttgt gatgtgagat tttccacctg tgacaaccag 60

aaatcctgca tgagcaactg cagcatcacc tccatctgtg agaagccaca ggaagtctgt 120

gtggctgtat ggagaaagaa tgacgagaac ataacactag agacagtttg ccatgacccc 180

aagctcccct accatgactt tattctggaa gatgctgctt ctccaaagtg cattatgaag 240

gaaaaaaaaa agcctggtga gactttcttc atgtgttcct gtagctctga tgagtgcaat 300

gacaacatca tcttctcaga agaatataac accagcaatc ctgactaaa 349

<210> 86

<211> 334

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 86

ctgtgtaaat tttgtgatgt gagatttcc acctgtgaca accagaaatc ctgcatgagc 60

aactgcagca tcacctccat ctgtgagaag ccacaggaag tctgtgtggc tgtatggaga 120

aagaatgacg agaacataac actagagaca gtttgccatg accccaagct cccctaccat 180

gactttattc tggaagatgc tgcttctcca aagtgcatta tgaaggaaaa aaaaaagcct 240

ggtgagactt tcttcatgtg ttcctgtagc tctgatgagt gcaatgacaa catcatcttc 300

tcagaagaat ataacaccag caatcctgac taaa 334

<210> 87

<211> 60

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 87

ggtggtggcg gttcaggcgg aggtggctct ggaggtggag gttcaggagg tggtggttct 60

<210> 88

<211> 623

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 88

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Gln Lys Ser Val

485 490 495

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

500 505 510

Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln

515 520 525

Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro

530 535 540

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

545 550 555 560

Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile

565 570 575

Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys

580 585 590

Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn

595 600 605

Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

610 615 620

<210> 89

<211> 611

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 89

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Asn Asn Gly Ala

485 490 495

Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr

500 505 510

Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile

515 520 525

Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp

530 535 540

Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr

545 550 555 560

His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys

565 570 575

Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser

580 585 590

Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser

595 600 605

Asn Pro Asp

610

<210> 90

<211> 609

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 90

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Gly Ala Val Lys

485 490 495

Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp

500 505 510

Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu

515 520 525

Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn

530 535 540

Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp

545 550 555 560

Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys

565 570 575

Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu

580 585 590

Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro

595 600 605

Asp

<210> 91

<211> 607

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 91

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Val Lys Phe Pro

485 490 495

Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln

500 505 510

Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro

515 520 525

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

530 535 540

Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile

545 550 555 560

Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys

565 570 575

Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn

580 585 590

Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600 605

<210> 92

<211> 603

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 92

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Gln Leu Cys Lys

485 490 495

Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met

500 505 510

Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys

515 520 525

Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val

530 535 540

Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala

545 550 555 560

Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr

565 570 575

Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile

580 585 590

Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 93

<211> 602

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 93

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Leu Cys Lys Phe

485 490 495

Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser

500 505 510

Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val

515 520 525

Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys

530 535 540

His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala

545 550 555 560

Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe

565 570 575

Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe

580 585 590

Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 94

<211> 601

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 94

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Cys Lys Phe Cys

485 490 495

Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn

500 505 510

Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala

515 520 525

Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His

530 535 540

Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser

545 550 555 560

Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe

565 570 575

Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser

580 585 590

Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 95

<211> 603

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 95

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Gln Leu Cys Lys

485 490 495

Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met

500 505 510

Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys

515 520 525

Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val

530 535 540

Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala

545 550 555 560

Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr

565 570 575

Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile

580 585 590

Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 96

<211> 601

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 96

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Leu Cys Lys Phe Cys

485 490 495

Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn

500 505 510

Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala

515 520 525

Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His

530 535 540

Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser

545 550 555 560

Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe

565 570 575

Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser

580 585 590

Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 97

<211> 600

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 97

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro Leu Cys Lys Phe Cys Asp

485 490 495

Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys

500 505 510

Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val

515 520 525

Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp

530 535 540

Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro

545 550 555 560

Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met

565 570 575

Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu

580 585 590

Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 98

<211> 599

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 98

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Leu Cys Lys Phe Cys Asp Val

485 490 495

Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser

500 505 510

Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp

515 520 525

Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro

530 535 540

Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys

545 550 555 560

Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys

565 570 575

Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu

580 585 590

Tyr Asn Thr Ser Asn Pro Asp

595

<210> 99

<211> 598

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 99

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Leu Cys Lys Phe Cys Asp Val Arg

485 490 495

Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile

500 505 510

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

515 520 525

Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys

530 535 540

Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys

545 550 555 560

Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser

565 570 575

Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr

580 585 590

Asn Thr Ser Asn Pro Asp

595

<210> 100

<211> 601

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 100

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Pro Pro His Val Leu Cys Lys Phe Cys

485 490 495

Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn

500 505 510

Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala

515 520 525

Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His

530 535 540

Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser

545 550 555 560

Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe

565 570 575

Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser

580 585 590

Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 101

<211> 600

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 101

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Pro His Val Leu Cys Lys Phe Cys Asp

485 490 495

Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys

500 505 510

Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val

515 520 525

Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp

530 535 540

Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro

545 550 555 560

Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met

565 570 575

Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu

580 585 590

Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 102

<211> 599

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 102

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser His Val Leu Cys Lys Phe Cys Asp Val

485 490 495

Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser

500 505 510

Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp

515 520 525

Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro

530 535 540

Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys

545 550 555 560

Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys

565 570 575

Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu

580 585 590

Tyr Asn Thr Ser Asn Pro Asp

595

<210> 103

<211> 598

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 103

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Val Leu Cys Lys Phe Cys Asp Val Arg

485 490 495

Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile

500 505 510

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

515 520 525

Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys

530 535 540

Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys

545 550 555 560

Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser

565 570 575

Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr

580 585 590

Asn Thr Ser Asn Pro Asp

595

<210> 104

<211> 604

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 104

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Gly Ala Val Lys Phe Pro Gln Leu Cys

485 490 495

Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys

500 505 510

Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val

515 520 525

Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr

530 535 540

Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp

545 550 555 560

Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu

565 570 575

Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile

580 585 590

Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 105

<211> 602

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 105

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Val Lys Phe Pro Gln Leu Cys Lys Phe

485 490 495

Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser

500 505 510

Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val

515 520 525

Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys

530 535 540

His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala

545 550 555 560

Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe

565 570 575

Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe

580 585 590

Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 106

<211> 597

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 106

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

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

20 25 30

Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe

35 40 45

Thr Thr Tyr Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Ile Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Leu Cys Lys Phe Cys Asp Val Arg Phe

485 490 495

Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr

500 505 510

Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys

515 520 525

Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu

530 535 540

Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile

545 550 555 560

Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys

565 570 575

Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn

580 585 590

Thr Ser Asn Pro Asp

595

<210> 107

<211> 1873

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 107

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccaccg cacgttcaga agtcggttaa taacgacatg 1500

atagtcactg acaacaacgg tgcagtcaag tttccacaac tgtgtaaatt ttgtgatgtg 1560

agattttcca cctgtgacaa ccagaaatcc tgcatgagca actgcagcat cacctccatc 1620

tgtgagaagc cacaggaagt ctgtgtggct gtatggagaa agaatgacga gaacataaca 1680

ctagagacag tttgccatga ccccaagctc ccctaccatg actttattct ggaagatgct 1740

gcttctccaa agtgcattat gaaggaaaaa aaaaagcctg gtgagacttt cttcatgtgt 1800

tcctgtagct ctgatgagtg caatgacaac atcatcttct cagaagaata taacaccagc 1860

aatcctgact aaa 1873

<210> 108

<211> 1837

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 108

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccaccg cacgttaaca acggtgcagt caagtttcca 1500

caactgtgta aattttgtga tgtgagattt tccacctgtg acaaccagaa atcctgcatg 1560

agcaactgca gcatcacctc catctgtgag aagccacagg aagtctgtgt ggctgtatgg 1620

agaaagaatg acgagaacat aacactagag acagtttgcc atgaccccaa gctcccctac 1680

catgacttta ttctggaaga tgctgcttct ccaaagtgca ttatgaagga aaaaaaaaag 1740

cctggtgaga ctttcttcat gtgttcctgt agctctgatg agtgcaatga caacatcatc 1800

ttctcagaag aatataacac cagcaatcct gactaaa 1837

<210> 109

<211> 1831

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 109

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccaccg cacgttggtg cagtcaagtt tccacaactg 1500

tgtaaatttt gtgatgtgag attttccacc tgtgacaacc agaaatcctg catgagcaac 1560

tgcagcatca cctccatctg tgagaagcca caggaagtct gtgtggctgt atggagaaag 1620

aatgacgaga acataacact agagacagtt tgccatgacc ccaagctccc ctaccatgac 1680

tttattctgg aagatgctgc ttctccaaag tgcattatga aggaaaaaaa aaagcctggt 1740

gagactttct tcatgtgttc ctgtagctct gatgagtgca atgacaacat catcttctca 1800

gaagaatata acaccagcaa tcctgactaa a 1831

<210> 110

<211> 1825

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 110

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccaccg cacgttgtca agtttccaca actgtgtaaa 1500

ttttgtgatg tgagattttc cacctgtgac aaccagaaat cctgcatgag caactgcagc 1560

atcacctcca tctgtgagaa gccacaggaa gtctgtgtgg ctgtatggag aaagaatgac 1620

gagaacataa cactagagac agtttgccat gaccccaagc tcccctacca tgactttatt 1680

ctggaagatg ctgcttctcc aaagtgcatt atgaaggaaa aaaaaaagcc tggtgagact 1740

ttcttcatgt gttcctgtag ctctgatgag tgcaatgaca acatcatctt ctcagaagaa 1800

tataacacca gcaatcctga ctaaa 1825

<210> 111

<211> 1813

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 111

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccaccg cacgttcaac tgtgtaaatt ttgtgatgtg 1500

agattttcca cctgtgacaa ccagaaatcc tgcatgagca actgcagcat cacctccatc 1560

tgtgagaagc cacaggaagt ctgtgtggct gtatggagaa agaatgacga gaacataaca 1620

ctagagacag tttgccatga ccccaagctc ccctaccatg actttattct ggaagatgct 1680

gcttctccaa agtgcattat gaaggaaaaa aaaaagcctg gtgagacttt cttcatgtgt 1740

tcctgtagct ctgatgagtg caatgacaac atcatcttct cagaagaata taacaccagc 1800

aatcctgact aaa 1813

<210> 112

<211> 1810

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 112

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccaccg cacgttctgt gtaaattttg tgatgtgaga 1500

ttttccacct gtgacaacca gaaatcctgc atgagcaact gcagcatcac ctccatctgt 1560

gagaagccac aggaagtctg tgtggctgta tggagaaaga atgacgagaa cataacacta 1620

gagacagttt gccatgaccc caagctcccc taccatgact ttattctgga agatgctgct 1680

tctccaaagt gcattatgaa ggaaaaaaaa aagcctggtg agactttctt catgtgttcc 1740

tgtagctctg atgagtgcaa tgacaacatc atcttctcag aagaatataa caccagcaat 1800

cctgactaaa 1810

<210> 113

<211> 1807

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 113

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccaccg cacgtttgta aattttgtga tgtgagattt 1500

tccacctgtg acaaccagaa atcctgcatg agcaactgca gcatcacctc catctgtgag 1560

aagccacagg aagtctgtgt ggctgtatgg agaaagaatg acgagaacat aacactagag 1620

acagtttgcc atgaccccaa gctccctac catgacttta ttctggaaga tgctgcttct 1680

ccaaagtgca ttatgaagga aaaaaaaaag cctggtgaga ctttcttcat gtgttcctgt 1740

agctctgatg agtgcaatga caacatcatc ttctcagaag aatataacac cagcaatcct 1800

gactaaa 1807

<210> 114

<211> 1813

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 114

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccaccg cacgttcagc tgtgtaaatt ttgtgatgtg 1500

agattttcca cctgtgacaa ccagaaatcc tgcatgagca actgcagcat cacctccatc 1560

tgtgagaagc cacaggaagt ctgtgtggct gtatggagaa agaatgacga gaacataaca 1620

ctagagacag tttgccatga ccccaagctc ccctaccatg actttattct ggaagatgct 1680

gcttctccaa agtgcattat gaaggaaaaa aaaaagcctg gtgagacttt cttcatgtgt 1740

tcctgtagct ctgatgagtg caatgacaac atcatcttct cagaagaata taacaccagc 1800

aatcctgact aaa 1813

<210> 115

<211> 1807

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 115

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccaccg cacctgtgta aattttgtga tgtgagattt 1500

tccacctgtg acaaccagaa atcctgcatg agcaactgca gcatcacctc catctgtgag 1560

aagccacagg aagtctgtgt ggctgtatgg agaaagaatg acgagaacat aacactagag 1620

acagtttgcc atgaccccaa gctccctac catgacttta ttctggaaga tgctgcttct 1680

ccaaagtgca ttatgaagga aaaaaaaaag cctggtgaga ctttcttcat gtgttcctgt 1740

agctctgatg agtgcaatga caacatcatc ttctcagaag aatataacac cagcaatcct 1800

gactaaa 1807

<210> 116

<211> 1804

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 116

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccaccg ctgtgtaaat tttgtgatgt gagattttcc 1500

acctgtgaca accagaaatc ctgcatgagc aactgcagca tcacctccat ctgtgagaag 1560

ccacaggaag tctgtgtggc tgtatggaga aagaatgacg agaacataac actagagaca 1620

gtttgccatg accccaagct cccctaccat gactttattc tggaagatgc tgcttctcca 1680

aagtgcatta tgaaggaaaa aaaaaagcct ggtgagactt tcttcatgtg ttcctgtagc 1740

tctgatgagt gcaatgacaa catcatcttc tcagaagaat ataacaccag caatcctgac 1800

taaa 1804

<210> 117

<211> 1801

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 117

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcccactg tgtaaatttt gtgatgtgag attttccacc 1500

tgtgacaacc agaaatcctg catgagcaac tgcagcatca cctccatctg tgagaagcca 1560

caggaagtct gtgtggctgt atggagaaag aatgacgaga acataacact agagacagtt 1620

tgccatgacc ccaagctccc ctaccatgac tttattctgg aagatgctgc ttctccaaag 1680

tgcattatga aggaaaaaaa aaagcctggt gagactttct tcatgtgttc ctgtagctct 1740

gatgagtgca atgacaacat catcttctca gaagaatata acaccagcaa tcctgactaa 1800

a 1801

<210> 118

<211> 1798

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 118

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tatcctgtgt aaattttgtg atgtgagatt ttccacctgt 1500

gacaaccaga aatcctgcat gagcaactgc agcatcacct ccatctgtga gaagccacag 1560

gaagtctgtg tggctgtatg gagaaagaat gacgagaaca taacactaga gacagtttgc 1620

catgacccca agctccccta ccatgacttt attctggaag atgctgcttc tccaaagtgc 1680

attatgaagg aaaaaaaaaa gcctggtgag actttcttca tgtgttcctg tagctctgat 1740

gagtgcaatg acaacatcat cttctcagaa gaatataaca ccagcaatcc tgactaaa 1798

<210> 119

<211> 1807

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 119

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tccaccgcac gttctgtgta aattttgtga tgtgagattt 1500

tccacctgtg acaaccagaa atcctgcatg agcaactgca gcatcacctc catctgtgag 1560

aagccacagg aagtctgtgt ggctgtatgg agaaagaatg acgagaacat aacactagag 1620

acagtttgcc atgaccccaa gctccctac catgacttta ttctggaaga tgctgcttct 1680

ccaaagtgca ttatgaagga aaaaaaaaag cctggtgaga ctttcttcat gtgttcctgt 1740

agctctgatg agtgcaatga caacatcatc ttctcagaag aatataacac cagcaatcct 1800

gactaaa 1807

<210> 120

<211> 1804

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 120

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tccgcacgtt ctgtgtaaat tttgtgatgt gagatttcc 1500

acctgtgaca accagaaatc ctgcatgagc aactgcagca tcacctccat ctgtgagaag 1560

ccacaggaag tctgtgtggc tgtatggaga aagaatgacg agaacataac actagagaca 1620

gtttgccatg accccaagct cccctaccat gactttattc tggaagatgc tgcttctcca 1680

aagtgcatta tgaaggaaaa aaaaaagcct ggtgagactt tcttcatgtg ttcctgtagc 1740

tctgatgagt gcaatgacaa catcatcttc tcagaagaat ataacaccag caatcctgac 1800

taaa 1804

<210> 121

<211> 1801

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 121

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tcacgttctg tgtaaatttt gtgatgtgag attttccacc 1500

tgtgacaacc agaaatcctg catgagcaac tgcagcatca cctccatctg tgagaagcca 1560

caggaagtct gtgtggctgt atggagaaag aatgacgaga acataacact agagacagtt 1620

tgccatgacc ccaagctccc ctaccatgac tttattctgg aagatgctgc ttctccaaag 1680

tgcattatga aggaaaaaaa aaagcctggt gagactttct tcatgtgttc ctgtagctct 1740

gatgagtgca atgacaacat catcttctca gaagaatata acaccagcaa tcctgactaa 1800

a 1801

<210> 122

<211> 1798

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 122

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tgttctgtgt aaattttgtg atgtgagatt ttccacctgt 1500

gacaaccaga aatcctgcat gagcaactgc agcatcacct ccatctgtga gaagccacag 1560

gaagtctgtg tggctgtatg gagaaagaat gacgagaaca taacactaga gacagtttgc 1620

catgacccca agctccccta ccatgacttt attctggaag atgctgcttc tccaaagtgc 1680

attatgaagg aaaaaaaaaa gcctggtgag actttcttca tgtgttcctg tagctctgat 1740

gagtgcaatg acaacatcat cttctcagaa gaatataaca ccagcaatcc tgactaaa 1798

<210> 123

<211> 1816

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 123

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tggtgcagtc aagtttccac aactgtgtaa attttgtgat 1500

gtgagatttt ccacctgtga caaccagaaa tcctgcatga gcaactgcag catcacctcc 1560

atctgtgaga agccacagga agtctgtgtg gctgtatgga gaaagaatga cgagaacata 1620

acactagaga cagtttgcca tgaccccaag ctcccctacc atgactttat tctggaagat 1680

gctgcttctc caaagtgcat tatgaaggaa aaaaaaaagc ctggtgagac tttcttcatg 1740

tgttcctgta gctctgatga gtgcaatgac aacatcatct tctcagaaga atataacacc 1800

agcaatcctg actaaa 1816

<210> 124

<211> 1810

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 124

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tgtcaagttt ccacaactgt gtaaattttg tgatgtgaga 1500

ttttccacct gtgacaacca gaaatcctgc atgagcaact gcagcatcac ctccatctgt 1560

gagaagccac aggaagtctg tgtggctgta tggagaaaga atgacgagaa cataacacta 1620

gagacagttt gccatgaccc caagctcccc taccatgact ttattctgga agatgctgct 1680

tctccaaagt gcattatgaa ggaaaaaaaa aagcctggtg agactttctt catgtgttcc 1740

tgtagctctg atgagtgcaa tgacaacatc atcttctcag aagaatataa caccagcaat 1800

cctgactaaa 1810

<210> 125

<211> 1795

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 125

atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagtgag 60

gtccaacttg tccagtctgg agcagaggtg aagaagcctg gagccacagt gaagatttcc 120

tgtaaggtgt ctggctacac cttcaccacc tactacaccc actgggtgaa gcaggctcct 180

ggcaagggat tggagtggat tggctggatt taccctggag atgtgaacac caaatacaat 240

gagaagttca agggcagggt gaccctgaca gcagacacca gcacagacac agcctatatg 300

gaactgtcct ccctgaggtc tgaggacaca gcagtctact actgtgccag ggaggaccct 360

ggcagcaact actttgacta ctggggacaa ggcaccctgg tgacagtgtc cagcgcaagc 420

accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct 720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca 780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 840

acgtgcgtgg tggtggacgt gagccacgaa gaccccgagg tcaagttcaa ctggtacgtg 900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1260

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1380

agcctctccc tgtctccggg tggtggtggc ggttcaggcg gaggtggctc tggaggtgga 1440

ggttcaggag gtggtggttc tctgtgtaaa ttttgtgatg tgagattttc cacctgtgac 1500

aaccagaaat cctgcatgag caactgcagc atcacctcca tctgtgagaa gccacaggaa 1560

gtctgtgtgg ctgtatggag aaagaatgac gagaacataa cactagagac agtttgccat 1620

gaccccaagc tcccctacca tgactttatt ctggaagatg ctgcttctcc aaagtgcatt 1680

atgaaggaaa aaaaaaagcc tggtgagact ttcttcatgt gttcctgtag ctctgatgag 1740

tgcaatgaca acatcatctt ctcagaagaa tataacacca gcaatcctga ctaaa 1795

<210> 126

<211> 233

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 126

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala

20 25 30

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val

35 40 45

Asn Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

50 55 60

Leu Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg

65 70 75 80

Phe Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

85 90 95

Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr

100 105 110

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

115 120 125

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

130 135 140

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

145 150 155 160

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

165 170 175

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

180 185 190

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

195 200 205

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

210 215 220

Thr Lys Ser Phe Asn Arg Gly Glu Cys

225 230

<210> 127

<211> 624

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 127

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

20 25 30

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

35 40 45

Lys Asp Thr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala

65 70 75 80

Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn

85 90 95

Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr

115 120 125

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly

130 135 140

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly

145 150 155 160

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val

165 170 175

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe

180 185 190

Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

195 200 205

Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val

210 215 220

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys

225 230 235 240

Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu

245 250 255

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

260 265 270

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

275 280 285

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

290 295 300

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

305 310 315 320

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

325 330 335

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

340 345 350

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

355 360 365

Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln

370 375 380

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

385 390 395 400

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

405 410 415

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

420 425 430

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

435 440 445

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

450 455 460

Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

465 470 475 480

Gly Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Gln Lys Ser

485 490 495

Val Asn Asn Asp Met Ile Val Thr Asp Asn Asn Gly Ala Val Lys Phe

500 505 510

Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn

515 520 525

Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys

530 535 540

Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile

545 550 555 560

Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe

565 570 575

Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys

580 585 590

Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys

595 600 605

Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

610 615 620

<210> 128

<211> 603

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 128

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

20 25 30

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

35 40 45

Lys Asp Thr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala

65 70 75 80

Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn

85 90 95

Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr

115 120 125

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly

130 135 140

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly

145 150 155 160

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val

165 170 175

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe

180 185 190

Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

195 200 205

Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val

210 215 220

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys

225 230 235 240

Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu

245 250 255

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

260 265 270

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

275 280 285

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

290 295 300

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

305 310 315 320

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

325 330 335

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

340 345 350

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

355 360 365

Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln

370 375 380

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

385 390 395 400

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

405 410 415

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

420 425 430

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

435 440 445

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

450 455 460

Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

465 470 475 480

Gly Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Leu Cys Lys

485 490 495

Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met

500 505 510

Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys

515 520 525

Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val

530 535 540

Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala

545 550 555 560

Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr

565 570 575

Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile

580 585 590

Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 129

<211> 233

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 129

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala

20 25 30

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Ser Ala Ser Gln Asp Ile

35 40 45

Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

50 55 60

Val Leu Ile Tyr Phe Thr Ser Ser Leu His Ser Gly Val Pro Ser Arg

65 70 75 80

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

85 90 95

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

100 105 110

Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr

115 120 125

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

130 135 140

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

145 150 155 160

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

165 170 175

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

180 185 190

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

195 200 205

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

210 215 220

Thr Lys Ser Phe Asn Arg Gly Glu Cys

225 230

<210> 130

<211> 627

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 130

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

20 25 30

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Phe

35 40 45

Thr Asn Tyr Gly Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Val Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala

65 70 75 80

Ala Asp Phe Lys Arg Arg Phe Thr Phe Ser Leu Asp Thr Ser Lys Ser

85 90 95

Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Lys Tyr Pro His Tyr Tyr Gly Ser Ser His Trp Tyr

115 120 125

Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser

130 135 140

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

145 150 155 160

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

165 170 175

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

180 185 190

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

195 200 205

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

210 215 220

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val

225 230 235 240

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

245 250 255

Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro

260 265 270

Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val

275 280 285

Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val

290 295 300

Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln

305 310 315 320

Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln

325 330 335

Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala

340 345 350

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

355 360 365

Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr

370 375 380

Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser

385 390 395 400

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr

405 410 415

Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

420 425 430

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe

435 440 445

Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys

450 455 460

Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly

465 470 475 480

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val

485 490 495

Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr Asp Asn Asn Gly Ala

500 505 510

Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr

515 520 525

Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile

530 535 540

Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp

545 550 555 560

Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr

565 570 575

His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys

580 585 590

Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser

595 600 605

Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser

610 615 620

Asn Pro Asp

625

<210> 131

<211> 606

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 131

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln

20 25 30

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Phe

35 40 45

Thr Asn Tyr Gly Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Val Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala

65 70 75 80

Ala Asp Phe Lys Arg Arg Phe Thr Phe Ser Leu Asp Thr Ser Lys Ser

85 90 95

Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Lys Tyr Pro His Tyr Tyr Gly Ser Ser His Trp Tyr

115 120 125

Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser

130 135 140

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

145 150 155 160

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

165 170 175

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

180 185 190

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

195 200 205

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

210 215 220

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val

225 230 235 240

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

245 250 255

Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro

260 265 270

Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val

275 280 285

Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val

290 295 300

Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln

305 310 315 320

Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln

325 330 335

Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala

340 345 350

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

355 360 365

Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr

370 375 380

Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser

385 390 395 400

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr

405 410 415

Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

420 425 430

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe

435 440 445

Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys

450 455 460

Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly

465 470 475 480

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val

485 490 495

Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys

500 505 510

Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln

515 520 525

Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu

530 535 540

Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu

545 550 555 560

Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro

565 570 575

Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp

580 585 590

Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600 605

<210> 132

<211> 233

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 132

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala

20 25 30

Ser Ile Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile

35 40 45

Asp Asn Trp Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

50 55 60

Leu Leu Ile Tyr Asp Ala Ser Asn Leu Asp Thr Gly Val Pro Ser Arg

65 70 75 80

Phe Ser Gly Ser Gly Ser Gly Thr Tyr Phe Thr Leu Thr Ile Ser Ser

85 90 95

Leu Gln Ala Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Ala Lys Ala

100 105 110

Phe Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys Arg Thr

115 120 125

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

130 135 140

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

145 150 155 160

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

165 170 175

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

180 185 190

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

195 200 205

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

210 215 220

Thr Lys Ser Phe Asn Arg Gly Glu Cys

225 230

<210> 133

<211> 620

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 133

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Lys

20 25 30

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

35 40 45

Ser Ser Tyr Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Val Ser Ser Ile Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Ala

65 70 75 80

Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn

85 90 95

Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Val Thr Asp Ala Phe Asp Ile Trp Gly Gln Gly

115 120 125

Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

130 135 140

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

145 150 155 160

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

165 170 175

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

180 185 190

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

195 200 205

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

210 215 220

Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys

225 230 235 240

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

245 250 255

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

260 265 270

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

275 280 285

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

290 295 300

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

305 310 315 320

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

325 330 335

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

340 345 350

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

355 360 365

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr

370 375 380

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

385 390 395 400

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

405 410 415

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

420 425 430

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

435 440 445

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

450 455 460

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

465 470 475 480

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

485 490 495

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

500 505 510

Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys

515 520 525

Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val

530 535 540

Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr

545 550 555 560

Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp

565 570 575

Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu

580 585 590

Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile

595 600 605

Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

610 615 620

<210> 134

<211> 599

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 134

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Lys

20 25 30

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

35 40 45

Ser Ser Tyr Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Val Ser Ser Ile Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Ala

65 70 75 80

Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn

85 90 95

Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Val Thr Asp Ala Phe Asp Ile Trp Gly Gln Gly

115 120 125

Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

130 135 140

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

145 150 155 160

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

165 170 175

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

180 185 190

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

195 200 205

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

210 215 220

Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys

225 230 235 240

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

245 250 255

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

260 265 270

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

275 280 285

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

290 295 300

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

305 310 315 320

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

325 330 335

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

340 345 350

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

355 360 365

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr

370 375 380

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

385 390 395 400

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

405 410 415

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

420 425 430

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

435 440 445

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

450 455 460

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

465 470 475 480

Gly Gly Gly Ser Ile Pro Pro His Val Leu Cys Lys Phe Cys Asp Val

485 490 495

Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser

500 505 510

Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp

515 520 525

Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro

530 535 540

Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys

545 550 555 560

Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys

565 570 575

Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu

580 585 590

Tyr Asn Thr Ser Asn Pro Asp

595

<210> 135

<211> 234

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 135

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu

20 25 30

Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val

35 40 45

Gly Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro

50 55 60

Arg Leu Leu Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp

65 70 75 80

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

85 90 95

Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly

100 105 110

Ser Ser Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg

115 120 125

Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln

130 135 140

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr

145 150 155 160

Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser

165 170 175

Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr

180 185 190

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

195 200 205

His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro

210 215 220

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

225 230

<210> 136

<211> 622

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 136

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln

20 25 30

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

35 40 45

Ser Ser Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Val Thr Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala

65 70 75 80

Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn

85 90 95

Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile

100 105 110

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

115 120 125

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

130 135 140

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

145 150 155 160

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

165 170 175

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

180 185 190

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

195 200 205

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

210 215 220

Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys

225 230 235 240

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

245 250 255

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

260 265 270

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

275 280 285

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

290 295 300

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr

305 310 315 320

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

325 330 335

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

340 345 350

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val

355 360 365

Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser

370 375 380

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu

385 390 395 400

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

405 410 415

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

420 425 430

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

435 440 445

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

450 455 460

Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

465 470 475 480

Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Gln Lys Ser Val Asn

485 490 495

Asn Asp Met Ile Val Thr Asp Asn Asn Gly Ala Val Lys Phe Pro Gln

500 505 510

Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys

515 520 525

Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln

530 535 540

Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu

545 550 555 560

Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu

565 570 575

Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro

580 585 590

Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp

595 600 605

Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

610 615 620

<210> 137

<211> 601

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 137

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln

20 25 30

Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe

35 40 45

Ser Ser Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

50 55 60

Glu Trp Val Thr Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala

65 70 75 80

Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn

85 90 95

Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile

100 105 110

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

115 120 125

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

130 135 140

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

145 150 155 160

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

165 170 175

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

180 185 190

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

195 200 205

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

210 215 220

Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys

225 230 235 240

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

245 250 255

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

260 265 270

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

275 280 285

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

290 295 300

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr

305 310 315 320

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

325 330 335

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

340 345 350

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val

355 360 365

Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser

370 375 380

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu

385 390 395 400

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

405 410 415

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

420 425 430

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

435 440 445

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

450 455 460

Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

465 470 475 480

Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Leu Cys Lys Phe Cys

485 490 495

Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn

500 505 510

Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala

515 520 525

Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His

530 535 540

Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser

545 550 555 560

Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe

565 570 575

Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser

580 585 590

Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 138

<211> 233

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 138

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Asp Ile Gln Met Thr Gln Ser Pro Ala Ala Leu Ser Ala

20 25 30

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile

35 40 45

Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

50 55 60

Leu Leu Ile Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg

65 70 75 80

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser

85 90 95

Leu Gln Pro Glu Asp Ile Ala Thr Tyr Phe Cys Gln His Phe Asp His

100 105 110

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

115 120 125

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu

130 135 140

Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro

145 150 155 160

Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly

165 170 175

Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr

180 185 190

Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

195 200 205

Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

210 215 220

Thr Lys Ser Phe Asn Arg Gly Glu Cys

225 230

<210> 139

<211> 623

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 139

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

20 25 30

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val

35 40 45

Ser Ser Gly Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr

65 70 75 80

Asn Pro Ser Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys

85 90 95

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

100 105 110

Ile Tyr Tyr Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp

115 120 125

Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Gln Lys Ser Val

485 490 495

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

500 505 510

Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln

515 520 525

Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro

530 535 540

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

545 550 555 560

Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile

565 570 575

Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys

580 585 590

Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn

595 600 605

Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

610 615 620

<210> 140

<211> 602

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 140

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg

1 5 10 15

Val Leu Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

20 25 30

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val

35 40 45

Ser Ser Gly Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr

65 70 75 80

Asn Pro Ser Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys

85 90 95

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

100 105 110

Ile Tyr Tyr Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp

115 120 125

Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

130 135 140

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

145 150 155 160

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

165 170 175

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

180 185 190

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

195 200 205

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

210 215 220

His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser

225 230 235 240

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

245 250 255

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

260 265 270

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

275 280 285

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

290 295 300

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

305 310 315 320

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

325 330 335

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

340 345 350

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

355 360 365

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

370 375 380

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

385 390 395 400

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

405 410 415

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

420 425 430

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

435 440 445

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

450 455 460

Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

465 470 475 480

Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His Val Leu Cys Lys Phe

485 490 495

Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser

500 505 510

Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val

515 520 525

Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys

530 535 540

His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala

545 550 555 560

Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe

565 570 575

Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe

580 585 590

Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp

595 600

<210> 141

<211> 583

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 141

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Thr Tyr

20 25 30

Tyr Thr His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Trp Ile Tyr Pro Gly Asp Val Asn Thr Lys Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Arg Val Thr Leu Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Asp Pro Gly Ser Asn Tyr Phe Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

450 455 460

Gly Gly Gly Ser Ile Pro Pro His Val Leu Cys Lys Phe Cys Asp Val

465 470 475 480

Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser

485 490 495

Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp

500 505 510

Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro

515 520 525

Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys

530 535 540

Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys

545 550 555 560

Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu

565 570 575

Tyr Asn Thr Ser Asn Pro Asp

580

<210> 142

<211> 699

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 142

atgacagtgc tggcgccagc ctggagccca aattcctccc tgttgctgct gttgctgctg 60

ctgagtcctt gcctgcgggg gacacctgac tgttacttca gccacagtcc catctcctcc 120

aacttcaaag tgaagtttag agagttgact gaccacctgc ttaaagatta cccagtcact 180

gtggccgtca atcttcagga cgagaagcac tgcaaggcct tgtggagcct cttcctagcc 240

cagcgctgga tagagcaact gaagactgtg gcagggtcta agatgcaaac gcttctggag 300

gacgtcaaca ccgagataca ttttgtcacc tcatgtacct tccagcccct accagaatgt 360

ctgcgattcg tccagaccaa catctcccac ctcctgaagg acacctgcac acagctgctt 420

gctctgaagc cctgtatcgg gaaggcctgc cagaatttct ctcggtgcct ggaggtgcag 480

tgccagccgg actcctccac cctgctgccc ccaaggagtc ccatagccct agaagccacg 540

gagctcccag agcctcggcc caggcagctg ttgctcctgc tgctgctgct gctgcctctc 600

acactggtgc tgctggcagc cgcctggggc cttcgctggc aaagggcaag aaggagggg 660

gagctccacc ctggggtgcc cctcccctcc catccctaa 699

<210> 143

<211> 426

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 143

atgtggctgc agaatttact tttcctgggc attgtggtct acagcctctc agcacccacc 60

cgctcaccca tcactgtcac ccggccttgg aagcatgtag aggccatcaa agaagccctg 120

aacctcctgg atgacatgcc tgtcacgttg aatgaagagg tagaagtcgt ctctaacgag 180

ttctccttca agaagctaac atgtgtgcag acccgcctga agatattcga gcagggtcta 240

cggggcaatt tcaccaaact caagggcgcc ttgaacatga cagccagcta ctaccagaca 300

tactgccccc caactccgga aacggactgt gaaacacaag ttaccaccta tgcggatttc 360

atagacagcc ttaaaacctt tctgactgat atcccctttg aatgcaaaaa accaggccaa 420

aaataa 426

<210> 144

<211> 3630

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 144

atgcgaccct ccgggacggc cggggcagcg ctcctggcgc tgctggctgc gctctgcccg 60

gcgagtcggg ctctggagga aaagaaagtt tgccaaggca cgagtaacaa gctcacgcag 120

ttgggcactt ttgaagatca ttttctcagc ctccagagga tgttcaataa ctgtgaggtg 180

gtccttggga atttggaaat tacctatgtg cagaggaatt atgatctttc cttcttaaag 240

accatccagg aggtggctgg ttatgtcctc attgccctca acacagtgga gcgaattcct 300

ttggaaaacc tgcagatcat cagaggaaat atgtactacg aaaattccta tgccttagca 360

gtcttatcta actatgatgc aaataaaacc ggactgaagg agctgcccat gagaaattta 420

caggaaatcc tgcatggcgc cgtgcggttc agcaacaacc ctgccctgtg caacgtggag 480

agcatccagt ggcgggacat agtcagcagt gactttctca gcaacatgtc gatggacttc 540

cagaaccacc tgggcagctg ccaaaagtgt gatccaagct gtcccaatgg gagctgctgg 600

ggtgcaggag aggagaactg ccagaaactg accaaaatca tctgtgccca gcagtgctcc 660

gggcgctgcc gtggcaagtc ccccagtgac tgctgccaca accagtgtgc tgcaggctgc 720

acaggccccc ggggagagcga ctgcctggtc tgccgcaaat tccgagacga agccacgtgc 780

aaggacacct gccccccact catgctctac aaccccacca cgtaccagat ggatgtgaac 840

cccgaggca aatacagctt tggtgccacc tgcgtgaaga agtgtccccg taattatgtg 900

gtgacagatc acggctcgtg cgtccgagcc tgtggggccg acagctatga gatggaggaa 960

gacggcgtcc gcaagtgtaa gaagtgcgaa gggccttgcc gcaaagtgtg taacggaata 1020

ggtattggtg aatttaaaga ctcactctcc ataaatgcta cgaatattaa acacttcaaa 1080

aactgcacct ccatcagtgg cgatctccac atcctgccgg tggcatttag gggtgactcc 1140

ttcacacata ctcctcctct ggatccacag gaactggata ttctgaaaac cgtaaaggaa 1200

atcacaggt ttttgctgat tcaggcttgg cctgaaaaca ggacggacct ccatgccttt 1260

gagaacctag aaatcatacg cggcaggacc aagcaacatg gtcagttttc tcttgcagtc 1320

gtcagcctga acataacatc cttgggatta cgctccctca aggagataag tgatggagat 1380

gtgataattt caggaaacaa aaatttgtgc tatgcaaata caataaactg gaaaaaactg 1440

tttgggacct ccggtcagaa aaccaaaatt ataagcaaca gaggtgaaaa cagctgcaag 1500

gccacaggcc aggtctgcca tgccttgtgc tcccccgagg gctgctgggg cccggagccc 1560

agggactgcg tctcttgccg gaatgtcagc cgaggcaggg aatgcgtgga caagtgcaac 1620

cttctggagg gtgagccaag ggagtttgtg gagaactctg agtgcataca gtgccaccca 1680

gagtgcctgc ctcaggccat gaacatcacc tgcacaggac ggggaccaga caactgtatc 1740

cagtgtgccc actacattga cggcccccac tgcgtcaaga cctgcccggc aggagtcatg 1800

ggagaaaaca acaccctggt ctggaagtac gcagacgccg gccatgtgtg ccacctgtgc 1860

catccaaact gcacctacgg atgcactggg ccaggtcttg aaggctgtcc aacgaatggg 1920

cctaagatcc cgtccatcgc cactgggatg gtggggggccc tcctcttgct gctggtggtg 1980

gccctgggga tcggcctctt catgcgaagg cgccacatcg ttcggaagcg cacgctgcgg 2040

aggctgctgc aggagaggga gcttgtggag cctcttacac ccagtggaga agctcccaac 2100

caagctctct tgaggatctt gaaggaaact gaattcaaaa agatcaaagt gctgggctcc 2160

ggtgcgttcg gcacggtgta taagggactc tggatcccag aaggtgagaa agttaaaatt 2220

cccgtcgcta tcaaggaatt aagagaagca acatctccga aagccaacaa ggaaatcctc 2280

gatgaagcct acgtgatggc cagcgtggac aacccccacg tgtgccgcct gctgggcatc 2340

tgcctcacct ccaccgtgca actcatcacg cagctcatgc ccttcggctg cctcctggac 2400

tatgtccggg aacacaaaga caatattggc tcccagtacc tgctcaactg gtgtgtgcag 2460

atcgcaaagg gcatgaacta cttggaggac cgtcgcttgg tgcaccgcga cctggcagcc 2520

aggaacgtac tggtgaaaac accgcagcat gtcaagatca cagattttgg gctggccaaa 2580

ctgctgggtg cggaagagaa agaataccat gcagaaggag gcaaagtgcc tatcaagtgg 2640

atggcattgg aatcaatttt acacagaatc tatacccacc agagtgatgt ctggagctac 2700

ggggtgaccg tttgggagtt gatgaccttt ggatccaagc catatgacgg aatccctgcc 2760

agcgagatct cctccatcct ggagaaagga gaacgcctcc ctcagccacc catatgtacc 2820

atcgatgtct acatgatcat ggtcaagtgc tggatgatag acgcagatag tcgcccaaag 2880

ttccgtgagt tgatcatcga attctccaaa atggcccgag acccccagcg ctaccttgtc 2940

attcagggg atgaaagaat gcatttgcca agtcctacag actccaactt ctaccgtgcc 3000

ctgatggatg aagaagacat ggacgacgtg gtggatgccg acgagtacct catcccacag 3060

cagggcttct tcagcagccc ctccacgtca cggactcccc tcctgagctc tctgagtgca 3120

accagcaaca attccaccgt ggcttgcatt gatagaaatg ggctgcaaag ctgtcccatc 3180

aaggaagaca gcttcttgca gcgatacagc tcagacccca caggcgcctt gactgaggac 3240

agcatagacg acaccttcct cccagtgcct gaatacataa accagtccgt tcccaaaagg 3300

cccgctggct ctgtgcagaa tcctgtctat cacaatcagc ctctgaaccc cgcgcccagc 3360

agagacccac actaccagga cccccacagc actgcagtgg gcaaccccga gtatctcaac 3420

actgtccagc ccacctgtgt caacagcaca ttcgacagcc ctgcccactg ggcccagaaa 3480

ggcagccacc aaattagcct ggacaaccct gactaccagc aggacttctt tcccaaggaa 3540

gccaagccaa atggcatctt taagggctcc acagctgaaa atgcagaata cctaagggtc 3600

gcgccacaaa gcagtgaatt tattggagca 3630

<210> 145

<211> 232

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 145

Met Thr Val Leu Ala Pro Ala Trp Ser Pro Asn Ser Ser Leu Leu Leu

1 5 10 15

Leu Leu Leu Leu Leu Ser Pro Cys Leu Arg Gly Thr Pro Asp Cys Tyr

20 25 30

Phe Ser His Ser Pro Ile Ser Ser Asn Phe Lys Val Lys Phe Arg Glu

35 40 45

Leu Thr Asp His Leu Leu Lys Asp Tyr Pro Val Thr Val Ala Val Asn

50 55 60

Leu Gln Asp Glu Lys His Cys Lys Ala Leu Trp Ser Leu Phe Leu Ala

65 70 75 80

Gln Arg Trp Ile Glu Gln Leu Lys Thr Val Ala Gly Ser Lys Met Gln

85 90 95

Thr Leu Leu Glu Asp Val Asn Thr Glu Ile His Phe Val Thr Ser Cys

100 105 110

Thr Phe Gln Pro Leu Pro Glu Cys Leu Arg Phe Val Gln Thr Asn Ile

115 120 125

Ser His Leu Leu Lys Asp Thr Cys Thr Gln Leu Leu Ala Leu Lys Pro

130 135 140

Cys Ile Gly Lys Ala Cys Gln Asn Phe Ser Arg Cys Leu Glu Val Gln

145 150 155 160

Cys Gln Pro Asp Ser Ser Thr Leu Leu Pro Pro Arg Ser Pro Ile Ala

165 170 175

Leu Glu Ala Thr Glu Leu Pro Glu Pro Arg Pro Arg Gln Leu Leu Leu

180 185 190

Leu Leu Leu Leu Leu Leu Pro Leu Thr Leu Val Leu Leu Ala Ala Ala

195 200 205

Trp Gly Leu Arg Trp Gln Arg Ala Arg Arg Arg Gly Glu Leu His Pro

210 215 220

Gly Val Pro Leu Pro Ser His Pro

225 230

<210> 146

<211> 141

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 146

Met Trp Leu Gln Asn Leu Leu Phe Leu Gly Ile Val Val Tyr Ser Leu

1 5 10 15

Ser Ala Pro Thr Arg Ser Pro Ile Thr Val Thr Arg Pro Trp Lys His

20 25 30

Val Glu Ala Ile Lys Glu Ala Leu Asn Leu Leu Asp Asp Met Pro Val

35 40 45

Thr Leu Asn Glu Glu Val Glu Val Val Ser Asn Glu Phe Ser Phe Lys

50 55 60

Lys Leu Thr Cys Val Gln Thr Arg Leu Lys Ile Phe Glu Gln Gly Leu

65 70 75 80

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

85 90 95

Tyr Tyr Gln Thr Tyr Cys Pro Pro Thr Pro Glu Thr Asp Cys Glu Thr

100 105 110

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

115 120 125

Thr Asp Ile Pro Phe Glu Cys Lys Lys Pro Gly Gln Lys

130 135 140

<210> 147

<211> 1210

<212> PRT

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 147

Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala

1 5 10 15

Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln

20 25 30

Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe

35 40 45

Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn

50 55 60

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

65 70 75 80

Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val

85 90 95

Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr

100 105 110

Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn

115 120 125

Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu

130 135 140

His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu

145 150 155 160

Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met

165 170 175

Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro

180 185 190

Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln

195 200 205

Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg

210 215 220

Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys

225 230 235 240

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

245 250 255

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

260 265 270

Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly

275 280 285

Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His

290 295 300

Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu

305 310 315 320

Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val

325 330 335

Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn

340 345 350

Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp

355 360 365

Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr

370 375 380

Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu

385 390 395 400

Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp

405 410 415

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

420 425 430

His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu

435 440 445

Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser

450 455 460

Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu

465 470 475 480

Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu

485 490 495

Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro

500 505 510

Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn

515 520 525

Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly

530 535 540

Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro

545 550 555 560

Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro

565 570 575

Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val

580 585 590

Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp

595 600 605

Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys

610 615 620

Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro Thr Asn Gly

625 630 635 640

Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala Leu Leu Leu

645 650 655

Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met Arg Arg Arg His

660 665 670

Ile Val Arg Lys Arg Thr Leu Arg Arg Leu Leu Gln Glu Arg Glu Leu

675 680 685

Val Glu Pro Leu Thr Pro Ser Gly Glu Ala Pro Asn Gln Ala Leu Leu

690 695 700

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

705 710 715 720

Gly Ala Phe Gly Thr Val Tyr Lys Gly Leu Trp Ile Pro Glu Gly Glu

725 730 735

Lys Val Lys Ile Pro Val Ala Ile Lys Glu Leu Arg Glu Ala Thr Ser

740 745 750

Pro Lys Ala Asn Lys Glu Ile Leu Asp Glu Ala Tyr Val Met Ala Ser

755 760 765

Val Asp Asn Pro His Val Cys Arg Leu Leu Gly Ile Cys Leu Thr Ser

770 775 780

Thr Val Gln Leu Ile Thr Gln Leu Met Pro Phe Gly Cys Leu Leu Asp

785 790 795 800

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

805 810 815

Trp Cys Val Gln Ile Ala Lys Gly Met Asn Tyr Leu Glu Asp Arg Arg

820 825 830

Leu Val His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Lys Thr Pro

835 840 845

Gln His Val Lys Ile Thr Asp Phe Gly Leu Ala Lys Leu Leu Gly Ala

850 855 860

Glu Glu Lys Glu Tyr His Ala Glu Gly Gly Lys Val Pro Ile Lys Trp

865 870 875 880

Met Ala Leu Glu Ser Ile Leu His Arg Ile Tyr Thr His Gln Ser Asp

885 890 895

Val Trp Ser Tyr Gly Val Thr Val Trp Glu Leu Met Thr Phe Gly Ser

900 905 910

Lys Pro Tyr Asp Gly Ile Pro Ala Ser Glu Ile Ser Ser Ile Leu Glu

915 920 925

Lys Gly Glu Arg Leu Pro Gln Pro Pro Ile Cys Thr Ile Asp Val Tyr

930 935 940

Met Ile Met Val Lys Cys Trp Met Ile Asp Ala Asp Ser Arg Pro Lys

945 950 955 960

Phe Arg Glu Leu Ile Ile Glu Phe Ser Lys Met Ala Arg Asp Pro Gln

965 970 975

Arg Tyr Leu Val Ile Gln Gly Asp Glu Arg Met His Leu Pro Ser Pro

980 985 990

Thr Asp Ser Asn Phe Tyr Arg Ala Leu Met Asp Glu Glu Asp Met Asp

995 1000 1005

Asp Val Val Asp Ala Asp Glu Tyr Leu Ile Pro Gln Gln Gly Phe

1010 1015 1020

Phe Ser Ser Pro Ser Thr Ser Arg Thr Pro Leu Leu Ser Ser Leu

1025 1030 1035

Ser Ala Thr Ser Asn Asn Ser Thr Val Ala Cys Ile Asp Arg Asn

1040 1045 1050

Gly Leu Gln Ser Cys Pro Ile Lys Glu Asp Ser Phe Leu Gln Arg

1055 1060 1065

Tyr Ser Ser Asp Pro Thr Gly Ala Leu Thr Glu Asp Ser Ile Asp

1070 1075 1080

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

1085 1090 1095

Lys Arg Pro Ala Gly Ser Val Gln Asn Pro Val Tyr His Asn Gln

1100 1105 1110

Pro Leu Asn Pro Ala Pro Ser Arg Asp Pro His Tyr Gln Asp Pro

1115 1120 1125

His Ser Thr Ala Val Gly Asn Pro Glu Tyr Leu Asn Thr Val Gln

1130 1135 1140

Pro Thr Cys Val Asn Ser Thr Phe Asp Ser Pro Ala His Trp Ala

1145 1150 1155

Gln Lys Gly Ser His Gln Ile Ser Leu Asp Asn Pro Asp Tyr Gln

1160 1165 1170

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

1175 1180 1185

Gly Ser Thr Ala Glu Asn Ala Glu Tyr Leu Arg Val Ala Pro Gln

1190 1195 1200

Ser Ser Glu Phe Ile Gly Ala

1205 1210

<210> 148

<211> 1816

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 148

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ccgcacgttc agaagtcggt taataacgac 1440

atgatagtca ctgacaacaa cggtgcagtc aagtttccac aactgtgtaa attttgtgat 1500

gtgagatttt ccacctgtga caaccagaaa tcctgcatga gcaactgcag catcacctcc 1560

atctgtgaga agccacagga agtctgtgtg gctgtatgga gaaagaatga cgagaacata 1620

acactagaga cagtttgcca tgaccccaag ctcccctacc atgactttat tctggaagat 1680

gctgcttctc caaagtgcat tatgaaggaa aaaaaaaagc ctggtgagac tttcttcatg 1740

tgttcctgta gctctgatga gtgcaatgac aacatcatct tctcagaaga atataacacc 1800

agcaatcctg actaaa 1816

<210> 149

<211> 1780

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 149

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ccgcacgtta acaacggtgc agtcaagttt 1440

ccacaactgt gtaaattttg tgatgtgaga ttttccacct gtgacaacca gaaatcctgc 1500

atgagcaact gcagcatcac ctccatctgt gagaagccac aggaagtctg tgtggctgta 1560

tggagaaaga atgacgagaa cataacacta gagacagttt gccatgaccc caagctcccc 1620

taccatgact ttattctgga agatgctgct tctccaaagt gcattatgaa ggaaaaaaaa 1680

aagcctggtg agactttctt catgtgttcc tgtagctctg atgagtgcaa tgacaacatc 1740

atcttctcag aagaatataa caccagcaat cctgactaaa 1780

<210> 150

<211> 1774

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 150

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ccgcacgttg gtgcagtcaa gtttccacaa 1440

ctgtgtaaat tttgtgatgt gagatttcc acctgtgaca accagaaatc ctgcatgagc 1500

aactgcagca tcacctccat ctgtgagaag ccacaggaag tctgtgtggc tgtatggaga 1560

aagaatgacg agaacataac actagagaca gtttgccatg accccaagct cccctaccat 1620

gactttattc tggaagatgc tgcttctcca aagtgcatta tgaaggaaaa aaaaaagcct 1680

ggtgagactt tcttcatgtg ttcctgtagc tctgatgagt gcaatgacaa catcatcttc 1740

tcagaagaat ataacaccag caatcctgac taaa 1774

<210> 151

<211> 1768

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 151

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ccgcacgttg tcaagtttcc acaactgtgt 1440

aaattttgtg atgtgagatt ttccacctgt gacaaccaga aatcctgcat gagcaactgc 1500

agcatcacct ccatctgtga gaagccacag gaagtctgtg tggctgtatg gagaaagaat 1560

gacgagaaca taacactaga gacagtttgc catgacccca agctccccta ccatgacttt 1620

attctggaag atgctgcttc tccaaagtgc attatgaagg aaaaaaaaaa gcctggtgag 1680

actttcttca tgtgttcctg tagctctgat gagtgcaatg acaacatcat cttctcagaa 1740

gaatataaca ccagcaatcc tgactaaa 1768

<210> 152

<211> 1756

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 152

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ccgcacgttc aactgtgtaa attttgtgat 1440

gtgagatttt ccacctgtga caaccagaaa tcctgcatga gcaactgcag catcacctcc 1500

atctgtgaga agccacagga agtctgtgtg gctgtatgga gaaagaatga cgagaacata 1560

acactagaga cagtttgcca tgaccccaag ctcccctacc atgactttat tctggaagat 1620

gctgcttctc caaagtgcat tatgaaggaa aaaaaaaagc ctggtgagac tttcttcatg 1680

tgttcctgta gctctgatga gtgcaatgac aacatcatct tctcagaaga atataacacc 1740

agcaatcctg actaaa 1756

<210> 153

<211> 1753

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 153

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ccgcacgttc tgtgtaaatt ttgtgatgtg 1440

agattttcca cctgtgacaa ccagaaatcc tgcatgagca actgcagcat cacctccatc 1500

tgtgagaagc cacaggaagt ctgtgtggct gtatggagaa agaatgacga gaacataaca 1560

ctagagacag tttgccatga ccccaagctc ccctaccatg actttattct ggaagatgct 1620

gcttctccaa agtgcattat gaaggaaaaa aaaaagcctg gtgagacttt cttcatgtgt 1680

tcctgtagct ctgatgagtg caatgacaac atcatcttct cagaagaata taacaccagc 1740

aatcctgact aaa 1753

<210> 154

<211> 1750

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 154

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ccgcacgttt gtaaattttg tgatgtgaga 1440

ttttccacct gtgacaacca gaaatcctgc atgagcaact gcagcatcac ctccatctgt 1500

gagaagccac aggaagtctg tgtggctgta tggagaaaga atgacgagaa cataacacta 1560

gagacagttt gccatgaccc caagctcccc taccatgact ttattctgga agatgctgct 1620

tctccaaagt gcattatgaa ggaaaaaaaa aagcctggtg agactttctt catgtgttcc 1680

tgtagctctg atgagtgcaa tgacaacatc atcttctcag aagaatataa caccagcaat 1740

cctgactaaa 1750

<210> 155

<211> 1756

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 155

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ccgcacgttc agctgtgtaa attttgtgat 1440

gtgagatttt ccacctgtga caaccagaaa tcctgcatga gcaactgcag catcacctcc 1500

atctgtgaga agccacagga agtctgtgtg gctgtatgga gaaagaatga cgagaacata 1560

acactagaga cagtttgcca tgaccccaag ctcccctacc atgactttat tctggaagat 1620

gctgcttctc caaagtgcat tatgaaggaa aaaaaaaagc ctggtgagac tttcttcatg 1680

tgttcctgta gctctgatga gtgcaatgac aacatcatct tctcagaaga atataacacc 1740

agcaatcctg actaaa 1756

<210> 156

<211> 1750

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 156

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ccgcacctgt gtaaattttg tgatgtgaga 1440

ttttccacct gtgacaacca gaaatcctgc atgagcaact gcagcatcac ctccatctgt 1500

gagaagccac aggaagtctg tgtggctgta tggagaaaga atgacgagaa cataacacta 1560

gagacagttt gccatgaccc caagctcccc taccatgact ttattctgga agatgctgct 1620

tctccaaagt gcattatgaa ggaaaaaaaa aagcctggtg agactttctt catgtgttcc 1680

tgtagctctg atgagtgcaa tgacaacatc atcttctcag aagaatataa caccagcaat 1740

cctgactaaa 1750

<210> 157

<211> 1747

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 157

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ccgctgtgta aattttgtga tgtgagattt 1440

tccacctgtg acaaccagaa atcctgcatg agcaactgca gcatcacctc catctgtgag 1500

aagccacagg aagtctgtgt ggctgtatgg agaaagaatg acgagaacat aacactagag 1560

acagtttgcc atgaccccaa gctccctac catgacttta ttctggaaga tgctgcttct 1620

ccaaagtgca ttatgaagga aaaaaaaaag cctggtgaga ctttcttcat gtgttcctgt 1680

agctctgatg agtgcaatga caacatcatc ttctcagaag aatataacac cagcaatcct 1740

gactaaa 1747

<210> 158

<211> 1744

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 158

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatccca ctgtgtaaat tttgtgatgt gagatttcc 1440

acctgtgaca accagaaatc ctgcatgagc aactgcagca tcacctccat ctgtgagaag 1500

ccacaggaag tctgtgtggc tgtatggaga aagaatgacg agaacataac actagagaca 1560

gtttgccatg accccaagct cccctaccat gactttattc tggaagatgc tgcttctcca 1620

aagtgcatta tgaaggaaaa aaaaaagcct ggtgagactt tcttcatgtg ttcctgtagc 1680

tctgatgagt gcaatgacaa catcatcttc tcagaagaat ataacaccag caatcctgac 1740

taaa 1744

<210> 159

<211> 1741

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 159

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctatcctg tgtaaatttt gtgatgtgag attttccacc 1440

tgtgacaacc agaaatcctg catgagcaac tgcagcatca cctccatctg tgagaagcca 1500

caggaagtct gtgtggctgt atggagaaag aatgacgaga acataacact agagacagtt 1560

tgccatgacc ccaagctccc ctaccatgac tttattctgg aagatgctgc ttctccaaag 1620

tgcattatga aggaaaaaaa aaagcctggt gagactttct tcatgtgttc ctgtagctct 1680

gatgagtgca atgacaacat catcttctca gaagaatata acaccagcaa tcctgactaa 1740

a 1741

<210> 160

<211> 1750

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 160

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctccaccg cacgttctgt gtaaattttg tgatgtgaga 1440

ttttccacct gtgacaacca gaaatcctgc atgagcaact gcagcatcac ctccatctgt 1500

gagaagccac aggaagtctg tgtggctgta tggagaaaga atgacgagaa cataacacta 1560

gagacagttt gccatgaccc caagctcccc taccatgact ttattctgga agatgctgct 1620

tctccaaagt gcattatgaa ggaaaaaaaa aagcctggtg agactttctt catgtgttcc 1680

tgtagctctg atgagtgcaa tgacaacatc atcttctcag aagaatataa caccagcaat 1740

cctgactaaa 1750

<210> 161

<211> 1747

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 161

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctccgcac gttctgtgta aattttgtga tgtgagattt 1440

tccacctgtg acaaccagaa atcctgcatg agcaactgca gcatcacctc catctgtgag 1500

aagccacagg aagtctgtgt ggctgtatgg agaaagaatg acgagaacat aacactagag 1560

acagtttgcc atgaccccaa gctccctac catgacttta ttctggaaga tgctgcttct 1620

ccaaagtgca ttatgaagga aaaaaaaaag cctggtgaga ctttcttcat gtgttcctgt 1680

agctctgatg agtgcaatga caacatcatc ttctcagaag aatataacac cagcaatcct 1740

gactaaa 1747

<210> 162

<211> 1744

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 162

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctcacgtt ctgtgtaaat tttgtgatgt gagatttcc 1440

acctgtgaca accagaaatc ctgcatgagc aactgcagca tcacctccat ctgtgagaag 1500

ccacaggaag tctgtgtggc tgtatggaga aagaatgacg agaacataac actagagaca 1560

gtttgccatg accccaagct cccctaccat gactttattc tggaagatgc tgcttctcca 1620

aagtgcatta tgaaggaaaa aaaaaagcct ggtgagactt tcttcatgtg ttcctgtagc 1680

tctgatgagt gcaatgacaa catcatcttc tcagaagaat ataacaccag caatcctgac 1740

taaa 1744

<210> 163

<211> 1741

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 163

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctgttctg tgtaaatttt gtgatgtgag attttccacc 1440

tgtgacaacc agaaatcctg catgagcaac tgcagcatca cctccatctg tgagaagcca 1500

caggaagtct gtgtggctgt atggagaaag aatgacgaga acataacact agagacagtt 1560

tgccatgacc ccaagctccc ctaccatgac tttattctgg aagatgctgc ttctccaaag 1620

tgcattatga aggaaaaaaa aaagcctggt gagactttct tcatgtgttc ctgtagctct 1680

gatgagtgca atgacaacat catcttctca gaagaatata acaccagcaa tcctgactaa 1740

a 1741

<210> 164

<211> 1759

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 164

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctggtgca gtcaagtttc cacaactgtg taaattttgt 1440

gatgtgagat tttccacctg tgacaaccag aaatcctgca tgagcaactg cagcatcacc 1500

tccatctgtg agaagccaca ggaagtctgt gtggctgtat ggagaaagaa tgacgagaac 1560

ataacactag agacagtttg ccatgacccc aagctcccct accatgactt tattctggaa 1620

gatgctgctt ctccaaagtg cattatgaag gaaaaaaaaa agcctggtga gactttcttc 1680

atgtgttcct gtagctctga tgagtgcaat gacaacatca tcttctcaga agaatataac 1740

accagcaatc ctgactaaa 1759

<210> 165

<211> 1753

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 165

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctgtcaag tttccacaac tgtgtaaatt ttgtgatgtg 1440

agattttcca cctgtgacaa ccagaaatcc tgcatgagca actgcagcat cacctccatc 1500

tgtgagaagc cacaggaagt ctgtgtggct gtatggagaa agaatgacga gaacataaca 1560

ctagagacag tttgccatga ccccaagctc ccctaccatg actttattct ggaagatgct 1620

gcttctccaa agtgcattat gaaggaaaaa aaaaagcctg gtgagacttt cttcatgtgt 1680

tcctgtagct ctgatgagtg caatgacaac atcatcttct cagaagaata taacaccagc 1740

aatcctgact aaa 1753

<210> 166

<211> 1738

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 166

gaggtccaac ttgtccagtc tggagcagag gtgaagaagc ctggagccac agtgaagatt 60

tcctgtaagg tgtctggcta caccttcacc acctactaca cccactgggt gaagcaggct 120

cctggcaagg gattggagtg gattggctgg atttaccctg gagatgtgaa caccaaatac 180

aatgagaagt tcaagggcag ggtgaccctg acagcagaca ccagcacaga cacagcctat 240

atggaactgt cctccctgag gtctgaggac acagcagtct actactgtgc cagggaggac 300

cctggcagca actactttga ctactgggga caaggcaccc tggtgacagt gtccagcgca 360

agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacgtgcg tggtggtgga cgtgagccac gaagaccccg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320

aagagcctct ccctgtctcc gggtggtggt ggcggttcag gcggaggtgg ctctggaggt 1380

ggaggttcag gaggtggtgg ttctctgtgt aaattttgtg atgtgagatt ttccacctgt 1440

gacaaccaga aatcctgcat gagcaactgc agcatcacct ccatctgtga gaagccacag 1500

gaagtctgtg tggctgtatg gagaaagaat gacgagaaca taacactaga gacagtttgc 1560

catgacccca agctccccta ccatgacttt attctggaag atgctgcttc tccaaagtgc 1620

attatgaagg aaaaaaaaaa gcctggtgag actttcttca tgtgttcctg tagctctgat 1680

gagtgcaatg acaacatcat cttctcagaa gaatataaca ccagcaatcc tgactaaa 1738

<210> 167

<211> 32

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 167

gtcaccgtcc tgacacgaag cttgccgcca cc 32

<210> 168

<211> 23

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 168

actatagaat agggccctct aga 23

<210> 169

<211> 27

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 169

ggcaaggctc caaagctgct gatttac 27

<210> 170

<211> 27

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 170

gtaaatcagc agctttggag ccttgcc 27

<210> 171

<211> 27

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 171

acctactact gtatgcagtc ctatgat 27

<210> 172

<211> 27

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 172

atcataggac tgcatacagt agtaggt 27

<210> 173

<211> 51

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 173

gctaccaggg tgctgagtga ggtccaactt gtccagtctg gagcagaggt g 51

<210> 174

<211> 33

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 174

cactgtggct ccaggcttct tcacctctgc tcc 33

<210> 175

<211> 33

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 175

cctggagcca cagtgaagat ttcctgtaag gtg 33

<210> 176

<211> 33

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 176

ggtggtgaag gtgtagccag acaccttaca gga 33

<210> 177

<211> 31

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 177

tacaccttca ccacctacta cacccactgg g 31

<210> 178

<211> 32

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 178

cttgccagga gcctgcttca cccagtgggt gt 32

<210> 179

<211> 31

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 179

caggctcctg gcaagggatt ggagtggatt g 31

<210> 180

<211> 32

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 180

atctccaggg taaatccagc caatccactc ca 32

<210> 181

<211> 31

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 181

atttaccctg gagatgtgaa caccaaatac a 31

<210> 182

<211> 32

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 182

cctgcccttg aacttctcat tgtatttggt gt 32

<210> 183

<211> 33

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 183

aagttcaagg gcagggtgac cctgacagca gac 33

<210> 184

<211> 33

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 184

ataggctgtg tctgtgctgg tgtctgctgt cag 33

<210> 185

<211> 33

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 185

acagacacag cctatatgga actgtcctcc ctg 33

<210> 186

<211> 33

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 186

gactgctgtg tcctcagacc tcagggagga cag 33

<210> 187

<211> 33

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 187

gaggacacag cagtctacta ctgtgccagg gag 33

<210> 188

<211> 33

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 188

aaagtagttg ctgccagggt cctccctggc aca 33

<210> 189

<211> 33

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 189

ggcagcaact actttgacta ctggggacaa ggc 33

<210> 190

<211> 51

<212> DNA

<213> Artificial

<220>

<223> The sequence is synthesized artificially

<400> 190

tgggcccttg gtgcttgcgc tggacactgt caccagggtg ccttgtcccc a 51

<---

Claims (27)

1. A transforming growth factor beta receptor type II (TGFβR2) molecule with a truncated extracellular domain as set forth in any of SEQ ID NOs: 48, 49, 52, 55, 56 and 59, wherein it is linked to an antibody targeting a cancer cell, and said molecule is more resistant to protease degradation compared to the natural form of the TGFβR2 molecule as set forth in SEQ ID NO: 47. 2. A fusion protein for the treatment of epidermal growth factor receptor (EGFR)-associated cancer containing a) a TGFβR2 molecule with a truncated extracellular domain according to claim 1; and b) an antibody against EGFR as a targeting moiety, wherein the N-terminus of said TGFβR2 molecule with a truncated extracellular domain is connected via a flexible _G4S peptide linker to the C-terminus of said heavy chain of the targeting moiety. 3. The fusion protein according to claim 2, characterized in that said linker is a peptide linker (G ₄ S) ₄ . 4. The fusion protein according to claim 2, characterized in that the antibody against EGFR contains a) a heavy chain variable region comprising a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3 comprising SEQ ID NOs: 19, 20, and 21, respectively, and b) a light chain variable region comprising light chain CDR1, light chain CDR2, and light chain CDR3 regions comprising SEQ ID NOs: 16, 17, and 18, respectively. 5. The fusion protein according to claim 4, characterized in that the antibody against EGFR contains a) a heavy chain variable region comprising the sequence of SEQ ID NO: 28 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to this sequence; and b) a light chain variable region comprising the sequence of SEQ ID NO: 29 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to this sequence. 6. The fusion protein according to claim 4, characterized in that the antibody against EGFR additionally comprises: a) a heavy chain constant region, preferably comprising the sequence of SEQ ID NO: 30 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to this sequence; and/or b) a light chain constant region, preferably comprising a sequence comprising SEQ ID NO: 31, or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to this sequence. 7. The fusion protein according to claims 2 and 3, characterized in that the targeting portion is selected from bevacizumab, ramucirumab, ipilimumab or panitumumab. 8. The fusion protein according to item 6, characterized in that a) said heavy chain amino acid sequence comprises SEQ ID NO: 141 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to this sequence; and b) said light chain amino acid sequence comprises SEQ ID NO: 23 or a sequence having at least 85%, 88%, 90%, 95%, 98%, or 99% identity to this sequence; wherein the fusion protein comprises two heavy chains and two light chains; a disulfide bond is formed between its first light chain and its first heavy chain, a disulfide bond is formed between its second light chain and its second heavy chain, and a disulfide bond is formed between its first heavy chain and its second heavy chain. 9. The fusion protein according to item 8, having a K _D value of 2.92 pM - 26.3 pM, preferably 7 pM - 9 pM, more preferably 8.77 pM in binding affinity to the human EGFR protein, and having a K _D value of 23 pM - 288.3 pM, preferably 64 pM - 144 pM, more preferably 96.1 pM in binding affinity to human TGF-β1 protein. 10. A nucleic acid encoding a TGFβR2 molecule with a truncated extracellular domain according to claim 1, which is mRNA or DNA. 11. A nucleic acid encoding a fusion protein according to any one of claims 2 to 8, which is mRNA or DNA. 12. A pharmaceutical composition for the treatment of a tumor associated with EGFR, comprising a) a fusion protein according to any one of claims 2 to 8, or a nucleic acid according to claim 11, and b) a pharmaceutically acceptable carrier.