RU2781542C2 - Pharmaceutical composition for treatment and/or prevention of malignant tumor - Google Patents

Abstract

FIELD: pharmaceutics; medicine.

SUBSTANCE: object 1 is the use of a combination of an antibody or its fragment with immunological reactivity to an extracellular domain of protein CAPRIN-1 present on the surface of cells of malignant tumor and having an amino acid sequence shown in any of even SEQ ID NO: from 2 to 30, or an amino acid sequence 80% or more identical to this amino acid sequence, and imiquimod together or separately in a combination for the treatment and/or prevention of malignant tumor expressing protein CAPRIN-1 on the surface of cell membrane. Objects 2 and 3 are the use of imiquimod and the use of an antibody or its fragment for increasing therapeutic efficiency of a pharmaceutical composition for the treatment and/or prevention of malignant tumor. Object 4 is a method for the treatment and/or prevention of malignant tumor, including the introduction to an individual of an antibody or its fragment and imiquimod together or separately.

EFFECT: synergetic antitumor effect in the treatment with the claimed combination of an antibody or its fragment and imiquimod.

11 cl, 3 ex

Description

Technical field

[0001] The present invention relates to a medicament for the treatment and/or prevention of cancer, comprising an antibody to the CAPRIN-1 protein, or a fragment thereof, and imiquimod.

Prior Art

[0002] Various drugs with antibodies targeting specific antigenic proteins on cancer cells are used as cancer therapeutics with fewer side effects in cancer treatment due to their cancer specificity. For example, protein 1 associated with cytoplasmic activation and proliferation (CAPRIN-1) is expressed on the surface of the cell membrane of solid malignant tumors. Antibodies to this CAPRIN-1 protein are known to be promising for pharmaceutical use in the treatment and/or prevention of cancer (Patent Literature 1).

[0003] In recent years, methods of treating cancer using combinations of multiple therapeutic agents have been clinically used as standard therapies to improve the efficacy of therapeutic agents for cancer. Basically, for example, colon cancer is treated by a method using a combination of irinotecan, folinic acid and fluorouracil; breast cancer is treated by a method using a combination of doxorubicin and cyclophosphamide or a combination of paclitaxel, trastuzumab and pertuzumab; and gastric cancer are treated using a variety of anti-cancer agents such as cisplatin and fluorouracil. Cancer therapeutics containing anti-CAPRIN-1 antibodies as active ingredients have also been confirmed to have a therapeutic effect on cancer through combinations with chemotherapy (Patent Literature 2). However, treatment of cancer with a combination of chemotherapeutic agents is not effective for all cancers treated, and some combinations of chemotherapeutic agents synergistically drastically enhance the therapeutic effect, although some combinations additively enhance the therapeutic effect.

[0004] Imiquimod is known as a toll-like receptor (TLR) 7 or 8 agonist. The main mechanism of action of imiquimod in vivo is believed to affect diseases associated with viral infection by inhibiting viral proliferation by stimulating IFN-α production and damaging virus-infected cells through the activation of a cell-mediated immune response. Based on this mechanism of action, imiquimod was initially approved as a therapeutic agent for acute warts as a mild drug, but not initially as a therapeutic agent for malignancy. Then it was confirmed its effectiveness in superficial diseases such as solar keratosis and Bowen's disease. In Europe and the US, the use of imiquimod for superficial basal cell carcinoma has also been approved, and imiquimod has been used to treat superficial skin cancer (Bowen's disease, melanoma, and cutaneous T-cell lymphoma) (Non-Patent Literature 1). It is believed that one of the mechanisms of action of imiquimod in superficial basal cell carcinoma involves a strong activation of the natural immune system by some of the immunocytes in vivo , such as monocytes and macrophages (non-patent literature 2). However, the use of imiquimod is only approved for certain cancers (superficial basal cell carcinoma). In addition, there are cases where imiquimod is used as maintenance therapy for extramammary Paget's cancer. Cohen et al. reported that a complete response was obtained in seven out of nine cases (non-patent literature 3).

[0005] A method for treating cancer using a combination of a drug with an antibody for cancer and an antigen-presenting cell activating factor containing a toll-like receptor agonist is known (Patent Literature 3), and a method for treating cancer using a combination of a targeted therapeutic drug containing an antibody drug; and an immunotherapeutic drug capable of activating plasmacyte-like dendritic cells, bone marrow, dendritic cells, or NK cells (Patent Literature 4). Imiquimod is described as one example of the above antigen-presenting cell activating factor and immunotherapeutic agent. Although some literature suggests methods for treating cancer using combinations of cancer antibody and imiquimod, there is no evidence in the literature of therapeutic effects on cancer caused by existing combinations of imiquimod and cancer antibody. Thus, the effectiveness of the combination is unknown. Rather, cases are described where imiquimod was administered to a basal cell malignancy that developed in patients with a history of administering a cancer drug with the antibody rituximab (a monoclonal antibody that specifically binds to the CD20 protein that is expressed on malignant cell surfaces) for the treatment of non-Hodgkin's lymphoma. , the antitumor effect of imiquimod was weakened (non-patent literature 4).

Link List

Patent Literature

[0006]

Patent Literature 1: WO2010/016526

Patent Literature 2: WO2011/096535

Patent Literature 3: WO2015/112749

Patent Literature 4: WO2016/004875

Non-Patent Literature

[0007]

Non-Patent Literature 1: Skin Therapy Lett. 2002, 7, 1-6

Non-Patent Literature 2: British J Dermatol. 2003, 149, 57-58

Non-Patent Literature 3: South Med J, 2006, 99, 396-402

Non-Patent Literature 4: Journal of Medical Case Reports (2016) 10:57

The essence of the invention

Goal to be achieved

[0008] The purpose of the present invention is a pharmaceutical composition for the treatment and/or prevention of a malignant tumor that specifically expresses the CAPRIN-1 protein on the cell surface.

Solution to achieve the goal

[0009] As noted above, cases have been described where imiquimod was administered to a basal cell cancer developed in patients with a history of administration of a cancer drug with the antibody rituximab (a monoclonal antibody that specifically binds to the CD20 protein that is expressed on the cell surfaces of the cancer). tumors) for the treatment of non-Hodgkin's lymphoma, the antitumor effect of imiquimod was attenuated. However, this report alerts those skilled in the art to the possibility that certain cancer antibody drugs targeting malignant cells attenuate the antitumor effect of imiquimod through their combination with imiquimod. However, as a result of intensive research, the present inventors have found that the combination of an antibody against the CAPRIN-1 protein or a fragment thereof, which has immunological reactivity to malignant cells, and imiquimod has a much stronger antitumor effect than an antibody against the CAPRIN-1 protein or only a fragment thereof. or only imiquimod; and the combination of an antibody against CAPRIN-1 protein or a fragment thereof and imiquimod is far superior in enhancing the antitumor effect to the combination of an existing anti-cancer antibody and imiquimod; and furthermore, the effect of enhancing the anti-tumor effect of the combination of an anti-CAPRIN-1 protein antibody or fragment thereof and imiquimod is far superior to the anti-tumor effect of the combination with an existing anti-malignant agent other than imiquimod. Based on these findings, the present invention has been completed.

[0010] Specifically, the present invention has the following features (1) to (14):

[0011] (1) A medicament for the treatment and/or prevention of cancer, comprising an antibody or fragment thereof having immunological reactivity to the CAPRIN-1 protein and imiquimod together or separately in combination.

[0012] (2) The drug according to (1), wherein the antibody or fragment has immunological reactivity to the CAPRIN-1 protein with the amino acid sequence shown in any of the even numbers of SEQ ID NO: 2 to 30, or an amino acid sequence with 80% or more sequence identity with that amino acid sequence.

[0013] (3) The drug according to (1) or (2), wherein the antibody or fragment thereof has immunological reactivity to the extracellular region of the CAPRIN-1 protein present on the surface of cancer cells.

[0014] (4) The drug according to any of (1) to (3), wherein the antibody or fragment thereof has immunological reactivity to a partial polypeptide of the CAPRIN-1 protein, the partial polypeptide has an amino acid sequence represented by any of SEQ ID NO: c 31 to 35, 296 to 299, 308 and 309, or an amino acid sequence with 80% or more sequence identity with that amino acid sequence.

[0015] (5) The drug according to any of (1) to (4), wherein the antibody is a monoclonal antibody or a polyclonal antibody.

[0016] (6) The drug according to any of (1) to (5), wherein the antibody or fragment thereof is any of (A) to (M):

(A) an antibody or fragment containing a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 36, 37 and 38 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NO: 40 , 41 and 42 (CDR1, CDR2 and CDR3, respectively), and having immunological reactivity with the CAPRIN-1 protein;

(B) an antibody or fragment containing a heavy chain variable region with complementarity determining regions from SEQ ID NO: 44, 45 and 46 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NO: 48 , 49 and 50 (CDR1, CDR2 and CDR3, respectively), and having immunological reactivity with the CAPRIN-1 protein;

(C) an antibody or fragment containing a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 52, 53 and 54 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NO: 56 , 57 and 58 (CDR1, CDR2 and CDR3, respectively), and having immunological reactivity with the CAPRIN-1 protein;

(D) an antibody or fragment containing a heavy chain variable region with complementarity determining regions from SEQ ID NO: 60, 61 and 62 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NO: 64 , 65 and 66 (CDR1, CDR2 and CDR3, respectively), and having immunological reactivity with the CAPRIN-1 protein;

(E) an antibody or fragment thereof comprising a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 170, 171 and 172 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 173, 174 and 175 (CDR1, CDR2 and CDR3, respectively) and having immunological reactivity with the CAPRIN-1 protein;

(F) an antibody or fragment thereof comprising a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 176, 177 and 178 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 179, 180 and 181 (CDR1, CDR2 and CDR3, respectively), and having immunological reactivity with the CAPRIN-1 protein;

(G) an antibody or fragment thereof comprising a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 182, 183 and 184 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 185, 186 and 187 (CDR1, CDR2 and CDR3, respectively), and having immunological reactivity with the CAPRIN-1 protein;

(H) an antibody or fragment thereof comprising a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 188, 189 and 190 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 191, 192 and 193 (CDR1, CDR2 and CDR3, respectively), and having immunological reactivity with the CAPRIN-1 protein;

(I) an antibody or fragment thereof comprising a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 146, 147 and 148 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 149, 150 and 151 (CDR1, CDR2 and CDR3, respectively) and having immunological reactivity with the CAPRIN-1 protein;

(J) an antibody or fragment thereof comprising a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 272, 273 and 274 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 275, 276 and 277 (CDR1, CDR2 and CDR3, respectively) and having immunological reactivity with the CAPRIN-1 protein;

(K) An antibody or fragment thereof comprising a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 290, 291 and 292 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 293, 294 and 295 (CDR1, CDR2 and CDR3, respectively), and having immunological reactivity with the CAPRIN-1 protein;

(L) an antibody or fragment thereof comprising a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 301, 302 and 303 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 305, 306 and 307 (CDR1, CDR2 and CDR3, respectively), and having immunological reactivity with the CAPRIN-1 protein; and

(M) an antibody or fragment thereof comprising a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 134, 135 and 136 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 137, 138 and 139 (CDR1, CDR2 and CDR3, respectively) and having immunological reactivity with the CAPRIN-1 protein.

[0017] (7) The drug according to any of (1) to (6), wherein the antibody or fragment thereof is any of (a) to (al):

(a) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 39 and a light chain variable region with the amino acid sequence of SEQ ID NO: 43;

(b) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 47 and a light chain variable region with the amino acid sequence of SEQ ID NO: 51;

(c) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 55 and a light chain variable region with the amino acid sequence of SEQ ID NO: 59;

(d) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 63 and a light chain variable region with the amino acid sequence of SEQ ID NO: 67;

(e) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 68 and a light chain variable region with the amino acid sequence of SEQ ID NO: 69;

(f) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 70 and a light chain variable region with the amino acid sequence of SEQ ID NO: 71;

(g) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 72 and a light chain variable region with the amino acid sequence of SEQ ID NO: 73;

(h) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 74 and a light chain variable region with the amino acid sequence of SEQ ID NO: 75;

(i) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 76 and a light chain variable region with the amino acid sequence of SEQ ID NO: 77;

(j) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 78 and a light chain variable region with the amino acid sequence of SEQ ID NO: 79;

(k) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 80 and a light chain variable region with the amino acid sequence of SEQ ID NO: 81;

(l) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 82 and a light chain variable region with the amino acid sequence of SEQ ID NO: 83;

(m) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 84 and a light chain variable region with the amino acid sequence of SEQ ID NO: 85;

(n) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 86 and a light chain variable region with the amino acid sequence of SEQ ID NO: 87;

(o) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 88 and a light chain variable region with the amino acid sequence of SEQ ID NO: 89;

(p) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 90 and a light chain variable region with the amino acid sequence of SEQ ID NO: 91;

(q) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 92 and a light chain variable region with the amino acid sequence of SEQ ID NO: 93;

(r) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 94 and a light chain variable region with the amino acid sequence of SEQ ID NO: 95;

(s) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 96 and a light chain variable region with the amino acid sequence of SEQ ID NO: 97;

(t) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 98 and a light chain variable region with the amino acid sequence of SEQ ID NO: 99;

(u) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 100 and a light chain variable region with the amino acid sequence of SEQ ID NO: 101;

(v) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 102 and a light chain variable region with the amino acid sequence of SEQ ID NO: 103;

(w) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 104 and a light chain variable region with the amino acid sequence of SEQ ID NO: 105;

(x) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 106 and a light chain variable region with the amino acid sequence of SEQ ID NO: 107;

(y) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 108 and a light chain variable region with the amino acid sequence of SEQ ID NO: 109;

(z) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 110 and a light chain variable region with the amino acid sequence of SEQ ID NO: 111;

(aa) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 112 and a light chain variable region with the amino acid sequence of SEQ ID NO: 113;

(ab) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 114 and a light chain variable region with the amino acid sequence of SEQ ID NO: 115;

(ac) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 116 and a light chain variable region with the amino acid sequence of SEQ ID NO: 117;

(ad) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 118 and a light chain variable region with the amino acid sequence of SEQ ID NO: 119;

(ae) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 120 and a light chain variable region with the amino acid sequence of SEQ ID NO: 121;

(af) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 122 and a light chain variable region with the amino acid sequence of SEQ ID NO: 123;

(ag) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 124 and a light chain variable region with the amino acid sequence of SEQ ID NO: 125;

(ah) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 126 and a light chain variable region with the amino acid sequence of SEQ ID NO: 127;

(ai) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 128 and a light chain variable region with the amino acid sequence of SEQ ID NO: 129;

(aj) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 130 and a light chain variable region with the amino acid sequence of SEQ ID NO: 131;

(ak) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 132 and a light chain variable region with the amino acid sequence of SEQ ID NO: 133; and

(al) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 300 and a light chain variable region with the amino acid sequence of SEQ ID NO: 304.

[0018] (8) The drug according to any of (1) to (7), wherein the antibody is a human antibody, a humanized antibody, a chimeric antibody, or a single chain antibody.

[0019] (9) The drug according to any of (1) to (8), wherein the cancer is a cancer expressing the CAPRIN-1 protein on the cell membrane surface.

[0020] (10) The drug according to any of (1) to (9), wherein the cancer is basal cell carcinoma, Paget's disease, skin cancer, breast cancer, kidney cancer, pancreatic cancer, colon cancer, cancer lung, brain tumor, stomach cancer, uterine cancer, ovarian cancer, prostate cancer, bladder cancer, esophageal cancer, leukemia, lymphoma, liver cancer, gallbladder cancer, sarcoma, mastocytoma, adrenal cortex cancer, Ewing's tumor, Hodgkin's lymphoma , mesothelioma, multiple myeloma, testicular cancer, thyroid cancer, or head and neck cancer.

[0021] (11) The medicament according to any of (1) to (10), wherein the dosage form of imiquimod is a transdermal formulation.

[0022] (12) An agent that enhances the drug efficacy of a pharmaceutical composition for the treatment and/or prevention of a malignant tumor, containing as an active ingredient an antibody or a fragment thereof with immunological reactivity with the CAPRIN-1 protein, in which imiquimod is used as an active ingredient.

[0023] (13) An agent that enhances the drug efficacy of a pharmaceutical composition for the treatment and/or prevention of cancer, containing imiquimod as an active ingredient, in which an antibody or a fragment thereof with immunological reactivity with the CAPRIN-1 protein is used as an active ingredient.

[0024] (14) A method for treating and/or preventing cancer, comprising administering to an individual an antibody or fragment thereof having immunological reactivity with the CAPRIN-1 protein and imiquimod together or separately.

Beneficial Effects of the Invention

[0025] The combination of an antibody against the CAPRIN-1 protein or a fragment thereof and imiquimod of the present invention not only exhibits a stronger antitumor effect than the antibody against the CAPRIN-1 protein alone and imiquimod alone, but also exhibits a better antitumor effect than the combination of an existing drug with an antibody for cancer and imiquimod. In addition, the combination of an antibody against the CAPRIN-1 protein or a fragment thereof and imiquimod of the present invention exhibits a stronger antitumor effect than the combination of existing chemotherapeutic drugs and antibodies against the CAPRIN-1 protein. Thus, the combination of an antibody against the CAPRIN-1 protein and imiquimod is effective in the treatment or prevention of cancer.

Description of Embodiments

[0026] The antitumor activity of the combination of an antibody against the CAPRIN-1 protein or a fragment thereof (hereinafter referred to as "anti-CAPRIN-1 antibody") and imiquimod used in the present invention can be assessed by in vivo tumor growth inhibition testing in an animal with a tumor, as mentioned below.

[0027] The term "combination" as used herein refers to the simultaneous administration or administration within a predetermined range of an anti-CAPRIN-1 antibody and imiquimod as independent active ingredients in the same organism. The interval may be simultaneous administration or may be 30 minutes late, 1 hour late, 3 hours late, 6 hours late, 12 hours late, 1 day late, 3 days late, 5 days late, 7 days later, 2 weeks later, 3 weeks later, or 4 weeks later. Anti-CAPRIN-1 antibody or imiquimod can be administered when the other active ingredient is active in vivo . An anti-CAPRIN-1 antibody may be administered first, or imiquimod may be administered first.

[0028] The anti-CAPRIN-1 antibody of the present invention may be a monoclonal antibody or a polyclonal antibody, and is preferably a monoclonal antibody. The antibody of the present invention may be any type of antibody, as long as it can exhibit antitumor activity. The antibody is a recombinant antibody, a human antibody, a humanized antibody, a chimeric antibody, or an antibody from a non-human animal.

[0029] Individuals in need of cancer treatment and/or prevention according to the present invention are mammals such as humans, pets, livestock, or sport animals. Preferably the individual is a human.

[0030] Anti-CAPRIN-1 antibodies, imiquimod, drugs containing them as active ingredients, and methods for the treatment and/or prevention of malignant tumors related to the present invention will be discussed below.

[0031] <Antibody to CAPRIN-1>

Among the CAPRIN-1 proteins with the amino acid sequence shown in any of the even numbered SEQ ID NOs: 2 to 30, which are specific examples of antigens with immunological reactivity with the anti-CAPRIN-1 antibody used in the present invention, the amino acid sequences shown in SEQ ID NOs: 6, 8, 10, 12 and 14 are the amino acid sequences of the canine CAPRIN-1 proteins; the amino acid sequences shown in SEQ ID NOs: 2 and 4 are the amino acid sequences of the human CAPRIN-1 proteins; the amino acid sequence shown in SEQ ID NO: 16 is the amino acid sequence of the bovine CAPRIN-1 protein; the amino acid sequence shown in SEQ ID NO: 18 is the amino acid sequence of the equine CAPRIN-1 protein; the amino acid sequences shown in SEQ ID NO: 20 to 28 are the amino acid sequences of mouse CAPRIN-1 proteins; and the amino acid sequence shown in SEQ ID NO: 30 is the amino acid sequence of the chicken protein CAPRIN-1.

[0032] An anti-CAPRIN-1 antibody used in the present invention may have immunological reactivity with a CAPRIN-1 protein variant having 80% or more, preferably 90% or more, more preferably 95% or more, and even more preferably 99% or more sequence identity with that amino acid sequence shown in any of the even-numbered SEQ ID NOs: 2 to 30. As used herein, the term "% sequence identity" means the percentage (%) of the number of identical amino acids (or nucleotides) relative to the total number of amino acids (or nucleotides) when two sequences are aligned in such a way that maximum similarity is achieved with or without gap insertion.

[0033] As used herein, an anti-CAPRIN-1 antibody refers to an antibody or fragment thereof with immunological reactivity with the full-length CAPRIN-1 protein or fragment thereof. The term "immunological reactivity" as used herein refers to the in vivo or in vitro binding characteristics of an antibody to the CAPRIN-1 protein or partial polypeptide thereof.

[0034] The anti-CAPRIN-1 antibody used in the present invention may be a monoclonal antibody or a polyclonal antibody.

[0035] Immunologically reactive polyclonal antibodies with full-length CAPRIN-1 protein or a fragment thereof (anti-CAPRIN-1 polyclonal antibodies) can be generated, for example, by the method described below. Serum is obtained from immunized mice that produce human antibodies, mice, rats, rabbits, chickens, or the like. using natural protein CAPRIN-1 or a protein fused with GST or the like, or a partial peptide thereof. The resulting serum is purified by precipitation with ammonium sulfate, protein A, protein G, using DEAE ion exchange columns, affinity columns to which CAPRIN-1 protein or partial peptide is attached, or the like.

[0036] With respect to the full-length CAPRIN-1 protein or fragment thereof used for immunization, the nucleotide sequences and amino acid sequences of CAPRIN-1 and its homologues can be obtained, for example, by accessing the GenBank site (NCBI, USA) and using the BLAST or FASTA algorithm (Karlin and Altschul, Proc. Natl. Acad. Sci. USA, 90: 5873-5877, 1993; and Altschul et al., Nucleic Acids Res. 25: 3389-3402, 1997). Methods for producing the CAPRIN-1 protein can be found in WO2014/012479, or cells or the like expressing the CAPRIN-1 protein can be used.

[0037] Monoclonal antibodies with immunological reactivity with full-length CAPRIN-1 protein or a fragment thereof (monoclonal antibodies to CAPRIN-1) can be obtained, for example, by the method described below. SK-BR-3 breast cancer cells expressing CAPRIN-1, full-length CAPRIN-1 protein or a fragment thereof, or the like are administered to mice for immunization. Splenocytes isolated from mice are fused with myeloma cells. Clones capable of producing monoclonal antibodies to CAPRIN-1 can be selected from the obtained cell fusions (hybridoma) to obtain these antibodies. Antibodies obtained from selected hybridomas can be obtained in the same way as the above method for the purification of polyclonal antibodies.

[0038] An antibody used in the present invention refers to human antibodies, humanized antibodies, chimeric antibodies, and non-human animal antibodies.

[0039] For human antibodies, Epstein-Barr virus-infected human lymphocytes are sensitized with protein, protein-expressing cells, or a lysate thereof. The sensitized lymphocytes are fused with human-derived myeloma cells such as U266 cells. Antibodies with immunological reactivity with full-length CAPRIN-1 protein or a fragment thereof can be obtained from the resulting cell fusion.

[0040] A humanized antibody is a modified antibody and is sometimes referred to as a reshaped human antibody. It is known that a humanized antibody is constructed by grafting complementarity-determining regions from an antibody derived from an immunized animal into complementarity-determining regions of a human antibody. In addition, the general mode of gene recombination is well known. Specifically, a DNA sequence designed in such a way that allows the complementarity-determining regions of a mouse or rabbit antibody to be joined to the framework regions of a human antibody is synthesized by a PCR method using several oligonucleotides prepared in such a way that the oligonucleotides have parts overlapping each other on one the end of each. A humanized antibody can be produced by combining the above described DNA with DNA encoding a human antibody constant region, then inserting the resulting construct into an expression vector, and introducing the vector into a host to generate the antibody (see EP-A-239400 and WO96/02576). Human antibody framework regions linked to each other via complementarity-determining regions are selected based on the assumption that complementarity-determining regions can form a good antigen-binding site. If necessary, amino acids in the framework regions of the antibody variable region can be substituted such that the complementarity-determining regions in the reshaped human antibody form the corresponding antigen-binding site (Sato K. et al., Cancer Research 1993, 53: 851-856). In addition, framework regions can be replaced with framework regions from another human antibody (see WO99/51743).

[0041] In general, antibodies are heteromultimeric glycoproteins containing at least two heavy chains and two light chains. The antibodies contain two identical light chains and two identical heavy chains. Each heavy chain has a heavy chain variable region at one end to which several constant regions are attached in series. Each light chain has a light chain variable region at one end to which several constant regions are attached in series. Variable regions create a specific variable region, called a complementarity determining region (CDR), that confers binding specificity to an antibody. The relatively conserved portion in the variable region is called the framework region (FR). The complete heavy or light chain variable region comprises 4 FRs linked to each other via 3 CDRs (CDR1 to CDR3).

[0042] Sequences for human heavy chain and light chain constant and variable regions can be obtained from, for example, NCBI (USA; GenBank, UniGene, etc.). For example, for the human IgG1 heavy chain constant region, see accession number J00228; for the human IgG2 heavy chain constant region, see accession number J00230; for the human κ light chain constant region, see sequences such as accession numbers V00557, X64135, and X64133; and for the human λ light chain constant region, see sequences such as accession numbers X64132 and X64134.

[0043] A chimeric antibody is an antibody obtained by combining sequences from different animals. An example thereof is an antibody composed of the heavy chain and light chain variable regions of a mouse antibody and the heavy chain and light chain constant regions of a human antibody. Such a chimeric antibody can be obtained in a known manner. For example, it can be obtained by ligating DNA encoding the V region of an antibody with DNA encoding the C region of a human antibody, introducing the resulting construct into an expression vector, and introducing the vector into a host to produce antibodies.

[0044] Non-human animal antibodies are obtained by immunizing animals with sensitizing antigens according to a known method, or by intraperitoneally, intradermally, or subcutaneously by injecting sensitizing antigens into animals, such as mice, as a general method. To administer sensitizing antigens, an appropriate amount of various adjuvants, including CFA (complete Freund's adjuvant), are mixed with them and the mixture is administered to animals several times. After immunizing the animals and confirming the content of anti-CAPRIN-1 antibody in the serum, serum is obtained, and the antibody can be obtained by purification by precipitation with ammonium sulfate, purification with protein A, protein G, ion exchange columns with DEAE, affinity columns to which CAPRIN-protein is bound 1 or its partial peptide, or the like, as above. In the case of obtaining monoclonal antibodies from non-human animals, the monoclonal antibody is obtained by collecting immunocytes from immunized animals and subjecting the immunocytes to fusion with myeloma cells. Fusion of immunocytes with myeloma cells can be carried out according to a known method (see Kohler, G. and Milstein, C. Methods Enzymol. (1981) 73, 3-46).

[0045] The antibody used in the present invention can also be obtained as an antibody after genetic recombination using a gene recombination method, wherein the antibody is obtained by cloning the antibody gene into a hybridoma, inserting the clone into a suitable vector, introducing the vector into a host, and generating an antibody ( see Carl, A. K. Borrebaeck, James, W. Larrick, THERAPEUTIC MONOCLONAL ANTIBODIES, published in the UK by MACMILLAN PUBLISHERS LTD, 1990).

[0046] Amino acids in the variable region (eg, FR) or constant region of an anti-CAPRIN-1 antibody used in the present invention can be substituted with various amino acids. An amino acid substitution is a substitution of one or more, for example, less than 15, less than 10, no more than 8, no more than 6, no more than 5, no more than 4, no more than 3, or no more than 2 amino acids , preferably 1 to 9 amino acids. The substituted antibody must have specific antigen binding characteristics and antigen binding affinity equivalent to or better than the unsubstituted antibody and must not be rejected when administered to humans. The amino acid substitution is preferably a conservative amino acid substitution, which is a substitution between amino acids with similar characteristics in terms of charge, side chains, polarity, aromaticity, and the like. For example, amino acids with similar characteristics can be classified into the following types: basic amino acids (arginine, lysine, and histidine); acidic amino acids (aspartic acid and glutamic acid); uncharged polar amino acids (glycine, asparagine, glutamine, serine, threonine, cysteine, and tyrosine); non-polar amino acids (leucine, isoleucine, alanine, valine, proline, phenylalanine, tryptophan, and methionine); branched amino acids (threonine, valine, isoleucine); and aromatic amino acids (phenylalanine, tyrosine, tryptophan, and histidine).

[0047] The anti-CAPRIN-1 antibody used in the present invention is expected to have a stronger antitumor effect with a higher binding affinity of the CAPRIN-1 protein on the surface of cancer cells. The association constant (affinity constant) Ka (k _on /k _off ) is preferably at least 10 ⁷ M ^-1 , at least 10 ⁸ M ^-1 , at least 5×10 ⁸ M ^-1 , according to at least 10 ⁹ M ^-1 , at least 5×10 ⁹ M ^-1 , at least 10 ¹⁰ M ^-1 , at least 5×10 ¹⁰ M ^-1 , at least 10 ¹¹ M ^-1 at least 5× 0 ¹¹ M ^-1 , at least 10 ¹² M ^-1 , or at least 10 ¹³ M ^-1 .

[0048] The anti-CAPRIN-1 antibody used in the present invention may be chemically modified. Examples of such antibody modification may include antibodies linked to various molecules such as polyethylene glycol (PEG) and anticancer compounds (eg, anticancer agents listed below). With respect to the antibody modifiers of the present invention, substances that bind to antibodies are not limited. Such an antibody modifier can be obtained by chemically modifying the resulting antibody. Methods for such modification have already been developed in the field associated with the present invention. The binding strength of the anti-CAPRIN-1 antibody used in the present invention to effector cells can be improved by substituting 1, 2, or more amino acids in the heavy chain constant region of the antibody, or by removing the fucose bound to N-acetylglucosamine in the attached N a sugar chain glycoside linked to the heavy chain constant region. The anti-CAPRIN-1 antibody described above may contain only an amino acid substitution or may be formulated with a fucose-linked antibody.

[0049] Antibodies in which 1, 2, or more amino acids are substituted in the heavy chain constant region can be prepared with reference to, for example, WO2004/063351, WO2011/120135, US Patent No. 8388955, WO2011/005481, US Patent No. 6737056 and WO2005/063351.

[0050] Antibodies in which fucose linked to N-acetylglucosamine in the sugar chain linked to N-glycoside in the heavy chain constant region has been removed or cells producing the same can be obtained with reference to US Pat. No. 6,602,684, EP Patent No. 1,914,244, and US patent No. 7579170. Antibody compositions in which the fucose associated with N-acetylglucosamine in the sugar chain associated with the N-glycoside in the constant region of the heavy chain is removed, or cells producing them can be obtained with reference to, for example, US patent No. 8642292.

[0051] An anti-CAPRIN-1 polyclonal antibody and an anti-CAPRIN-1 monoclonal antibody used in the present invention, methods for producing or purifying antibodies, and methods for producing a CAPRIN-1 protein or a partial polypeptide thereof used in immunization can be obtained with reference to WO2010 /016526, WO2011/096517, WO2011/096528, WO2011/096519, WO2011/096533, WO2011/096534, WO2011/096535, WO2013/018886, WO2013/018894, WO2013/018892, WO2013/018891, WO2013/018889, WO2013/018883 , WO2013/125636, WO2013/125654, WO2013/125630, WO2013/125640, WO2013/147169, WO2013/147176 and WO2015/020212.

[0052] Specific examples of the anti-CAPRIN-1 antibody of the present invention include the anti-CAPRIN-1 antibodies described in WO2010/016526, WO2011/096517, WO2011/096528, WO2011/096519, WO2011/096533, WO2011/096535/096514, WO2011/096535, WO2011. Wo2013/018886, Wo2013/018894, Wo2013/01892, Wo2013/018891, Wo2013/018889, Wo2013/018883, Wo2013/125636, Wo2013/125654, Wo2013/125640, Wo2013/147/11/147/147/147/147/1476 and 147/1476 and 1476 and 147/1476 and 1476 and 147 and 147/125640. 020212 mentioned above. Preferred examples of anti-CAPRIN-1 antibodies include the following.

[0053] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein with the amino acid sequence shown in SEQ ID NO: 2 or SEQ ID NO: 4 or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90% or more, more preferably 95% or more, and even more preferably 99% or more) sequence identity with that amino acid sequence.

[0054] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 31, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOS: 36, 37 and 38 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 40, 41 and 42 (CDR1, CDR2 and CDR3, respectively), and with immunological reactivity with the CAPRIN-1 protein, an antibody or fragment thereof containing the variable region heavy chain with complementarity determining regions from SEQ ID NOs: 140, 141 and 142 (CDR1, CDR2 and CDR3, respectively respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 143, 144 and 145 (CDR1, CDR2 and CDR3, respectively), and with immunological reactivity with the CAPRIN-1 protein, or an antibody or fragment thereof containing the variable region a heavy chain with complementarity determining regions from SEQ ID NOs: 164, 165 and 166 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 167, 168 and 169 (CDR1, CDR2 and CDR3 , respectively), and immunologically reactive with the CAPRIN-1 protein, and more preferably, an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 39 and a light chain variable region with the amino acid sequence of SEQ ID NO: 43, an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 70 and a light chain variable region with am a foreign acid sequence from SEQ ID NO: 71, or an antibody or fragment thereof containing a heavy chain variable region with an amino acid sequence from SEQ ID NO: 78 and a light chain variable region with an amino acid sequence from SEQ ID NO: 79.

[0055] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 33, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOS: 60, 61 and 62 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 64, 65, and 66 (CDR1, CDR2, and CDR3, respectively), and immunologically reactive with the CAPRIN-1 protein, and more preferably, an antibody or fragment thereof containing the heavy chain variable region with the amino acid sequence of SEQ ID NO: 63 and the variable region There is a light chain with the amino acid sequence of SEQ ID NO: 67.

[0056] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 32, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOS: 52, 53 and 54 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 56, 57, and 58 (CDR1, CDR2, and CDR3, respectively), and immunologically reactive with the CAPRIN-1 protein, and more preferably, an antibody or fragment thereof containing the heavy chain variable region with the amino acid sequence of SEQ ID NO: 55 and the variable region There is a light chain with the amino acid sequence of SEQ ID NO: 59.

[0057] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 34, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOS: 170, 171 and 172 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 173, 174 and 175 (CDR1, CDR2 and CDR3, respectively), and with immunological reactivity with the CAPRIN-1 protein, or an antibody or fragment thereof containing a variable heavy chain region with complementarity determining regions from SEQ ID NOs: 176, 177 and 178 (CDR1, CDR2 and C DR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 179, 180 and 181 (CDR1, CDR2 and CDR3, respectively), and with immunological reactivity with the CAPRIN-1 protein, and more preferably, the antibody or its a fragment containing a heavy chain variable region with the amino acid sequence of SEQ ID NO: 80 and a light chain variable region with the amino acid sequence of SEQ ID NO: 81, or an antibody or fragment thereof containing a heavy chain variable region with the amino acid sequence of SEQ ID NO: 82 and a light chain variable region with the amino acid sequence of SEQ ID NO: 83.

[0058] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 35, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 182, 183 and 184 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 185, 186 and 187 (CDR1, CDR2 and CDR3, respectively), and with immunological reactivity with the CAPRIN-1 protein, or an antibody or fragment thereof containing a variable heavy chain region with complementarity determining regions from SEQ ID NOs: 188, 189 and 190 (CDR1, CDR2 and C DR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 191, 192, and 193 (CDR1, CDR2, and CDR3, respectively), and with immunological reactivity with the CAPRIN-1 protein, and more preferably, the antibody or its a fragment containing a heavy chain variable region with the amino acid sequence of SEQ ID NO: 84 and a light chain variable region with the amino acid sequence of SEQ ID NO: 85, or an antibody or fragment thereof containing a heavy chain variable region with the amino acid sequence of SEQ ID NO: 86 and a light chain variable region with the amino acid sequence of SEQ ID NO: 87.

[0059] An antibody or fragment thereof comprising a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 44, 45 and 46 (CDR1, CDR2 and CDR3, respectively) and a light chain variable region with complementarity determining regions from SEQ ID NO: 48, 49 and 50 (CDR1, CDR2 and CDR3, respectively), and with immunological reactivity with the CAPRIN-1 protein, and preferably an antibody or fragment thereof containing a heavy chain variable region with the amino acid sequence of SEQ ID NO: 47 and a light variable region chains with the amino acid sequence of SEQ ID NO: 51.

[0060] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 296, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 146, 147 and 148 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 149, 150, and 151 (CDR1, CDR2, and CDR3, respectively), and immunologically reactive with the CAPRIN-1 protein, and more preferably, an antibody or fragment thereof containing the heavy chain variable region with the amino acid sequence of SEQ ID NO: 72 and the variable th region of the light chain with the amino acid sequence from SEQ ID NO: 73.

[0061] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 297, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 272, 273 and 274 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 275, 276 and 277 (CDR1, CDR2 and CDR3, respectively), and with immunological reactivity with the CAPRIN-1 protein, and more preferably an antibody or fragment thereof, containing a heavy chain variable region with the amino acid sequence of SEQ ID NO: 114 and variable th region of the light chain with the amino acid sequence from SEQ ID NO: 115.

[0062] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 298, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 290, 291 and 292 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 293, 294 and 295 (CDR1, CDR2 and CDR3, respectively), and with immunological reactivity with the CAPRIN-1 protein, and more preferably an antibody or fragment thereof, containing a heavy chain variable region with the amino acid sequence of SEQ ID NO: 120 and a variable light chain region with the amino acid sequence from SEQ ID NO: 121.

[0063] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 299, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 301, 302 and 303 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 305, 306, and 307 (CDR1, CDR2, and CDR3, respectively), and immunologically reactive with the CAPRIN-1 protein, and more preferably, an antibody or fragment thereof containing the heavy chain variable region with the amino acid sequence of SEQ ID NO: 300 and the variable light chain region with the amino acid sequence from SEQ ID NO: 304.

[0064] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 308, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 134, 135 and 136 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 137, 138 and 139 (CDR1, CDR2 and CDR3, respectively), and with immunological reactivity with the CAPRIN-1 protein, and more preferably an antibody or fragment thereof, containing a heavy chain variable region with the amino acid sequence of SEQ ID NO: 68 and variable ju light chain region with the amino acid sequence of SEQ ID NO: 69.

[0065] An antibody or fragment thereof with immunological reactivity with a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with the amino acid sequence shown in SEQ ID NO: 309, or an amino acid sequence having 80% or more (preferably 85% or more, more preferably 90 % or more, and more preferably 95% or more) of sequence identity with that amino acid sequence, preferably an antibody or fragment thereof containing a heavy chain variable region with complementarity determining regions from SEQ ID NOs: 134, 135 and 136 (CDR1, CDR2 and CDR3 , respectively) and a light chain variable region with complementarity determining regions from SEQ ID NOs: 137, 138, and 139 (CDR1, CDR2, and CDR3, respectively), and immunologically reactive with the CAPRIN-1 protein, and more preferably, an antibody or fragment thereof containing the heavy chain variable region with the amino acid sequence of SEQ ID NO: 68 and the variable th region of the light chain with the amino acid sequence of SEQ ID NO: 69.

[0066] In addition, the following anti-CAPRIN-1 antibodies are preferably used.

[0067] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 68 and a light chain variable region with the amino acid sequence of SEQ ID NO: 69.

[0068] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 70 and a light chain variable region with the amino acid sequence of SEQ ID NO: 71.

[0069] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 72 and a light chain variable region with the amino acid sequence of SEQ ID NO: 73.

[0070] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 74 and a light chain variable region with the amino acid sequence of SEQ ID NO: 75.

[0071] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 76 and a light chain variable region with the amino acid sequence of SEQ ID NO: 77.

[0072] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 78 and a light chain variable region with the amino acid sequence of SEQ ID NO: 79.

[0073] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 80 and a light chain variable region with the amino acid sequence of SEQ ID NO: 81.

[0074] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 82 and a light chain variable region with the amino acid sequence of SEQ ID NO: 83.

[0075] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 84 and a light chain variable region with the amino acid sequence of SEQ ID NO: 85.

[0076] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 86 and a light chain variable region with the amino acid sequence of SEQ ID NO: 87.

[0077] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 88 and a light chain variable region with the amino acid sequence of SEQ ID NO: 89.

[0078] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 90 and a light chain variable region with the amino acid sequence of SEQ ID NO: 91.

[0079] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 92 and a light chain variable region with the amino acid sequence of SEQ ID NO: 93.

[0080] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 94 and a light chain variable region with the amino acid sequence of SEQ ID NO: 95.

[0081] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 96 and a light chain variable region with the amino acid sequence of SEQ ID NO: 97.

[0082] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 98 and a light chain variable region with the amino acid sequence of SEQ ID NO: 99.

[0083] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 100 and a light chain variable region with the amino acid sequence of SEQ ID NO: 101.

[0084] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 102 and a light chain variable region with the amino acid sequence of SEQ ID NO: 103.

[0085] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 104 and a light chain variable region with the amino acid sequence of SEQ ID NO: 105.

[0086] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 106 and a light chain variable region with the amino acid sequence of SEQ ID NO: 107.

[0087] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 108 and a light chain variable region with the amino acid sequence of SEQ ID NO: 109.

[0088] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 110 and a light chain variable region with the amino acid sequence of SEQ ID NO: 111.

[0089] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 112 and a light chain variable region with the amino acid sequence of SEQ ID NO: 113.

[0090] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 114 and a light chain variable region with the amino acid sequence of SEQ ID NO: 115.

[0091] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 116 and a light chain variable region with the amino acid sequence of SEQ ID NO: 117.

[0092] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 118 and a light chain variable region with the amino acid sequence of SEQ ID NO: 119.

[0093] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 120 and a light chain variable region with the amino acid sequence of SEQ ID NO: 121.

[0094] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 122 and a light chain variable region with the amino acid sequence of SEQ ID NO: 123.

[0095] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 124 and a light chain variable region with the amino acid sequence of SEQ ID NO: 125.

[0096] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 126 and a light chain variable region with the amino acid sequence of SEQ ID NO: 127.

[0097] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 128 and a light chain variable region with the amino acid sequence of SEQ ID NO: 129.

[0098] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 130 and a light chain variable region with the amino acid sequence of SEQ ID NO: 131.

[0099] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 132 and a light chain variable region with the amino acid sequence of SEQ ID NO: 133.

[0100] An antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 300 and a light chain variable region with the amino acid sequence of SEQ ID NO: 304.

[0101] In the examples mentioned below, a strong antitumor effect on cancer organisms was confirmed for a polyclonal antibody or a monoclonal antibody against the full-length CAPRIN-1 protein or against a polypeptide of a portion of the region expressed on the surface of the cell membrane of malignant cells in combination with imiquimod.

[0102] <Imiquimod>

Imiquimod of the present invention is a compound which is listed in CAS (American Chemical Society) No. 99011-02-6 and has a molecular weight of approximately 240.3, and is a toll-like receptor (TLR) 7 or 8 binding agonist. The name of imiquimod according to IUPAC 4-amino-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinoline and according to other nomenclature R837, S-26308, 1-(2-methylpropyl)-1H-imidazo[4,5 -c]quinoline-4-amine; 4-amino-1-isobutyl-1H-imidazo[4,5-c]quinoline, or 1-isobutyl-1H-inudazole[4,5-c]quinoline-4-amine; 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinoline-4-amine.

[0103] While imiquimod can be obtained by chemical synthesis according to methods known to those skilled in the art, in Japan "BESELNA CREAM 5%" and in Europe and the United States "Aldara(R) Cream 5%" have been launched as medicinal products. products containing imiquimod as the active ingredient. These drugs can be used appropriately when imiquimod is used in the present invention.

[0104] <Other Anticancer Agents>

The drug of the present invention may include, as an active ingredient, an antitumor agent known in the literature, etc., in addition to an anti-CAPRIN-1 antibody and imiquimod without inhibiting the effects as a drug of the present invention. Specific examples of known antitumor agents include, but are not specifically limited to, paclitaxel, doxorubicin, daunorubicin, cyclophosphamide, methotrexate, 5-fluorouracil, thiotepa, busulfan, improsulfan, piposulfan, benzodopa, carbokwone, meturedopa, uredopa, altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide, Trimethylomelamin, Bullatacin, Bullatacinone, Camptothecin, Bryostatin, Callistatin, Cryptophycin 1, Cryptophycin 8, Dolastatin, Duocarmycin, Eleuterobine, Pancratistatin, Sarcodictyin, Spongistatin, Chlorambucil, ChloRNAphasin, Holophosphamide, Estramustine, Ifosfamide, Mechlorethamine, Hydromethamine Oxide, Mellorethamine Oxide, Mellorethamine Oxide fenesterol, prednimustine, trofosfamide, uramustine, carmustine, chlorzotocin, fotemustine, lomustine, nimustine, ranimustine, calichimicin, dinemycin, clodronate, esperamycin, aclacinomycin, actinomycin, autramycin, azaserin, bleomycin, cactinomycin, carabicin, carminomycin, chromotinomycin, dacinophylline, detorbicin, 6-diazo-5-oxo- L-norleucine, adriamycin, epirubicin, esorubicin, idarubicin, marcellomycin, mitomycin C, mycophenolic acid, nogalamycin, olivomycin, peplomycin, potfiromycin, puromycin, quelamycin, rhodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin, pteropterin, trimetrexate, fludarabine, 6-mercaptopurine, thiamiprin, thioguanine, ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxyfluridine, enocytabine, floxuridine, androgens such as calusterone, dromostanolone propionate, epithiostanolone, mepitiostanol, mepitiostane , trilostane, frolinic acid, aseglaton, aldophosphamide glycoside, aminolevulinic acid, eniluracil, amsacrine, bestrabucil, bisantrene, edatraxate, defofamine, demecolcin, diaziquone, elfornithine, elliptinium acetate, epothilone, etoglucid, lentinan, lonidamine, maytansine, ansamitocasone, mitokazon , mopidanmol, nitraerin, pentostatin, fenamet, pyrarubicin, losoxantrone, podophyllin acid lotu, 2-ethylhydrazide, procarbazine, razoxane, rizoxin, schizophyllan, spirogermanium, tenuazonic acid, triaziquone, roridin A, anvidine, urethane, vindesine, dacarbazine, mannomustine, mitobronitol, mitolactol, pipobroman, hacytosine, docetaxel, chlorambucil, gemcitabine, 6- thioguanine, mercaptopurine, cisplatin, oxaliplatin, carboplatin, vinblastine, etoposide, ifosfamide, mitoxantrone, vincristine, vinorelbine, novantrone, teniposide, edatrexate, daunomycin, aminopterin, xelodu, ibandronate, irinotecan, topoisomerase inhibitor, difluoromethylornithine (DMFO), retitanic acid , and their pharmacologically acceptable (known) salts or (known) derivatives.

[0105] <Antineoplastic effect of the present invention>

The combination of an anti-CAPRIN-1 antibody and imiquimod of the present invention has cytotoxic activity in vivo . Thus, the antitumor effect of the present invention can be determined by examining the cytotoxic activity against a malignant tumor. Cytotoxic activity can be assessed by administering an anti-CAPRIN-1 antibody and imiquimod to a cancer host, measuring the size of the tumor after administration, and examining the size of the cancer over time. Also, the antitumor effect of the present invention can be evaluated by examining the survival rate. Alternatively, the antitumor effect of the present invention can be assessed by examining the ability to produce cytokines or chemokines. The antitumor effect of the combination of an anti-CAPRIN-1 antibody and imiquimod of the present invention can be further determined by evaluating cancer prevention, metastasis prevention, or relapse prevention.

[0106] It is expected that the anti-CAPRIN-1 antibody used in the present invention will have a stronger antitumor effect with a higher binding affinity of the CAPRIN-1 protein on the surface of cancer cells. The association constant (affinity constant) Ka (k _on /k _off ) is preferably at least 10 ⁷ M ^-1 , at least 10 ⁸ M ^-1 , at least 5×10 ⁸ M ^-1 , according to at least 10 ⁹ M ^-1 , at least 5×10 ⁹ M ^-1 , at least 10 ¹⁰ M ^-1 , at least 5×10 ¹⁰ M ^-1 , at least 10 ¹¹ M ^-1 at least 5× 0 ¹¹ M ^-1 , at least 10 ¹² M ^-1 , or at least 10 ¹³ M ^-1 .

[0107] The ability of an anti-CAPRIN-1 antibody used in the present invention to bind to CAPRIN-1 can be determined by a binding assay using, for example, ELISA, Western blotting, immunofluorescence, or flow cytometry analysis.

[0108] Administration of the combination of an anti-CAPRIN-1 antibody and imiquimod of the present invention to a cancerous organism enhances the anti-tumor effect compared to an anti-CAPRIN-1 antibody alone as described above. The magnification level is preferably 30% or more, more preferably 40% or more, more preferably 50% or more, even more preferably 60% or more, even more preferably 65% or more, and most preferably 70% or more. The level of increase in the antitumor effect of the combination of an anti-CAPRIN-1 antibody and imiquimod of the present invention relative to the administration of an anti-CAPRIN-1 antibody alone can be calculated by administering their respective effective amounts to mice bearing malignant tumors under the same conditions and comparing tumor volumes. on the seventh day or later after the start of administration.

[0109] <Medication for the treatment and/or prevention of cancer>

The drug of the present invention is aimed at the treatment and/or prevention of cancer. The cancer targeted by the drug of the present invention is not particularly limited as long as it is a cancer (cells) expressing the CAPRIN-1 protein.

[0110] The term "treatment" as used herein refers to the treatment of cancer based on the aforementioned antitumor effect. The term "prevention" as used herein refers not only to preventing the development of a malignant tumor, but also to preventing metastasis or recurrence of a malignant tumor.

[0111] Both the terms "tumor" and "malignant tumor" as used herein refer to a malignant neoplasm, and thus are used interchangeably.

[0112] A cancer that is a target in the present invention is any cancer, provided that the cancer expresses the CAPRIN-1 protein on the surface of the cell membrane. The malignant tumor is preferably basal cell carcinoma, Paget's disease, skin cancer, breast cancer, kidney cancer, pancreatic cancer, colon cancer, lung cancer, brain tumor, gastric cancer, uterine cancer, ovarian cancer, prostate cancer, cancer bladder cancer, esophageal cancer, leukemia, lymphoma, liver cancer, gallbladder cancer, sarcoma, mastocytoma, adrenal cortex cancer, Ewing's tumor, Hodgkin's lymphoma, mesothelioma, multiple myeloma, testicular cancer, thyroid cancer, head and neck cancer mentioned above , and more preferably a palpable cancer, a subcutaneous cancer, an intradermal cancer, a superficial cancer, a cancer located in the dermis, or a cancer located in a non-parenchymal organ. In addition, these cancers may be primary cancers, metastatic cancers, cancers that metastasize, or cancers that recur.

[0113] More specifically, non-limiting examples of a malignant tumor include, for example, Bowen's disease, melanoma, spiny cell cancer, extramammary Paget's disease, mycosis fungoides, Cesari's syndrome, cutaneous T/NK cell lymphoma, T cell leukemia, or lymphoma skin-only lesions, cutaneous B-cell lymphoma (slow-growing group), cutaneous T-cell lymphatic or mammary adenoma, mammary adenoma syndrome, malignant mixed breast tumor, intraductal papillary carcinoma of the breast, adenocarcinoma of the lung, squamous cell carcinoma, small cell carcinoma , large cell carcinoma, glioma, which is a tumor of neuroepithelial tissue, glioblastoma, neuroblastoma, ependymoma, neuronal tumor, neuroectodermal tumor, neurilemmoma, neurofibromatosis, meningioma, chronic lymphocytic leukemia, lymphoma, alimentary lymphoma, gastrointestinal lymphoma, small cell and medium cell lymphoma, cancer is blind colon, ascending colon cancer, descending colon cancer, transverse colon cancer, sigmoid colon cancer, rectal cancer, ovarian epithelial cancer, germ cell tumor, interstitial cell tumor, pancreatic duct cancer, invasive pancreatic duct cancer, pancreatic adenocarcinoma , acinar cell carcinoma, adenosquamous carcinoma, giant cell carcinoma, intraductal papillary mucinous tumor, mucinous cystadenocarcinoma, pancreatoblastoma, pancreatic islet cell tumor, Franz tumor, serous cystadenocarcinoma, solid pseudopapillary carcinoma, gastrinoma, glucagonoma, insulinoma, multiple endocrine neoplasia type 1 (Wermer's syndrome) , non-functional insulinoma, somatostatinoma, VIPoma, cervical cancer, uterine body cancer, fibrosarcoma, osteosarcoma, joint sarcoma, Ewing's sarcoma, Wilm's tumor, hepatoblastoma, soft tissue sarcoma, acute leukemia, chronic leukemia, spinal cord tumor, ra soft tissue, teratoma, and head and neck cancers, including laryngopharyngeal cancer, oropharyngeal cancer, tongue cancer, nasopharyngeal cancer, oral cavity cancer, lip cancer, sinus cancer, and laryngeal cancer. Cancer also includes palpable cancer, subcutaneous cancer, intradermal cancer, superficial cancer, dermal cancer, or non-parenchymal organ cancer that originated from the above-described cancers and have metastasized and recurred.

[0114] The preferred individual (patient) that can be a target is a mammal and is, for example, a mammal, including primates, domestic animals, livestock and animals for sport. Most preferred are humans, dogs and cats.

[0115] The drug of the present invention can be formulated in a manner known to those skilled in the art. For example, the drug can be used parenterally in the form of a parenteral injection: an aseptic solution containing water, or a pharmacologically acceptable non-aqueous solution; or liquid suspension. For example, a drug can be formulated with the combined use of a pharmacologically acceptable carrier or medium and specifically sterilized water, saline, vegetable oil, emulsifier, suspension, surfactant, stabilizer, flavoring agent, excipient, or binder, as appropriate by mixing in a standard dosage form. the form required, as a rule, for an acceptable pharmaceutical composition. The amount of active ingredient in the formulation is determined so that an appropriate dosage within the indicated range can be achieved.

[0116] An aseptic composition for injection can be prepared according to common formulation practice using a carrier such as distilled water for injection. The aqueous solution for injection includes, for example, saline or isotonic solutions containing glucose and other adjuvants such as D-sorbitol, D-mannose, D-mannitol and sodium chloride. Such a solution can be used with a suitable dissolution agent. Such dissolution agent includes, for example, alcohols such as ethanol and a polyalcohol such as propylene glycol, polyethylene glycol, or non-ionic surfactants such as polysorbate 80 (TM) and HCO-60. The oily liquid includes, for example, sesame oil or soybean oil. Such an oily liquid can be used in combination with a dissolving agent such as benzyl benzoate or benzyl alcohol. In addition, it can be mixed with a buffering agent such as a phosphate buffer solution or a sodium acetate buffer solution, a sedative such as procaine hydrochloride, a stabilizer such as benzyl alcohol or phenol, or an antioxidant. As a rule, a ready-made solution for injection is administered in more than sufficient quantities. The oily liquid includes, for example, sesame oil or soybean oil. Such an oily liquid can be used in combination with a dissolving agent such as benzyl benzoate or benzyl alcohol. In addition, it can be mixed with a buffering agent such as a phosphate buffer solution or a sodium acetate buffer solution, a sedative such as procaine hydrochloride, a stabilizer such as benzyl alcohol or phenol, or an antioxidant. As a rule, a ready-made solution for injection is administered in more than sufficient quantities.

[0117] The above pharmaceutical composition is administered orally or parenterally. Preferably it is administered parenterally. In particular, dosage forms include injectables, intranasal agents, pulmonary agents, and dermal agents. For example, injectables can be administered systemically or topically by intravenous injection, intramuscular injection, intraperitoneal injection, subcutaneous injection, or intratumoral injection. Transdermal agents include, for example, agents called liniments and topical drugs. Topical preparations include, for example, solids, solutions, sprays, ointments, creams and gels.

[0118] The route of administration can be determined appropriately depending on the age, weight, sex, and symptoms of the patient. A single dose of a pharmaceutical composition comprising an antibody or a polynucleotide encoding an antibody can be selected in the range, for example, from 0.0001 mg to 1000 mg per kg of body weight. Alternatively, the dose may be selected in the range of, for example, 0.001 to 100,000 mg per patient, or 1 to 30 mg per kg of patient body weight; however, it need not be limited to this. The dose and route of administration will vary depending on the age, weight, sex and symptoms of the patient. However, those skilled in the art can adjust the dosage and method accordingly.

[0119] Imiquimod has proven to be effective as a percutaneously administered anti-cancer agent and, based on the results, has been launched as an anti-cancer agent marketed under the name Aldara(R) (Imiquimod) Cream, 5%. Thus, the dosage form of imiquimod for administration to patients is preferably transdermal, preferably in the form of a cream. In the case of administering imiquimod to an individual, it may be administered according to the dosage and administration described in the package insert for Aldara(R) Cream, 5%.

[0120] <Administration method>

The treatment and/or prevention of cancer with the medicament for the treatment and/or prevention of cancer of the present invention relates to various methods, in addition to the administration as a medicine mentioned above. For example, the respective active ingredients in the medicament of the present invention may be administered simultaneously or individually in a staggered manner. As a specific example, the active ingredients can be administered over a period of time up to about three weeks, i. the second active ingredient can be administered either immediately or within about three weeks after administration of the first active ingredient. These administrations may be carried out prior to the surgical procedure, or the surgical procedure may be carried out between the administrations of the first and second drug. In addition, the therapeutic and/or prophylactic agent for cancer of the present invention may be administered according to a plurality of administration cycles. For example, in the case of simultaneous administration of respective active ingredients in a therapeutic and/or prophylactic agent for cancer of the present invention, a pharmaceutical composition containing both active ingredients is administered once over a period of about 2 days to about 3 weeks per cycle. Then this cycle of treatment can be repeated, if necessary, at the discretion of the attending physician. Similarly, in the case of a staggered formulation, the respective injection periods of the individual agents are adjusted to cover the same period. The interval between cycles can vary from 0 to 2 months. Appropriate doses of active ingredients of the therapeutic and/or prophylactic agent for cancer of the present invention can be set in the same manner as the corresponding doses of active ingredients in a pharmaceutical composition.

[0121] <Pharmaceutical Kit>

The cancer treatment and/or prevention drug of the present invention may be in the form of a pharmaceutical kit. A pharmaceutical kit is a package for the use of active ingredients in the form of separate pharmaceutical compositions in a method for the treatment and/or prevention of cancer. The package includes instructions for the introduction of each active ingredient. Suitable active ingredients in pharmaceutical compositions for the treatment and/or prevention of cancer contained in a pharmaceutical kit may be in the form of pharmaceutical compositions, each formulated as above, such that the active ingredients may be administered together or separately. In addition, the pharmaceutical kit contains the active ingredients in amounts sufficient for one or more doses, such that the active ingredients can be administered in accordance with the mode of administration described above.

[0122] Based on the content specifically described above, the present invention further relates to a method for treating and/or preventing a cancer, comprising administering a medicament of the present invention to an individual suspected of having a cancer. In this embodiment, the antibody or fragment thereof and the antitumor agent contained in the drug are administered to the individual simultaneously or separately.

Examples

[0123] The present invention is described in detail below with reference to the following examples, although the scope of the present invention is not limited to them.

[0124] Example 1 Anti-CAPRIN-1 Antibody Production

Anti-CAPRIN-1 antibodies with immunological reactivity with the CAPRIN-1 protein used in the present invention were prepared for use as described below.

[0125] (Polyclonal antibody)

One (1) mg of recombinant human CAPRIN-1 protein prepared according to Example 3 of WO2010/016526 was mixed with Incomplete Freund's Adjuvant (IFA) solution in an amount equivalent to the recombinant protein. The mixture was subcutaneously administered to the rabbit 4 times every 2 weeks. Then, blood was collected such that an antiserum containing a polyclonal antibody was obtained. In addition, antisera were purified with protein G vehicle (GE Healthcare Bio-Sciences) and replaced with PBS (-), and then a polyclonal anti-CAPRIN-1 protein antibody (anti-CAPRIN-1 polyclonal antibody #1) was obtained.

[0126] (Monoclonal antibody)

One hundred (100) μg of recombinant human CAPRIN-1 protein prepared according to Example 3 of WO2010/016526 was mixed with an MPL+TDM adjuvant (Sigma) in an amount equivalent to that of the antigenic protein. The mixture was used as an antigen solution per mouse. The antigen solution was intraperitoneally administered to 6-week-old Balb/c mice (Japan SLC Inc.) and then additionally administered 3 times and 24 times every week to complete the immunization. The spleen was removed on day 3 after the final immunization and then rubbed between two sterilized glass slides. Spleen cells were obtained by washing with PBS (-), centrifugation at 1500 rpm. for 10 minutes, and remove the supernatant, repeating the above 3 times. The resulting spleen cells were mixed with SP2/0 mouse myeloma cell (purchased from ATCC) at a ratio of 10:1. PEG solution prepared by mixing 200 µl of RPMI1640 medium containing 10% FBS heated to 37°C and 800 µl of PEG1500 (Boehringer) was added to the cells. The solution was incubated for 5 minutes for cell fusion. Centrifugation was carried out at 1700 rpm. for 5 minutes to remove supernatants. Cells were suspended in 150 ml of RPMI1640 medium (HAT selective medium) containing 15% FBS, to which was added a 2% equivalent of HAT solution (Gibco), and then seeded into fifteen 96-well plates (Nunc) at 100 μl per well. Cells were cultured for 7 days at 37° C. and 5% CO2, and thus hybridomas were obtained from the fusion of spleen cells with myeloma cells. Hybridomas were selected using the CAPRIN-1 protein binding affinity of the antibody produced by the resulting hybridomas as an indicator. CAPRIN-1 protein solution (1 μg/ml) was added at 100 μl per well to 96-well plates and then incubated at 4° C. for 18 hours. Each well was then washed 3 times with PBS-T, 0.5% bovine serum albumin (BSA) (Sigma) was added at 400 μl per well, and then the plates were incubated at room temperature for 3 hours. The solution was removed and then each well was washed 3 times with 400 μl PBS-T. Each culture supernatant from the hybridomas obtained above was added at 100 μl per well, and then incubated at room temperature for 2 hours. After each well was washed 3 times with PBS-T, HRP labeled anti-mouse IgG (H+L) (Invitrogen) diluted 5000-fold with PBS was added at 100 µl per well and incubated at room temperature for 1 hours. Then, each well was washed 3 times with PBS-T, a TMB substrate solution (Thermo) was added, 100 μl per well was added, and then incubated for 15-30 minutes, and thus a color reaction was performed. After the appearance of color, 1 N sulfuric acid was added at 100 μl per well to stop the reaction. The absorbance at 450 nm and the absorbance at 595 nm were measured using an absorption spectrometer. As a result, a plurality of hybridomas producing highly absorbing antibodies were selected. Selected hybridomas were added at 0.5 hybridomas per well to 96-well plates and then cultured. A week later, hybridomas were observed forming single colonies in the wells. The cells in these wells were further cultured. Hybridomas were selected using the CAPRIN-1 protein binding affinity of the antibody produced by the cloned hybridomas as an indicator. CAPRIN-1 protein solution (1 μg/ml) was added at 100 μl per well to 96-well plates and then incubated at 4° C. for 18 hours. Each well was then washed 3 times with PBS-T, 0.5% bovine serum albumin (BSA) (Sigma) was added at 400 μl per well, and then incubated at room temperature for 3 hours. The solution was removed and then each well was washed 3 times with 400 μl PBS-T. Each culture supernatant from the hybridomas obtained above was added at 100 μl per well, and then incubated at room temperature for 2 hours. After each well was washed 3 times with PBS-T, HRP labeled anti-mouse IgG (H+L) (Invitrogen) diluted 5000-fold with PBS was added at 100 µl per well and incubated at room temperature for 1 hours. Each well was washed 3 times with PBS-T, a TMB substrate solution (Thermo) was added, 100 μl per well was added, and then incubated for 15-30 minutes, and thus a color reaction was performed. After the appearance of color, 1 N sulfuric acid was added at 100 μl per well to stop the reaction. The absorbance at 450 nm and the absorbance at 595 nm were measured using an absorption spectrometer. As a result, a plurality of mouse monoclonal antibodies were obtained showing reactivity with the CAPRIN-1 protein.

[0127] The reactivity of each monoclonal antibody with human malignant cells with confirmed expression of the CAPRIN-1 protein on the surface of the cell membrane was further confirmed by flow cytometry. A control mouse IgG antibody showing no reactivity with malignant cells was used as a negative control. As a result of confirmation, several monoclonal antibodies were obtained which had a higher fluorescence intensity towards malignant cells than control mouse IgG antibodies and strongly reacted with the cell membrane surface of malignant cells expressing CAPRIN-1 on the cell membrane surface. Of these, the anti-CAPRIN-1 monoclonal antibody described in WO2013/125630, which was an antibody with the amino acid sequence of the heavy chain variable region shown in SEQ ID NO: 114 and the amino acid sequence of the light chain variable region shown in SEQ ID NO: 115 , was chosen as a monoclonal antibody showing reactivity with the CAPRIN-1 protein.

[0128] The heavy chain variable region CDR1-CDR3 of selected antibodies were identified. The nucleotide sequence was designed to express a heavy chain variable region in which the framework regions contain a human antibody sequence. This nucleotide sequence was inserted into a mammalian expression vector containing the human IgG1 heavy chain constant region insert. Light chain variable region CDR1-CDR3 were similarly identified. The nucleotide sequence was designed to express a light chain variable region in which the framework regions contained a human antibody sequence. This nucleotide sequence was inserted into a mammalian expression vector containing the human IgG1 light chain constant region insert. These two recombinant expression vectors were introduced into mammalian cells according to the conventional method, and then a culture supernatant containing a humanized monoclonal antibody #1 (humanized antibody #1) against CAPRIN-1 was obtained.

[0129] The obtained culture supernatant containing the obtained humanized monoclonal antibody #1 to CAPRIN-1 was purified using Hitrap Protein A Sepharose FF (GE Healthcare Bio-Sciences) according to the conventional method, replaced with PBS (-), and filtered through 0, 22 M filter (Millipore) to obtain the filtrate.

[0130] The specific reactivity of an anti-CAPRIN-1 antibody to the CAPRIN-1 protein was detected and confirmed by ELISA using the plate-immobilized CAPRIN-1 protein.

[0131] The reactivity of the anti-CAPRIN-1 antibody with malignant cells without treatment for cell membrane permeability was examined by flow cytometry to confirm that a portion of CAPRIN-1 is expressed on the cell membrane surface of malignant cells, as shown in the examples below.

[0132] Flow cytometry confirmed that against all samples including breast cancer cells (BT-474), colon cancer cells (HT-29), lung cancer cells (QG56 and H1650), gastric cancer cells (NCI-N87) , uterine cancer cells (HEC-1-A), prostate cancer cells (22Rv1), pancreatic cancer cells (Panc10.5), liver cancer cells (Hep3B), ovarian cancer cells (SKOV3), kidney cancer cells (Caki- 2), brain tumor cells (U-87MG), bladder cancer cells (T24), esophageal cancer cells (OE33), leukemia cells (OCI-AML5), lymphoma cells (Ramos), gallbladder cancer cells (TGBC14TKB), fibrosarcoma cells (HT-1080), and melanoma cells (G-361), which are human malignant cells with confirmed expression of the CAPRIN-1 gene, and mouse kidney cancer cells (Renca) and mouse mammary cancer cells (4T1) with confirmed expression gene CAPRIN-1, gu Manized antibody #1 had a stronger fluorescence intensity than the control human IgG antibody and rabbit IgG antibody serving as negative controls, which did not show reactivity with malignant cells, and strongly reacted with the cell membrane surfaces of malignant cells expressing CAPRIN-1.

[0133] Example 2 Antitumor effect of anti-CAPRIN-1 antibody and imiquimod combination.

Next, in vivo antitumor effects were evaluated in a cancerous mouse by administering combinations of anti-CAPRIN-1 antibody (anti-CAPRIN-1 polyclonal antibody #1 and humanized antibody #1) obtained in Example 1 and imiquimod.

[0134] In particular, the antitumor effect of the combination of an anti-CAPRIN-1 antibody and imiquimod of the present invention was studied using NOD-SCID mice subcutaneously transplanted with human malignant cells expressing the CAPRIN-1 protein. BT474 human breast cancer cells were subcutaneously transplanted at 10 ⁷ cells/mouse as a mixture with Matrigel (Sigma) and allowed to grow until the tumor reached a size of about 60 mm ³ to obtain a mouse with a malignant tumor. BT474 malignant cells express the CAPRIN-1 protein on cell membrane surfaces, and the anti-CAPRIN-1 antibodies prepared in Example 1 were confirmed to react with the portion of CAPRIN-1 present on cell membrane surfaces. Each anti-CAPRIN-1 antibody prepared in Example 1 was administered at a dose of 10 mg/kg once a week into the tail veins of the ten cancer mice described above. In these mice, imiquimod was started at the same time as the initial administration of anti-CAPRIN-1 antibody. "BESELNA CREAM 5%" containing imiquimod as an active ingredient (Mochida Pharmaceutical Co., Ltd; hereinafter referred to as "imiquimod cream") was applied for five consecutive days a week to the skin surface into which the malignant cells, and the next two days were not used. Similar antibody administration and imiquimod cream application as above was performed on day 8 from the start of antibody administration.

[0135] For the comparison group: the same dose of the same anti-CAPRIN-1 antibody as above was administered weekly to cancerous mice. The other control comparison group applied imiquimod at the same intervals as above to the surface of the skin into which the malignant cells had been transplanted to other individual mice with malignant tumor. Cancer mice in the no-treatment group were used as negative controls. After initiation of administration, the sizes of the malignant tumors in the malignant mice were measured over time with a caliper. Tumor volumes were calculated according to the standard method using the calculation equation: (length of the major axis of the tumor)×(length of the minor axis of the tumor) ² ×0.5.

[0136] As a result of the evaluation, the tumor volume was less than 60% in mice with a malignant tumor treated with polyclonal antibody #1 against CAPRIN-1 obtained in Example 1 and cream with imiquimod 45 days after the start of administration of polyclonal antibody #1 against CAPRIN- 1 when the tumor volume of the negative control was defined as 100%. As for the mice with malignant tumor in the control comparison groups, tumor volume was 78% in the group treated with anti-CAPRIN-1 polyclonal antibody #1 alone and 69% in the group treated with imiquimod cream alone.

[0137] Tumor volume was less than 33% in cancer mice treated with humanized antibody #1 prepared in Example 1 and imiquimod cream on day 48 after initiation of humanized antibody #1, which was a monoclonal antibody against CAPRIN -1 when the tumor volume of the negative control was defined as 100%. As for the cancer mice in the control comparison groups, tumor volume was 65% in the humanized antibody #1 group alone and 69% in the imiquimod cream alone group.

[0138] The results of this evaluation demonstrated that administration of a combination of anti-CAPRIN-1 antibody and imiquimod has a much stronger antitumor effect than administration of anti-CAPRIN-1 antibody alone or administration of imiquimod alone.

[0139] Example 3 Comparison with the antitumor effect of a combination of an anti-CAPRIN-1 antibody and an antitumor agent.

The in vivo antitumor effect was then comparatively studied in cancer mice for combinations of anti-CAPRIN-1 antibodies (polyclonal anti-CAPRIN-1 antibody #1 and humanized antibody #1) obtained in Example 1 with imiquimod and for combinations of these antibodies with existing an anticancer drug other than imiquimod.

[0140] In particular, the antitumor effect of the combination of an anti-CAPRIN-1 antibody and imiquimod of the present invention was studied using NOD-SCID mice subcutaneously transplanted with human malignant cells expressing the CAPRIN-1 protein. BT474 human breast cancer cells were subcutaneously transplanted at 10 ⁷ cells/mouse as a mixture with Matrigel (Sigma) and allowed to grow until the tumor reached a size of about 90 mm ³ to obtain a mouse with a malignant tumor. BT474 malignant cells express the CAPRIN-1 protein on cell membrane surfaces, and the anti-CAPRIN-1 antibodies prepared in Example 1 were confirmed to react with the portion of CAPRIN-1 present on cell membrane surfaces.

[0141] For the anti-CAPRIN-1 antibody/imiquimod combination treatment group, the anti-CAPRIN-1 antibody (humanized antibody #1) obtained in Example 1 was administered at a dose of 10 mg/kg once a week into the tail veins of ten cancer mice, described above. In these mice, imiquimod was additionally applied to the skin surface at the location of the malignant tumor simultaneously with the initial administration of anti-CAPRIN-1 antibody. "BESELNA CREAM 5%" containing imiquimod as an active ingredient (Mochida Pharmaceutical Co., Ltd .; hereinafter referred to as "imiquimod cream") was applied for five consecutive days a week to the surface of the skin in which transplanted malignant cells, and the next two days were not used. Similar antibody administration and imiquimod cream application as above was performed on day 8 from the start of antibody administration.

[0142] For the anti-CAPRIN-1 antibody/antitumor combination treatment group, the anti-CAPRIN-1 antibody (humanized antibody #1) obtained in Example 1 was administered at a dose of 10 mg/kg once a week into the tail veins of ten cancer mice . These mice were treated with the antitumor agents paclitaxel and docetaxel intraperitoneally at 7 mg/kg and 8 mg/kg, respectively, once a week, simultaneously with the initial administration of anti-CAPRIN-1 antibody.

[0143] For the control comparison group: the same dose of the same anti-CAPRIN-1 antibody as above was administered once a week to mice with a malignant tumor. After initiation of administration, the sizes of the malignant tumors in the malignant mice were measured over time with a caliper. Tumor volumes were calculated according to the standard method using the calculation equation: (length of the major axis of the tumor)×(length of the minor axis of the tumor) ² ×0.5.

[0144] As a result of comparative evaluation, the tumor volume was less than 20% in mice with a malignant tumor treated with the anti-CAPRIN-1 antibody prepared in Example 1 and imiquimod cream on day 53 after the start of administration of the humanized antibody #1, when the volume tumors in mice treated with anti-CAPRIN-1 antibody alone were defined as 100%. On the other hand, tumor volume was 47% or more for the respective combinations of paclitaxel and docetaxel with humanized antibody #1.

[0145] Similarly, in the same comparative evaluation as above for anti-CAPRIN-1 polyclonal antibody #1, tumor volume was less than 46% in cancer mice treated with the combination of anti-CAPRIN-1 polyclonal antibody #1 and imiquimod cream on day 30 after initiation of anti-CAPRIN-1 polyclonal antibody #1, when the tumor volume in mice treated with anti-CAPRIN-1 polyclonal antibody #1 alone was determined to be 100%. On the other hand, tumor volume was 65% or more for the respective combinations of paclitaxel and docetaxel with anti-CAPRIN-1 #1 polyclonal antibody.

[0146] The results of this evaluation demonstrated that the antitumor effect of treatment with a combination of an anti-CAPRIN-1 antibody and imiquimod has a much stronger synergistic antitumor effect compared to the antitumor effect of treatment with a combination of an anti-CAPRIN-1 antibody and an existing antitumor agent other than imiquimod.

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SEQUENCE LIST

<110> TORAY Industries, Inc.

<120> PHARMACEUTICAL COMPOSITION FOR THE TREATMENT AND/OR PREVENTION OF CANCER

<130> 19014

<150> JP 2018-067453

<151> 2018-03-30

<160> 309

<170>PatentIn version 3.5

<210> 1

<211> 5562

<212> DNA

<213> Homo sapiens

<220>

<221> CDS

<222> (190)..(2319)

<400> 1

cagagggctg ctggctggct aagtccctcc cgctcccggc tctcgcctca ctaggagcgg 60

ctctcggtgc agcgggacag ggcgaagcgg cctgcgccca cggagcgcgc gacactgccc 120

180

gcgcgcacg atg ccc tcg gcc acc agc cac agc ggg agc ggc agc aag tcg 231

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser

1 5 10

tcc gga ccg cca ccg ccg tcg ggt tcc tcc ggg agt gag gcg gcc gcg 279

Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala

15 20 25 30

gga gcc ggg gcc gcc gcg ccg gct tct cag cac ccc gca acc ggc acc 327

Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr

35 40 45

ggc gct gtc cag acc gag gcc atg aag cag att ctc ggg gtg atc gac 375

Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp

50 55 60

aag aaa ctt cgg aac ctg gag aag aaa aag ggt aag ctt gat gat tac 423

Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr

65 70 75

cag gaa cga atg aac aaa ggg gaa agg ctt aat caa gat cag ctg gat 471

Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp

80 85 90

gcc gtt tct aag tac cag gaa gtc aca aat aat ttg gag ttt gca aaa 519

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

95 100 105 110

gaa tta cag agg agt ttc atg gca cta agt caa gat att cag aaa aca 567

Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr

115 120 125

ata aag aag aca gca cgt cgg gag cag ctt atg aga gaa gaa gct gaa 615

Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu

130 135 140

cag aaa cgt tta aaa act gta ctt gag cta cag tat gtt ttg gac aaa 663

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

145 150 155

ttg gga gat gat gaa gtg cgg act gac ctg aaa caa ggt ttg aat gga 711

Leu Gly Asp Asp Glu Val Arg Thr Asp Leu Lys Gln Gly Leu Asn Gly

160 165 170

gtg cca ata ttg tcc gaa gag gag ttg tca ttg ttg gat gaa ttc tat 759

Val Pro Ile Leu Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr

175 180 185 190

aag cta gta gac cct gaa cgg gac atg agc ttg agg ttg aat gaa cag 807

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

195 200 205

tat gaa cat gcc tcc att cac ctg tgg gac ctg ctg gaa ggg aag gaa 855

Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu

210 215 220

aaa cct gta tgt gga acc acc tat aaa gtt cta aag gaa att gtt gag 903

Lys Pro Val Cys Gly Thr Thr Tyr Lys Val Leu Lys Glu Ile Val Glu

225 230 235

cgt gtt ttt cag tca aac tac ttt gac agc acc cac aac cac cag aat 951

Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn

240 245 250

ggg ctg tgt gag gaa gaa gag gca gcc tca gca cct gca gtt gaa gac 999

Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Ala Val Glu Asp

255 260 265 270

cag gta cct gaa gct gaa cct gag cca gca gaa gag tac act gag caa 1047

Gln Val Pro Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln

275 280 285

agt gaa gtt gaa tca aca gag tat gta aat aga cag ttc atg gca gaa 1095

Ser Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu

290 295 300

aca cag ttc acc agt ggt gaa aag gag cag gta gat gag tgg aca gtt 1143

Thr Gln Phe Thr Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val

305 310 315

gaa acg gtt gag gtg gta aat tca ctc cag cag caa cct cag gct gca 1191

Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala

320 325 330

tcc cct tca gta cca gag ccc cac tct ttg act cca gtg gct cag gca 1239

Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ala

335 340 345 350

gat ccc ctt gtg aga aga cag cga gta caa gac ctt atg gca caa atg 1287

Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met

355 360 365

cag ggt ccc tat aat ttc ata cag gat tca atg ctg gat ttt gaa aat 1335

Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn

370 375 380

cag aca ctt gat cct gcc att gta tct gca cag cct atg aat cca aca 1383

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

385 390 395

caa aac atg gac atg ccc cag ctg gtt tgc cct cca gtt cat tct gaa 1431

Gln Asn Met Asp Met Pro Gln Leu Val Cys Pro Pro Val His Ser Glu

400 405 410

tct aga ctt gct cag cct aat caa gtt cct gta caa cca gaa gcg aca 1479

Ser Arg Leu Ala Gln Pro Asn Gln Val Pro Val Gln Pro Glu Ala Thr

415 420 425 430

cag gtt cct ttg gta tca tcc aca agt gag ggg tac aca gca tct caa 1527

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

435 440 445

ccc ttg tac cag cct tct cat gct aca gag caa cga cca cag aag gaa 1575

Pro Leu Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu

450 455 460

cca att gat cag att cag gca aca atc tct tta aat aca gac cag act 1623

Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr

465 470 475

aca gca tca tca tcc ctt cct gct gcg tct cag cct caa gta ttt cag 1671

Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln

480 485 490

gct ggg aca agc aaa cct tta cat agc agt gga atc aat gta aat gca 1719

Ala Gly Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala

495 500 505 510

gct cca ttc caa tcc atg caa acg gtg ttc aat atg aat gcc cca gtt 1767

Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val

515 520 525

cct cct gtt aat gaa cca gaa act tta aaa cag caa aat cag tac cag 1815

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

530 535 540

gcc agt tat aac cag agc ttt tct agt cag cct cac caa gta gaa caa 1863

Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln

545 550 555

aca gag ctt cag caa gaa cag ctt caa aca gtg gtt ggc act tac cat 1911

Thr Glu Leu Gln Gln Glu Gln Leu Gln Thr Val Val Gly Thr Tyr His

560 565 570

ggt tcc cca gac cag tcc cat caa gtg act ggt aac cac cag cag cct 1959

Gly Ser Pro Asp Gln Ser His Gln Val Thr Gly Asn His Gln Gln Pro

575 580 585 590

cct cag cag aac act gga ttt cca cgt agc aat cag ccc tat tac aat 2007

Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr Tyr Asn

595 600 605

agt cgt ggt gtg tct cgt gga ggc tcc cgt ggt gct aga ggc ttg atg 2055

Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met

610 615 620

aat gga tac cgg ggc cct gcc aat gga ttc aga gga gga tat gat ggt 2103

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

625 630 635

tac cgc cct tca ttc tct aac act cca aac agt ggt tat aca cag tct 2151

Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Thr Gln Ser

640 645 650

cag ttc agt gct ccc cgg gat tac tct ggc tat caa cgg gat gga tat 2199

Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr

655 660 665 670

cag cag aat ttc aag cga ggc tct ggg cag agt gga cca cgg gga gcc 2247

Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala

675 680 685

cca cga ggt cgt gga ggg ccc cca aga ccc aac aga ggg atg ccg caa 2295

Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln

690 695 700

atg aac act cag caa gtg aat taa tctgattcac aggattatgt ttaatcgcca 2349

Met Asn Thr Gln Gln Val Asn

705

aaaacacact ggccagtgta ccataatatg ttaccagaag agttattatc tattgttct 2409

ccctttcagg aaacttattg taaagggact gttttcatcc cataaagaca ggactacaat 2469

tgtcagcttt ctattacctg gatatggaag gaaactattt ttactctgca tgttctgtcc 2529

taagcgtcat cttgagcctt gcacatgata ctcagattcc tcacccttgc ttaggagtaa 2589

2649

gcaagattga cttttatgac attggataaa atctacaaat cagccctcga gttattcaat 2709

gataactgac aaactaaatt attccctag aaaggaagat gaaaggagtg gagtgtggtt 2769

tggcagaaca actgcatttc acagcttttc cagttaaatt ggagcactga acgttcagat 2829

gcataccaaa ttatgcatgg gtcctaatca cacatataag gctggctacc agctttgaca 2889

cagcactgtt catctggcca aacaactgtg gttaaaaaca catgtaaaat gctttttaac 2949

agctgatact gtataagaca aagccaagat gcaaaattag gctttgattg gcactttttg 3009

aaaaatatgc aacaaatatg ggatgtaatc cggatggccg cttctgtact taatgtgaaa 3069

3129

3189 tggtactatc tatcattcct tatgacatgt

ctgtattgtc acctaaattg gtacaggtac tgatgaaaat ctctagtgga taatcataac 3249

actctcggtc acatgttttt ccttcagctt gaaagctttt ttttaaaagg aaaagatacc 3309

aaatgcctgc tgctaccacc cttttcaatt gctatctttt gaaaggcacc agtatgtgtt 3369

ttagattgat ttccctgttt cagggaaatc acggacagta gtttcagttc tgatggtata 3429

agcaaaacaa ataaaacgtt tataaaagtt gtatcttgaa acactggtgt tcaacagcta 3489

gcagcttatg tgattcaccc catgccacgt tagtgtcaca aattttatgg tttatctcca 3549

gcaacatttc tctagtactt gcacttatta tcttttgtct aatttaacct taactgaatt 3609

ctccgtttct cctggaggca tttatattca gtgataattc cttcccttag atgcataggg 3669

agagtctcta aatttgatgg aaatggacac ttgagtagtg acttagcctt atgtactctg 3729

ttggaatttg tgctagcagt ttgagcacta gttctgtgtg cctaggaagt taatgctgct 3789

tattgtctca ttctgacttc atggagaatt aatcccacct ttaagcaaag gctactaagt 3849

taatggtatt ttctgtgcag aaattaaatt ttatttttcag catttagccc aggaattctt 3909

ccagtaggtg ctcagctatt taaaaacaaa actattctca aacattcatc attagacaac 3969

tggagtttt gctggttttg taacctacca aaatggatag gctgttgaac attccacatt 4029

caaaagtttt gtagggtggt gggaaatgggg ggatcttcaa tgtttatttt aaaataaaat 4089

aaaataagtt cttgactttt ctcatgtgtg gttgtggtac atcatattgg aagggttaac 4149

ctgttacttt ggcaaatgag tatttttttg ctagcacctc cccttgcgtg ctttaaatga 4209

catctgcctg ggatgtacca caaccatatg ttacctgtat cttaggggaa tggataaaat 4269

atttgtggtt tactgggtaa tccctagatg atgtatgctt gcagtcctat ataaaactaa 4329

atttgctatc tgtgtagaaa ataatttcat gacatttaca atcaggactg aagtaagttc 4389

ttcacacagt gacctctgaa tcagtttcag agaagggatg ggggagaaaa tgccttctag 4449

4509 gttttgaact tctatgcatt agtgcagatg ttgtgaatgt

actgtttcta tgtatgtttt ttcaaagaat tgttcctttt tttgaactat aatttttctt 4569

tttttggtta ttttaccatc acagtttaaa tgtatatctt ttatgtctct actcagacca 4629

tatttttaaa ggggtgcctc attatggggc agagaacttt tcaataagtc tcattaagat 4689

ctgaatcttg gttctaagca ttctgtataa tatgtgattg cttgtcctag ctgcagaagg 4749

ccttttgttt ggtcaaatgc atattttagc agagtttcaa ggaaatgatt gtcacacatg 4809

tcactgtagc ctcttggtgt agcaagctca catacaaaat acttttgtat atgcataata 4869

taaatcatct catgtggata tgaaacttct tttttaaaac ttaaaaaggt agaatgttat 4929

tgattacctt gattagggca gttttatttc cagatcctaa taattcctaa aaaatatgga 4989

aaagtttttt ttcaatcatt gtaccttgat attaaaacaa atatccttta agtatttcta 5049

atcagttagc ttctacagtt cttttgtctc cttttatatg cagctcttac gtgggagact 5109

tttccactta aaggagacat agaatgtgtg cttattctca gaaggttcat taactgaggt 5169

gatgagttaa caactagttg agcagtcagc ttcctaagtg ttttaggaca tttgttcatt 5229

atattttccg tcatataact agaggaagtg gaatgcagat aagtgccgaa ttcaaaccct 5289

tcatttttg tttaagctcc tgaatctgca ttccacttgg gttgttttta agcattctaa 5349

attttagttg attataagtt agatttcaca gaatcagtat tgcccttgat cttgtccttt 5409

ttatggagtt aacgggggagg aagacccctc aggaaaacga aagtaaattg ttaaggctca 5469

tcttcatacc tttttccatt ttgaatccta caaaaatact gcaaaagact agtgaatgtt 5529

taaaattaca ctagattaaa taatatgaaa gtc 5562

<210> 2

<211> 709

<212> Protein

<213> Homo sapiens

<400> 2

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala

20 25 30

Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala

35 40 45

Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys

50 55 60

Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu

65 70 75 80

Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val

85 90 95

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

100 105 110

Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys

115 120 125

Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Glu Ala Glu Gln Lys

130 135 140

Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly

145 150 155 160

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

165 170 175

Ile Leu Ser Glu Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu

180 185 190

Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu

195 200 205

His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro

210 215 220

Val Cys Gly Thr Thr Tyr Lys Val Leu Lys Glu Ile Val Glu Arg Val

225 230 235 240

Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu

245 250 255

Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Ala Val Glu Asp Gln Val

260 265 270

Pro Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu

275 280 285

Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln

290 295 300

Phe Thr Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr

305 310 315 320

Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro

325 330 335

Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ala Asp Pro

340 345 350

Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly

355 360 365

Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr

370 375 380

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

385 390 395 400

Met Asp Met Pro Gln Leu Val Cys Pro Val His Ser Glu Ser Arg

405 410 415

Leu Ala Gln Pro Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val

420 425 430

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

435 440 445

Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Ile

450 455 460

Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala

465 470 475 480

Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly

485 490 495

Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro

500 505 510

Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro

515 520 525

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

530 535 540

Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu

545 550 555 560

Leu Gln Gln Glu Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser

565 570 575

Pro Asp Gln Ser His Gln Val Thr Gly Asn His Gln Gln Pro Pro Gln

580 585 590

Gln Asn Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr Tyr Asn Ser Arg

595 600 605

Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly

610 615 620

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

625 630 635 640

Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Thr Gln Ser Gln Phe

645 650 655

Ser Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln

660 665 670

Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg

675 680 685

Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln Met Asn

690 695 700

Thr Gln Gln Val Asn

705

<210> 3

<211> 3553

<212> DNA

<213> Homo sapiens

<220>

<221> CDS

<222> (190)..(2274)

<400> 3

cagagggctg ctggctggct aagtccctcc cgctcccggc tctcgcctca ctaggagcgg 60

ctctcggtgc agcgggacag ggcgaagcgg cctgcgccca cggagcgcgc gacactgccc 120

180

gcgcgcacg atg ccc tcg gcc acc agc cac agc ggg agc ggc agc aag tcg 231

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser

1 5 10

tcc gga ccg cca ccg ccg tcg ggt tcc tcc ggg agt gag gcg gcc gcg 279

Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala

15 20 25 30

gga gcc ggg gcc gcc gcg ccg gct tct cag cac ccc gca acc ggc acc 327

Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr

35 40 45

ggc gct gtc cag acc gag gcc atg aag cag att ctc ggg gtg atc gac 375

Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp

50 55 60

aag aaa ctt cgg aac ctg gag aag aaa aag ggt aag ctt gat gat tac 423

Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr

65 70 75

cag gaa cga atg aac aaa ggg gaa agg ctt aat caa gat cag ctg gat 471

Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp

80 85 90

gcc gtt tct aag tac cag gaa gtc aca aat aat ttg gag ttt gca aaa 519

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

95 100 105 110

gaa tta cag agg agt ttc atg gca cta agt caa gat att cag aaa aca 567

Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr

115 120 125

ata aag aag aca gca cgt cgg gag cag ctt atg aga gaa gaa gct gaa 615

Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu

130 135 140

cag aaa cgt tta aaa act gta ctt gag cta cag tat gtt ttg gac aaa 663

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

145 150 155

ttg gga gat gat gaa gtg cgg act gac ctg aaa caa ggt ttg aat gga 711

Leu Gly Asp Asp Glu Val Arg Thr Asp Leu Lys Gln Gly Leu Asn Gly

160 165 170

gtg cca ata ttg tcc gaa gag gag ttg tca ttg ttg gat gaa ttc tat 759

Val Pro Ile Leu Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr

175 180 185 190

aag cta gta gac cct gaa cgg gac atg agc ttg agg ttg aat gaa cag 807

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

195 200 205

tat gaa cat gcc tcc att cac ctg tgg gac ctg ctg gaa ggg aag gaa 855

Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu

210 215 220

aaa cct gta tgt gga acc acc tat aaa gtt cta aag gaa att gtt gag 903

Lys Pro Val Cys Gly Thr Thr Tyr Lys Val Leu Lys Glu Ile Val Glu

225 230 235

cgt gtt ttt cag tca aac tac ttt gac agc acc cac aac cac cag aat 951

Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn

240 245 250

ggg ctg tgt gag gaa gaa gag gca gcc tca gca cct gca gtt gaa gac 999

Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Ala Val Glu Asp

255 260 265 270

cag gta cct gaa gct gaa cct gag cca gca gaa gag tac act gag caa 1047

Gln Val Pro Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln

275 280 285

agt gaa gtt gaa tca aca gag tat gta aat aga cag ttc atg gca gaa 1095

Ser Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu

290 295 300

aca cag ttc acc agt ggt gaa aag gag cag gta gat gag tgg aca gtt 1143

Thr Gln Phe Thr Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val

305 310 315

gaa acg gtt gag gtg gta aat tca ctc cag cag caa cct cag gct gca 1191

Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala

320 325 330

tcc cct tca gta cca gag ccc cac tct ttg act cca gtg gct cag gca 1239

Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ala

335 340 345 350

gat ccc ctt gtg aga aga cag cga gta caa gac ctt atg gca caa atg 1287

Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met

355 360 365

cag ggt ccc tat aat ttc ata cag gat tca atg ctg gat ttt gaa aat 1335

Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn

370 375 380

cag aca ctt gat cct gcc att gta tct gca cag cct atg aat cca aca 1383

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

385 390 395

caa aac atg gac atg ccc cag ctg gtt tgc cct cca gtt cat tct gaa 1431

Gln Asn Met Asp Met Pro Gln Leu Val Cys Pro Pro Val His Ser Glu

400 405 410

tct aga ctt gct cag cct aat caa gtt cct gta caa cca gaa gcg aca 1479

Ser Arg Leu Ala Gln Pro Asn Gln Val Pro Val Gln Pro Glu Ala Thr

415 420 425 430

cag gtt cct ttg gta tca tcc aca agt gag ggg tac aca gca tct caa 1527

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

435 440 445

ccc ttg tac cag cct tct cat gct aca gag caa cga cca cag aag gaa 1575

Pro Leu Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu

450 455 460

cca att gat cag att cag gca aca atc tct tta aat aca gac cag act 1623

Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr

465 470 475

aca gca tca tca tcc ctt cct gct gcg tct cag cct caa gta ttt cag 1671

Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln

480 485 490

gct ggg aca agc aaa cct tta cat agc agt gga atc aat gta aat gca 1719

Ala Gly Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala

495 500 505 510

gct cca ttc caa tcc atg caa acg gtg ttc aat atg aat gcc cca gtt 1767

Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val

515 520 525

cct cct gtt aat gaa cca gaa act tta aaa cag caa aat cag tac cag 1815

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

530 535 540

gcc agt tat aac cag agc ttt tct agt cag cct cac caa gta gaa caa 1863

Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln

545 550 555

aca gag ctt cag caa gaa cag ctt caa aca gtg gtt ggc act tac cat 1911

Thr Glu Leu Gln Gln Glu Gln Leu Gln Thr Val Val Gly Thr Tyr His

560 565 570

ggt tcc cca gac cag tcc cat caa gtg act ggt aac cac cag cag cct 1959

Gly Ser Pro Asp Gln Ser His Gln Val Thr Gly Asn His Gln Gln Pro

575 580 585 590

cct cag cag aac act gga ttt cca cgt agc aat cag ccc tat tac aat 2007

Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr Tyr Asn

595 600 605

agt cgt ggt gtg tct cgt gga ggc tcc cgt ggt gct aga ggc ttg atg 2055

Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met

610 615 620

aat gga tac cgg ggc cct gcc aat gga ttc aga gga gga tat gat ggt 2103

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

625 630 635

tac cgc cct tca ttc tct aac act cca aac agt ggt tat aca cag tct 2151

Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Thr Gln Ser

640 645 650

cag ttc agt gct ccc cgg gat tac tct ggc tat caa cgg gat gga tat 2199

Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr

655 660 665 670

cag cag aat ttc aag cga ggc tct ggg cag agt gga cca cgg gga gcc 2247

Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala

675 680 685

cca cga ggt aat att ttg tgg tgg tga tcctagctcc taagtggagc 2294

Pro Arg Gly Asn Ile Leu Trp Trp

690

ttctgttctg gccttggaag agctgttaat agtctgcatg ttaggaatac atttatcctt 2354

tccagacttg ttgctagggga ttaaatgaaa tgctctgttt ctaaaactta atcttggacc 2414

caaattttaa tttttgaatg atttaatttt ccctgttact atataaactg tcttgaaaac 2474

tagaacatat tctcttctca gaaaaagtgt ttttccaact gaaaattatt tttcaggtcc 2534

taaaacctgc taaatgtttt taggaagtac ttactgaaac atttttgtaa gacatttttg 2594

gaatgagatt gaacatttat ataaatttat tattcctctt tcattttttt gaaacatgcc 2654

tattatattt tagggccaga caccctttaa tggccggata agccatagtt aacatttaga 2714

gaaccattta gaagtgatag aactaatgga atttgcaatg ccttttggac ctctattagt 2774

gatataaata tcaagttatt tctgactttt aaacaaaact cccaaattcc taacttattg 2834

agctatactt aaaaaaaatt acaggtttag agagtttttt gtttttcttt tactgttgga 2894

aaactacttc ccattttggc aggaagttaa cctatttaac aattagagct agcatttcat 2954

gtagtctgaa attctaaatg gttctctgat ttgagggagg ttaaacatca aacaggtttc 3014

ctctattggc cataacatgt ataaaatgtg tgttaaggag gaattacaac gtactttgat 3074

ttgaatacta gtagaaactg gccaggaaaa aggtacattt ttctaaaaat taatggatca 3134

cttgggaatt actgacttga ctagaagtat caaagggatgt ttgcatgtga atgtgggtta 3194

tgttctttcc caccttgtag catattcgat gaaagttgag ttaactgata gctaaaaatc 3254

tgttttaaca gcatgtaaaa agttatttta tctgttaaaa gtcattatac agttttgaat 3314

3374

attaattttg atagtatgat gttacttact actgaaatgt aagctagagt gtacactaga 3434

atgtaagctc catgagagca ggtaccttgt ctgtcttctc tgctgtatct attcccaacg 3494

cttgatgatg gtgcctggca catagtaggc actcaataaa tatttgttga atgaatgaa 3553

<210> 4

<211> 694

<212> Protein

<213> Homo sapiens

<400> 4

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala

20 25 30

Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala

35 40 45

Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys

50 55 60

Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu

65 70 75 80

Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val

85 90 95

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

100 105 110

Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys

115 120 125

Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Glu Ala Glu Gln Lys

130 135 140

Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly

145 150 155 160

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

165 170 175

Ile Leu Ser Glu Glu Glu Glu Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu

180 185 190

Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu

195 200 205

His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro

210 215 220

Val Cys Gly Thr Thr Tyr Lys Val Leu Lys Glu Ile Val Glu Arg Val

225 230 235 240

Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu

245 250 255

Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Ala Val Glu Asp Gln Val

260 265 270

Pro Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu

275 280 285

Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln

290 295 300

Phe Thr Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr

305 310 315 320

Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro

325 330 335

Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ala Asp Pro

340 345 350

Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly

355 360 365

Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr

370 375 380

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

385 390 395 400

Met Asp Met Pro Gln Leu Val Cys Pro Val His Ser Glu Ser Arg

405 410 415

Leu Ala Gln Pro Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val

420 425 430

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

435 440 445

Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Ile

450 455 460

Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala

465 470 475 480

Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe Gln Ala Gly

485 490 495

Thr Ser Lys Pro Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro

500 505 510

Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro

515 520 525

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

530 535 540

Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu

545 550 555 560

Leu Gln Gln Glu Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser

565 570 575

Pro Asp Gln Ser His Gln Val Thr Gly Asn His Gln Gln Pro Pro Gln

580 585 590

Gln Asn Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr Tyr Asn Ser Arg

595 600 605

Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly

610 615 620

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

625 630 635 640

Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Thr Gln Ser Gln Phe

645 650 655

Ser Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln

660 665 670

Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg

675 680 685

Gly Asn Ile Leu Trp Trp

690

<210> 5

<211> 1605

<212> DNA

<213> Canis familiaris

<220>

<221> CDS

<222> (46)..(1392)

<400> 5

gtcacaaata acttggagtt tgcaaaagaa ttacagagga gtttc atg gca tta agt 57

Met Ala Leu Ser

one

caa gat att cag aaa aca ata aag aag act gca cgt cgg gag cag ctt 105

Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu

5 10 15 20

atg aga gag gaa gcg gaa caa aaa cgt tta aaa act gta ctt gag ctc 153

Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu

25 30 35

cag tat gtt ttg gac aaa ttg gga gat gat gaa gtg aga act gac ctg 201

Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu

40 45 50

aag caa ggt ttg aat gga gtg cca ata ttg tct gaa gaa gaa ttg tcg 249

Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Glu Leu Ser

55 60 65

ttg ttg gat gaa ttc tac aaa tta gca gac cct gaa cgg gac atg agc 297

Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser

70 75 80

ttg agg ttg aat gag cag tat gaa cat gct tcc att cac ctg tgg gac 345

Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp

85 90 95 100

ttg ctg gaa gga aag gaa aag tct gta tgt gga aca acc tat aaa gca 393

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

105 110 115

cta aag gaa att gtt gag cgt gtt ttc cag tca aat tac ttt gac agc 441

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

120 125 130

act cac aac cac cag aat ggg cta tgt gag gaa gaa gag gca gcc tca 489

Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser

135 140 145

gca cct aca gtt gaa gac cag gta gct gaa gct gag cct gag cca gca 537

Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala

150 155 160

gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat gta aat 585

Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn

165 170 175 180

aga caa ttt atg gca gaa aca cag ttc agc agt ggt gaa aag gag cag 633

Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln

185 190 195

gta gat gag tgg acg gtc gaa aca gtg gag gtg gtg aat tca ctc cag 681

Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln

200 205 210

cag caa cct cag gct gcg tct cct tca gta cca gag ccc cac tct ttg 729

Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu

215 220 225

act ccg gtg gct cag gca gat ccc ctt gtg aga aga cag cga gtc cag 777

Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln

230 235 240

gac ctt atg gcg cag atg cag ggg ccc tat aat ttc ata cag gat tca 825

Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser

245 250 255 260

atg ctg gat ttt gaa aac cag aca ctc gat cct gcc att gta tct gca 873

Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala

265 270 275

cag cct atg aat ccg aca caa aac atg gac atg ccc cag ctg gtt tgc 921

Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys

280 285 290

cct cca gtt cat tct gaa tct aga ctt gct caa cct aat caa gtt cct 969

Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro

295 300 305

gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt gag 1017

Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu

310 315 320

ggg tat aca gca tct caa ccc ttg tac cag cct tct cat gct aca gag 1065

Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu

325 330 335 340

caa cga cca caa aag gaa cca att gac cag att cag gca aca atc tct 1113

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

345 350 355

tta aat aca gac cag act aca gcg tca tca tcc ctt ccg gct gct tct 1161

Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser

360 365 370

cag cct cag gta ttc cag gct ggg aca agc aaa cca tta cat agc agt 1209

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

375 380 385

gga atc aat gta aat gca gct cca ttc caa tcc atg caa acg gtg ttc 1257

Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe

390 395 400

aat atg aat gcc cca gtt cct cct gtt aat gaa cca gaa act ttg aaa 1305

Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys

405 410 415 420

caa caa aat cag tac cag gcc agt tat aac cag agc ttt tct agt cag 1353

Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln

425 430 435

cct cac caa gta gaa caa aca gag gga tgc cgc aaa tga acactcagca 1402

Pro His Gln Val Glu Gln Thr Glu Gly Cys Arg Lys

440 445

agtgaattaa tctgattcac aggattatgt ttaaacgcca aaaacacact ggccagtgta 1462

ccataatatg ttaccagaag agttattatc tatttgttct ccctttcagg aaacttattg 1522

taaagggact gttttcatcc cataaagaca ggactacaat tgtcagcttt atattacctg 1582

gaaaaaaaaaaaaaaaaaaaaa 1605

<210> 6

<211> 448

<212> Protein

<213> Canis familiaris

<400> 6

Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg

1 5 10 15

Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr

20 25 30

Val Leu Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val

35 40 45

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

50 55 60

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

65 70 75 80

Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile

85 90 95

His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Ser Val Cys Gly Thr

100 105 110

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

115 120 125

Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu

130 135 140

Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu

145 150 155 160

Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr

165 170 175

Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly

180 185 190

Glu Lys Glu Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val

195 200 205

Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu

210 215 220

Pro His Ser Leu Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg

225 230 235 240

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

245 250 255

Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala

260 265 270

Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro

275 280 285

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

290 295 300

Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser

305 310 315 320

Ser Thr Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser

325 330 335

His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln Ile Gln

340 345 350

Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu

355 360 365

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

370 375 380

Leu His Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met

385 390 395 400

Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro

405 410 415

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

420 425 430

Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Gly Cys Arg Lys

435 440 445

<210> 7

<211> 4154

<212> DNA

<213> Canis familiaris

<220>

<221> CDS

<222> (1)..(2154)

<400> 7

atg ccg tcg gcc acc agc ctc agc gga agc ggc agc aag tcg tcg ggc 48

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

1 5 10 15

ccg ccg ccc ccg tcg ggt tcc tcc ggg agc gag gcg gcg gcg gcg gcg 96

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala

20 25 30

ggg gcg gcg ggg gcg gcg ggg gcc ggg gcg gct gcg ccc gcc tcc cag 144

Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln

35 40 45

cac ccc gcg acc ggc acc ggc gct gtc cag acc gag gcc atg aag cag 192

His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln

50 55 60

atc ctc ggg gtg atc gac aag aaa ctc cgg aac ctg gag aag aaa aag 240

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

65 70 75 80

ggc aag ctt gat gat tac cag gaa cga atg aac aaa ggg gaa agg ctt 288

Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu

85 90 95

aat caa gat cag ctg gat gcc gta tct aag tac cag gaa gtc aca aat 336

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

100 105 110

aac ttg gag ttt gca aaa gaa tta cag agg agt ttc atg gca tta agt 384

Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser

115 120 125

caa gat att cag aaa aca ata aag aag act gca cgt cgg gag cag ctt 432

Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu

130 135 140

atg aga gag gaa gcg gaa caa aaa cgt tta aaa act gta ctt gag ctc 480

Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu

145 150 155 160

cag tat gtt ttg gac aaa ttg gga gat gat gaa gtg aga act gac ctg 528

Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu

165 170 175

aag caa ggt ttg aat gga gtg cca ata ttg tct gaa gaa gaa ttg tcg 576

Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Glu Leu Ser

180 185 190

ttg ttg gat gaa ttc tac aaa tta gca gac cct gaa cgg gac atg agc 624

Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser

195 200 205

ttg agg ttg aat gag cag tat gaa cat gct tcc att cac ctg tgg gac 672

Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp

210 215 220

ttg ctg gaa gga aag gaa aag tct gta tgt gga aca acc tat aaa gca 720

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

225 230 235 240

cta aag gaa att gtt gag cgt gtt ttc cag tca aat tac ttt gac agc 768

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

245 250 255

act cac aac cac cag aat ggg cta tgt gag gaa gaa gag gca gcc tca 816

Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser

260 265 270

gca cct aca gtt gaa gac cag gta gct gaa gct gag cct gag cca gca 864

Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala

275 280 285

gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat gta aat 912

Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn

290 295 300

aga caa ttt atg gca gaa aca cag ttc agc agt ggt gaa aag gag cag 960

Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln

305 310 315 320

gta gat gag tgg acg gtc gaa aca gtg gag gtg gtg aat tca ctc cag 1008

Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln

325 330 335

cag caa cct cag gct gcg tct cct tca gta cca gag ccc cac tct ttg 1056

Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu

340 345 350

act ccg gtg gct cag gca gat ccc ctt gtg aga aga cag cga gtc cag 1104

Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln

355 360 365

gac ctt atg gcg cag atg cag ggg ccc tat aat ttc ata cag gat tca 1152

Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser

370 375 380

atg ctg gat ttt gaa aac cag aca ctc gat cct gcc att gta tct gca 1200

Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala

385 390 395 400

cag cct atg aat ccg aca caa aac atg gac atg ccc cag ctg gtt tgc 1248

Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys

405 410 415

cct cca gtt cat tct gaa tct aga ctt gct caa cct aat caa gtt cct 1296

Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro

420 425 430

gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt gag 1344

Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu

435 440 445

ggg tat aca gca tct caa ccc ttg tac cag cct tct cat gct aca gag 1392

Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu

450 455 460

caa cga cca caa aag gaa cca att gac cag att cag gca aca atc tct 1440

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

465 470 475 480

tta aat aca gac cag act aca gcg tca tca tcc ctt ccg gct gct tct 1488

Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser

485 490 495

cag cct cag gta ttc cag gct ggg aca agc aaa cca tta cat agc agt 1536

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

500 505 510

gga atc aat gta aat gca gct cca ttc caa tcc atg caa acg gtg ttc 1584

Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe

515 520 525

aat atg aat gcc cca gtt cct cct gtt aat gaa cca gaa act ttg aaa 1632

Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys

530 535 540

caa caa aat cag tac cag gcc agt tat aac cag agc ttt tct agt cag 1680

Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln

545 550 555 560

cct cac caa gta gaa caa aca gac ctt cag caa gaa cag ctt caa aca 1728

Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr

565 570 575

gtg gtt ggc act tac cat ggt tcc cag gac cag ccc cac caa gtg act 1776

Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr

580 585 590

ggt aac cat cag cag cct ccc cag cag aac act gga ttt cca cgt agc 1824

Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser

595 600 605

agt cag ccc tat tac aat agt cgt ggt gtg tct cgt ggt ggt tcc cgt 1872

Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg

610 615 620

ggt gct aga ggc tta atg aat gga tac agg ggc cct gcc aat gga ttc 1920

Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe

625 630 635 640

aga gga gga tat gat ggt tac cgc cct tca ttc tct aac act cca aac 1968

Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn

645 650 655

agt ggt tat aca cag tct cag ttc agt gct ccc cgg gac tac tct ggc 2016

Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly

660 665 670

tat cag cgg gat gga tat cag cag aat ttc aag cga ggc tct ggg cag 2064

Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln

675 680 685

agt gga cca cgg gga gcc cca cga ggt cgt gga ggg ccc cca aga ccc 2112

Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro

690 695 700

aac aga ggg atg ccg caa atg aac act cag caa gtg aat taa 2154

Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn

705 710 715

tctgattcac aggattatgt ttaaacgcca aaaacacact ggccagtgta ccataatatg 2214

ttaccagaag agttattatc tatttgttct ccctttcagg aaacttattg taaagggact 2274

gttttcatcc cataaagaca ggactacaat tgtcagcttt atattacctg gatatggaag 2334

gaaactattt ttattctgca tgttcttcct aagcgtcatc ttgagccttg cacatgatac 2394

tcagattcct cacccttgct taggagtaaa acataataca ctttacaggg tgatatctcc 2454

atagttattt gaagtggctt ggaaaaagca agattaactt ctgacattgg ataaaaatca 2514

acaaatcagc cctagagtta ttcaaatggt aattgacaaa aactaaaata tttcccttcg 2574

agaaggagtg gaatgtggtt tggcagaaca actgcatttc acagcttttc cggttaaatt 2634

ggagcactaa acgtttagat gcataccaaa ttatgcatgg gcccttaata taaaaggctg 2694

gctaccagct ttgacacagc actattcatc ctctggccaa acaactgtgg ttaaacaaca 2754

catgtaaatt gctttttaac agctgatact ataataagac aaagccaaaa tgcaaaaatt 2814

gggctttgat tggcactttt tgaaaaatat gcaacaaata tgggatgtaa tctggatggc 2874

2934

gacaatgact tttgtaagga ttggtactat ctatcattcc ttataatgta cattgtctgt 2994

cactaatcct cagatctgc tgtattgtca cctaaattgg tacaggtact gatgaaaata 3054

tctaatggat aatcataaca ctcttggtca catgtttttc ctgcagcctg aaggttttta 3114

3174

gcaccagtat gtgttttaga ttgatttccc tattttaggg aaatgacaga cagtagtttc 3234

agttctgatg gtataagcaa aacaaataaa acatgtttat aaaagttgta tcttgaaaca 3294

ctggtgttca acagctagca gcttatgtgg ttcaccccat gcattgttag tgtttcagat 3354

tttatggtta tctccagcag ctgtttctgt agtacttgca tttatctttt gtctaaccct 3414

aatattctca cggaggcatt tatattcaaa gtggtgatcc cttcacttag acgcataggg 3474

agagtcacaa gtttgatgaa gaggacagtg tagtaattta tatgctgttg gaatttgtgc 3534

tagcagtttg agcactagtt ctgtgtgcct atgaacttaa tgctgcttgt catattccac 3594

tttgacttca tggagaatta atcccatcta ctcagcaaag gctatactaa tactaagtta 3654

atggtatttt ctgtgcagaa attgaatttt gttttattag catttagcta aggaattttt 3714

ccagtaggtg ctcagctact aaagaaaaac aaaaacaaga cacaaaacta ttctcaaaca 3774

ttcattgtta gacaactgga gtttttgctg gttttgtaac ctactaaaat ggataggctg 3834

ttgaacattc cacattcaaa agttttttgt agggtggtgg ggaagggggg gtgtcttcaa 3894

tgtttatttt aaaataaaat aagttcttga cttttctcat gtgtggttgt ggtacatcat 3954

4014

tgtgcgcttt aaatgacatc tgcctgggat gtaccacaac catatgttag ctgtatttta 4074

tggggaatag ataaaatatt cgtggtttat tgggtaatcc ctagatgtgt atgcttacaa 4134

tcctatatat aaaactaaat 4154

<210> 8

<211> 717

<212> Protein

<213> Canis familiaris

<400> 8

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

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala

20 25 30

Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln

35 40 45

His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln

50 55 60

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

65 70 75 80

Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu

85 90 95

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

100 105 110

Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser

115 120 125

Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu

130 135 140

Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu

145 150 155 160

Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu

165 170 175

Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Glu Leu Ser

180 185 190

Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser

195 200 205

Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp

210 215 220

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

225 230 235 240

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

245 250 255

Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser

260 265 270

Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala

275 280 285

Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn

290 295 300

Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln

305 310 315 320

Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln

325 330 335

Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu

340 345 350

Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln

355 360 365

Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser

370 375 380

Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala

385 390 395 400

Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys

405 410 415

Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro

420 425 430

Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu

435 440 445

Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu

450 455 460

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

465 470 475 480

Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser

485 490 495

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

500 505 510

Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe

515 520 525

Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys

530 535 540

Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln

545 550 555 560

Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr

565 570 575

Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr

580 585 590

Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser

595 600 605

Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg

610 615 620

Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe

625 630 635 640

Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn

645 650 655

Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly

660 665 670

Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln

675 680 685

Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro

690 695 700

Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn

705 710 715

<210> 9

<211> 4939

<212> DNA

<213> Canis familiaris

<220>

<221> CDS

<222> (1)..(2109)

<400> 9

atg ccg tcg gcc acc agc ctc agc gga agc ggc agc aag tcg tcg ggc 48

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

1 5 10 15

ccg ccg ccc ccg tcg ggt tcc tcc ggg agc gag gcg gcg gcg gcg gcg 96

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala

20 25 30

ggg gcg gcg ggg gcg gcg ggg gcc ggg gcg gct gcg ccc gcc tcc cag 144

Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln

35 40 45

cac ccc gcg acc ggc acc ggc gct gtc cag acc gag gcc atg aag cag 192

His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln

50 55 60

atc ctc ggg gtg atc gac aag aaa ctc cgg aac ctg gag aag aaa aag 240

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

65 70 75 80

ggc aag ctt gat gat tac cag gaa cga atg aac aaa ggg gaa agg ctt 288

Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu

85 90 95

aat caa gat cag ctg gat gcc gta tct aag tac cag gaa gtc aca aat 336

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

100 105 110

aac ttg gag ttt gca aaa gaa tta cag agg agt ttc atg gca tta agt 384

Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser

115 120 125

caa gat att cag aaa aca ata aag aag act gca cgt cgg gag cag ctt 432

Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu

130 135 140

atg aga gag gaa gcg gaa caa aaa cgt tta aaa act gta ctt gag ctc 480

Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu

145 150 155 160

cag tat gtt ttg gac aaa ttg gga gat gat gaa gtg aga act gac ctg 528

Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu

165 170 175

aag caa ggt ttg aat gga gtg cca ata ttg tct gaa gaa gaa ttg tcg 576

Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Glu Leu Ser

180 185 190

ttg ttg gat gaa ttc tac aaa tta gca gac cct gaa cgg gac atg agc 624

Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser

195 200 205

ttg agg ttg aat gag cag tat gaa cat gct tcc att cac ctg tgg gac 672

Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp

210 215 220

ttg ctg gaa gga aag gaa aag tct gta tgt gga aca acc tat aaa gca 720

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

225 230 235 240

cta aag gaa att gtt gag cgt gtt ttc cag tca aat tac ttt gac agc 768

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

245 250 255

act cac aac cac cag aat ggg cta tgt gag gaa gaa gag gca gcc tca 816

Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser

260 265 270

gca cct aca gtt gaa gac cag gta gct gaa gct gag cct gag cca gca 864

Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala

275 280 285

gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat gta aat 912

Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn

290 295 300

aga caa ttt atg gca gaa aca cag ttc agc agt ggt gaa aag gag cag 960

Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln

305 310 315 320

gta gat gag tgg acg gtc gaa aca gtg gag gtg gtg aat tca ctc cag 1008

Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln

325 330 335

cag caa cct cag gct gcg tct cct tca gta cca gag ccc cac tct ttg 1056

Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu

340 345 350

act ccg gtg gct cag gca gat ccc ctt gtg aga aga cag cga gtc cag 1104

Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln

355 360 365

gac ctt atg gcg cag atg cag ggg ccc tat aat ttc ata cag gat tca 1152

Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser

370 375 380

atg ctg gat ttt gaa aac cag aca ctc gat cct gcc att gta tct gca 1200

Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala

385 390 395 400

cag cct atg aat ccg aca caa aac atg gac atg ccc cag ctg gtt tgc 1248

Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys

405 410 415

cct cca gtt cat tct gaa tct aga ctt gct caa cct aat caa gtt cct 1296

Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro

420 425 430

gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt gag 1344

Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu

435 440 445

ggg tat aca gca tct caa ccc ttg tac cag cct tct cat gct aca gag 1392

Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu

450 455 460

caa cga cca caa aag gaa cca att gac cag att cag gca aca atc tct 1440

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

465 470 475 480

tta aat aca gac cag act aca gcg tca tca tcc ctt ccg gct gct tct 1488

Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser

485 490 495

cag cct cag gta ttc cag gct ggg aca agc aaa cca tta cat agc agt 1536

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

500 505 510

gga atc aat gta aat gca gct cca ttc caa tcc atg caa acg gtg ttc 1584

Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe

515 520 525

aat atg aat gcc cca gtt cct cct gtt aat gaa cca gaa act ttg aaa 1632

Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys

530 535 540

caa caa aat cag tac cag gcc agt tat aac cag agc ttt tct agt cag 1680

Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln

545 550 555 560

cct cac caa gta gaa caa aca gac ctt cag caa gaa cag ctt caa aca 1728

Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr

565 570 575

gtg gtt ggc act tac cat ggt tcc cag gac cag ccc cac caa gtg act 1776

Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr

580 585 590

ggt aac cat cag cag cct ccc cag cag aac act gga ttt cca cgt agc 1824

Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser

595 600 605

agt cag ccc tat tac aat agt cgt ggt gtg tct cgt ggt ggt tcc cgt 1872

Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg

610 615 620

ggt gct aga ggc tta atg aat gga tac agg ggc cct gcc aat gga ttc 1920

Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe

625 630 635 640

aga gga gga tat gat ggt tac cgc cct tca ttc tct aac act cca aac 1968

Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn

645 650 655

agt ggt tat aca cag tct cag ttc agt gct ccc cgg gac tac tct ggc 2016

Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly

660 665 670

tat cag cgg gat gga tat cag cag aat ttc aag cga ggc tct ggg cag 2064

Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln

675 680 685

agt gga cca cgg gga gcc cca cga ggt aat att ttg tgg tgg tga 2109

Ser Gly Pro Arg Gly Ala Pro Arg Gly Asn Ile Leu Trp Trp

690 695 700

tcctagctcc taagtggagc ttctgttctg gccttggaag agctgttcca tagtctgcat 2169

gtaggttaca tgttaggaat acatttatca ttaccagact tgttgctagg gattaaatga 2229

aatgctctgt ttctaaaact tctcttgaac ccaaatttaa ttttttgaat gactttccct 2289

gttactatat aaattgtctt gaaaactaga acatttctcc tcctcagaaa aagtgttttt 2349

ccaactgcaa attatttttc aggtcctaaa acctgctaaa tgtttttagg aagtacttac 2409

2469

attcctcttt catttttgaa catgcatatt atattttagg gtcagaaatc ctttaatggc 2529

caaataagcc atagttacat ttagagaacc atttagaagt gatagaacta actgaaattt 2589

2649

aacatccaaa atcctaacta acttcctgaa ctatatttaa aaattacagg tttaaggagt 2709

ttctggtttt ttttctctta ccataggaaa actgtttcct gtttggccag gaagtcaacc 2769

tgtgtaataa ttagaagtag catttcatat gatctgaagt tctaaatggt tctctgattt 2829

aagggaagtt aaattgaata ggttttcctct agttattggc cataacatgt ataaaatgta 2889

tattaaggag gaatacaaag tactttgatt tcaatgctag tagaaactgg ccagcaaaaa 2949

ggtgcatttt atttttaaat taatggatca cttgggaatt actgacttga agtatcaaag 3009

gatatttgca tgtgaatgtg ggttatgttc tttctcacct tgtagcatat tctatgaaag 3069

3129

tacaagtcat tatacaattt tgaatgttat gtagtttctt tttaacagtt taggtaacaa 3189

ggtctgtttt tcattctggg gcttttatta attttgatag tatgatgtta cttactactg 3249

aaatgtaagc tagagtgtac actagaatgt aagctccatg agagcaggta ccttgtctgt 3309

cttcactgct gtatctattt ccaacgcctg atgacagtgc ctgacacata gtaggcactc 3369

aataaatact tgttgaatga atgaatgaat gagtactggt ggaatactcc attagctcta 3429

ctcttctttt agctagagaa catgagcaaa tttgcgcatg acaacttcca ggacaggtga 3489

acactgaaga attgacctct taaacctaat aatgtggtga caagctgccc acatgcttct 3549

3609

tgccattttt gtcttctagg tcgtggaggg cccccaagac ccaacagagg gatgccgcaa 3669

atgaacactc agcaagtgaa ttaatctgat tcacaggatt atgtttaaac gccaaaaaca 3729

cactggccag tgtaccataa tatgttacca gaagagttat tatctatttg ttctcccttt 3789

3849

3909

catcttgagc cttgcacatg atactcagat tcctcaccct tgcttaggag taaaacataa 3969

tacactttac agggtgatat ctccatagtt atttgaagtg gcttggaaaa agcaagatta 4029

acttctgaca ttggataaaa atcaacaaat cagccctaga gttattcaaa tggtaattga 4089

caaaaactaa aatatttccc ttcgagaagg agtggaatgt ggtttggcag aacaactgca 4149

tttcacagct tttccggtta aattggagca ctaaacgttt agatgcatac caaattatgc 4209

atgggccctt aatataaaag gctggctacc agctttgaca cagcactatt catcctctgg 4269

ccaaacaact gtggttaaac aacacatgta aattgctttt taacagctga tactataata 4329

agacaaagcc aaaatgcaaa aattgggctt tgattggcac tttttgaaaa atatgcaaca 4389

aatatgggat gtaatctgga tggccgcttc tgtacttaat gtgaagtatt tagatacctt 4449

4509

ttccttataa tgtacattgt ctgtcactaa tcctcagatc ttgctgtatt gtcacctaaa 4569

ttggtacagg tactgatgaa aatatctaat ggataatcat aacactcttg gtcacatgtt 4629

tttcctgcag cctgaaggtt tttaaaagaa aaagatatca aatgcctgct gctaccaccc 4689

ttttaaattg ctatcttttg aaaagcacca gtatgtgttt tagattgatt tccctatttt 4749

agggaaatga cagacagtag tttcagttct gatggtataa gcaaaacaaa taaaacatgt 4809

ttataaaagt tgtatcttga aacactggtg ttcaacagct agcagcttat gtggttcacc 4869

ccatgcattg ttagtgtttc agattttatg gttatctcca gcagctgttt ctgtagtact 4929

tgcatttatc 4939

<210> 10

<211> 702

<212> Protein

<213> Canis familiaris

<400> 10

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

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala

20 25 30

Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln

35 40 45

His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln

50 55 60

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

65 70 75 80

Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu

85 90 95

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

100 105 110

Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser

115 120 125

Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu

130 135 140

Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu

145 150 155 160

Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu

165 170 175

Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Glu Leu Ser

180 185 190

Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser

195 200 205

Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp

210 215 220

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

225 230 235 240

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

245 250 255

Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser

260 265 270

Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala

275 280 285

Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn

290 295 300

Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln

305 310 315 320

Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln

325 330 335

Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu

340 345 350

Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln

355 360 365

Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser

370 375 380

Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala

385 390 395 400

Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys

405 410 415

Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro

420 425 430

Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu

435 440 445

Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu

450 455 460

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

465 470 475 480

Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser

485 490 495

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

500 505 510

Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe

515 520 525

Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys

530 535 540

Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln

545 550 555 560

Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr

565 570 575

Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr

580 585 590

Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser

595 600 605

Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg

610 615 620

Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe

625 630 635 640

Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn

645 650 655

Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly

660 665 670

Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln

675 680 685

Ser Gly Pro Arg Gly Ala Pro Arg Gly Asn Ile Leu Trp Trp

690 695 700

<210> 11

<211> 3306

<212> DNA

<213> Canis familiaris

<220>

<221> CDS

<222> (1)..(2040)

<400> 11

atg ccg tcg gcc acc agc ctc agc gga agc ggc agc aag tcg tcg ggc 48

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

1 5 10 15

ccg ccg ccc ccg tcg ggt tcc tcc ggg agc gag gcg gcg gcg gcg gcg 96

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala

20 25 30

ggg gcg gcg ggg gcg gcg ggg gcc ggg gcg gct gcg ccc gcc tcc cag 144

Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln

35 40 45

cac ccc gcg acc ggc acc ggc gct gtc cag acc gag gcc atg aag cag 192

His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln

50 55 60

atc ctc ggg gtg atc gac aag aaa ctc cgg aac ctg gag aag aaa aag 240

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

65 70 75 80

ggc aag ctt gat gat tac cag gaa cga atg aac aaa ggg gaa agg ctt 288

Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu

85 90 95

aat caa gat cag ctg gat gcc gta tct aag tac cag gaa gtc aca aat 336

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

100 105 110

aac ttg gag ttt gca aaa gaa tta cag agg agt ttc atg gca tta agt 384

Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser

115 120 125

caa gat att cag aaa aca ata aag aag act gca cgt cgg gag cag ctt 432

Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu

130 135 140

atg aga gag gaa gcg gaa caa aaa cgt tta aaa act gta ctt gag ctc 480

Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu

145 150 155 160

cag tat gtt ttg gac aaa ttg gga gat gat gaa gtg aga act gac ctg 528

Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu

165 170 175

aag caa ggt ttg aat gga gtg cca ata ttg tct gaa gaa gaa ttg tcg 576

Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Glu Leu Ser

180 185 190

ttg ttg gat gaa ttc tac aaa tta gca gac cct gaa cgg gac atg agc 624

Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser

195 200 205

ttg agg ttg aat gag cag tat gaa cat gct tcc att cac ctg tgg gac 672

Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp

210 215 220

ttg ctg gaa gga aag gaa aag tct gta tgt gga aca acc tat aaa gca 720

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

225 230 235 240

cta aag gaa att gtt gag cgt gtt ttc cag tca aat tac ttt gac agc 768

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

245 250 255

act cac aac cac cag aat ggg cta tgt gag gaa gaa gag gca gcc tca 816

Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser

260 265 270

gca cct aca gtt gaa gac cag gta gct gaa gct gag cct gag cca gca 864

Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala

275 280 285

gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat gta aat 912

Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn

290 295 300

aga caa ttt atg gca gaa aca cag ttc agc agt ggt gaa aag gag cag 960

Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln

305 310 315 320

gta gat gag tgg acg gtc gaa aca gtg gag gtg gtg aat tca ctc cag 1008

Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln

325 330 335

cag caa cct cag gct gcg tct cct tca gta cca gag ccc cac tct ttg 1056

Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu

340 345 350

act ccg gtg gct cag gca gat ccc ctt gtg aga aga cag cga gtc cag 1104

Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln

355 360 365

gac ctt atg gcg cag atg cag ggg ccc tat aat ttc ata cag gat tca 1152

Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser

370 375 380

atg ctg gat ttt gaa aac cag aca ctc gat cct gcc att gta tct gca 1200

Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala

385 390 395 400

cag cct atg aat ccg aca caa aac atg gac atg ccc cag ctg gtt tgc 1248

Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys

405 410 415

cct cca gtt cat tct gaa tct aga ctt gct caa cct aat caa gtt cct 1296

Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro

420 425 430

gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt gag 1344

Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu

435 440 445

ggg tat aca gca tct caa ccc ttg tac cag cct tct cat gct aca gag 1392

Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu

450 455 460

caa cga cca caa aag gaa cca att gac cag att cag gca aca atc tct 1440

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

465 470 475 480

tta aat aca gac cag act aca gcg tca tca tcc ctt ccg gct gct tct 1488

Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser

485 490 495

cag cct cag gta ttc cag gct ggg aca agc aaa cca tta cat agc agt 1536

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

500 505 510

gga atc aat gta aat gca gct cca ttc caa tcc atg caa acg gtg ttc 1584

Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe

515 520 525

aat atg aat gcc cca gtt cct cct gtt aat gaa cca gaa act ttg aaa 1632

Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys

530 535 540

caa caa aat cag tac cag gcc agt tat aac cag agc ttt tct agt cag 1680

Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln

545 550 555 560

cct cac caa gta gaa caa aca gac ctt cag caa gaa cag ctt caa aca 1728

Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr

565 570 575

gtg gtt ggc act tac cat ggt tcc cag gac cag ccc cac caa gtg act 1776

Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr

580 585 590

ggt aac cat cag cag cct ccc cag cag aac act gga ttt cca cgt agc 1824

Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser

595 600 605

agt cag ccc tat tac aat agt cgt ggt gtg tct cgt ggt ggt tcc cgt 1872

Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg

610 615 620

ggt gct aga ggc tta atg aat gga tac agg ggc cct gcc aat gga ttc 1920

Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe

625 630 635 640

aga gga gga tat gat ggt tac cgc cct tca ttc tct aac act cca aac 1968

Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn

645 650 655

agt ggt tat aca cag tct cag ttc agt gct ccc cgg gac tac tct ggc 2016

Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly

660 665 670

tat cag cgg gga tgc cgc aaa tga acactcagca agtgaattaa tctgattcac 2070

Tyr Gln Arg Gly Cys Arg Lys

675

aggattatgt ttaaacgcca aaaacacact ggccagtgta ccataatatg ttaccagaag 2130

agttattatc tatttgttct ccctttcagg aaacttattg taaagggact gttttcatcc 2190

cataaagaca ggactacaat tgtcagcttt atattacctg gatatggaag gaaactattt 2250

ttattctgca tgttcttcct aagcgtcatc ttgagccttg cacatgatac tcagattcct 2310

cacccttgct taggagtaaa acataataca ctttacaggg tgatatctcc atagttattt 2370

gaagtggctt ggaaaaagca agattaactt ctgacattgg ataaaaatca acaaatcagc 2430

aattgacaaa aactaaaata tttcccttcg agaaggagtg 2490

gaatgtggtt tggcagaaca actgcatttc acagcttttc cggttaaatt ggagcactaa 2550

2610

ttgacacagc actattcatc ctctggccaa acaactgtgg ttaaacaaca catgtaaatt 2670

gctttttaac agctgatact ataataagac aaagccaaaa tgcaaaaatt gggctttgat 2730

tggcactttt tgaaaaatat gcaacaaata tgggatgtaa tctggatggc cgcttctgta 2790

2850

tttgtaagga ttggtactat ctatcattcc ttataatgta cattgtctgt cactaatcct 2910

cagatcttgc tgtattgtca cctaaattgg tacaggtact gatgaaaata tctaatggat 2970

aatcataaca ctcttggtca catgtttttc ctgcagcctg aaggttttta aaagaaaaag 3030

3090

3150

gtataagcaa aacaaataaa acatgtttat aaaagttgta tcttgaaaca ctggtgttca 3210

acagctagca gcttatgtgg ttcaccccat gcattgttag tgtttcagat tttatggtta 3270

tctccagcag ctgtttctgt agtacttgca tttatc 3306

<210> 12

<211> 679

<212> Protein

<213> Canis familiaris

<400> 12

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

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala

20 25 30

Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln

35 40 45

His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln

50 55 60

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

65 70 75 80

Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu

85 90 95

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

100 105 110

Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser

115 120 125

Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu

130 135 140

Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu

145 150 155 160

Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu

165 170 175

Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Glu Leu Ser

180 185 190

Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser

195 200 205

Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp

210 215 220

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

225 230 235 240

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

245 250 255

Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser

260 265 270

Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala

275 280 285

Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn

290 295 300

Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln

305 310 315 320

Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln

325 330 335

Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu

340 345 350

Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln

355 360 365

Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser

370 375 380

Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala

385 390 395 400

Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys

405 410 415

Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro

420 425 430

Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu

435 440 445

Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu

450 455 460

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

465 470 475 480

Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser

485 490 495

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

500 505 510

Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe

515 520 525

Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys

530 535 540

Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln

545 550 555 560

Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr

565 570 575

Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr

580 585 590

Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser

595 600 605

Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg

610 615 620

Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe

625 630 635 640

Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn

645 650 655

Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly

660 665 670

Tyr Gln Arg Gly Cys Arg Lys

675

<210> 13

<211> 2281

<212> DNA

<213> Canis familiaris

<220>

<221> CDS

<222> (1)..(2154)

<400> 13

atg ccg tcg gcc acc agc ctc agc gga agc ggc agc aag tcg tcg ggc 48

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

1 5 10 15

ccg ccg ccc ccg tcg ggt tcc tcc ggg agc gag gcg gcg gcg gcg gcg 96

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala

20 25 30

ggg gcg gcg ggg gcg gcg ggg gcc ggg gcg gct gcg ccc gcc tcc cag 144

Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln

35 40 45

cac ccc gcg acc ggc acc ggc gct gtc cag acc gag gcc atg aag cag 192

His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln

50 55 60

atc ctc ggg gtg atc gac aag aaa ctc cgg aac ctg gag aag aaa aag 240

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

65 70 75 80

ggc aag ctt gat gat tac cag gaa cga atg aac aaa ggg gaa agg ctt 288

Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu

85 90 95

aat caa gat cag ctg gat gcc gta tct aag tac cag gaa gtc aca aat 336

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

100 105 110

aac ttg gag ttt gca aaa gaa tta cag agg agt ttc atg gca tta agt 384

Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser

115 120 125

caa gat att cag aaa aca ata aag aag act gca cgt cgg gag cag ctt 432

Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu

130 135 140

atg aga gag gaa gcg gaa caa aaa cgt tta aaa act gta ctt gag ctc 480

Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu

145 150 155 160

cag tat gtt ttg gac aaa ttg gga gat gat gaa gtg aga act gac ctg 528

Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu

165 170 175

aag caa ggt ttg aat gga gtg cca ata ttg tct gaa gaa gaa ttg tcg 576

Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Glu Leu Ser

180 185 190

ttg ttg gat gaa ttc tac aaa tta gca gac cct gaa cgg gac atg agc 624

Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser

195 200 205

ttg agg ttg aat gag cag tat gaa cat gct tcc att cac ctg tgg gac 672

Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp

210 215 220

ttg ctg gaa gga aag gaa aag tct gta tgt gga aca acc tat aaa gca 720

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

225 230 235 240

cta aag gaa att gtt gag cgt gtt ttc cag tca aat tac ttt gac agc 768

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

245 250 255

act cac aac cac cag aat ggg cta tgt gag gaa gaa gag gca gcc tca 816

Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser

260 265 270

gca cct aca gtt gaa gac cag gta gct gaa gct gag cct gag cca gca 864

Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala

275 280 285

gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat gta aat 912

Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn

290 295 300

aga caa ttt atg gca gaa aca cag ttc agc agt ggt gaa aag gag cag 960

Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln

305 310 315 320

gta gat gag tgg acg gtc gaa aca gtg gag gtg gtg aat tca ctc cag 1008

Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln

325 330 335

cag caa cct cag gct gcg tct cct tca gta cca gag ccc cac tct ttg 1056

Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu

340 345 350

act ccg gtg gct cag gca gat ccc ctt gtg aga aga cag cga gtc cag 1104

Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln

355 360 365

gac ctt atg gcg cag atg cag ggg ccc tat aat ttc ata cag gat tca 1152

Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser

370 375 380

atg ctg gat ttt gaa aac cag aca ctc gat cct gcc att gta tct gca 1200

Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala

385 390 395 400

cag cct atg aat ccg aca caa aac atg gac atg ccc cag ctg gtt tgc 1248

Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys

405 410 415

cct cca gtt cat tct gaa tct aga ctt gct caa cct aat caa gtt cct 1296

Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro

420 425 430

gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt gag 1344

Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu

435 440 445

ggg tat aca gca tct caa ccc ttg tac cag cct tct cat gct aca gag 1392

Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu

450 455 460

caa cga cca caa aag gaa cca att gac cag att cag gca aca atc tct 1440

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

465 470 475 480

tta aat aca gac cag act aca gcg tca tca tcc ctt ccg gct gct tct 1488

Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser

485 490 495

cag cct cag gta ttc cag gct ggg aca agc aaa cca tta cat agc agt 1536

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

500 505 510

gga atc aat gta aat gca gct cca ttc caa tcc atg caa acg gtg ttc 1584

Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe

515 520 525

aat atg aat gcc cca gtt cct cct gtt aat gaa cca gaa act ttg aaa 1632

Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys

530 535 540

caa caa aat cag tac cag gcc agt tat aac cag agc ttt tct agt cag 1680

Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln

545 550 555 560

cct cac caa gta gaa caa aca gac ctt cag caa gaa cag ctt caa aca 1728

Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr

565 570 575

gtg gtt ggc act tac cat ggt tcc cag gac cag ccc cac caa gtg act 1776

Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr

580 585 590

ggt aac cat cag cag cct ccc cag cag aac act gga ttt cca cgt agc 1824

Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser

595 600 605

agt cag ccc tat tac aat agt cgt ggt gtg tct cgt ggt ggt tcc cgt 1872

Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg

610 615 620

ggt gct aga ggc tta atg aat gga tac agg ggc cct gcc aat gga ttc 1920

Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe

625 630 635 640

aga gga gga tat gat ggt tac cgc cct tca ttc tct aac act cca aac 1968

Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn

645 650 655

agt ggt tat aca cag tct cag ttc agt gct ccc cgg gac tac tct ggc 2016

Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly

660 665 670

tat cag cgg gat gga tat cag cag aat ttc aag cga ggc tct ggg cag 2064

Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln

675 680 685

agt gga cca cgg gga gcc cca cga ggt cgt gga ggg ccc cca aga ccc 2112

Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro

690 695 700

aac aga ggg atg ccg caa atg aac act cag caa gtg aat taa 2154

Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn

705 710 715

tctgattcac aggattatgt ttaaacgcca aaaacacact ggccagtgta ccataatatg 2214

ttaccagaag agttattatc tatttggact gttttcatcc cataaagaca ggactacaat 2274

tgtcagc 2281

<210> 14

<211> 717

<212> Protein

<213> Canis familiaris

<400> 14

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

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Ala Ala

20 25 30

Gly Ala Ala Gly Ala Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln

35 40 45

His Pro Ala Thr Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln

50 55 60

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

65 70 75 80

Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu

85 90 95

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

100 105 110

Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser

115 120 125

Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu

130 135 140

Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu

145 150 155 160

Gln Tyr Val Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu

165 170 175

Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Glu Leu Ser

180 185 190

Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser

195 200 205

Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp

210 215 220

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

225 230 235 240

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

245 250 255

Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser

260 265 270

Ala Pro Thr Val Glu Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala

275 280 285

Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn

290 295 300

Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln

305 310 315 320

Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln

325 330 335

Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu

340 345 350

Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln

355 360 365

Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser

370 375 380

Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala

385 390 395 400

Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys

405 410 415

Pro Pro Val His Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Pro

420 425 430

Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser Glu

435 440 445

Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu

450 455 460

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

465 470 475 480

Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser

485 490 495

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

500 505 510

Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe

515 520 525

Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys

530 535 540

Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln

545 550 555 560

Pro His Gln Val Glu Gln Thr Asp Leu Gln Gln Glu Gln Leu Gln Thr

565 570 575

Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr

580 585 590

Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser

595 600 605

Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg

610 615 620

Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe

625 630 635 640

Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn

645 650 655

Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly

660 665 670

Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln

675 680 685

Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro

690 695 700

Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn

705 710 715

<210> 15

<211> 3386

<212> DNA

<213> Bos taurus

<220>

<221> CDS

<222> (82)..(2208)

<400> 15

cgcgtctcgc cccgtccacc gattgactcg ccgctcttgt ccttcctccc gctctttctt 60

ctctcccctt acggtttcaa g atg cct tcg gcc acc agc cac agc gga agc 111

Met Pro Ser Ala Thr Ser His Ser Gly Ser

1 5 10

ggc agc aag tcg tcc gga ccg cca ccg ccg tcg ggt tcc tcc ggg aat 159

Gly Ser Lys Ser Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Asn

15 20 25

gag gcg ggg gcc ggg gcc gcc gcg ccg gct tcc caa cac ccc atg acc 207

Glu Ala Gly Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Met Thr

30 35 40

ggc acc ggg gct gtc cag acc gag gcc atg aag cag att ctc ggg gtg 255

Gly Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val

45 50 55

atc gac aag aaa ctt cgg aac ctg gag aag aaa aag ggc aag ctt gat 303

Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp

60 65 70

gat tat cag gaa cga atg aac aaa ggg gaa agg ctt aat caa gat cag 351

Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln

75 80 85 90

ctg gat gcc gtg tct aag tac cag gaa gtc aca aat aac ttg gag ttt 399

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

95 100 105

gca aaa gaa tta cag agg agt ttc atg gca tta agc caa gat att cag 447

Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln

110 115 120

aaa aca ata aag aag aca gca cgt cgg gag cag ctt atg aga gag gaa 495

Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu

125 130 135

gct gaa cag aaa cgt tta aaa aca gta ctt gag ctg cag tat gtt ttg 543

Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu

140 145 150

gac aaa cta gga gat gat gaa gtg aga act gac ctg aag caa ggt ttg 591

Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu Lys Gln Gly Leu

155 160 165 170

aat gga gtg cca ata ttg tct gaa gag gag ttg tcg ttg tta gat gag 639

Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu Ser Leu Leu Asp Glu

175 180 185

ttc tac aaa tta gca gac cct gaa cga gac atg agc ttg agg ttg aat 687

Phe Tyr Lys Leu Ala Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn

190 195 200

gag cag tat gaa cat gcc tcc att cac ctg tgg gac ttg ctg gaa gga 735

Glu Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly

205 210 215

aag gaa aaa cct gta tgt gga aca act tat aaa gct cta aag gaa att 783

Lys Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile

220 225 230

gtt gag cgt gtt ttc cag tca aac tac ttt gac agc acc cac aac cac 831

Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His

235 240 245 250

cag aat ggt ctg tgt gag gaa gag gag gca gcc tca gca cct aca gtt 879

Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Thr Val

255 260 265

gaa gac cag gca gct gaa gct gaa cct gag cca gtg gaa gaa tat act 927

Glu Asp Gln Ala Ala Glu Ala Glu Pro Glu Pro Val Glu Glu Tyr Thr

270 275 280

gaa caa aat gag gtt gaa tca aca gag tat gta aat aga caa ttt atg 975

Glu Gln Asn Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met

285 290 295

gca gaa aca cag ttc agc agt ggt gaa aag gag cag gta gat gat tgg 1023

Ala Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln Val Asp Asp Trp

300 305 310

aca gtt gaa aca gtt gag gtg gta aat tca ctc cag cag caa cct cag 1071

Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln

315 320 325 330

gct gca tct cct tca gta cca gaa ccc cac tct ttg acc cca gtg gct 1119

Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala

335 340 345

caa gcc gat ccc ctc gtg aga aga cag cga gta cag gac ctt atg gca 1167

Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala

350 355 360

caa atg cag ggg ccc tat aat ttc ata cag gat tca atg ttg gat ttt 1215

Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe

365 370 375

gaa aac cag aca ctt gat cct gcc att gta tct gca cag ccg atg aat 1263

Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser Ala Gln Pro Met Asn

380 385 390

cca gca cag aac atg gac ata ccc cag ctg gtt tgc cct cca gtt cat 1311

Pro Ala Gln Asn Met Asp Ile Pro Gln Leu Val Cys Pro Pro Val His

395 400 405 410

tct gaa tct aga ctt gct caa cct aat caa gtt tct gta cag cca gaa 1359

Ser Glu Ser Arg Leu Ala Gln Pro Asn Gln Val Ser Val Gln Pro Glu

415 420 425

gct aca cag gtt cct ttg gtt tca tcc aca agt gag gga tat aca gca 1407

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

430 435 440

tct caa ccc ttg tac caa cct tct cat gct act gac caa cga cca caa 1455

Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Asp Gln Arg Pro Gln

445 450 455

aag gaa ccg att gat cag att cag gcg acg atc tct tta aat aca gac 1503

Lys Glu Pro Ile Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp

460 465 470

cag act aca gca tca tca tcc ctt cct gct gct tct cag cct caa gtg 1551

Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val

475 480 485 490

ttc cag gct ggg aca agc aaa cct tta cat agc agt gga atc aat gta 1599

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

495 500 505

aat gca gct cca ttc caa tcc atg caa acg gta ttc aat atg aat gcc 1647

Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala

510 515 520

cca gtt cct cct gtt aat gaa cca gaa act tta aaa cag caa aat cag 1695

Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu Lys Gln Gln Asn Gln

525 530 535

tac cag gcc agt tac aac cag agc ttt tcc agt cag cct cac caa gta 1743

Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val

540 545 550

gaa caa aca gag ctt cag caa gaa cag ctt caa aca gtg gtt ggc act 1791

Glu Gln Thr Glu Leu Gln Gln Glu Gln Leu Gln Thr Val Val Gly Thr

555 560 565 570

tat cat ggt tct cag gac cag ccc cat caa gtg act ggt aac cac cag 1839

Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Thr Gly Asn His Gln

575 580 585

cag cct cct cag cag aac act gga ttt cca cgt agc aat cag ccc tat 1887

Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr

590 595 600

tac aac agt cgt ggt gtg tct cgt gga ggt tcc cgt ggt gct aga ggc 1935

Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly

605 610 615

ttg atg aat gga tac aga gga cct gct aat gga ttc aga gga gga tat 1983

Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr

620 625 630

gat ggt tac cgc cct tca ttc tct act aac act cca aac agt ggt tat 2031

Asp Gly Tyr Arg Pro Ser Phe Ser Thr Asn Thr Pro Asn Ser Gly Tyr

635 640 645 650

aca caa tct caa ttc agt gct ccc cgg gac tac tct ggc tat cag cgg 2079

Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg

655 660 665

gat gga tat cag cag aat ttc aag cga ggc tct ggg cag agt gga cca 2127

Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro

670 675 680

cgg gga gcc cca cga ggt cgt gga ggg ccc cca aga ccc aac aga ggg 2175

Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly

685 690 695

atg ccg caa atg aac act cag caa gtg aat taa tctgattcac aggattatgt 2228

Met Pro Gln Met Asn Thr Gln Gln Val Asn

700 705

ttaatcgcca aaaacacact ggccagtgta ccataatatg ttaccagaag agttattatc 2288

tatttgttct ccctttcagg aaacttattg taaagggact gttttcatcc cataaagaca 2348

ggactacaat tgtcagcttt atattacctg gatatggaag gaaactattt ttactctgca 2408

tgttctgtcc taagcgtcat cttgagcctt gcacatgata ctcagattcc tcacccttgc 2468

ttaggagtaa aacataatat actttaatgg ggtgatatct ccatagttat ttgaagtggc 2528

ttggataaag caagactgac ttctgacatt ggataaaatc tacaaatcag ccctagagtc 2588

attcagtggt aactgacaaa actaaaatat ttcccttgaa aggaagatgg aaggagtgga 2648

gtgtggtttg gcagaacaac tgcatttcac agcttttcca cttaaattgg agcactgaac 2708

atttagatgc ataccgaatt atgcatgggc cctaatcaca cagacaaggc tggtgccagc 2768

cttaggcttg acacggcagt gttcaccctc tggccagacg actgtggttc aagacacatg 2828

taaattgctt tttaacagct gatactgtat aagacaaagc caaaatgcaa aattaggctt 2888

tgattggcac ttttcgaaaa atatgcaaca attaagggat ataatctgga tggccgcttc 2948

tgtacttaat gtgaaatatt tagatacctt tcaaacactt aacagtttct ttgacaatga 3008

gttttgtaag gattggtagt aaatatcatt ccttatgacg tacattgtct gtcactaatc 3068

cttggatctt gctgtattgt cacctaaatt ggtacaggta ctgatgaaaa tctaatggat 3128

aatcataaca ctcttggtta catgtttttc ctgcagcctg aaagttttta taagaaaaag 3188

acatcaaatg cctgctgctg ccaccctttt aaattgctat cttttgaaaa gcaccagtat 3248

gtgttttaga ttgatttccc tattttaggg aaatgacagt cagtagtttc acttctgatg 3308

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa

aaaaaaaaaaaaaaaaaa 3386

<210> 16

<211> 708

<212> Protein

<213> Bos taurus

<400> 16

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Asn Glu Ala Gly Ala Gly Ala

20 25 30

Ala Ala Pro Ala Ser Gln His Pro Met Thr Gly Thr Gly Ala Val Gln

35 40 45

Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg

50 55 60

Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met

65 70 75 80

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

85 90 95

Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg

100 105 110

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

115 120 125

Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala

195 200 205

Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys

210 215 220

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

225 230 235 240

Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu

245 250 255

Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Ala Ala Glu

260 265 270

Ala Glu Pro Glu Pro Val Glu Glu Tyr Thr Glu Gln Asn Glu Val Glu

275 280 285

Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser

290 295 300

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

305 310 315 320

Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val

325 330 335

Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ala Asp Pro Leu Val

340 345 350

Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr

355 360 365

Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp

370 375 380

Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Ala Gln Asn Met Asp

385 390 395 400

Ile Pro Gln Leu Val Cys Pro Val His Ser Glu Ser Arg Leu Ala

405 410 415

Gln Pro Asn Gln Val Ser Val Gln Pro Glu Ala Thr Gln Val Pro Leu

420 425 430

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

435 440 445

Pro Ser His Ala Thr Asp Gln Arg Pro Gln Lys Glu Pro Ile Asp Gln

450 455 460

Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser

465 470 475 480

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

485 490 495

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

500 505 510

Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn

515 520 525

Glu Pro Glu Thr Leu Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn

530 535 540

Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln

545 550 555 560

Gln Glu Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp

565 570 575

Gln Pro His Gln Val Thr Gly Asn His Gln Gln Pro Pro Gln Gln Asn

580 585 590

Thr Gly Phe Pro Arg Ser Asn Gln Pro Tyr Tyr Asn Ser Arg Gly Val

595 600 605

Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg

610 615 620

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

625 630 635 640

Phe Ser Thr Asn Thr Pro Asn Ser Gly Tyr Thr Gln Ser Gln Phe Ser

645 650 655

Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn

660 665 670

Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly

675 680 685

Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln Met Asn Thr

690 695 700

Gln Gln Val Asn

705

<210> 17

<211> 3150

<212> DNA

<213> Equus caballus

<220>

<221> CDS

<222> (1)..(1917)

<400> 17

atg gag ggc aag ctc gat gat tac caa gag cga atg aac aaa gga gaa 48

Met Glu Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu

1 5 10 15

agg ctt aat cag gat cag ctg gat gct gtg tct aag tac cag gaa gtc 96

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

20 25 30

aca aat aac ttg gag ttt gcg aaa gaa ttg cag agg agt ttc atg gcg 144

Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala

35 40 45

ttg agt cag gat att cag aaa aca ata aag aag acg gca cgt cgg gag 192

Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu

50 55 60

cag ctt atg aga gaa gaa gct gaa cag aaa cgt tta aaa act gta ctt 240

Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu

65 70 75 80

gag ctg cag tat gtt ttg gac aaa ttg gga gat gaa gaa gtg cga act 288

Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Glu Glu Val Arg Thr

85 90 95

gac ctg aaa caa ggt ttg aat gga gtg cca ata ctc tct gaa gaa gag 336

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

100 105 110

ttg tcg ctg ttg gat gag ttc tac aag tta gca gac cct gta cgg gac 384

Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Val Arg Asp

115 120 125

atg agc ttg agg ttg aat gag cag tat gag cat gcc tcc att cac ctg 432

Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu

130 135 140

tgg gac ttg ctg gaa ggg aag gaa aaa tct gtc tgt gga aca acc tat 480

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

145 150 155 160

aaa gct ctg agg gaa att gtt gag cgt gtt ttc cag tcc aac tac ttt 528

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

165 170 175

gac agc acc cac aac cac cag aat ggg ctc tgt gag gag gaa gag gct 576

Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala

180 185 190

acc tca gct cca aca gct gaa gac cag gga gct gaa gct gaa cct gag 624

Thr Ser Ala Pro Thr Ala Glu Asp Gln Gly Ala Glu Ala Glu Pro Glu

195 200 205

cca gca gaa gaa tac act gaa caa agt gaa gtt gaa tca aca gag tat 672

Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr

210 215 220

gta aat aga cag ttt atg gca gaa gcg cag ttc agt ggt gag aag gag 720

Val Asn Arg Gln Phe Met Ala Glu Ala Gln Phe Ser Gly Glu Lys Glu

225 230 235 240

cag gtg gat gag tgg aca gtc gag acg gtc gag gtg gta aat tca ctc 768

Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu

245 250 255

cag cag caa cct cag gct gca tct cct tca gta ccg gag ccc cac tct 816

Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser

260 265 270

ttg act cca gtg gct cag gca gat ccc ctt gtg aga aga cag cga gta 864

Leu Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val

275 280 285

cag gac ctt atg gcg caa atg cag ggg ccc tat aat ttc ata cag gat 912

Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp

290 295 300

tca atg ctg gat ttt gaa aac cag aca ctt gat cct gcc att gta tct 960

Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser

305 310 315 320

gca cag cct atg aat cca gca cag aat atg gac atg ccc cag ctg gtt 1008

Ala Gln Pro Met Asn Pro Ala Gln Asn Met Asp Met Pro Gln Leu Val

325 330 335

tgc cct cca gtt cat gct gaa tct aga ctt gct caa cct aat caa gtt 1056

Cys Pro Pro Val His Ala Glu Ser Arg Leu Ala Gln Pro Asn Gln Val

340 345 350

cct gta caa cca gaa gct aca cag gtt cct ttg gtt tca tcc aca agt 1104

Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser

355 360 365

gag ggg tat aca gca tct cag ccc ttg tac cag cct tct cat gct aca 1152

Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr

370 375 380

gag caa cga ccg caa aag gaa ccg act gac cag atc cag gca aca atc 1200

Glu Gln Arg Pro Gln Lys Glu Pro Thr Asp Gln Ile Gln Ala Thr Ile

385 390 395 400

tct tta aat aca gac cag act aca gca tca tca tcc ctt cct gct gct 1248

Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Ser Leu Pro Ala Ala

405 410 415

tct cag cct cag gtg ttc cag gct ggg aca agc aaa cct tta cac agc 1296

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

420 425 430

agt ggg atc aat gta aat gca gcg cca ttc cag tcc atg caa acg gtg 1344

Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val

435 440 445

ttc aac atg aat gcc ccg gtt cct cct gtt aat gaa cca gaa act tta 1392

Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu

450 455 460

aaa cag caa aat cag tac cag gcc agc tat aac cag agc ttt tcc agt 1440

Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser

465 470 475 480

ccg cct cac caa gta gag cag aca gag ctt ccg caa gag cag ctt cag 1488

Pro Pro His Gln Val Glu Gln Thr Glu Leu Pro Gln Glu Gln Leu Gln

485 490 495

acg gtg gtt ggt act tac cat gct tcc caa gac cag ccc cat caa gtg 1536

Thr Val Val Gly Thr Tyr His Ala Ser Gln Asp Gln Pro His Gln Val

500 505 510

acc ggt aac cac cag cag cct ccc cag cag aac act ggg ttt cca cgt 1584

Thr Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg

515 520 525

agc agt cag ccc tat tac aac agt cgt ggt gtg tct cgt gga ggc tcc 1632

Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser

530 535 540

cgt ggt gct aga ggc ttg atg aat gga tac agg ggc cct gcc aat gga 1680

Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly

545 550 555 560

ttc aga gga gga tat gat ggt tac cgc cct tcg ttc tct aac act cca 1728

Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro

565 570 575

aac agc ggt tac aca cag tct cag ttc agt gct ccc cgg gac tac tct 1776

Asn Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser

580 585 590

ggc tat cag cgg gat gga tat cag cag aat ttc aag cga ggc tct ggg 1824

Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly

595 600 605

cag agt gga ccc cgg gga gcc cca cga ggt cgt gga ggg ccc cca aga 1872

Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg

610 615 620

ccc aac aga ggg atg ccg caa atg aac act cag caa gtg aat taa 1917

Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn

625 630 635

tctgattcac aggattatct ttaatcgcca aaacacactg gccagtgtac cataatatgt 1977

taccagaaga gttattatct atttgttctc cctttcagga aacttattgt aaagggactg 2037

ttttcatccc ataaagacag gactacagtt gtcagcttta tattacctgg atatggaagg 2097

aaactatttt tactctgcat gttctgtcct aagcgtcatc ttgagccttg cacatgatac 2157

tcagattcct ttcccttgct taggagtaaa acataatata ctttatgggg tgataatatc 2217

tccatagtta tttgaagtgg cttggaaaaa gcaagattga cttttgacat tggataaaat 2277

ctacaaatca gccctagagt ttcatggtca ttcacaaaac taaaatattt cccttgaaag 2337

2397

taaattggag cactgaatgt taaatgcata ccaaattatg catgggccct taatcacaca 2457

tacatggcta ccagctttga cacagcacta ttcatcctct ggccaaacga ctgtggttaa 2517

aaacacgtgt aaattgcttt ttaacagctg atactgtaaa agacaaagct aaaatgcaaa 2577

attaggcttt cattggcact tttcgaaaaa tatgcaacaa atttgggatg taatctggat 2637

ggccacttct gtacttaatg tgaagtattt agataccttt ttgaacactt aacagtttct 2697

2757

gttgctaatc cttggatctt gctgtattgt cacctaaatt ggtacaggta ctgatgaaaa 2817

tctctcatgg ataaacctaa cactcttcgt cacatgtttt tcctgcagcc tgaaggtttt 2877

taaaaggaaa agatatcaaa tgcctgctgc taccaccctt ttaaattgct atcttttgaa 2937

2997

ttcagttctg atggtataag caaagcaaat aaaacgtgtt tataaaagtt gtatcttgaa 3057

acactggtgt tcaacagcta gcagcttctg tggttcaccc cctgccttgt tagtgttacc 3117

catttatggt tatctccagc agcaatttct cta 3150

<210> 18

<211> 638

<212> Protein

<213> Equus caballus

<400> 18

Met Glu Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu

1 5 10 15

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

20 25 30

Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala

35 40 45

Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu

50 55 60

Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu

65 70 75 80

Glu Leu Gln Tyr Val Leu Asp Lys Leu Gly Asp Glu Glu Val Arg Thr

85 90 95

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

100 105 110

Leu Ser Leu Leu Asp Glu Phe Tyr Lys Leu Ala Asp Pro Val Arg Asp

115 120 125

Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala Ser Ile His Leu

130 135 140

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

145 150 155 160

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

165 170 175

Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Ala

180 185 190

Thr Ser Ala Pro Thr Ala Glu Asp Gln Gly Ala Glu Ala Glu Pro Glu

195 200 205

Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr

210 215 220

Val Asn Arg Gln Phe Met Ala Glu Ala Gln Phe Ser Gly Glu Lys Glu

225 230 235 240

Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu

245 250 255

Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser

260 265 270

Leu Thr Pro Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val

275 280 285

Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp

290 295 300

Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser

305 310 315 320

Ala Gln Pro Met Asn Pro Ala Gln Asn Met Asp Met Pro Gln Leu Val

325 330 335

Cys Pro Pro Val His Ala Glu Ser Arg Leu Ala Gln Pro Asn Gln Val

340 345 350

Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser

355 360 365

Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr

370 375 380

Glu Gln Arg Pro Gln Lys Glu Pro Thr Asp Gln Ile Gln Ala Thr Ile

385 390 395 400

Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Ser Leu Pro Ala Ala

405 410 415

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

420 425 430

Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val

435 440 445

Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr Leu

450 455 460

Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Ser

465 470 475 480

Pro Pro His Gln Val Glu Gln Thr Glu Leu Pro Gln Glu Gln Leu Gln

485 490 495

Thr Val Val Gly Thr Tyr His Ala Ser Gln Asp Gln Pro His Gln Val

500 505 510

Thr Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg

515 520 525

Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser

530 535 540

Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly

545 550 555 560

Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro

565 570 575

Asn Ser Gly Tyr Thr Gln Ser Gln Phe Ser Ala Pro Arg Asp Tyr Ser

580 585 590

Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly

595 600 605

Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg

610 615 620

Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn

625 630 635

<210> 19

<211> 6181

<212> DNA

<213> Mus musculus

<220>

<221> CDS

<222> (179)..(2302)

<400> 19

gctggctggc taagtccctc ccgcgccggc tcttgtccca ctaggagcag ctcagagccg 60

cggggacagg gcgaagcggc ctgcgcccac ggagcgcacg tctctgttct caacgcagca 120

ccacccttgc ccccctcggc tgcccactcc agacgtccag cggctccgcg cgcgcacg 178

atg ccc tcg gcc acc agc cac agc gga agc ggc agc aaa tcg tcg gga 226

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly

1 5 10 15

ccg ccg ccg ccg tcc ggt tcc tcc ggg agt gag gcg gcg gcc ggg gca 274

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala

20 25 30

gct gcg ccg gct tct cag cat ccg gca acc ggc acc ggc gcc gtc cag 322

Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln

35 40 45

acc gag gcc atg aag cag att ctc ggc gta atc gac aag aaa ctt cgg 370

Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg

50 55 60

aac ctg gag aag aaa aag ggt aaa ctt gat gat tac cag gaa cga atg 418

Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met

65 70 75 80

aat aaa ggg gaa agg ctc aat caa gac cag ctg gat gcc gta tct aag 466

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

85 90 95

tac cag gaa gtc aca aat aat ttg gag ttt gca aag gaa tta cag agg 514

Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg

100 105 110

agt ttc atg gca tta agt caa gat att cag aaa aca ata aag aag aca 562

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

115 120 125

gca cgt cgg gaa cag ctt atg aga gaa gaa gca gaa cag aag cgc tta 610

Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu

130 135 140

aaa act gta ctt gag tta cag tat gta ttg gat aag ctg gga gat gat 658

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

145 150 155 160

gat gtg aga aca gat ctg aaa caa ggt ttg agt gga gtg cca ata ttg 706

Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu

165 170 175

tct gag gag gag ttg tca ttg ctg gat gag ttc tac aag ctc gta gat 754

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

180 185 190

cct gag cgt gac atg agt tta agg tta aat gag cag tat gaa cat gcc 802

Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala

195 200 205

tca att cac ttg tgg gat ttg ctg gaa ggg aaa gaa aag cct gtg tgt 850

Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys

210 215 220

gga aca acc tat aaa gct cta aag gaa att gtt gag cgt gtt ttc cag 898

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

225 230 235 240

tca aac tac ttt gat agc act cac aat cat caa aat ggg ttg tgt gag 946

Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu

245 250 255

gag gaa gag gcg gct tca gcg ccc aca gtg gag gac cag gta gct gaa 994

Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu

260 265 270

gct gaa cct gag cca gcg gaa gaa tac aca gag caa agt gag gtt gaa 1042

Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu

275 280 285

tca aca gag tat gtc aat agg cag ttc atg gca gaa aca cag ttc agc 1090

Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser

290 295 300

agt ggt gag aag gag caa gtg gat gag tgg aca gtt gaa aca gtt gag 1138

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

305 310 315 320

gtt gta aac tca ctc cag cag caa cct cag gct gcg tcc cct tca gtc 1186

Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val

325 330 335

cca gag ccc cac tct ttg act cca gtg gct cag tca gat cca ctt gtg 1234

Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val

340 345 350

aga agg cag cgt gta caa gat ctt atg gca caa atg caa ggg ccc tat 1282

Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr

355 360 365

aat ttc ata cag gat tca atg ttg gat ttt gaa aat cag acg ctt gat 1330

Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp

370 375 380

cct gcc att gta tcc gca cag cct atg aac cct acc cag aac atg gat 1378

Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp

385 390 395 400

atg cct cag ctg gtt tgc cct cag gtt cat tct gaa tct aga ctt gcc 1426

Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala

405 410 415

caa tct aat caa gtt cct gta caa cca gaa gcc aca cag gtt cct ttg 1474

Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu

420 425 430

gtt tca tcc aca agt gag ggg tat aca gca tct cag ccc ttg tac cag 1522

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

435 440 445

cca tct cat gct acg gag cag cgg ccg cag aaa gag cca atg gat cag 1570

Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln

450 455 460

att cag gca aca ata tct ttg aat aca gac cag act aca gca tcc tca 1618

Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser

465 470 475 480

tcc ctt cct gct gct tct cag cct caa gtg ttc cag gct ggg aca agt 1666

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

485 490 495

aaa cct ttg cac agc agt gga atc aat gta aat gca gct cca ttc cag 1714

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

500 505 510

tcc atg caa acg gtg ttc aat atg aat gct cca gtc cct cct gct aat 1762

Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn

515 520 525

gaa cca gaa acg tta aaa caa cag agt cag tac cag gcc act tat aac 1810

Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn

530 535 540

cag agt ttt tcc agt cag cct cac caa gtg gaa caa aca gag ctt caa 1858

Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln

545 550 555 560

caa gac caa ctg caa acg gtg gtt ggc act tac cat gga tcc cag gac 1906

Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp

565 570 575

cag cct cat caa gtg cct ggt aac cac cag caa ccc cca cag cag aac 1954

Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn

580 585 590

act ggc ttt cca cgt agc agt cag cct tat tac aac agt cgt ggg gta 2002

Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val

595 600 605

tct cga gga ggg tct cgt ggt gcc aga ggc ttg atg aat gga tac agg 2050

Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg

610 615 620

ggc cct gcc aat gga ttt aga gga gga tat gat ggt tac cgc cct tca 2098

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

625 630 635 640

ttc tcg aac act cca aac agt ggt tat tca cag tct cag ttc act gct 2146

Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala

645 650 655

ccc cgg gac tac tct ggt tac cag cgg gat gga tat cag cag aat ttc 2194

Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe

660 665 670

aag cga ggc tct ggg cag agt gga cca cgg gga gcc cca cga ggt cgt 2242

Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg

675 680 685

gga ggg ccc cca aga ccc aac aga ggg atg ccg caa atg aac act cag 2290

Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln

690 695 700

caa gtg aat taa tgtgatacac aggattatgt ttaatcgcca aaaacacact 2342

Gln Val Asn

705

ggccagtgta ccataatatg ttaccagaag agttattatc tatttgttct ccctttcagg 2402

aaacttattg taaagggact gttttcatcc cataaagaca ggactgcaat tgtcagcttt 2462

acattacctg gatatggaag gaaactattt ttattctgca tgttctgtcc taagcgtcat 2522

cttgagcctt gcacacaata caatactcag attcctcacc cttgcttagg agtaaaacat 2582

tatatactta tggggtgata atatctccat agttagttga agtggcttgg aaaaaaaatg 2642

caagattgaa tttttgacct tggataaaat ctacaatcag ccctagaact attcagtggt 2702

2762

gcaaaactgc atttcatagc ttttcccatta aattggagca ccgacagatt aaaagcatac 2822

caaattatgc atgggtcctt actcacacaa gtgaggctgg ctaccagcct tgacatagca 2882

ctcactagtc ttctggccaa acgactgtga ttaaaacaca tgtaaattgc tctttagtag 2942

tggatactgt gtaagacaaa gccaaattgc aaatcaggct ttgattggct cttctggaaa 3002

atatgcatca aatatggggg ataatctgga tgggctgctg ctgtgctcaa tgtgaactat 3062

ttagatacct ttggaacact taacagtttc tctgaacaat gacttacatg gggattggtc 3122

ctgtttgtca ttcctcacca taattgcatt gtcatcacta atccttggat cttgctgtat 3182

tgttactcaa attggtaata ggtactgatg gaaatcgcta atggatggat aatcataaca 3242

cttttggtca catgttttct cctgcagcct gaaagttctt aaagaaaaag atatcaaatg 3302

cctgctgcta ccaccctttt aaattgctat ctttagaaaa gcaccggtat gtgttttaga 3362

ttcatttccc tgttttaggg aaatgacagg cagtagtttc agttctgatg gcaaaacaaa 3422

3482

agtaattcaa cccatgcatt gctagtgtca cagcctttgg ttatgtctag tagctgtttc 3542

3602

aaggagacac ttatgttcaa agtgttgatt ctttgcctta ggtgcataga gagtagacag 3662

tttggagatg gaaaggttag cagtgactta gccatatgtt ctgtgttgga atttgtgcta 3722

gcagtttgag cactagctct gcgtgcctat gaactgaatg ctgcttgtcc cattccattt 3782

3842

tacagaaatt aaattttact tttagccttt tgtaaacttt tttttttttt ttccaagccg 3902

gtatcagcta ctcaaaacaa ttctcagata ttcatcatta gacaactgga gtttttgctg 3962

gttttgtagc ctactaaaac tgctgaggct gttgaacatt ccacattcaa aagttttgta 4022

4082

acttttctca tgtgtggtta tggtacatca tattggaagg gttatctgtt tacttttgcc 4142

aagactattt tgccagcacc tacacttgtg tgctttaaaa gacaactacc tgggatgtac 4202

cacaaccata tgttaattgt attttattgg gatggataaa atgtttgtgg tttattggat 4262

aatccctaga tggtgtgtta cgtgtgtaga atataatttt atgatagtaa gaaagcaaaa 4322

ttgaagaaaa taagtttagt attgaatttg agttctgaag tgaattcagg gaatgtctca 4382

4442

ttgtttattt tttaagttgc ttattccttt caacagcaac atatcattag ctgtcattct 4502

accattgcag ttctagtgag ttttaacgtc tgcattcaag actgttttaa aagcaacctc 4562

actggacaga gaactgctaa agtcttttcc ttaagatctg agtctttgtt actcagtatc 4622

ttctataata tgcaaatgct tgtctagagg cagagacct tttgtttggt caagtgtgta 4682

ttttaccaga gtacagggaa ctgatggtcc tacatgtctc ttagtgtagt aagactataa 4742

aatcttttgt acatgcacaa ttcacagtat gtttagatac cacgtgtata atgccccccc 4802

ctcccccagg tagcatgcca ttgatgactt tttgcttagg gccattttat taccagggcc 4862

ttaatattcc taaaaagatg atttttttttc atccttttctc ctcttttgat cattgtatct 4922

tgatattaaa aacatgacct tccaatgatt gtagtaaatt aacttctata gttcttttgt 4982

ctctatatgt attcatatat atgctattgt

tgcttattct caggttcatt cactaaggtg cttggcagac aaccagtttc taagtgcaga 5102

atgtagttaa gcagcttcat atatgtgcca ggcaatttgt tttgttaaat tttcatctac 5162

ttaaggaaat agggtattgt agcttaggct gatcataccc ttcatttcaa ccttaagctc 5222

tcaacctgca tccatccgac ttgagctatt aagtacttta gttttatcga gtataagtta 5282

5342

acttagaaac tgttgtatat ttcattagat taaattatat gaaaatgtga ttgtttatag 5402

caaagcctgt gagttgcata caccctaagg aaaactcctt aagtgctcct tgaagagaga 5462

agaaacaatt ctgggtctgg tctttttaag aacaaagcta gactactgta tgttagcact 5522

gtacattaat agtctgttgt gaagcttgag cagtttcctg catagccttg atccttcacc 5582

gttggcattg aaaatagcag tatccctgat gtacttaaaa cttaaagtca ggttttggta 5642

tatttatttg taagtcttaa ttttcctctaa atactatatc tctttagcga gacaacctga 5702

aatttattag cacatttggg tatctcttgc ttggcattat ggccagtgtt aactattcag 5762

tggtgaaaaa attacccctc aagacactgg agtgacccca gatgtgtgta gtaagtggca 5822

tggttcaact gtgtggttaa tgataaatat atgacttagt cggtatgatc tggaaagact 5882

tgattgaaag ataattcagc tgacataagg atgagtgagg agtggcaaac tggataaaag 5942

agtcaagaga cctgtattcc agtgactcct gttttgttta agcattagca agatctgtct 6002

ggggaaactg gatagggcag ttttcttcca tgtttagttt ttgtctcaac atttggaagc 6062

tattgaaggt tttaaaatgg tgtgtattgt ttttttttgg ggggggggtg gccagaatag 6122

tgggtcatct aataaaactg ccatttaaaa gatcaaaaaa aaaaaaaaaa aaaaaaaaa 6181

<210> 20

<211> 707

<212> Protein

<213> Mus musculus

<400> 20

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala

20 25 30

Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln

35 40 45

Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg

50 55 60

Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met

65 70 75 80

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

85 90 95

Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg

100 105 110

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

115 120 125

Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu

130 135 140

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

145 150 155 160

Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu

165 170 175

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

180 185 190

Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala

195 200 205

Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys

210 215 220

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

225 230 235 240

Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu

245 250 255

Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu

260 265 270

Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu

275 280 285

Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser

290 295 300

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

305 310 315 320

Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val

325 330 335

Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val

340 345 350

Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr

355 360 365

Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp

370 375 380

Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp

385 390 395 400

Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala

405 410 415

Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu

420 425 430

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

435 440 445

Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln

450 455 460

Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser

465 470 475 480

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

485 490 495

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

500 505 510

Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn

515 520 525

Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn

530 535 540

Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln

545 550 555 560

Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp

565 570 575

Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn

580 585 590

Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val

595 600 605

Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg

610 615 620

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

625 630 635 640

Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala

645 650 655

Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe

660 665 670

Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg

675 680 685

Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln

690 695 700

Gln Val Asn

705

<210> 21

<211> 6141

<212> DNA

<213> Mus musculus

<220>

<221> CDS

<222> (139)..(2262)

<400> 21

60

tctccccgtc cgtctcctga cttgctggtc ttgtccttcc ctcccgcttt tttcctctcc 120

tctcttctcg gtctaaag atg ccc tcg gcc acc agc cac agc gga agc ggc 171

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly

1 5 10

agc aaa tcg tcg gga ccg ccg ccg ccg tcc ggt tcc tcc ggg agt gag 219

Ser Lys Ser Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu

15 20 25

gcg gcg gcc ggg gca gct gcg ccg gct tct cag cat ccg gca acc ggc 267

Ala Ala Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly

30 35 40

acc ggc gcc gtc cag acc gag gcc atg aag cag att ctc ggc gta atc 315

Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile

45 50 55

gac aag aaa ctt cgg aac ctg gag aag aaa aag ggt aaa ctt gat gat 363

Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp

60 65 70 75

tac cag gaa cga atg aat aaa ggg gaa agg ctc aat caa gac cag ctg 411

Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu

80 85 90

gat gcc gta tct aag tac cag gaa gtc aca aat aat ttg gag ttt gca 459

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

95 100 105

aag gaa tta cag agg agt ttc atg gca tta agt caa gat att cag aaa 507

Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys

110 115 120

aca ata aag aag aca gca cgt cgg gaa cag ctt atg aga gaa gaa gca 555

Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala

125 130 135

gaa cag aag cgc tta aaa act gta ctt gag tta cag tat gta ttg gat 603

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

140 145 150 155

aag ctg gga gat gat gat gtg aga aca gat ctg aaa caa ggt ttg agt 651

Lys Leu Gly Asp Asp Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser

160 165 170

gga gtg cca ata ttg tct gag gag gag ttg tca ttg ctg gat gag ttc 699

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

175 180 185

tac aag ctc gta gat cct gag cgt gac atg agt tta agg tta aat gag 747

Tyr Lys Leu Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu

190 195 200

cag tat gaa cat gcc tca att cac ttg tgg gat ttg ctg gaa ggg aaa 795

Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys

205 210 215

gaa aag cct gtg tgt gga aca acc tat aaa gct cta aag gaa att gtt 843

Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val

220 225 230 235

gag cgt gtt ttc cag tca aac tac ttt gat agc act cac aat cat caa 891

Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln

240 245 250

aat ggg ttg tgt gag gag gaa gag gcg gct tca gcg ccc aca gtg gag 939

Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu

255 260 265

gac cag gta gct gaa gct gaa cct gag cca gcg gaa gaa tac aca gag 987

Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu

270 275 280

caa agt gag gtt gaa tca aca gag tat gtc aat agg cag ttc atg gca 1035

Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala

285 290 295

gaa aca cag ttc agc agt ggt gag aag gag caa gtg gat gag tgg aca 1083

Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr

300 305 310 315

gtt gaa aca gtt gag gtt gta aac tca ctc cag cag caa cct cag gct 1131

Val Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala

320 325 330

gcg tcc cct tca gtc cca gag ccc cac tct ttg act cca gtg gct cag 1179

Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln

335 340 345

tca gat cca ctt gtg aga agg cag cgt gta caa gat ctt atg gca caa 1227

Ser Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln

350 355 360

atg caa ggg ccc tat aat ttc ata cag gat tca atg ttg gat ttt gaa 1275

Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu

365 370 375

aat cag acg ctt gat cct gcc att gta tcc gca cag cct atg aac cct 1323

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

380 385 390 395

acc cag aac atg gat atg cct cag ctg gtt tgc cct cag gtt cat tct 1371

Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys Pro Gln Val His Ser

400 405 410

gaa tct aga ctt gcc caa tct aat caa gtt cct gta caa cca gaa gcc 1419

Glu Ser Arg Leu Ala Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala

415 420 425

aca cag gtt cct ttg gtt tca tcc aca agt gag ggg tat aca gca tct 1467

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

430 435 440

cag ccc ttg tac cag cca tct cat gct acg gag cag cgg ccg cag aaa 1515

Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys

445 450 455

gag cca atg gat cag att cag gca aca ata tct ttg aat aca gac cag 1563

Glu Pro Met Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln

460 465 470 475

act aca gca tcc tca tcc ctt cct gct gct tct cag cct caa gtg ttc 1611

Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe

480 485 490

cag gct ggg aca agt aaa cct ttg cac agc agt gga atc aat gta aat 1659

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

495 500 505

gca gct cca ttc cag tcc atg caa acg gtg ttc aat atg aat gct cca 1707

Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro

510 515 520

gtc cct cct gct aat gaa cca gaa acg tta aaa caa cag agt cag tac 1755

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

525 530 535

cag gcc act tat aac cag agt ttt tcc agt cag cct cac caa gtg gaa 1803

Gln Ala Thr Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu

540 545 550 555

caa aca gag ctt caa caa gac caa ctg caa acg gtg gtt ggc act tac 1851

Gln Thr Glu Leu Gln Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr

560 565 570

cat gga tcc cag gac cag cct cat caa gtg cct ggt aac cac cag caa 1899

His Gly Ser Gln Asp Gln Pro His Gln Val Pro Gly Asn His Gln Gln

575 580 585

ccc cca cag cag aac act ggc ttt cca cgt agc agt cag cct tat tac 1947

Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr

590 595 600

aac agt cgt ggg gta tct cga gga ggg tct cgt ggt gcc aga ggc ttg 1995

Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu

605 610 615

atg aat gga tac agg ggc cct gcc aat gga ttt aga gga gga tat gat 2043

Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp

620 625 630 635

ggt tac cgc cct tca ttc tcg aac act cca aac agt ggt tat tca cag 2091

Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln

640 645 650

tct cag ttc act gct ccc cgg gac tac tct ggt tac cag cgg gat gga 2139

Ser Gln Phe Thr Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly

655 660 665

tat cag cag aat ttc aag cga ggc tct ggg cag agt gga cca cgg gga 2187

Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly

670 675 680

gcc cca cga ggt cgt gga ggg ccc cca aga ccc aac aga ggg atg ccg 2235

Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro

685 690 695

caa atg aac act cag caa gtg aat taa tgtgatacac aggattatgt 2282

Gln Met Asn Thr Gln Gln Val Asn

700 705

ttaatcgcca aaaacacact ggccagtgta ccataatatg ttaccagaag agttattatc 2342

tatttgttct ccctttcagg aaacttattg taaagggact gttttcatcc cataaagaca 2402

ggactgcaat tgtcagcttt acattacctg gatatggaag gaaactattt ttattctgca 2462

tgttctgtcc taagcgtcat cttgagcctt gcacacaata caatactcag attcctcacc 2522

cttgcttagg agtaaaacat tatatactta tggggtgata atatctccat agttagttga 2582

agtggcttgg aaaaaaaatg caagattgaa tttttgacct tggataaaat ctacaatcag 2642

ccctagaact attcagtggt aattgacaaa gttaaagcat tttctttgaa aggaagatgg 2702

aaggagtgga gtgtggttta gcaaaactgc atttcatagc tttcccatta aattggagca 2762

ccgacagatt aaaagcatac caaattatgc atgggtcctt actcacacaa gtgaggctgg 2822

ctaccagcct tgacatagca ctcactagtc ttctggccaa acgactgtga ttaaaacaca 2882

tgtaaattgc tctttagtag tggatactgt gtaagacaaa gccaaattgc aaatcaggct 2942

ttgattggct cttctggaaa atatgcatca aatatggggg ataatctggga tgggctgctg 3002

ctgtgctcaa tgtgaactat ttagatacct ttggaacact taacagtttc tctgaacaat 3062

3122 gacttacatg gggattggtc ctgtttgtca ttcctcacca

atccttggat cttgctgtat tgttactcaa attggtaata ggtactgatg gaaatcgcta 3182

atggatggat aatcataaca cttttggtca catgttttct cctgcagcct gaaagttctt 3242

3302

gcaccggtat gtgttttaga ttcatttccc tgttttaggg aaatgacagg cagtagtttc 3362

agttctgatg gcaaaacaaa taaaaacatg tttctaaaag ttgtatcttg aaacactggt 3422

3482

3542

3602

3662

ctgtgttgga atttgtgcta gcagtttgag cactagctct gcgtgcctat gaactgaatg 3722

ctgcttgtcc cattccattt tatgtcatgg agaaataatt ccacttggta acacaaaggc 3782

3842

tttttttttt ttccaagccg gtatcagcta ctcaaaacaa ttctcagata ttcatcatta 3902

gacaactgga gtttttgctg gttttgtagc ctactaaaac tgctgaggct gttgaacatt 3962

ccacattcaa aagttttgta gggtggtgga taatggggaa gcttcaatgt ttattttaaa 4022

ataaataaaa taagttcttg acttttctca tgtgtggtta tggtacatca tattggaagg 4082

gttatctgtt tacttttgcc aagactattt tgccagcacc tacacttgtg tgctttaaaa 4142

gacaactacc tgggatgtac cacaaccata tgttaattgt attttattgg gatggataaa 4202

atgtttgtgg tttattggat aatccctaga tggtgtgtta cgtgtgtaga atataatttt 4262

4322

tgaattcagg gaatgtctca cgtttcgggc ttctacccaa agtgtagggc agaaggtgta 4382

aaagttgttt gtagtttgac ttgtttattt tttaagttgc ttattccttt caacagcaac 4442

atatcattag ctgtcattct accattgcag ttctagtgag ttttaacgtc tgcattcaag 4502

actgttttaa aagcaacctc actggacaga gaactgctaa agtcttttcc ttaagatctg 4562

agtctttgtt actcagtatc ttctataata tgcaaatgct tgtctagagg cagaagacct 4622

tttgtttggt caagtgtgta tttttaccaga gtacagggaa ctgatggtcc tacatgtctc 4682

ttagtgtagt aagactataa aatcttttgt acatgcacaa ttcacagtat gtttagatac 4742

cacgtgtata atgccccccc ctcccccagg tagcatgcca ttgatgactt tttgcttagg 4802

gccattttat taccagggcc ttaatattcc taaaaagatg atttttttttc atcctttctc 4862

ctcttttgat cattgtatct tgatattaaa aacatgacct tccaatgatt gtagtaaatt 4922

aacttctata gttcttttgt ctctatatgt attcatatat atgctattgt atagagactt 4982

caaggagaca tggagatgca tgcttattct caggttcatt cactaaggtg cttggcagac 5042

aaccagtttc taagtgcaga atgtagttaa gcagcttcat atatgtgcca ggcaatttgt 5102

tttgttaaat tttcatctac ttaaggaaat agggtattgt agcttaggct gatcataccc 5162

ttcatttcaa ccttaagctc tcaacctgca tccatccgac ttgagctatt aagtacttta 5222

5282

tttatataca ttctggaaaa acttagaaac tgttgtatat ttcattagat taaattatat 5342

gaaaatgtga ttgtttatag caaagcctgt gagttgcata caccctaagg aaaactcctt 5402

aagtgctcct tgaagagaga agaaacaatt ctgggtctgg tctttttaag aacaaagcta 5462

gactactgta tgttagcact gtacattaat agtctgttgt gaagcttgag cagtttcctg 5522

catagccttg atccttcacc gttggcattg aaaatagcag tatccctgat gtacttaaaa 5582

cttaaagtca ggttttggta tatttatttg taagtcttaa ttttcctctaa atactatatc 5642

tctttagcga gacaacctga aatttattag cacatttggg tatctcttgc ttggcattat 5702

ggccagtgtt aactattcag tggtgaaaaa attacccctc aagacactgg agtgacccca 5762

gatgtgtgta gtaagtggca tggttcaact gtgtggttaa tgataaatat atgacttagt 5822

cggtatgatc tggaaagact tgattgaaag ataattcagc tgacataagg atgagtgagg 5882

agtggcaaac tggataaaag agtcaagaga cctgtattcc agtgactcct gttttgttta 5942

agcattagca agatctgtct ggggaaactg gatagggcag ttttcttcca tgtttagttt 6002

6062

ggggggggtg gccagaatag tgggtcatct aataaaactg ccatttaaaa gatcaaaaaa 6122

aaaaaaaaaaaaaaaaaaa 6141

<210> 22

<211> 707

<212> Protein

<213> Mus musculus

<400> 22

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala

20 25 30

Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln

35 40 45

Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg

50 55 60

Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met

65 70 75 80

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

85 90 95

Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg

100 105 110

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

115 120 125

Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu

130 135 140

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

145 150 155 160

Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu

165 170 175

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

180 185 190

Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala

195 200 205

Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys

210 215 220

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

225 230 235 240

Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu

245 250 255

Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu

260 265 270

Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu

275 280 285

Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser

290 295 300

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

305 310 315 320

Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val

325 330 335

Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val

340 345 350

Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr

355 360 365

Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp

370 375 380

Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp

385 390 395 400

Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala

405 410 415

Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu

420 425 430

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

435 440 445

Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln

450 455 460

Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser

465 470 475 480

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

485 490 495

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

500 505 510

Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn

515 520 525

Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn

530 535 540

Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln

545 550 555 560

Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp

565 570 575

Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn

580 585 590

Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val

595 600 605

Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg

610 615 620

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

625 630 635 640

Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala

645 650 655

Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe

660 665 670

Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg

675 680 685

Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln

690 695 700

Gln Val Asn

705

<210> 23

<211> 6114

<212> DNA

<213> Mus musculus

<220>

<221> CDS

<222> (139)..(2235)

<400> 23

60

tctccccgtc cgtctcctga cttgctggtc ttgtccttcc ctcccgcttt tttcctctcc 120

tctcttctcg gtctaaag atg ccc tcg gcc acc agc cac agc gga agc ggc 171

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly

1 5 10

agc aaa tcg tcg gga ccg ccg ccg ccg tcc ggt tcc tcc ggg agt gag 219

Ser Lys Ser Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu

15 20 25

gcg gcg gcc ggg gca gct gcg ccg gct tct cag cat ccg gca acc ggc 267

Ala Ala Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly

30 35 40

acc ggc gcc gtc cag acc gag gcc atg aag cag att ctc ggc gta atc 315

Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile

45 50 55

gac aag aaa ctt cgg aac ctg gag aag aaa aag ggt aaa ctt gat gat 363

Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp

60 65 70 75

tac cag gaa cga atg aat aaa ggg gaa agg ctc aat caa gac cag ctg 411

Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu

80 85 90

gat gcc gta tct aag tac cag gaa gtc aca aat aat ttg gag ttt gca 459

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

95 100 105

aag gaa tta cag agg agt ttc atg gca tta agt caa gat att cag aaa 507

Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys

110 115 120

aca ata aag aag aca gca cgt cgg gaa cag ctt atg aga gaa gaa gca 555

Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala

125 130 135

gaa cag aag cgc tta aaa act gta ctt gag tta cag tat gta ttg gat 603

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

140 145 150 155

aag ctg gga gat gat gat gtg aga aca gat ctg aaa caa ggt ttg agt 651

Lys Leu Gly Asp Asp Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser

160 165 170

gga gtg cca ata ttg tct gag gag gag ttg tca ttg ctg gat gag ttc 699

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

175 180 185

tac aag ctc gta gat cct gag cgt gac atg agt tta agg tta aat gag 747

Tyr Lys Leu Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu

190 195 200

cag tat gaa cat gcc tca att cac ttg tgg gat ttg ctg gaa ggg aaa 795

Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys

205 210 215

gaa aag cct gtg tgt gga aca acc tat aaa gct cta aag gaa att gtt 843

Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val

220 225 230 235

gag cgt gtt ttc cag tca aac tac ttt gat agc act cac aat cat caa 891

Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln

240 245 250

aat ggg ttg tgt gag gag gaa gag gcg gct tca gcg ccc aca gtg gag 939

Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu

255 260 265

gac cag gta gct gaa gct gaa cct gag cca gcg gaa gaa tac aca gag 987

Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu

270 275 280

caa agt gag gtt gaa tca aca gag tat gtc aat agg cag ttc atg gca 1035

Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala

285 290 295

gaa aca cag ttc agc agt ggt gag aag gag caa gtg gat gag tgg aca 1083

Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr

300 305 310 315

gtt gaa aca gtt gag gtt gta aac tca ctc cag cag caa cct cag gct 1131

Val Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala

320 325 330

gcg tcc cct tca gtc cca gag ccc cac tct ttg act cca gtg gct cag 1179

Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln

335 340 345

tca gat cca ctt gtg aga agg cag cgt gta caa gat ctt atg gca caa 1227

Ser Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln

350 355 360

atg caa ggg ccc tat aat ttc ata cag acg ctt gat cct gcc att gta 1275

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

365 370 375

tcc gca cag cct atg aac cct acc cag aac atg gat atg cct cag ctg 1323

Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu

380 385 390 395

gtt tgc cct cag gtt cat tct gaa tct aga ctt gcc caa tct aat caa 1371

Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala Gln Ser Asn Gln

400 405 410

gtt cct gta caa cca gaa gcc aca cag gtt cct ttg gtt tca tcc aca 1419

Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr

415 420 425

agt gag ggg tat aca gca tct cag ccc ttg tac cag cca tct cat gct 1467

Ser Glu Gly Tyr Thr Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala

430 435 440

acg gag cag cgg ccg cag aaa gag cca atg gat cag att cag gca aca 1515

Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln Ile Gln Ala Thr

445 450 455

ata tct ttg aat aca gac cag act aca gca tcc tca tcc ctt cct gct 1563

Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala

460 465 470 475

gct tct cag cct caa gtg ttc cag gct ggg aca agt aaa cct ttg cac 1611

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

480 485 490

agc agt gga atc aat gta aat gca gct cca ttc cag tcc atg caa acg 1659

Ser Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr

495 500 505

gtg ttc aat atg aat gct cca gtc cct cct gct aat gaa cca gaa acg 1707

Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn Glu Pro Glu Thr

510 515 520

tta aaa caa cag agt cag tac cag gcc act tat aac cag agt ttt tcc 1755

Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn Gln Ser Phe Ser

525 530 535

agt cag cct cac caa gtg gaa caa aca gag ctt caa caa gac caa ctg 1803

Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln Gln Asp Gln Leu

540 545 550 555

caa acg gtg gtt ggc act tac cat gga tcc cag gac cag cct cat caa 1851

Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln

560 565 570

gtg cct ggt aac cac cag caa ccc cca cag cag aac act ggc ttt cca 1899

Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro

575 580 585

cgt agc agt cag cct tat tac aac agt cgt ggg gta tct cga gga ggg 1947

Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly

590 595 600

tct cgt ggt gcc aga ggc ttg atg aat gga tac agg ggc cct gcc aat 1995

Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn

605 610 615

gga ttt aga gga gga tat gat ggt tac cgc cct tca ttc tcg aac act 2043

Gly Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr

620 625 630 635

cca aac agt ggt tat tca cag tct cag ttc act gct ccc cgg gac tac 2091

Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala Pro Arg Asp Tyr

640 645 650

tct ggt tac cag cgg gat gga tat cag cag aat ttc aag cga ggc tct 2139

Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser

655 660 665

ggg cag agt gga cca cgg gga gcc cca cga ggt cgt gga ggg ccc cca 2187

Gly Glyn Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro

670 675 680

aga ccc aac aga ggg atg ccg caa atg aac act cag caa gtg aat taa 2235

Arg Pro Asn Arg Gly Met Pro Gln Met Asn Thr Gln Gln Val Asn

685 690 695

tgtgatacac aggattatgt ttaatcgcca aaaacacact ggccagtgta ccataatatg 2295

ttaccagaag agttattatc tatttgttct ccctttcagg aaacttattg taaagggact 2355

gttttcatcc cataaagaca ggactgcaat tgtcagcttt acattacctg gatatggaag 2415

gaaactattt ttattctgca tgttctgtcc taagcgtcat cttgagcctt gcacacaata 2475

caatactcag attcctcacc cttgcttagg agtaaaacat tatatactta tggggtgata 2535

atatctccat agttagttga agtggcttgg aaaaaaaatg caagattgaa tttttgacct 2595

tggataaaat ctacaatcag ccctagaact attcagtggt aattgacaaa gttaaagcat 2655

tttctttgaa aggaagatgg aaggagtgga gtgtggttta gcaaaactgc atttcatagc 2715

tttcccatta aattggagca ccgacagatt aaaagcatac caaattatgc atgggtcctt 2775

actcacacaa gtgaggctgg ctaccagcct tgacatagca ctcactagtc ttctggccaa 2835

acgactgtga ttaaaacaca tgtaaattgc tctttagtag tggatactgt gtaagacaaa 2895

gccaaattgc aaatcaggct ttgattggct cttctggaaa atatgcatca aatatggggg 2955

ataatctgga tgggctgctg ctgtgctcaa tgtgaactat ttagatacct ttggaacact 3015

taacagtttc tctgaacaat gacttacatg gggattggtc ctgtttgtca ttcctcacca 3075

taattgcatt gtcatcacta atccttggat cttgctgtat tgttactcaa attggtaata 3135

ggtactgatg gaaatcgcta atggatggat aatcataaca cttttggtca catgttttct 3195

3255

aaattgctat ctttagaaaa gcaccggtat gtgttttaga ttcatttccc tgttttaggg 3315

3375

ttgtatcttg aaacactggt gttcaacagc tagcagctaa agtaattcaa cccatgcatt 3435

3495

3555

3615

cagtgactta gccatatgtt ctgtgttgga atttgtgcta gcagtttgag cactagctct 3675

gcgtgcctat gaactgaatg ctgcttgtcc cattccattt tatgtcatgg agaaataatt 3735

ccacttggta acacaaaggc taagttaatg ttatttttctg tacagaaatt aaattttact 3795

tttagcctttt tgtaaacttt tttttttttt ttccaagccg gtatcagcta ctcaaaacaa 3855

ttctcagata ttcatcatta gacaactgga gttttttgctg gttttgtagc ctactaaaac 3915

tgctgaggct gttgaacatt ccacattcaa aagttttgta gggtggtgga taatggggaa 3975

gcttcaatgt ttattttaaa ataaataaaa taagttcttg acttttctca tgtgtggtta 4035

tggtacatca tattggaagg gttatctgtt tacttttgcc aagactattt tgccagcacc 4095

tacacttgtg tgctttaaaa gacaactacc tgggatgtac cacaaccata tgttaattgt 4155

attttattgg gatggataaa atgtttgtgg tttattggat aatccctaga tggtgtgtta 4215

4275

attgaatttg agttctgaag tgaattcagg gaatgtctca cgtttcgggc ttctacccaa 4335

agtgtagggc agaaggtgta aaagttgttt gtagtttgac ttgtttattt tttaagttgc 4395

ttattccttt caacagcaac atatcattag ctgtcattct accattgcag ttctagtgag 4455

ttttaacgtc tgcattcaag actgttttaa aagcaacctc actggacaga gaactgctaa 4515

agtcttttcc ttaagatctg agtctttgtt actcagtatc ttctataata tgcaaatgct 4575

tgtctagagg cagaagacct tttgtttggt caagtgtgta ttttaccaga gtacagggaa 4635

ctgatggtcc tacatgtctc ttagtgtagt aagactataa aatcttttgt acatgcacaa 4695

ttcacagtat gtttagatac cacgtgtata atgccccccc ctcccccagg tagcatgcca 4755

ttgatgactt tttgcttagg gccattttat taccagggcc ttaatattcc taaaaagatg 4815

attttttttc atcctttctc ctcttttgat cattgtatct tgatattaaa aacatgacct 4875

tccaatgatt gtagtaaatt aacttctata gttcttttgt ctctatatgt attcatatat 4935

atgctattgt atagagactt caaggagaca tggagatgca tgcttattct caggttcatt 4995

cactaaggtg cttggcagac aaccagtttc taagtgcaga atgtagttaa gcagcttcat 5055

atatgtgcca ggcaatttgt tttgttaaat tttcatctac ttaaggaaat agggtattgt 5115

agcttaggct gatcataccc ttcatttcaa ccttaagctc tcaacctgca tccatccgac 5175

ttgagctatt aagtacttta gttttatcga gtataagtta acagaaaaag taaattaagc 5235

tttgccttta ctattttgaa tttatataca ttctggaaaa acttagaaac tgttgtatat 5295

ttcattagat taaattatat gaaaatgtga ttgtttatag caaagcctgt gagttgcata 5355

caccctaagg aaaactcctt aagtgctcct tgaagagaga agaaacaatt ctgggtctgg 5415

tctttttaag aacaaagcta gactactgta tgttagcact gtacattaat agtctgttgt 5475

gaagcttgag cagtttcctg catagccttg atccttcacc gttggcattg aaaatagcag 5535

tatccctgat gtacttaaaa cttaaagtca ggttttggta tatttatttg taagtcttaa 5595

tttcctctaa atactatatc tctttagcga gacaacctga aatttattag cacatttggg 5655

tatctcttgc ttggcattat ggccagtgtt aactattcag tggtgaaaaa attacccctc 5715

aagacactgg agtgacccca gatgtgtgta gtaagtggca tggttcaact gtgtggttaa 5775

tgataaatat atgacttagt cggtatgatc tggaaagact tgattgaaag ataattcagc 5835

tgacataagg atgagtgagg agtggcaaac tggataaaag agtcaagaga cctgtattcc 5895

agtgactcct gttttgttta agcattagca agatctgtct ggggaaactg gatagggcag 5955

6015

tgtgtattgt ttttttttgg ggggggggtg gccagaatag tgggtcatct aataaaactg 6075

6114

<210> 24

<211> 698

<212> Protein

<213> Mus musculus

<400> 24

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala

20 25 30

Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln

35 40 45

Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg

50 55 60

Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met

65 70 75 80

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

85 90 95

Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg

100 105 110

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

115 120 125

Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu

130 135 140

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

145 150 155 160

Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu

165 170 175

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

180 185 190

Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala

195 200 205

Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys

210 215 220

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

225 230 235 240

Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu

245 250 255

Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu

260 265 270

Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu

275 280 285

Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser

290 295 300

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

305 310 315 320

Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val

325 330 335

Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val

340 345 350

Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr

355 360 365

Asn Phe Ile Gln Thr Leu Asp Pro Ala Ile Val Ser Ala Gln Pro Met

370 375 380

Asn Pro Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys Pro Gln Val

385 390 395 400

His Ser Glu Ser Arg Leu Ala Gln Ser Asn Gln Val Pro Val Gln Pro

405 410 415

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

420 425 430

Ala Ser Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro

435 440 445

Gln Lys Glu Pro Met Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr

450 455 460

Asp Gln Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln

465 470 475 480

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

485 490 495

Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn

500 505 510

Ala Pro Val Pro Pro Ala Asn Glu Pro Glu Thr Leu Lys Gln Gln Ser

515 520 525

Gln Tyr Gln Ala Thr Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln

530 535 540

Val Glu Gln Thr Glu Leu Gln Gln Asp Gln Leu Gln Thr Val Val Gly

545 550 555 560

Thr Tyr His Gly Ser Gln Asp Gln Pro His Gln Val Pro Gly Asn His

565 570 575

Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Ser Gln Pro

580 585 590

Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg

595 600 605

Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly

610 615 620

Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr

625 630 635 640

Ser Gln Ser Gln Phe Thr Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg

645 650 655

Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro

660 665 670

Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly

675 680 685

Met Pro Gln Met Asn Thr Gln Gln Val Asn

690 695

<210> 25

<211> 3548

<212> DNA

<213> Mus musculus

<220>

<221> CDS

<222> (179)..(2257)

<400> 25

gctggctggc taagtccctc ccgcgccggc tcttgtccca ctaggagcag ctcagagccg 60

cggggacagg gcgaagcggc ctgcgcccac ggagcgcacg tctctgttct caacgcagca 120

ccacccttgc ccccctcggc tgcccactcc agacgtccag cggctccgcg cgcgcacg 178

atg ccc tcg gcc acc agc cac agc gga agc ggc agc aaa tcg tcg gga 226

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly

1 5 10 15

ccg ccg ccg ccg tcc ggt tcc tcc ggg agt gag gcg gcg gcc ggg gca 274

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala

20 25 30

gct gcg ccg gct tct cag cat ccg gca acc ggc acc ggc gcc gtc cag 322

Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln

35 40 45

acc gag gcc atg aag cag att ctc ggc gta atc gac aag aaa ctt cgg 370

Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg

50 55 60

aac ctg gag aag aaa aag ggt aaa ctt gat gat tac cag gaa cga atg 418

Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met

65 70 75 80

aat aaa ggg gaa agg ctc aat caa gac cag ctg gat gcc gta tct aag 466

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

85 90 95

tac cag gaa gtc aca aat aat ttg gag ttt gca aag gaa tta cag agg 514

Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg

100 105 110

agt ttc atg gca tta agt caa gat att cag aaa aca ata aag aag aca 562

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

115 120 125

gca cgt cgg gaa cag ctt atg aga gaa gaa gca gaa cag aag cgc tta 610

Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu

130 135 140

aaa act gta ctt gag tta cag tat gta ttg gat aag ctg gga gat gat 658

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

145 150 155 160

gat gtg aga aca gat ctg aaa caa ggt ttg agt gga gtg cca ata ttg 706

Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu

165 170 175

tct gag gag gag ttg tca ttg ctg gat gag ttc tac aag ctc gta gat 754

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

180 185 190

cct gag cgt gac atg agt tta agg tta aat gag cag tat gaa cat gcc 802

Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala

195 200 205

tca att cac ttg tgg gat ttg ctg gaa ggg aaa gaa aag cct gtg tgt 850

Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys

210 215 220

gga aca acc tat aaa gct cta aag gaa att gtt gag cgt gtt ttc cag 898

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

225 230 235 240

tca aac tac ttt gat agc act cac aat cat caa aat ggg ttg tgt gag 946

Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu

245 250 255

gag gaa gag gcg gct tca gcg ccc aca gtg gag gac cag gta gct gaa 994

Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu

260 265 270

gct gaa cct gag cca gcg gaa gaa tac aca gag caa agt gag gtt gaa 1042

Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu

275 280 285

tca aca gag tat gtc aat agg cag ttc atg gca gaa aca cag ttc agc 1090

Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser

290 295 300

agt ggt gag aag gag caa gtg gat gag tgg aca gtt gaa aca gtt gag 1138

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

305 310 315 320

gtt gta aac tca ctc cag cag caa cct cag gct gcg tcc cct tca gtc 1186

Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val

325 330 335

cca gag ccc cac tct ttg act cca gtg gct cag tca gat cca ctt gtg 1234

Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val

340 345 350

aga agg cag cgt gta caa gat ctt atg gca caa atg caa ggg ccc tat 1282

Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr

355 360 365

aat ttc ata cag gat tca atg ttg gat ttt gaa aat cag acg ctt gat 1330

Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp

370 375 380

cct gcc att gta tcc gca cag cct atg aac cct acc cag aac atg gat 1378

Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp

385 390 395 400

atg cct cag ctg gtt tgc cct cag gtt cat tct gaa tct aga ctt gcc 1426

Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala

405 410 415

caa tct aat caa gtt cct gta caa cca gaa gcc aca cag gtt cct ttg 1474

Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu

420 425 430

gtt tca tcc aca agt gag ggg tat aca gca tct cag ccc ttg tac cag 1522

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

435 440 445

cca tct cat gct acg gag cag cgg ccg cag aaa gag cca atg gat cag 1570

Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln

450 455 460

att cag gca aca ata tct ttg aat aca gac cag act aca gca tcc tca 1618

Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser

465 470 475 480

tcc ctt cct gct gct tct cag cct caa gtg ttc cag gct ggg aca agt 1666

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

485 490 495

aaa cct ttg cac agc agt gga atc aat gta aat gca gct cca ttc cag 1714

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

500 505 510

tcc atg caa acg gtg ttc aat atg aat gct cca gtc cct cct gct aat 1762

Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn

515 520 525

gaa cca gaa acg tta aaa caa cag agt cag tac cag gcc act tat aac 1810

Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn

530 535 540

cag agt ttt tcc agt cag cct cac caa gtg gaa caa aca gag ctt caa 1858

Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln

545 550 555 560

caa gac caa ctg caa acg gtg gtt ggc act tac cat gga tcc cag gac 1906

Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp

565 570 575

cag cct cat caa gtg cct ggt aac cac cag caa ccc cca cag cag aac 1954

Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn

580 585 590

act ggc ttt cca cgt agc agt cag cct tat tac aac agt cgt ggg gta 2002

Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val

595 600 605

tct cga gga ggg tct cgt ggt gcc aga ggc ttg atg aat gga tac agg 2050

Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg

610 615 620

ggc cct gcc aat gga ttt aga gga gga tat gat ggt tac cgc cct tca 2098

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

625 630 635 640

ttc tcg aac act cca aac agt ggt tat tca cag tct cag ttc act gct 2146

Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala

645 650 655

ccc cgg gac tac tct ggt tac cag cgg gat gga tat cag cag aat ttc 2194

Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe

660 665 670

aag cga ggc tct ggg cag agt gga cca cgg gga gcc cca cga ggt aat 2242

Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Asn

675 680 685

ata ttg tgg tgg tga tcctagctcc tatgtggagc ttctgttctg gccttggaag 2297

Ile Leu Trp Trp

690

aactgttcat agtccgcatg taggttacat gttaggaata catttatctt ttccagactt 2357

gttgctaaag attaaatgaa atgctctgtt tctaaaattt catcttgaat ccaaatttta 2417

atttttgaat gactttccct gctgttgtct tcaaaatcag aacattttct ctgcctcaga 2477

aaagcgtttt tccaactgga aatttatttt tcaggtctta aaacctgcta aatgttttta 2537

ggaagtacct actgaaactt tttgtaagac atttttggaa cgagcttgaa catttatata 2597

aatttattac cctctttgat ttttgaaaca tgcatattat atttaggctg agaagccctt 2657

caaatggcca gataagccac agttttagct agagaaccat ttagaattga cataactaat 2717

ctaaacttga acacttttag gaccaatgtt agtgttctaa ataccaacat atttctgatg 2777

tttaaacaga tctcccaaat tcttaggacc ttgatgtcat taaaatttag aatgacaagc 2837

2897

gatagttaat ttgttgaaca attacaggta gcatttcatg taatctgatg ttctaaatgg 2957

ttctcttatt gaaggaggtt aaagaattag

tgtataaaat gtatattaag gaggaattat aaagtacttt aatttgaatg ctagtggcaa 3077

ttgatcatta agaaagtact ttaaagcaaa aggttaatgg gtcatctggg aaaaatactg 3137

3197

tattctatga aagttgagtt aaatgatagc taaaatatct gtttcaacag catgtaaaaa 3257

3317

agtttaggta caaaggtctg ttttcattct ggtgcttttt attaattttg atagtatgat 3377

gtcacttcct attgaaatgt aagctagcgt gtaccttaga atgtgagctc catgagagca 3437

ggtaccttgt ttgtcttcac tgctgtatct attcccaacg cctcatgaca gtgcctggca 3497

catagtagggc actcaataaa tacttgttga atgaatgaaa aaaaaaaaaa a 3548

<210> 26

<211> 692

<212> Protein

<213> Mus musculus

<400> 26

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala

20 25 30

Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln

35 40 45

Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg

50 55 60

Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met

65 70 75 80

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

85 90 95

Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg

100 105 110

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

115 120 125

Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu

130 135 140

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

145 150 155 160

Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu

165 170 175

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

180 185 190

Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala

195 200 205

Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys

210 215 220

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

225 230 235 240

Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu

245 250 255

Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu

260 265 270

Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu

275 280 285

Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser

290 295 300

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

305 310 315 320

Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val

325 330 335

Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val

340 345 350

Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr

355 360 365

Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp

370 375 380

Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp

385 390 395 400

Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala

405 410 415

Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu

420 425 430

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

435 440 445

Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln

450 455 460

Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser

465 470 475 480

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

485 490 495

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

500 505 510

Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn

515 520 525

Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn

530 535 540

Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln

545 550 555 560

Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp

565 570 575

Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn

580 585 590

Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val

595 600 605

Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg

610 615 620

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

625 630 635 640

Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala

645 650 655

Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe

660 665 670

Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Asn

675 680 685

Ile Leu Trp Trp

690

<210> 27

<211> 3508

<212> DNA

<213> Mus musculus

<220>

<221> CDS

<222> (139)..(2217)

<400> 27

60

tctccccgtc cgtctcctga cttgctggtc ttgtccttcc ctcccgcttt tttcctctcc 120

tctcttctcg gtctaaag atg ccc tcg gcc acc agc cac agc gga agc ggc 171

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly

1 5 10

agc aaa tcg tcg gga ccg ccg ccg ccg tcc ggt tcc tcc ggg agt gag 219

Ser Lys Ser Ser Gly Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu

15 20 25

gcg gcg gcc ggg gca gct gcg ccg gct tct cag cat ccg gca acc ggc 267

Ala Ala Ala Gly Ala Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly

30 35 40

acc ggc gcc gtc cag acc gag gcc atg aag cag att ctc ggc gta atc 315

Thr Gly Ala Val Gln Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile

45 50 55

gac aag aaa ctt cgg aac ctg gag aag aaa aag ggt aaa ctt gat gat 363

Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp

60 65 70 75

tac cag gaa cga atg aat aaa ggg gaa agg ctc aat caa gac cag ctg 411

Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu

80 85 90

gat gcc gta tct aag tac cag gaa gtc aca aat aat ttg gag ttt gca 459

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

95 100 105

aag gaa tta cag agg agt ttc atg gca tta agt caa gat att cag aaa 507

Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys

110 115 120

aca ata aag aag aca gca cgt cgg gaa cag ctt atg aga gaa gaa gca 555

Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala

125 130 135

gaa cag aag cgc tta aaa act gta ctt gag tta cag tat gta ttg gat 603

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

140 145 150 155

aag ctg gga gat gat gat gtg aga aca gat ctg aaa caa ggt ttg agt 651

Lys Leu Gly Asp Asp Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser

160 165 170

gga gtg cca ata ttg tct gag gag gag ttg tca ttg ctg gat gag ttc 699

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

175 180 185

tac aag ctc gta gat cct gag cgt gac atg agt tta agg tta aat gag 747

Tyr Lys Leu Val Asp Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu

190 195 200

cag tat gaa cat gcc tca att cac ttg tgg gat ttg ctg gaa ggg aaa 795

Gln Tyr Glu His Ala Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys

205 210 215

gaa aag cct gtg tgt gga aca acc tat aaa gct cta aag gaa att gtt 843

Glu Lys Pro Val Cys Gly Thr Thr Tyr Lys Ala Leu Lys Glu Ile Val

220 225 230 235

gag cgt gtt ttc cag tca aac tac ttt gat agc act cac aat cat caa 891

Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln

240 245 250

aat ggg ttg tgt gag gag gaa gag gcg gct tca gcg ccc aca gtg gag 939

Asn Gly Leu Cys Glu Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu

255 260 265

gac cag gta gct gaa gct gaa cct gag cca gcg gaa gaa tac aca gag 987

Asp Gln Val Ala Glu Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu

270 275 280

caa agt gag gtt gaa tca aca gag tat gtc aat agg cag ttc atg gca 1035

Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala

285 290 295

gaa aca cag ttc agc agt ggt gag aag gag caa gtg gat gag tgg aca 1083

Glu Thr Gln Phe Ser Ser Gly Glu Lys Glu Gln Val Asp Glu Trp Thr

300 305 310 315

gtt gaa aca gtt gag gtt gta aac tca ctc cag cag caa cct cag gct 1131

Val Glu Thr Val Glu Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala

320 325 330

gcg tcc cct tca gtc cca gag ccc cac tct ttg act cca gtg gct cag 1179

Ala Ser Pro Ser Val Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln

335 340 345

tca gat cca ctt gtg aga agg cag cgt gta caa gat ctt atg gca caa 1227

Ser Asp Pro Leu Val Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln

350 355 360

atg caa ggg ccc tat aat ttc ata cag gat tca atg ttg gat ttt gaa 1275

Met Gln Gly Pro Tyr Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu

365 370 375

aat cag acg ctt gat cct gcc att gta tcc gca cag cct atg aac cct 1323

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

380 385 390 395

acc cag aac atg gat atg cct cag ctg gtt tgc cct cag gtt cat tct 1371

Thr Gln Asn Met Asp Met Pro Gln Leu Val Cys Pro Gln Val His Ser

400 405 410

gaa tct aga ctt gcc caa tct aat caa gtt cct gta caa cca gaa gcc 1419

Glu Ser Arg Leu Ala Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala

415 420 425

aca cag gtt cct ttg gtt tca tcc aca agt gag ggg tat aca gca tct 1467

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

430 435 440

cag ccc ttg tac cag cca tct cat gct acg gag cag cgg ccg cag aaa 1515

Gln Pro Leu Tyr Gln Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys

445 450 455

gag cca atg gat cag att cag gca aca ata tct ttg aat aca gac cag 1563

Glu Pro Met Asp Gln Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln

460 465 470 475

act aca gca tcc tca tcc ctt cct gct gct tct cag cct caa gtg ttc 1611

Thr Thr Ala Ser Ser Ser Leu Pro Ala Ala Ser Gln Pro Gln Val Phe

480 485 490

cag gct ggg aca agt aaa cct ttg cac agc agt gga atc aat gta aat 1659

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

495 500 505

gca gct cca ttc cag tcc atg caa acg gtg ttc aat atg aat gct cca 1707

Ala Ala Pro Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro

510 515 520

gtc cct cct gct aat gaa cca gaa acg tta aaa caa cag agt cag tac 1755

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

525 530 535

cag gcc act tat aac cag agt ttt tcc agt cag cct cac caa gtg gaa 1803

Gln Ala Thr Tyr Asn Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu

540 545 550 555

caa aca gag ctt caa caa gac caa ctg caa acg gtg gtt ggc act tac 1851

Gln Thr Glu Leu Gln Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr

560 565 570

cat gga tcc cag gac cag cct cat caa gtg cct ggt aac cac cag caa 1899

His Gly Ser Gln Asp Gln Pro His Gln Val Pro Gly Asn His Gln Gln

575 580 585

ccc cca cag cag aac act ggc ttt cca cgt agc agt cag cct tat tac 1947

Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr

590 595 600

aac agt cgt ggg gta tct cga gga ggg tct cgt ggt gcc aga ggc ttg 1995

Asn Ser Arg Gly Val Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu

605 610 615

atg aat gga tac agg ggc cct gcc aat gga ttt aga gga gga tat gat 2043

Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly Phe Arg Gly Gly Tyr Asp

620 625 630 635

ggt tac cgc cct tca ttc tcg aac act cca aac agt ggt tat tca cag 2091

Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln

640 645 650

tct cag ttc act gct ccc cgg gac tac tct ggt tac cag cgg gat gga 2139

Ser Gln Phe Thr Ala Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly

655 660 665

tat cag cag aat ttc aag cga ggc tct ggg cag agt gga cca cgg gga 2187

Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly

670 675 680

gcc cca cga ggt aat ata ttg tgg tgg tga tcctagctcc tatgtggagc 2237

Ala Pro Arg Gly Asn Ile Leu Trp Trp

685 690

ttctgttctg gccttggaag aactgttcat agtccgcatg taggttacat gttaggaata 2297

catttatctt ttccagactt gttgctaaag attaaatgaa atgctctgtt tctaaaattt 2357

catcttgaat ccaaatttta atttttgaat gactttccct gctgttgtct tcaaaatcag 2417

aacattttct ctgcctcaga aaagcgtttt tccaactgga aatttatttt tcaggtctta 2477

aaacctgcta aatgttttta ggaagtacct actgaaactt tttgtaagac atttttggaa 2537

cgagcttgaa catttata aatttattac cctctttgat ttttgaaaca tgcatattat 2597

2657

ttagaattga cataactaat ctaaacttga acacttttag gaccaatgtt agtgttctaa 2717

ataccaacat atttctgatg tttaaacaga tctcccaaat tcttaggacc ttgatgtcat 2777

taaaatttag aatgacaagc ttaagaggct ttagtttcat ttgtttttca agtaatgaaa 2837

aataatttct tacatgggca gatagttaat ttgttgaaca attacaggta gcatttcatg 2897

taatctgatg ttctaaatgg ttctcttatt gaaggaggtt aaagaattag gtttcttaca 2957

3017

aatttgaatg ctagtggcaa ttgatcatta agaaagtact ttaaagcaaa aggttaatgg 3077

gtcatctggg aaaaatactg aagtatcaaa ggtatttgca tgtgaatgtg ggttatgttc 3137

ttctatccca ccttgtagca tattctatga aagttgagtt aaatgatagc taaaatatctct 3197

gtttcaacag catgtaaaaa gttattttaa ctgttacaag tcattataca attttgaatg 3257

3317

attaattttg atagtatgat gtcacttcct attgaaatgt aagctagcgt gtaccttaga 3377

atgtgagctc catgagagca ggtaccttgt ttgtcttcac tgctgtatct attcccaacg 3437

cctcatgaca gtgcctggca catagtaggc actcaataaa tacttgttga atgaatgaaa 3497

aaaaaaaaaa 3508

<210> 28

<211> 692

<212> Protein

<213> Mus musculus

<400> 28

Met Pro Ser Ala Thr Ser His Ser Gly Ser Gly Ser Lys Ser Ser Gly

1 5 10 15

Pro Pro Pro Pro Ser Gly Ser Ser Gly Ser Glu Ala Ala Ala Gly Ala

20 25 30

Ala Ala Pro Ala Ser Gln His Pro Ala Thr Gly Thr Gly Ala Val Gln

35 40 45

Thr Glu Ala Met Lys Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg

50 55 60

Asn Leu Glu Lys Lys Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met

65 70 75 80

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

85 90 95

Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg

100 105 110

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

115 120 125

Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu

130 135 140

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

145 150 155 160

Asp Val Arg Thr Asp Leu Lys Gln Gly Leu Ser Gly Val Pro Ile Leu

165 170 175

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

180 185 190

Pro Glu Arg Asp Met Ser Leu Arg Leu Asn Glu Gln Tyr Glu His Ala

195 200 205

Ser Ile His Leu Trp Asp Leu Leu Glu Gly Lys Glu Lys Pro Val Cys

210 215 220

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

225 230 235 240

Ser Asn Tyr Phe Asp Ser Thr His Asn His Gln Asn Gly Leu Cys Glu

245 250 255

Glu Glu Glu Ala Ala Ser Ala Pro Thr Val Glu Asp Gln Val Ala Glu

260 265 270

Ala Glu Pro Glu Pro Ala Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu

275 280 285

Ser Thr Glu Tyr Val Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser

290 295 300

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

305 310 315 320

Val Val Asn Ser Leu Gln Gln Gln Pro Gln Ala Ala Ser Pro Ser Val

325 330 335

Pro Glu Pro His Ser Leu Thr Pro Val Ala Gln Ser Asp Pro Leu Val

340 345 350

Arg Arg Gln Arg Val Gln Asp Leu Met Ala Gln Met Gln Gly Pro Tyr

355 360 365

Asn Phe Ile Gln Asp Ser Met Leu Asp Phe Glu Asn Gln Thr Leu Asp

370 375 380

Pro Ala Ile Val Ser Ala Gln Pro Met Asn Pro Thr Gln Asn Met Asp

385 390 395 400

Met Pro Gln Leu Val Cys Pro Gln Val His Ser Glu Ser Arg Leu Ala

405 410 415

Gln Ser Asn Gln Val Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu

420 425 430

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

435 440 445

Pro Ser His Ala Thr Glu Gln Arg Pro Gln Lys Glu Pro Met Asp Gln

450 455 460

Ile Gln Ala Thr Ile Ser Leu Asn Thr Asp Gln Thr Thr Ala Ser Ser

465 470 475 480

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

485 490 495

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

500 505 510

Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro Ala Asn

515 520 525

Glu Pro Glu Thr Leu Lys Gln Gln Ser Gln Tyr Gln Ala Thr Tyr Asn

530 535 540

Gln Ser Phe Ser Ser Gln Pro His Gln Val Glu Gln Thr Glu Leu Gln

545 550 555 560

Gln Asp Gln Leu Gln Thr Val Val Gly Thr Tyr His Gly Ser Gln Asp

565 570 575

Gln Pro His Gln Val Pro Gly Asn His Gln Gln Pro Pro Gln Gln Asn

580 585 590

Thr Gly Phe Pro Arg Ser Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val

595 600 605

Ser Arg Gly Gly Ser Arg Gly Ala Arg Gly Leu Met Asn Gly Tyr Arg

610 615 620

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

625 630 635 640

Phe Ser Asn Thr Pro Asn Ser Gly Tyr Ser Gln Ser Gln Phe Thr Ala

645 650 655

Pro Arg Asp Tyr Ser Gly Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe

660 665 670

Lys Arg Gly Ser Gly Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Asn

675 680 685

Ile Leu Trp Trp

690

<210> 29

<211> 2109

<212> DNA

<213> Gallus gallus

<220>

<221> CDS

<222> (1)..(2109)

<400> 29

atg ccc tcg gct acc aac ggc acc atg gcg agc agc agc ggg aag gcg 48

Met Pro Ser Ala Thr Asn Gly Thr Met Ala Ser Ser Ser Gly Lys Ala

1 5 10 15

ggc ccg ggc ggc aac gag cag gcc ccg gcg gcg gca gcg gcg gcc ccg 96

Gly Pro Gly Gly Asn Glu Gln Ala Pro Ala Ala Ala Ala Ala Ala Pro

20 25 30

cag gcg tcg ggc ggc agc atc acc tcg gtt cag acc gag gcc atg aag 144

Gln Ala Ser Gly Gly Ser Ile Thr Ser Val Gln Thr Glu Ala Met Lys

35 40 45

cag atc ttg gga gtg atc gac aaa aag ctc cgc aac ctc gag aag aaa 192

Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys

50 55 60

aag agc aaa ctt gac gat tac cag gaa cga atg aac aag ggg gaa cgt 240

Lys Ser Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg

65 70 75 80

cta aat caa gat caa ctg gat gca gtg tca aaa tac cag gaa gtg aca 288

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

85 90 95

aat aac ctg gaa ttc gct aaa gaa ctg cag agg agc ttt atg gca ctg 336

Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu

100 105 110

agc caa gat atc cag aaa aca ata aaa aag acg gct cgc agg gag cag 384

Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln

115 120 125

ctg atg aga gaa gag gct gag cag aag cgt tta aag act gtg cta gag 432

Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu

130 135 140

ctg cag ttc att ttg gac aag ttg ggt gac gat gaa gtg cgc agt gac 480

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

145 150 155 160

ttg aaa caa gga tca aat gga gta ccg gta ctg aca gag gag gaa ctg 528

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

165 170 175

aca atg ctg gat gaa ttt tac aag cta gtt tac cct gaa agg gac atg 576

Thr Met Leu Asp Glu Phe Tyr Lys Leu Val Tyr Pro Glu Arg Asp Met

180 185 190

aac atg agg ttg aat gag cag tat gag caa gca tct gtt cac ctg tgg 624

Asn Met Arg Leu Asn Glu Gln Tyr Glu Gln Ala Ser Val His Leu Trp

195 200 205

gac tta ctg gaa ggg aag gaa aaa ccc gtt tgt gga aca acc tat aaa 672

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

210 215 220

gcc ctg aag gag gtt gtt gaa cgt att ctt caa act agt tac ttt gat 720

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

225 230 235 240

agc acc cat aac cat cag aac ggg tta tgt gag gaa gaa gag gca gca 768

Ser Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Glu Ala Ala

245 250 255

ccc aca cct gca gta gaa gac act gta gca gaa gct gag cct gat cca 816

Pro Thr Pro Ala Val Glu Asp Thr Val Ala Glu Ala Glu Pro Asp Pro

260 265 270

gca gaa gaa ttt act gaa cct act gaa gtt gaa tcg act gag tat gta 864

Ala Glu Glu Phe Thr Glu Pro Thr Glu Val Glu Ser Thr Glu Tyr Val

275 280 285

aac aga caa ttc atg gca gag act cag ttc agc agt agt gag aag gaa 912

Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Ser Glu Lys Glu

290 295 300

cag gta gat gag tgg aca gtt gaa acg gtt gag gtt gta aat tca ctg 960

Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu

305 310 315 320

cag caa caa aca caa gct aca tct cct cca gtt cct gaa cct cat aca 1008

Gln Gln Gln Thr Gln Ala Thr Ser Pro Pro Val Pro Glu Pro His Thr

325 330 335

ctc act act gtg gct caa gca gat cct ctt gtt aga aga cag aga gta 1056

Leu Thr Thr Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val

340 345 350

cag gac ctt atg gcc cag atg cag ggt cca tat aac ttc atg cag gac 1104

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

355 360 365

tct atg ctg gag ttt gag aac cag aca ctt gat cct gcc att gta tct 1152

Ser Met Leu Glu Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser

370 375 380

gca cag ccc atg aat cca gca cag aat ttg gac atg ccg caa atg gtc 1200

Ala Gln Pro Met Asn Pro Ala Gln Asn Leu Asp Met Pro Gln Met Val

385 390 395 400

tgc cct cca gtt cat act gag tca aga ctt gcc cag cct aat caa gtt 1248

Cys Pro Pro Val His Thr Glu Ser Arg Leu Ala Gln Pro Asn Gln Val

405 410 415

cct gtg caa cca gaa gct acg cag gtt ccc ttg gtt tca tct aca agt 1296

Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser

420 425 430

gag gga tat aca gcc tcc cag ccc atg tat cag cct tct cat acc aca 1344

Glu Gly Tyr Thr Ala Ser Gln Pro Met Tyr Gln Pro Ser His Thr Thr

435 440 445

gag caa cgg cca cag aag gaa tcc att gac cag att cag gct tca atg 1392

Glu Gln Arg Pro Gln Lys Glu Ser Ile Asp Gln Ile Gln Ala Ser Met

450 455 460

tca ctg aat gca gac cag acc ccg tca tca tca tca ctt ccc act gca 1440

Ser Leu Asn Ala Asp Gln Thr Pro Ser Ser Ser Ser Leu Pro Thr Ala

465 470 475 480

tcc cag ccg caa gtt ttc caa gct gga tct agc aaa cct ttg cat agc 1488

Ser Gln Pro Gln Val Phe Gln Ala Gly Ser Ser Lys Pro Leu His Ser

485 490 495

agc gga atc aat gtt aat gca gct cca ttc caa tcc atg caa aca gta 1536

Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val

500 505 510

ttc aac atg aat gca cct gtt cct cct gtt aat gag cca gaa gcc ctt 1584

Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Ala Leu

515 520 525

aag caa caa aat cag tac cag gcc agt tac aac cag agt ttc tcc aat 1632

Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Asn

530 535 540

cag cca cac caa gta gaa caa tca gat ctt cag caa gaa cag ctc cag 1680

Gln Pro His Gln Val Glu Gln Ser Asp Leu Gln Gln Glu Gln Leu Gln

545 550 555 560

aca gtg gtt ggt act tac cat ggt tct ccg gac cag acc cat caa gtg 1728

Thr Val Val Gly Thr Tyr His Gly Ser Pro Asp Gln Thr His Gln Val

565 570 575

gca gga aac cac cag caa cct ccc cag cag aat act gga ttt cca cgc 1776

Ala Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg

580 585 590

aac agt cag cct tat tac aac agt cgg gga gtg tct cgt ggt gga tca 1824

Asn Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser

595 600 605

cgt ggg act cgt gga ttg atg aat ggt tac agg gga cct gca aat gga 1872

Arg Gly Thr Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly

610 615 620

ttt aga gga gga tat gat ggc tac cgt cct tca ttt tcc aac act ccg 1920

Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro

625 630 635 640

aac agt ggt tac acg cag ccc caa ttt aat gct cct cga gat tat tca 1968

Asn Ser Gly Tyr Thr Gln Pro Gln Phe Asn Ala Pro Arg Asp Tyr Ser

645 650 655

aac tac cag cgg gat gga tat cag cag aac ttc aaa cgt ggt tct gga 2016

Asn Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly

660 665 670

caa agt ggg cct cgg gga gct cct cga ggt cgt gga ggg ccc cca aga 2064

Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg

675 680 685

cca aac aga ggg atg cct caa atg aac gct cag caa gtg aat taa 2109

Pro Asn Arg Gly Met Pro Gln Met Asn Ala Gln Gln Val Asn

690 695 700

<210> 30

<211> 702

<212> Protein

<213> Gallus gallus

<400> 30

Met Pro Ser Ala Thr Asn Gly Thr Met Ala Ser Ser Ser Gly Lys Ala

1 5 10 15

Gly Pro Gly Gly Asn Glu Gln Ala Pro Ala Ala Ala Ala Ala Ala Pro

20 25 30

Gln Ala Ser Gly Gly Ser Ile Thr Ser Val Gln Thr Glu Ala Met Lys

35 40 45

Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys

50 55 60

Lys Ser Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg

65 70 75 80

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

85 90 95

Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu

100 105 110

Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln

115 120 125

Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu

130 135 140

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

145 150 155 160

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

165 170 175

Thr Met Leu Asp Glu Phe Tyr Lys Leu Val Tyr Pro Glu Arg Asp Met

180 185 190

Asn Met Arg Leu Asn Glu Gln Tyr Glu Gln Ala Ser Val His Leu Trp

195 200 205

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

210 215 220

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

225 230 235 240

Ser Thr His Asn His Gln Asn Gly Leu Cys Glu Glu Glu Glu Glu Ala Ala

245 250 255

Pro Thr Pro Ala Val Glu Asp Thr Val Ala Glu Ala Glu Pro Asp Pro

260 265 270

Ala Glu Glu Phe Thr Glu Pro Thr Glu Val Glu Ser Thr Glu Tyr Val

275 280 285

Asn Arg Gln Phe Met Ala Glu Thr Gln Phe Ser Ser Ser Glu Lys Glu

290 295 300

Gln Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu

305 310 315 320

Gln Gln Gln Thr Gln Ala Thr Ser Pro Pro Val Pro Glu Pro His Thr

325 330 335

Leu Thr Thr Val Ala Gln Ala Asp Pro Leu Val Arg Arg Gln Arg Val

340 345 350

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

355 360 365

Ser Met Leu Glu Phe Glu Asn Gln Thr Leu Asp Pro Ala Ile Val Ser

370 375 380

Ala Gln Pro Met Asn Pro Ala Gln Asn Leu Asp Met Pro Gln Met Val

385 390 395 400

Cys Pro Pro Val His Thr Glu Ser Arg Leu Ala Gln Pro Asn Gln Val

405 410 415

Pro Val Gln Pro Glu Ala Thr Gln Val Pro Leu Val Ser Ser Thr Ser

420 425 430

Glu Gly Tyr Thr Ala Ser Gln Pro Met Tyr Gln Pro Ser His Thr Thr

435 440 445

Glu Gln Arg Pro Gln Lys Glu Ser Ile Asp Gln Ile Gln Ala Ser Met

450 455 460

Ser Leu Asn Ala Asp Gln Thr Pro Ser Ser Ser Ser Leu Pro Thr Ala

465 470 475 480

Ser Gln Pro Gln Val Phe Gln Ala Gly Ser Ser Lys Pro Leu His Ser

485 490 495

Ser Gly Ile Asn Val Asn Ala Ala Pro Phe Gln Ser Met Gln Thr Val

500 505 510

Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Ala Leu

515 520 525

Lys Gln Gln Asn Gln Tyr Gln Ala Ser Tyr Asn Gln Ser Phe Ser Asn

530 535 540

Gln Pro His Gln Val Glu Gln Ser Asp Leu Gln Gln Glu Gln Leu Gln

545 550 555 560

Thr Val Val Gly Thr Tyr His Gly Ser Pro Asp Gln Thr His Gln Val

565 570 575

Ala Gly Asn His Gln Gln Pro Pro Gln Gln Asn Thr Gly Phe Pro Arg

580 585 590

Asn Ser Gln Pro Tyr Tyr Asn Ser Arg Gly Val Ser Arg Gly Gly Ser

595 600 605

Arg Gly Thr Arg Gly Leu Met Asn Gly Tyr Arg Gly Pro Ala Asn Gly

610 615 620

Phe Arg Gly Gly Tyr Asp Gly Tyr Arg Pro Ser Phe Ser Asn Thr Pro

625 630 635 640

Asn Ser Gly Tyr Thr Gln Pro Gln Phe Asn Ala Pro Arg Asp Tyr Ser

645 650 655

Asn Tyr Gln Arg Asp Gly Tyr Gln Gln Asn Phe Lys Arg Gly Ser Gly

660 665 670

Gln Ser Gly Pro Arg Gly Ala Pro Arg Gly Arg Gly Gly Pro Pro Arg

675 680 685

Pro Asn Arg Gly Met Pro Gln Met Asn Ala Gln Gln Val Asn

690 695 700

<210> 31

<211> 63

<212> Protein

<213> Homo sapiens

<400> 31

Glu Glu Tyr Thr Glu Gln Ser Glu Val Glu Ser Thr Glu Tyr Val Asn

1 5 10 15

Arg Gln Phe Met Ala Glu Thr Gln Phe Thr Ser Gly Glu Lys Glu Gln

20 25 30

Val Asp Glu Trp Thr Val Glu Thr Val Glu Val Val Asn Ser Leu Gln

35 40 45

Gln Gln Pro Gln Ala Ala Ser Pro Ser Val Pro Glu Pro His Ser

50 55 60

<210> 32

<211> 18

<212> Protein

<213> Homo sapiens

<400> 32

Val Phe Asn Met Asn Ala Pro Val Pro Pro Val Asn Glu Pro Glu Thr

1 5 10 15

Leu Lys

<210> 33

<211> 16

<212> Protein

<213> Homo sapiens

<400> 33

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

1 5 10 15

<210> 34

<211> 25

<212> Protein

<213> Homo sapiens

<400> 34

Gln Ile Leu Gly Val Ile Asp Lys Lys Leu Arg Asn Leu Glu Lys Lys

1 5 10 15

Lys Gly Lys Leu Asp Asp Tyr Gln Glu

20 25

<210> 35

<211> 23

<212> Protein

<213> Homo sapiens

<400> 35

Pro Arg Gly Arg Gly Gly Pro Pro Arg Pro Asn Arg Gly Met Pro Gln

1 5 10 15

Met Asn Thr Gln Gln Val Asn

twenty

<210> 36

<211> 5

<212> Protein

<213> Gallus gallus

<400> 36

Ser Tyr Gln Met Asn

fifteen

<210> 37

<211> 17

<212> Protein

<213> Gallus gallus

<400> 37

Ala Ile Asn Lys Phe Gly Asn Ser Thr Gly His Gly Ala Ala Val Lys

1 5 10 15

gly

<210> 38

<211> 19

<212> Protein

<213> Gallus gallus

<400> 38

His Ala Tyr Gly Tyr Cys Gly Ser Gly Thr Trp Cys Ala Ala Gly Glu

1 5 10 15

Ile Asp Ala

<210> 39

<211> 128

<212> Protein

<213> Gallus gallus

<400> 39

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

1 5 10 15

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

20 25 30

Gln Met Asn Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Phe Val

35 40 45

Ala Ala Ile Asn Lys Phe Gly Asn Ser Thr Gly His Gly Ala Ala Val

50 55 60

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

65 70 75 80

Leu Gln Leu Asn Asn Leu Arg Ala Glu Asp Thr Ala Ile Tyr Phe Cys

85 90 95

Thr Lys His Ala Tyr Gly Tyr Cys Gly Ser Gly Thr Trp Cys Ala Ala

100 105 110

Gly Glu Ile Asp Ala Trp Gly His Gly Thr Glu Val Ile Val Ser Ser

115 120 125

<210> 40

<211> 9

<212> Protein

<213> Gallus gallus

<400> 40

Ser Gly Gly Gly Ser Tyr Ser Tyr Gly

fifteen

<210> 41

<211> 7

<212> Protein

<213> Gallus gallus

<400> 41

Asn Asn Lys Arg Pro Ser Asp

fifteen

<210> 42

<211> 10

<212> Protein

<213> Gallus gallus

<400> 42

Ser Gly Asp Ser Thr Asp Thr Ala Val Phe

1 5 10

<210> 43

<211> 108

<212> Protein

<213> Gallus gallus

<400> 43

Gln Ala Ala Ser Thr Gln Pro Ser Ser Val Ser Ala Asn Pro Gly Glu

1 5 10 15

Thr Val Glu Ile Thr Cys Ser Gly Gly Gly Ser Tyr Ser Tyr Gly Trp

20 25 30

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

35 40 45

Asn Asn Lys Arg Pro Ser Asp Ile Pro Ser Arg Phe Ser Gly Ser Lys

50 55 60

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

65 70 75 80

Glu Ala Val Tyr Tyr Cys Gly Ser Gly Asp Ser Thr Asp Thr Ala Val

85 90 95

Phe Gly Ala Gly Thr Thr Leu Thr Val Leu Gly Gln

100 105

<210> 44

<211> 5

<212> Protein

<213> Rabbit

<400> 44

Ser His Ser Leu Gly

fifteen

<210> 45

<211> 16

<212> Protein

<213> Rabbit

<400> 45

Asp Ile Arg Ser Gly Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys Gly

1 5 10 15

<210> 46

<211> 13

<212> Protein

<213> Rabbit

<400> 46

Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu

1 5 10

<210> 47

<211> 121

<212> Protein

<213> Homo sapiens

<400> 47

Glu Gln Ser Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His

20 25 30

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

35 40 45

Gly Asp Ile Arg Ser Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys

50 55 60

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

65 70 75 80

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

85 90 95

Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 48

<211> 13

<212> Protein

<213> Rabbit

<400> 48

Gln Ala Ser Gln Ser Leu Tyr Asn Asn Glu Asn Leu Ala

1 5 10

<210> 49

<211> 7

<212> Protein

<213> Rabbit

<400> 49

Gly Ala Ser Thr Leu Ala Ser

fifteen

<210> 50

<211> 13

<212> Protein

<213> Rabbit

<400> 50

Leu Gly Glu Phe Ser Cys Gly Ser Ala Asp Cys Phe Ala

1 5 10

<210> 51

<211> 112

<212> Protein

<213> Homo sapiens

<400> 51

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

1 5 10 15

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

20 25 30

Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu

35 40 45

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

50 55 60

Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln

65 70 75 80

Cys Glu Asp Phe Ala Ile Tyr Tyr Cys Leu Gly Glu Phe Ser Cys Gly

85 90 95

Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 52

<211> 4

<212> Protein

<213> Gallus gallus

<400> 52

Phe Asp Met Gly

one

<210> 53

<211> 17

<212> Protein

<213> Gallus gallus

<400> 53

Gln Ile Asn Asp Ala Gly Ser Arg Thr Trp Tyr Ala Thr Ala Val Lys

1 5 10 15

gly

<210> 54

<211> 12

<212> Protein

<213> Gallus gallus

<400> 54

Gly Ser Gly Tyr Val Gly Ala Gly Ala Ile Asp Ala

1 5 10

<210> 55

<211> 120

<212> Protein

<213> Gallus gallus

<400> 55

Ala Val Thr Leu Asp Glu Ser Gly Gly Gly Leu Gln Thr Pro Gly Gly

1 5 10 15

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

20 25 30

Asp Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Phe Val

35 40 45

Ala Gln Ile Asn Asp Ala Gly Ser Arg Thr Trp Tyr Ala Thr Ala Val

50 55 60

Lys Gly Arg Ala Thr Ile Ser Arg Asp Asn Gly Gln Thr Thr Val Arg

65 70 75 80

Leu Gln Leu Asn Asn Leu Arg Ala Glu Asp Thr Gly Thr Tyr Tyr Cys

85 90 95

Thr Arg Gly Ser Gly Tyr Val Gly Ala Gly Ala Ile Asp Ala Trp Gly

100 105 110

His Gly Thr Glu Val Ile Val Ser

115 120

<210> 56

<211> 8

<212> Protein

<213> Gallus gallus

<400> 56

Ser Gly Gly Ser Gly Tyr Tyr Gly

fifteen

<210> 57

<211> 7

<212> Protein

<213> Gallus gallus

<400> 57

Asn Asp Lys Arg Pro Ser Asp

fifteen

<210> 58

<211> 10

<212> Protein

<213> Gallus gallus

<400> 58

Arg Tyr Asp Ser Thr Asp Ser Gly Ile Phe

1 5 10

<210> 59

<211> 105

<212> Protein

<213> Gallus gallus

<400> 59

Ala Ala Leu Thr Gln Pro Ser Ser Val Ser Ala Asn Pro Gly Glu Thr

1 5 10 15

Val Lys Ile Thr Cys Ser Gly Gly Ser Gly Tyr Tyr Gly Trp Tyr Gln

20 25 30

Gln Gln Lys Ser Pro Gly Ser Ala Pro Val Thr Val Ile Tyr Gln Asn

35 40 45

Asp Lys Arg Pro Ser Asp Ile Pro Ser Arg Phe Ser Gly Ser Gly Ser

50 55 60

Gly Ser Thr Asn Thr Leu Thr Ile Thr Gly Val Gln Ala Glu Asp Glu

65 70 75 80

Ala Val Tyr Phe Cys Gly Arg Tyr Asp Ser Thr Asp Ser Gly Ile Phe

85 90 95

Gly Ala Gly Thr Thr Leu Thr Val Leu

100 105

<210> 60

<211> 6

<212> Protein

<213> Oryctolagus cuniculus

<400> 60

Gly Ser Tyr Tyr Met Ser

fifteen

<210> 61

<211> 17

<212> Protein

<213> Oryctolagus cuniculus

<400> 61

Tyr Ile Tyr Ile Gly Asp Gly Val Thr Ala Tyr Ala Asn Trp Ala Lys

1 5 10 15

gly

<210> 62

<211> 4

<212> Protein

<213> Oryctolagus cuniculus

<400> 62

Gly Asn Lys Leu

one

<210> 63

<211> 112

<212> Protein

<213> Oryctolagus cuniculus

<400> 63

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

1 5 10 15

Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe Ser Gly Ser Tyr

20 25 30

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Ala Tyr Ile Tyr Ile Gly Asp Gly Val Thr Ala Tyr Ala Asn Trp Ala

50 55 60

Lys Gly Arg Phe Thr Ile Ser Lys Ala Ser Ser Thr Thr Val Thr Leu

65 70 75 80

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

85 90 95

Arg Gly Asn Lys Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser

100 105 110

<210> 64

<211> 11

<212> Protein

<213> Oryctolagus cuniculus

<400> 64

Gln Ala Ser Gln Ser Ile Ser Ser Tyr Leu Ala

1 5 10

<210> 65

<211> 7

<212> Protein

<213> Oryctolagus cuniculus

<400> 65

Asp Ala Ser Asn Leu Asp Ser

fifteen

<210> 66

<211> 14

<212> Protein

<213> Oryctolagus cuniculus

<400> 66

Gln Cys Thr Ala Val Ser Ser Ala Thr Ile Tyr Gly Asn Ala

1 5 10

<210> 67

<211> 112

<212> Protein

<213> Oryctolagus cuniculus

<400> 67

Asp Val Val Met Thr Gln Thr Pro Ala Ser Val Glu Ala Ala Val Gly

1 5 10 15

Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

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

35 40 45

Tyr Asp Ala Ser Asn Leu Asp Ser Gly Val Pro Ser Arg Phe Lys Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Ile Thr Ile Ser Asp Leu Glu Cys

65 70 75 80

Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Cys Thr Ala Val Ser Ser Ala

85 90 95

Thr Ile Tyr Gly Asn Ala Phe Gly Gly Gly Thr Glu Val Val Val Lys

100 105 110

<210> 68

<211> 127

<212> Protein

<213> Gallus gallus

<400> 68

Ala Val Thr Leu Asp Glu Ser Gly Gly Gly Leu Gln Thr Pro Gly Gly

1 5 10 15

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

20 25 30

Asp Met Leu Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ala Gly Ile Gly Ser Thr Gly Gly Gly Thr Asp Tyr Gly Ala Ala Val

50 55 60

Lys Gly Arg Ala Thr Ile Ser Arg Asp Asn Gly Gln Ser Thr Val Arg

65 70 75 80

Leu Gln Leu Asn Asn Leu Arg Ala Glu Asp Thr Ala Thr Tyr Tyr Cys

85 90 95

Ala Lys Val Ala Gly Gly Cys Asn Ser Gly Tyr Cys Arg Asp Ser Pro

100 105 110

Gly Ser Ile Asp Ala Trp Gly His Gly Thr Glu Val Ile Val Ser

115 120 125

<210> 69

<211> 107

<212> Protein

<213> Gallus gallus

<400> 69

Ala Val Thr Gln Gln Pro Ala Ser Val Ser Ala Asn Pro Gly Glu Thr

1 5 10 15

Val Lys Ile Thr Cys Ser Gly Gly Gly Ser Arg Asn Tyr Tyr Gly Trp

20 25 30

Tyr Gln Gln Lys Ser Pro Gly Ser Val Pro Val Thr Val Ile Tyr Tyr

35 40 45

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

50 55 60

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

65 70 75 80

Glu Ala Val Tyr Phe Cys Gly Ser Ala Asp Ser Asn Thr Tyr Glu Gly

85 90 95

Ser Phe Gly Ala Gly Thr Thr Leu Thr Val Leu

100 105

<210> 70

<211> 148

<212> Protein

<213> Mus musculus

<400> 70

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

1 5 10 15

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

20 25 30

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

35 40 45

Thr Asp Tyr Asn Met Asp Trp Val Lys Gln Ser His Gly Lys Ser Leu

50 55 60

Glu Trp Ile Gly Asp Ile Asn Pro Asn Tyr Asp Ser Thr Ser Tyr Asn

65 70 75 80

Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser

85 90 95

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

100 105 110

Tyr Tyr Cys Ala Arg Ser Arg Ser Tyr Asp Tyr Glu Gly Phe Ala Tyr

115 120 125

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

130 135 140

Pro Ser Val Tyr

145

<210> 71

<211> 105

<212> Protein

<213> Mus musculus

<400> 71

Gly Leu Phe Cys Ser Val Glu Arg Cys His Tyr Gln Leu Gln Ser Ser

1 5 10 15

Gln Asn Leu Leu Ser Ile Val Asn Arg Tyr His Tyr Met Ser Gly Asn

20 25 30

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

35 40 45

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

50 55 60

Thr Asn Phe Thr Leu Thr Ile Asn Phe Val His Ala Asp Asp Leu Ile

65 70 75 80

Phe Tyr Tyr Cys Gln His Asn Arg Gly Ser Phe Leu Pro Ser Ser Ser

85 90 95

Val Gln Val Pro Arg Arg Arg Ser Asn

100 105

<210> 72

<211> 109

<212> Protein

<213> Mus musculus

<400> 72

Pro Arg Ala Ser Leu Gly Val Ser Glu Thr Leu Leu Cys Thr Ser Gly

1 5 10 15

Phe Thr Phe Thr Asp Tyr Tyr Met Ser Trp Val Arg Gln Pro Pro Gly

20 25 30

Lys Ala Leu Glu Trp Leu Gly Phe Ile Arg Asn Lys Ala Asn Gly Tyr

35 40 45

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

50 55 60

Asp Asn Ser Gln Ser Ile Leu Tyr Leu Gln Met Asn Thr Leu Arg Ala

65 70 75 80

Glu Asp Ser Ala Thr Tyr Tyr Cys Ala Arg Ala Asn Trp Ala Phe Asp

85 90 95

Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Lys

100 105

<210> 73

<211> 94

<212> Protein

<213> Mus musculus

<400> 73

Ser Gly Asp Arg Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser

1 5 10 15

Asn Tyr Leu His Trp Tyr Gln Gln Lys Ser His Glu Ser Pro Arg Leu

20 25 30

Leu Ile Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe

35 40 45

Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val

50 55 60

Glu Thr Glu Asp Phe Gly Met Tyr Phe Cys Gln Gln Ser Asn Ser Trp

65 70 75 80

Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gln

85 90

<210> 74

<211> 118

<212> Protein

<213> Mus musculus

<400> 74

Ala Ala Glu Leu Val Arg Pro Gly Thr Ser Val Lys Val Ser Cys Lys

1 5 10 15

Ala Ser Gly Tyr Ala Phe Thr Asn Tyr Leu Ile Val Trp Ile Lys Gln

20 25 30

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

35 40 45

Gly Gly Thr Asn Tyr Asn Glu Lys Phe Lys Gly Lys Ala Ile Leu Thr

50 55 60

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

65 70 75 80

Ser Asp Glu Phe Ala Val Tyr Phe Cys Ala Arg Glu Lys Ile Tyr Asp

85 90 95

Asp Tyr Tyr Glu Gly Tyr Phe Asp Val Trp Gly Ala Gly Pro Arg His

100 105 110

Leu Leu Ala Ser Leu Ser

115

<210> 75

<211> 107

<212> Protein

<213> Mus musculus

<400> 75

Gly Thr Arg Cys Asp Ile Arg Leu Thr Gln Thr Thr Ser Ser Leu Ser

1 5 10 15

Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Ser Ala Ser Leu Gly

20 25 30

Ile Gly Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val

35 40 45

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

50 55 60

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

65 70 75 80

Asn Leu Glu Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln His Tyr Ser

85 90 95

Lys Leu Pro Leu Thr Phe Gly Ala Gly Pro Ser

100 105

<210> 76

<211> 113

<212> Protein

<213> Mus musculus

<400> 76

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

1 5 10 15

Ala Ser Gly Tyr Ser Phe Thr Asp Tyr Asn Met Tyr Trp Val Lys Gln

20 25 30

Thr Pro Gly Gln Gly Leu Glu Trp Ile Gly Tyr Ile Tyr Pro Gly Asn

35 40 45

Gly Gly Thr Asn Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr

50 55 60

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

65 70 75 80

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

85 90 95

Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser

100 105 110

Ser

<210> 77

<211> 117

<212> Protein

<213> Mus musculus

<400> 77

Leu Leu Leu Trp Leu Thr Gly Ala Arg Cys Asp Ile Gln Met Thr Gln

1 5 10 15

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

20 25 30

Cys Arg Ala Ser Gly Asn Ile His Asn Tyr Leu Thr Trp Tyr Gln Gln

35 40 45

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

50 55 60

Ala Asp Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln

65 70 75 80

Tyr Ser Leu Lys Ile Asn Arg Leu Gln Pro Glu Asp Phe Gly Ser Tyr

85 90 95

Tyr Cys Gln His Phe Trp Asn Ile Pro Trp Thr Phe Gly Gly Gly Thr

100 105 110

Lys Leu Asn Ser Arg

115

<210> 78

<211> 114

<212> Protein

<213> Mus musculus

<400> 78

Asp Ala Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys

1 5 10 15

Ala Ser Gly Tyr Thr Phe Thr Asp His Ser Ile His Trp Val Gln Gln

20 25 30

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

35 40 45

Gly Asn Ile Lys Tyr Asn Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr

50 55 60

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

65 70 75 80

Ser Glu Asp Ser Ala Val Tyr Phe Cys Lys Arg Ser Leu Gly Arg Gly

85 90 95

Gly Pro Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val

100 105 110

Ser Ser

<210> 79

<211> 108

<212> Protein

<213> Mus musculus

<400> 79

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

1 5 10 15

Glu Ser Val Ser Ile Ser Cys Arg Ser Ser Lys Ser Leu Leu His Ser

20 25 30

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

35 40 45

Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Arg Ile

65 70 75 80

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

85 90 95

Arg Glu Tyr Pro Val Thr Phe Gly Ser Gly Pro Asn

100 105

<210> 80

<211> 111

<212> Protein

<213> Mus musculus

<400> 80

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Ser Tyr Tyr Trp Tyr Phe Asp Val Trp Ala Gln Asp His Val

100 105 110

<210> 81

<211> 109

<212> Protein

<213> Mus musculus

<400> 81

Ile Val Met Thr Gln Ala Ala Phe Ser Asn Pro Val Thr Leu Gly Thr

1 5 10 15

Ser Ala Ser Ile Ser Cys Arg Ser Ser Lys Asn Leu Leu His Ser Asn

20 25 30

Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Arg Pro Gly Gln Ser Pro

35 40 45

Gln Leu Leu Ile Tyr Arg Val Ser Asn Leu Ala Ser Gly Val Pro Asn

50 55 60

Arg Phe Ser Gly Ser Glu Ser Gly Thr Asp Phe Thr Leu Arg Ile Ser

65 70 75 80

Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gln Leu Leu

85 90 95

Glu Leu Pro Tyr Thr Ser Glu Gly Thr Lys Arg Trp Glu

100 105

<210> 82

<211> 109

<212> Protein

<213> Mus musculus

<400> 82

Gly Gly Gly Leu Val Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala

1 5 10 15

Ala Ser Gly Phe Ala Phe Ser Ser Tyr Asp Met Ser Trp Ile Arg Gln

20 25 30

Thr Pro Glu Lys Arg Leu Glu Trp Val Ala Tyr Ile Ser Ser Gly Ala

35 40 45

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

50 55 60

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

65 70 75 80

Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala Arg His Phe Tyr Arg Phe

85 90 95

Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

100 105

<210> 83

<211> 113

<212> Protein

<213> Mus musculus

<400> 83

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

1 5 10 15

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

20 25 30

Cys Lys Ala Ser Gln Ser Val Ser Asn Asp Val Ala Trp Tyr Gln Gln

35 40 45

Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Tyr Ala Ser Asn Arg

50 55 60

Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Tyr Gly Thr Asp

65 70 75 80

Phe Thr Phe Thr Ile Ser Thr Val Gln Ala Glu Asp Leu Ala Val Tyr

85 90 95

Phe Cys Gln Gln Asp Asp Arg Phe Pro Leu Thr Phe Gly Ala Gly Pro

100 105 110

Ser

<210> 84

<211> 112

<212> Protein

<213> Mus musculus

<400> 84

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

1 5 10 15

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

20 25 30

Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Met

35 40 45

Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Asp Asp Phe

50 55 60

Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Tyr

65 70 75 80

Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe Cys

85 90 95

Ala Thr Gly Ala Trp Phe Ala Tyr Trp Ala Lys Asp Ser Ser Arg His

100 105 110

<210> 85

<211> 107

<212> Protein

<213> Mus musculus

<400> 85

Gly Val Glu Gly Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser

1 5 10 15

Thr Ser Val Gly Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp

20 25 30

Val Gly Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro

35 40 45

Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp

50 55 60

Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

65 70 75 80

Asn Val Gln Ser Glu Asp Leu Ala Asp Tyr Phe Cys Gln Gln Tyr Ser

85 90 95

Ser Tyr Pro Leu Thr Phe Gly Ala Gly Pro Ser

100 105

<210> 86

<211> 118

<212> Protein

<213> Mus musculus

<400> 86

Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Met Lys Val Ser Cys Val

1 5 10 15

Ala Ser Gly Phe Ser Phe Ile Asp Phe Trp Met Asn Trp Val Arg Gln

20 25 30

Ser Pro Glu Lys Gly Leu Glu Trp Val Ala Glu Ile Arg Leu Lys Ser

35 40 45

Asn Asn Tyr Ala Thr His Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr

50 55 60

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

65 70 75 80

Leu Arg Pro Glu Asp Thr Gly Ile Tyr Tyr Cys Thr Ser Leu Phe Tyr

85 90 95

Tyr Tyr Asp Gly Thr Ser Gly Phe Ala Tyr Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Leu Leu Lys

115

<210> 87

<211> 109

<212> Protein

<213> Mus musculus

<400> 87

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

1 5 10 15

Glu Lys Val Thr Met His Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser

20 25 30

Gly Asp Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Asn

85 90 95

Asp Tyr Asp Tyr Pro Leu Thr Phe Gly Ala Gly Pro Ser

100 105

<210> 88

<211> 148

<212> Protein

<213> Mus musculus

<400> 88

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

1 5 10 15

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

20 25 30

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

35 40 45

Thr Asp Tyr Asn Met Asp Trp Val Lys Gln Ser His Gly Lys Ser Leu

50 55 60

Glu Trp Ile Gly Asp Ile Asn Pro Asn Tyr Asp Ser Thr Ser Tyr Asn

65 70 75 80

Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser

85 90 95

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

100 105 110

Tyr Tyr Cys Ala Arg Ser Arg Ser Tyr Asp Tyr Glu Gly Phe Ala Tyr

115 120 125

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

130 135 140

Pro Ser Val Tyr

145

<210> 89

<211> 139

<212> Protein

<213> Mus musculus

<400> 89

Met Ser Val Leu Thr Gln Val Leu Gly Leu Leu Leu Leu Trp Leu Thr

1 5 10 15

Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser

20 25 30

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

35 40 45

Ile His Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro

50 55 60

Gln Leu Leu Val Tyr Asn Ala Lys Thr Leu Ala Asp Gly Val Pro Ser

65 70 75 80

Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Asn

85 90 95

Ser Leu Gln Pro Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His Phe Trp

100 105 110

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

115 120 125

Asp Ala Ala Pro Thr Val Ser Asn Pro Tyr Asp

130 135

<210> 90

<211> 100

<212> Protein

<213> Mus musculus

<400> 90

Asp Ile Leu Gln Ala Ser Gly Tyr Ser Phe Thr Gly Tyr Thr Met Asn

1 5 10 15

Trp Val Lys Gln Ser His Gly Lys Asn Leu Glu Trp Ile Gly Leu Ile

20 25 30

Asn Pro Tyr Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys

35 40 45

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

50 55 60

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

65 70 75 80

Gly Val Trp Ser Ala Met Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr

85 90 95

Val Ser Ser Lys

100

<210> 91

<211> 90

<212> Protein

<213> Mus musculus

<400> 91

Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asn Val Arg Thr Ala

1 5 10 15

Val Ala Trp Tyr Gln Gln Lys Pro Arg Gln Ser Pro Lys Ala Leu Ile

20 25 30

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

35 40 45

Arg Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile Thr Asn Val Gln Ser

50 55 60

Glu Asp Leu Glu Asp Tyr Phe Cys Leu Gln His Cys Asn Tyr Pro Asn

65 70 75 80

Glu Phe Arg Gly Cys Thr Lys Val Pro Ile

85 90

<210> 92

<211> 116

<212> Protein

<213> Mus musculus

<400> 92

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

1 5 10 15

Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Trp Met Gln

20 25 30

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

35 40 45

Tyr Pro Gly Asp Gly Asp Thr Arg Tyr Thr Gln Lys Phe Lys Gly Lys

50 55 60

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

65 70 75 80

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

85 90 95

Glu Tyr Gly Asn Tyr Phe Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser Asn

115

<210> 93

<211> 100

<212> Protein

<213> Mus musculus

<400> 93

Thr Ser Asp Ala Ser Leu Gly Glu Arg Val Thr Ile Thr Cys Lys Ala

1 5 10 15

Ser Gln Asp Ile Asn Ser Tyr Leu Ser Trp Phe Gln Gln Lys Pro Gly

20 25 30

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

35 40 45

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Gln Asp Tyr Ser Leu

50 55 60

Thr Ile Ser Ser Leu Glu Tyr Glu Asp Met Gly Ile Tyr Tyr Cys Leu

65 70 75 80

Gln Tyr Asp Glu Phe Pro Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu

85 90 95

Ile Lys Gln Lys

100

<210> 94

<211> 108

<212> Protein

<213> Mus musculus

<400> 94

Ala Trp Leu Ser Gln Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys

1 5 10 15

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

20 25 30

Trp Ile Gly Arg Ile Asp Pro Ala Asn Gly Asn Thr Lys Tyr Asp Pro

35 40 45

Lys Phe Gln Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr

50 55 60

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

65 70 75 80

Tyr Cys Ala Arg Pro Ile His Tyr Tyr Tyr Gly Ser Ser Leu Ala Tyr

85 90 95

Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Lys

100 105

<210> 95

<211> 104

<212> Protein

<213> Mus musculus

<400> 95

Glu Phe His Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg

1 5 10 15

Ala Ser Glu Ser Val Asp Ser Tyr Gly Asn Ser Phe Met His Trp Tyr

20 25 30

Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser

35 40 45

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

50 55 60

Thr Asp Phe Thr Leu Thr Ile Asn Pro Val Glu Ala Asp Asp Val Ala

65 70 75 80

Thr Tyr Tyr Cys Gln Gln Ser Asn Glu Asp Pro Gly Arg Ser Glu Val

85 90 95

Val Pro Ser Trp Arg Ser Asn Lys

100

<210> 96

<211> 109

<212> Protein

<213> Mus musculus

<400> 96

Pro Arg Ala Ser Leu Gly Val Ser Glu Thr Leu Leu Cys Thr Ser Gly

1 5 10 15

Phe Thr Phe Thr Asp Tyr Tyr Met Ser Trp Val Arg Gln Pro Pro Gly

20 25 30

Lys Ala Leu Glu Trp Leu Gly Phe Ile Arg Asn Lys Ala Asn Gly Tyr

35 40 45

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

50 55 60

Asp Asn Ser Gln Ser Ile Leu Tyr Leu Gln Met Asn Thr Leu Arg Ala

65 70 75 80

Glu Asp Ser Ala Thr Tyr Tyr Cys Ala Arg Ala Asn Trp Ala Phe Asp

85 90 95

Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Lys

100 105

<210> 97

<211> 94

<212> Protein

<213> Mus musculus

<400> 97

Ser Gly Asp Arg Val Ser Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser

1 5 10 15

Asn Tyr Leu His Trp Tyr Gln Gln Lys Ser His Glu Ser Pro Arg Leu

20 25 30

Leu Ile Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser Arg Phe

35 40 45

Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val

50 55 60

Glu Thr Glu Asp Phe Gly Met Tyr Phe Cys Gln Gln Ser Asn Ser Trp

65 70 75 80

Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gln

85 90

<210> 98

<211> 111

<212> Protein

<213> Mus musculus

<400> 98

Pro Ala Cys Leu Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Thr Ser

1 5 10 15

Gly Phe Thr Phe Thr Asp Tyr Tyr Met Ser Trp Val Arg Gln Pro Pro

20 25 30

Gly Lys Ala Leu Glu Trp Leu Gly Phe Ile Arg Asn Lys Ala Asn Gly

35 40 45

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

50 55 60

Arg Asp Asn Ser Gln Ser Ile Leu Tyr Leu Gln Met Asn Thr Leu Arg

65 70 75 80

Ala Glu Asp Ser Ala Thr Tyr Tyr Cys Ala Arg Ala Pro Leu Leu Tyr

85 90 95

Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser

100 105 110

<210> 99

<211> 102

<212> Protein

<213> Mus musculus

<400> 99

Arg Leu Pro Phe Tyr Ser Leu Glu Gln Arg Ala Thr Ile Ser Tyr Arg

1 5 10 15

Ala Ser Lys Asn Val Ser Thr Ser Gly Tyr Ser Tyr Met His Trp Asn

20 25 30

Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Leu Val Ser

35 40 45

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

50 55 60

Thr Asp Phe Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala

65 70 75 80

Thr Tyr Tyr Cys Gln His Ile Arg Glu Leu Thr Arg Ser Glu Leu Val

85 90 95

Pro Ser Trp Lys Ser Asn

100

<210> 100

<211> 101

<212> Protein

<213> Mus musculus

<400> 100

Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Trp Met His

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Leu Arg His Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Thr Val

85 90 95

Thr Val Ser Ser Lys

100

<210> 101

<211> 99

<212> Protein

<213> Mus musculus

<400> 101

Thr Ile Leu Trp Arg Glu Gly Pro Phe Ser Tyr Arg Ala Ser Lys Ser

1 5 10 15

Val Ser Thr Ser Gly Tyr Ser Tyr Met His Trp Asn Gln Gln Lys Pro

20 25 30

Gly Gln Pro Pro Arg Leu Leu Ile Tyr Leu Val Ser Asn Leu Glu Ser

35 40 45

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

50 55 60

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

65 70 75 80

Gln His Ile Arg Glu Leu Thr Arg Ser Glu Glu Val Pro Ser Trp Arg

85 90 95

Ser Asn Lys

<210> 102

<211> 110

<212> Protein

<213> Mus musculus

<400> 102

Gly Gly Gly Leu Val Lys Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala

1 5 10 15

Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly Met Ser Trp Val Arg Gln

20 25 30

Thr Pro Glu Lys Arg Leu Glu Trp Val Ala Thr Ile Ser Ser Gly Gly

35 40 45

Ser Tyr Thr Tyr Tyr Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser

50 55 60

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

65 70 75 80

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

85 90 95

Phe Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser

100 105 110

<210> 103

<211> 113

<212> Protein

<213> Mus musculus

<400> 103

Gly Ala Arg Cys Asp Val Gln Met Ile Gln Ser Pro Ser Ser Leu Ser

1 5 10 15

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

20 25 30

Thr Ser Ile Asn Leu Asn Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro

35 40 45

Lys Leu Leu Ile Tyr Gly Ala Ser Ser Leu Glu Asp Gly Val Pro Ser

50 55 60

Arg Phe Ser Gly Ser Cys Phe Gly Thr Asp Phe Thr Leu Thr Ile Ser

65 70 75 80

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

85 90 95

Tyr Leu Pro Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys

100 105 110

Arg

<210> 104

<211> 111

<212> Protein

<213> Mus musculus

<400> 104

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

1 5 10 15

Val Ser Gly Phe Ser Leu Thr Thr Tyr Asp Leu His Trp Val Arg Gln

20 25 30

Ser Pro Gly Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Ser Gly Gly

35 40 45

Ser Thr Asp Tyr Asn Ala Ala Phe Ile Ser Arg Leu Ser Ile Ser Lys

50 55 60

Asp Asn Ser Lys Ser Gln Val Phe Phe Lys Met Asn Ser Leu Gln Ala

65 70 75 80

Asn Asp Thr Ala Ile Tyr Tyr Cys Ala Arg Asn Tyr Gly Tyr Ser Ala

85 90 95

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

100 105 110

<210> 105

<211> 118

<212> Protein

<213> Mus musculus

<400> 105

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

1 5 10 15

Pro Val Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln

20 25 30

Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln

35 40 45

Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg

50 55 60

Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

65 70 75 80

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

85 90 95

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

100 105 110

Lys Leu Glu Leu Lys Arg

115

<210> 106

<211> 114

<212> Protein

<213> Mus musculus

<400> 106

Gly Phe Glu Leu Lys Lys Pro Gly Glu Thr Val Lys Ile Ser Cys Lys

1 5 10 15

Ala Ser Gly Tyr Thr Phe Thr Ala Tyr Ser Met His Trp Val Lys Gln

20 25 30

Thr Pro Gly Lys Gly Leu Lys Trp Leu Gly Trp Ile Asn Thr Glu Thr

35 40 45

Gly Glu Pro Thr Tyr Thr Asp Asp Phe Lys Gly Arg Phe Thr Phe Ser

50 55 60

Leu Glu Thr Ser Ala Arg Ile Ala Tyr Leu Gln Ile Asn Asp Leu Lys

65 70 75 80

Asn Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Arg Ile Tyr Tyr Phe

85 90 95

Gly Arg Gly Gly Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val

100 105 110

Ser Ser

<210> 107

<211> 118

<212> Protein

<213> Mus musculus

<400> 107

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

1 5 10 15

Pro Val Arg Leu Gly Asp Gln Ser Ser Ile Ser Cys Arg Ser Ser Gln

20 25 30

Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln

35 40 45

Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg

50 55 60

Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

65 70 75 80

Phe Thr Leu Lys Ile Ser Arg Val Glu Pro Glu Asp Leu Gly Val Tyr

85 90 95

Tyr Cys Phe Gln Gly Ser His Val Pro Tyr Thr Ser Glu Gly Asp Gln

100 105 110

Ala Glu Ile Lys Leu Ala

115

<210> 108

<211> 114

<212> Protein

<213> Mus musculus

<400> 108

Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Met Arg Leu Ser Cys Val

1 5 10 15

Ala Ser Gly Phe Thr Phe Ser Asn Ser Trp Phe Asn Trp Val Arg Gln

20 25 30

Ser Pro Glu Lys Gly Leu Glu Trp Val Ala Glu Ile Arg Leu Thr Ser

35 40 45

Asp Asn Tyr Ala Ile Tyr Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr

50 55 60

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

65 70 75 80

Leu Arg Ala Glu Asp Thr Gly Ile Tyr Tyr Cys Thr Arg Pro Glu Thr

85 90 95

Ala Arg Ala Thr Phe Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val

100 105 110

Ser Ser

<210> 109

<211> 118

<212> Protein

<213> Mus musculus

<400> 109

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

1 5 10 15

Pro Val Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln

20 25 30

Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln

35 40 45

Lys Pro Gly Gln Ser Pro Lys Val Leu Ile Tyr Lys Val Phe Asn Arg

50 55 60

Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

65 70 75 80

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

85 90 95

Tyr Cys Phe Gln Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr

100 105 110

Lys Leu Asn Gln Thr Gly

115

<210> 110

<211> 111

<212> Protein

<213> Mus musculus

<400> 110

Gly Pro Asp Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys

1 5 10 15

Ala Ser Gly Tyr Ser Phe Thr Ala Tyr Tyr Met His Trp Val Lys Gln

20 25 30

Ser His Gly Lys Ser Leu Glu Trp Ile Gly Arg Val Asn Pro Asn Asn

35 40 45

Gly Gly Thr Thr Tyr Asn Gln Lys Phe Lys Gly Lys Ala Ile Leu Thr

50 55 60

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

65 70 75 80

Phe Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Arg Ile Tyr Tyr Gly

85 90 95

Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

100 105 110

<210> 111

<211> 104

<212> Protein

<213> Mus musculus

<400> 111

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

1 5 10 15

Ala Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn Trp Tyr

20 25 30

Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Val Ala Ser

35 40 45

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

50 55 60

Thr Asp Phe Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala

65 70 75 80

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

85 90 95

Gly Thr Lys Leu Glu Ile Lys Gln

100

<210> 112

<211> 106

<212> Protein

<213> Mus musculus

<400> 112

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

1 5 10 15

Ala Ser Gly Leu Asn Ile Arg Asp Ile Tyr Met His Trp Val Lys Gln

20 25 30

Arg Pro Glu Gln Gly Leu Glu Trp Ile Gly Lys Ile Asp Pro Ala Asn

35 40 45

Gly Asn Thr Lys Tyr Asp Pro Lys Phe Gln Gly Lys Ala Thr Ile Thr

50 55 60

Ala Asp Thr Ser Ser Asn Thr Ala Tyr Val Gln Leu Ser Ser Leu Thr

65 70 75 80

Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly Thr Gly Asp Tyr Trp

85 90 95

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

100 105

<210> 113

<211> 112

<212> Protein

<213> Mus musculus

<400> 113

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

1 5 10 15

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

20 25 30

Leu Leu Asn Ser Arg Thr Arg Lys Asn Tyr Leu Ala Trp Val Gln His

35 40 45

Lys Pro Gly Gln Ser Pro Arg Leu Leu Ile Tyr Trp Ala Ser Thr Arg

50 55 60

Glu Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp

65 70 75 80

Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr

85 90 95

Tyr Cys Arg Gln Ser Tyr Asn Leu Val Thr Phe Gly Ala Gly Pro Ser

100 105 110

<210> 114

<211> 112

<212> Protein

<213> Mus musculus

<400> 114

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

1 5 10 15

Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Val Met His Trp Val Lys Gln

20 25 30

Lys Pro Gly Gln Gly Leu Glu Trp Ile Gly Tyr Ile Asn Pro Tyr Asn

35 40 45

Asp Gly Thr Lys Tyr Asn Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr

50 55 60

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

65 70 75 80

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

85 90 95

Ser Ser Gly Gly Tyr Phe Asp Val Trp Ala Gln Asp His Val Arg Thr

100 105 110

<210> 115

<211> 108

<212> Protein

<213> Mus musculus

<400> 115

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

1 5 10 15

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

20 25 30

Leu Ala Trp Tyr Gln Glu Lys Pro Gly Lys Thr Asn Lys Leu Leu Ile

35 40 45

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

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Met Tyr Tyr Cys Gln Gln His Asn Glu Tyr Pro Tyr

85 90 95

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

100 105

<210> 116

<211> 113

<212> Protein

<213> Mus musculus

<400> 116

Gly Pro Glu Leu Val Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys

1 5 10 15

Ala Ser Gly Tyr Ser Phe Thr Gly Tyr Phe Met Asn Trp Val Met Gln

20 25 30

Ser His Gly Lys Ser Leu Glu Trp Ile Gly Arg Ile Asn Pro Tyr Asn

35 40 45

Gly Asp Thr Phe Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr

50 55 60

Val Asp Lys Ser Ser Ser Thr Ala His Met Glu Leu Arg Ser Leu Ala

65 70 75 80

Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Arg Ile His Tyr Tyr

85 90 95

Tyr Gly Ser Ser Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Glu Pro His

100 105 110

His

<210> 117

<211> 108

<212> Protein

<213> Mus musculus

<400> 117

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

1 5 10 15

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

20 25 30

Leu Ala Trp Tyr Gln Glu Lys Pro Gly Lys Thr Asn Lys Leu Leu Ile

35 40 45

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

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Met Tyr Tyr Cys Gln Gln His Asn Glu Tyr Pro Trp

85 90 95

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

100 105

<210> 118

<211> 113

<212> Protein

<213> Mus musculus

<400> 118

Gly Ala Gly Leu Val Lys Pro Gly Ala Ser Val Lys Leu Ser Cys Lys

1 5 10 15

Ala Ser Gly Tyr Thr Phe Thr Glu Tyr Ile Ile His Trp Val Lys Gln

20 25 30

Arg Ser Gly Gln Gly Leu Glu Trp Ile Gly Trp Phe Tyr Pro Gly Ser

35 40 45

Gly Ser Ile Lys Tyr Asn Glu Lys Phe Lys Asp Lys Ala Thr Leu Thr

50 55 60

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

65 70 75 80

Ser Glu Asp Ser Ala Val Tyr Phe Cys Ala Arg His Glu Val Tyr Tyr

85 90 95

Asp Tyr Asp Lys Ser Met Leu Trp Thr Thr Gly Val Lys Asn Leu Ile

100 105 110

Arg

<210> 119

<211> 108

<212> Protein

<213> Mus musculus

<400> 119

Ser Pro Ser Ser Leu Ala Val Ser Val Gly Glu Lys Val Thr Met Ser

1 5 10 15

Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser Ser Ser Asn Gln Lys Asn Tyr

20 25 30

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

35 40 45

Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Thr Gly

50 55 60

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

65 70 75 80

Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Tyr Pro Tyr

85 90 95

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

100 105

<210> 120

<211> 113

<212> Protein

<213> Mus musculus

<400> 120

Gly Ala Glu Leu Val Arg Pro Gly Thr Ser Val Lys Val Ser Cys Lys

1 5 10 15

Ala Ser Val Tyr Ala Phe Thr Asn Tyr Leu Ile Glu Trp Val Lys Gln

20 25 30

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

35 40 45

Gly Gly Thr Lys Tyr Asn Glu Lys Phe Arg Gly Lys Ala Thr Leu Thr

50 55 60

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

65 70 75 80

Ser Gly Asp Ser Ala Val Tyr Phe Cys Ala Ile Thr Gly Thr Asp Tyr

85 90 95

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

100 105 110

Pro

<210> 121

<211> 113

<212> Protein

<213> Mus musculus

<400> 121

Gln Gly Thr Arg Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu

1 5 10 15

Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Ser Ala Ser Gln

20 25 30

Gly Ile Asn Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr

35 40 45

Val Lys Leu Leu Ile Tyr Tyr Thr Ser Ser Leu Arg Ser Gly Val Pro

50 55 60

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

65 70 75 80

Ser Asn Leu Glu Pro Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr

85 90 95

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

100 105 110

Arg

<210> 122

<211> 121

<212> Protein

<213> Homo sapiens

<400> 122

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His

20 25 30

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

35 40 45

Gly Asp Ile Arg Ser Gly Ser Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys

50 55 60

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

65 70 75 80

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

85 90 95

Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 123

<211> 112

<212> Protein

<213> Homo sapiens

<400> 123

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

1 5 10 15

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

20 25 30

Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu

35 40 45

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

50 55 60

Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln

65 70 75 80

Cys Glu Asp Phe Ala Ile Tyr Tyr Cys Leu Gly Glu Phe Ser Cys Gly

85 90 95

Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 124

<211> 121

<212> Protein

<213> Homo sapiens

<400> 124

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His

20 25 30

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

35 40 45

Gly Asp Ile Arg Ser Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys

50 55 60

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

65 70 75 80

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

85 90 95

Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 125

<211> 112

<212> Protein

<213> Homo sapiens

<400> 125

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

1 5 10 15

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

20 25 30

Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg Leu

35 40 45

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

50 55 60

Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln

65 70 75 80

Cys Glu Asp Phe Ala Ile Tyr Tyr Cys Leu Gly Glu Phe Ser Cys Gly

85 90 95

Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 126

<211> 121

<212> Protein

<213> Homo sapiens

<400> 126

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His

20 25 30

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

35 40 45

Gly Asp Ile Arg Ser Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys

50 55 60

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

65 70 75 80

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

85 90 95

Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 127

<211> 113

<212> Protein

<213> Homo sapiens

<400> 127

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

1 5 10 15

Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn

20 25 30

Glu Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg

35 40 45

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

50 55 60

Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu

65 70 75 80

Gln Pro Glu Asp Phe Ala Ile Tyr Tyr Cys Leu Gly Glu Phe Ser Cys

85 90 95

Gly Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 128

<211> 121

<212> Protein

<213> Homo sapiens

<400> 128

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His

20 25 30

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

35 40 45

Gly Asp Ile Arg Ser Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys

50 55 60

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

65 70 75 80

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

85 90 95

Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 129

<211> 113

<212> Protein

<213> Homo sapiens

<400> 129

Glu Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn

20 25 30

Glu Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg

35 40 45

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

50 55 60

Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu

65 70 75 80

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

85 90 95

Gly Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 130

<211> 121

<212> Protein

<213> Homo sapiens

<400> 130

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His

20 25 30

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

35 40 45

Gly Asp Ile Arg Ser Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys

50 55 60

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

65 70 75 80

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

85 90 95

Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 131

<211> 113

<212> Protein

<213> Homo sapiens

<400> 131

Glu Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn

20 25 30

Glu Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg

35 40 45

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

50 55 60

Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu

65 70 75 80

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

85 90 95

Gly Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 132

<211> 121

<212> Protein

<213> Homo sapiens

<400> 132

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Ser His

20 25 30

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

35 40 45

Gly Asp Ile Arg Ser Gly Ser Gly Ser Ala Tyr Tyr Ala Asn Trp Ala Lys

50 55 60

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

65 70 75 80

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

85 90 95

Arg Thr Asn Gly Pro Ser Asp Leu Thr Asn Arg Leu Asp Leu Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 133

<211> 113

<212> Protein

<213> Homo sapiens

<400> 133

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

1 5 10 15

Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Leu Tyr Asn Asn

20 25 30

Glu Asn Leu Ala Trp Phe Gln Gln Lys Pro Gly Lys Val Pro Lys Arg

35 40 45

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

50 55 60

Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Asn Leu

65 70 75 80

Gln Pro Glu Asp Phe Ala Ile Tyr Tyr Cys Leu Gly Glu Phe Ser Cys

85 90 95

Gly Ser Ala Asp Cys Phe Ala Phe Gly Gly Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 134

<211> 5

<212> Protein

<213> Gallus gallus

<400> 134

Gly Tyr Asp Met Leu

fifteen

<210> 135

<211> 17

<212> Protein

<213> Gallus gallus

<400> 135

Gly Ile Gly Ser Thr Gly Gly Gly Thr Asp Tyr Gly Ala Ala Val Lys

1 5 10 15

gly

<210> 136

<211> 19

<212> Protein

<213> Gallus gallus

<400> 136

Val Ala Gly Gly Cys Asn Ser Gly Tyr Cys Arg Asp Ser Pro Gly Ser

1 5 10 15

Ile Asp Ala

<210> 137

<211> 10

<212> Protein

<213> Gallus gallus

<400> 137

Ser Gly Gly Gly Ser Arg Asn Tyr Tyr Gly

1 5 10

<210> 138

<211> 7

<212> Protein

<213> Gallus gallus

<400> 138

Asp Asp Gln Arg Pro Ser Asn

fifteen

<210> 139

<211> 11

<212> Protein

<213> Gallus gallus

<400> 139

Ser Ala Asp Ser Asn Thr Tyr Glu Gly Ser Phe

1 5 10

<210> 140

<211> 5

<212> Protein

<213> Mus musculus

<400> 140

Asp Tyr Asn Met Asp

fifteen

<210> 141

<211> 17

<212> Protein

<213> Mus musculus

<400> 141

Asp Ile Asn Pro Asn Tyr Asp Ser Thr Ser Tyr Asn Gln Lys Phe Lys

1 5 10 15

gly

<210> 142

<211> 11

<212> Protein

<213> Mus musculus

<400> 142

Ser Arg Ser Tyr Asp Tyr Glu Gly Phe Ala Tyr

1 5 10

<210> 143

<211> 11

<212> Protein

<213> Mus musculus

<400> 143

Leu Ser Ile Val Asn Arg Tyr His Tyr Met Ser

1 5 10

<210> 144

<211> 6

<212> Protein

<213> Mus musculus

<400> 144

Glu Ala Ser Ile Thr Lys

fifteen

<210> 145

<211> 9

<212> Protein

<213> Mus musculus

<400> 145

Gln His Asn Arg Gly Ser Phe Leu Pro

fifteen

<210> 146

<211> 5

<212> Protein

<213> Mus musculus

<400> 146

Asp Tyr Tyr Met Ser

fifteen

<210> 147

<211> 17

<212> Protein

<213> Mus musculus

<400> 147

Arg Asn Lys Ala Asn Gly Tyr Thr Thr Glu Tyr Ser Ala Ser Val Lys

1 5 10 15

gly

<210> 148

<211> 9

<212> Protein

<213> Mus musculus

<400> 148

Ala Arg Ala Asn Trp Ala Phe Asp Tyr

fifteen

<210> 149

<211> 11

<212> Protein

<213> Mus musculus

<400> 149

Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu His

1 5 10

<210> 150

<211> 7

<212> Protein

<213> Mus musculus

<400> 150

Tyr Ala Ser Gln Ser Ile Ser

fifteen

<210> 151

<211> 7

<212> Protein

<213> Mus musculus

<400> 151

Tyr Ala Ser Gln Ser Ile Ser

fifteen

<210> 152

<211> 5

<212> Protein

<213> Mus musculus

<400> 152

Asn Tyr Leu Ile Val

fifteen

<210> 153

<211> 17

<212> Protein

<213> Mus musculus

<400> 153

Val Ile Ser Pro Gly Ser Gly Gly Thr Asn Tyr Asn Glu Lys Phe Lys

1 5 10 15

gly

<210> 154

<211> 11

<212> Protein

<213> Mus musculus

<400> 154

Glu Lys Ile Tyr Asp Asp Tyr Tyr Glu Gly Tyr

1 5 10

<210> 155

<211> 15

<212> Protein

<213> Mus musculus

<400> 155

Thr Ile Ser Cys Ser Ala Ser Leu Gly Ile Gly Asn Tyr Leu Asn

1 5 10 15

<210> 156

<211> 7

<212> Protein

<213> Mus musculus

<400> 156

Thr Ser Asn Leu His Ser Gly

fifteen

<210> 157

<211> 9

<212> Protein

<213> Mus musculus

<400> 157

His Tyr Ser Lys Leu Pro Leu Thr Phe

fifteen

<210> 158

<211> 5

<212> Protein

<213> Mus musculus

<400> 158

Asp Tyr Asn Met Tyr

fifteen

<210> 159

<211> 17

<212> Protein

<213> Mus musculus

<400> 159

Tyr Ile Tyr Pro Gly Asn Gly Gly Thr Asn Tyr Asn Gln Lys Phe Lys

1 5 10 15

gly

<210> 160

<211> 11

<212> Protein

<213> Mus musculus

<400> 160

Asp Tyr Asp Asp Gly Gly Tyr Ala Met Asp Tyr

1 5 10

<210> 161

<211> 15

<212> Protein

<213> Mus musculus

<400> 161

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

1 5 10 15

<210> 162

<211> 7

<212> Protein

<213> Mus musculus

<400> 162

Asn Ala Lys Thr Leu Ala Asp

fifteen

<210> 163

<211> 9

<212> Protein

<213> Mus musculus

<400> 163

Gln His Phe Trp Asn Ile Pro Trp Thr

fifteen

<210> 164

<211> 5

<212> Protein

<213> Mus musculus

<400> 164

Asp His Ser Ile His

fifteen

<210> 165

<211> 17

<212> Protein

<213> Mus musculus

<400> 165

Tyr Ile Ser Pro Gly Asn Gly Asn Ile Lys Tyr Asn Glu Lys Phe Lys

1 5 10 15

gly

<210> 166

<211> 12

<212> Protein

<213> Mus musculus

<400> 166

Ser Leu Gly Arg Gly Gly Pro Tyr Tyr Phe Asp Tyr

1 5 10

<210> 167

<211> 16

<212> Protein

<213> Mus musculus

<400> 167

Arg Ser Ser Lys Ser Leu Leu His Ser Asn Gly Asn Thr Tyr Leu Tyr

1 5 10 15

<210> 168

<211> 7

<212> Protein

<213> Mus musculus

<400> 168

Arg Met Ser Asn Leu Ala Ser

fifteen

<210> 169

<211> 9

<212> Protein

<213> Mus musculus

<400> 169

Met Gln His Arg Glu Tyr Pro Val Thr

fifteen

<210> 170

<211> 5

<212> Protein

<213> Mus musculus

<400> 170

Ser Tyr Trp Ile Glu

fifteen

<210> 171

<211> 17

<212> Protein

<213> Mus musculus

<400> 171

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asn Glu Lys Phe Lys

1 5 10 15

gly

<210> 172

<211> 11

<212> Protein

<213> Mus musculus

<400> 172

Tyr Tyr Trp Tyr Phe Asp Val Trp Ala Gln Asp

1 5 10

<210> 173

<211> 15

<212> Protein

<213> Mus musculus

<400> 173

Ser Ser Lys Asn Leu Leu His Ser Asn Gly Ile Thr Tyr Leu Tyr

1 5 10 15

<210> 174

<211> 7

<212> Protein

<213> Mus musculus

<400> 174

Arg Val Ser Asn Leu Ala Ser

fifteen

<210> 175

<211> 9

<212> Protein

<213> Mus musculus

<400> 175

Ala Gln Leu Leu Glu Leu Pro Tyr Thr

fifteen

<210> 176

<211> 5

<212> Protein

<213> Mus musculus

<400> 176

Ser Tyr Asp Met Ser

fifteen

<210> 177

<211> 17

<212> Protein

<213> Mus musculus

<400> 177

Tyr Ile Ser Ser Gly Ala Gly Ser Thr Tyr Tyr Pro Asp Thr Val Lys

1 5 10 15

gly

<210> 178

<211> 11

<212> Protein

<213> Mus musculus

<400> 178

His Phe Tyr Arg Phe Asp Tyr Trp Gly Gln Gly

1 5 10

<210> 179

<211> 15

<212> Protein

<213> Mus musculus

<400> 179

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

1 5 10 15

<210> 180

<211> 7

<212> Protein

<213> Mus musculus

<400> 180

Tyr Ala Ser Asn Arg Tyr Thr

fifteen

<210> 181

<211> 9

<212> Protein

<213> Mus musculus

<400> 181

Gln Gln Asp Asp Arg Phe Pro Leu Thr

fifteen

<210> 182

<211> 5

<212> Protein

<213> Mus musculus

<400> 182

Asn Tyr Gly Met Asn

fifteen

<210> 183

<211> 17

<212> Protein

<213> Mus musculus

<400> 183

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

1 5 10 15

gly

<210> 184

<211> 11

<212> Protein

<213> Mus musculus

<400> 184

Gly Ala Trp Phe Ala Tyr Trp Ala Lys Asp Ser

1 5 10

<210> 185

<211> 15

<212> Protein

<213> Mus musculus

<400> 185

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

1 5 10 15

<210> 186

<211> 7

<212> Protein

<213> Mus musculus

<400> 186

Trp Ala Ser Thr Arg His Thr

fifteen

<210> 187

<211> 9

<212> Protein

<213> Mus musculus

<400> 187

Gln Gln Tyr Ser Ser Tyr Pro Leu Thr

fifteen

<210> 188

<211> 5

<212> Protein

<213> Mus musculus

<400> 188

Asp Phe Trp Met Asn

fifteen

<210> 189

<211> 19

<212> Protein

<213> Mus musculus

<400> 189

Glu Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala Glu Ser

1 5 10 15

Val Lys Gly

<210> 190

<211> 13

<212> Protein

<213> Mus musculus

<400> 190

Leu Phe Tyr Tyr Tyr Asp Gly Thr Ser Gly Phe Ala Tyr

1 5 10

<210> 191

<211> 17

<212> Protein

<213> Mus musculus

<400> 191

Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly Asp Gln Lys Asn Tyr Leu

1 5 10 15

Thr

<210> 192

<211> 7

<212> Protein

<213> Mus musculus

<400> 192

Trp Ala Ser Thr Arg Glu Ser

fifteen

<210> 193

<211> 9

<212> Protein

<213> Mus musculus

<400> 193

Gln Asn Asp Tyr Asp Tyr Pro Leu Thr

fifteen

<210> 194

<211> 5

<212> Protein

<213> Mus musculus

<400> 194

Asp Tyr Asn Met Asp

fifteen

<210> 195

<211> 17

<212> Protein

<213> Mus musculus

<400> 195

Asp Ile Asn Pro Asn Tyr Asp Ser Thr Ser Tyr Asn Gln Lys Phe Lys

1 5 10 15

gly

<210> 196

<211> 11

<212> Protein

<213> Mus musculus

<400> 196

Ser Arg Ser Tyr Asp Tyr Glu Gly Phe Ala Tyr

1 5 10

<210> 197

<211> 11

<212> Protein

<213> Mus musculus

<400> 197

Arg Ala Ser Gly Asn Ile His Asn Tyr Leu Ala

1 5 10

<210> 198

<211> 7

<212> Protein

<213> Mus musculus

<400> 198

Asn Ala Lys Thr Leu Ala Asp

fifteen

<210> 199

<211> 8

<212> Protein

<213> Mus musculus

<400> 199

Gln His Phe Trp Ser Thr Leu Thr

fifteen

<210> 200

<211> 5

<212> Protein

<213> Mus musculus

<400> 200

Gly Tyr Thr Met Asn

fifteen

<210> 201

<211> 16

<212> Protein

<213> Mus musculus

<400> 201

Asn Pro Tyr Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys

1 5 10 15

<210> 202

<211> 9

<212> Protein

<213> Mus musculus

<400> 202

Trp Gly Val Trp Ser Ala Met Asp Tyr

fifteen

<210> 203

<211> 11

<212> Protein

<213> Mus musculus

<400> 203

Lys Ala Ser Gln Asn Val Arg Thr Ala Val Ala

1 5 10

<210> 204

<211> 7

<212> Protein

<213> Mus musculus

<400> 204

Leu Ala Ser Asn Arg Asp Thr

fifteen

<210> 205

<211> 9

<212> Protein

<213> Mus musculus

<400> 205

Leu Gln His Cys Asn Tyr Pro Asn Glu

fifteen

<210> 206

<211> 5

<212> Protein

<213> Mus musculus

<400> 206

Ser Tyr Trp Met Gln

fifteen

<210> 207

<211> 17

<212> Protein

<213> Mus musculus

<400> 207

Ala Ile Tyr Pro Gly Asp Gly Asp Thr Arg Tyr Thr Gln Lys Phe Lys

1 5 10 15

gly

<210> 208

<211> 11

<212> Protein

<213> Mus musculus

<400> 208

Ala Arg Gly Glu Tyr Gly Asn Tyr Phe Ala Tyr

1 5 10

<210> 209

<211> 11

<212> Protein

<213> Mus musculus

<400> 209

Lys Ala Ser Gln Asp Ile Asn Ser Tyr Leu Ser

1 5 10

<210> 210

<211> 7

<212> Protein

<213> Mus musculus

<400> 210

Arg Ala Asn Arg Leu Val Asp

fifteen

<210> 211

<211> 9

<212> Protein

<213> Mus musculus

<400> 211

Leu Gln Tyr Asp Glu Phe Pro Leu Thr

fifteen

<210> 212

<211> 5

<212> Protein

<213> Mus musculus

<400> 212

Asp Thr Tyr Met His

fifteen

<210> 213

<211> 17

<212> Protein

<213> Mus musculus

<400> 213

Arg Ile Asp Pro Ala Asn Gly Asn Thr Lys Tyr Asp Pro Lys Phe Gln

1 5 10 15

gly

<210> 214

<211> 14

<212> Protein

<213> Mus musculus

<400> 214

Ala Arg Pro Ile His Tyr Tyr Tyr Gly Ser Ser Leu Ala Tyr

1 5 10

<210> 215

<211> 11

<212> Protein

<213> Mus musculus

<400> 215

Ser Val Asp Ser Tyr Gly Asn Ser Phe Met His

1 5 10

<210> 216

<211> 7

<212> Protein

<213> Mus musculus

<400> 216

Arg Ala Ser Asn Leu Glu Ser

fifteen

<210> 217

<211> 9

<212> Protein

<213> Mus musculus

<400> 217

Gln Gln Ser Asn Glu Asp Pro Gly Arg

fifteen

<210> 218

<211> 5

<212> Protein

<213> Mus musculus

<400> 218

Asp Tyr Tyr Met Ser

fifteen

<210> 219

<211> 17

<212> Protein

<213> Mus musculus

<400> 219

Arg Asn Lys Ala Asn Gly Tyr Thr Thr Glu Tyr Ser Ala Ser Val Lys

1 5 10 15

gly

<210> 220

<211> 9

<212> Protein

<213> Mus musculus

<400> 220

Ala Arg Ala Asn Trp Ala Phe Asp Tyr

fifteen

<210> 221

<211> 11

<212> Protein

<213> Mus musculus

<400> 221

Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu His

1 5 10

<210> 222

<211> 7

<212> Protein

<213> Mus musculus

<400> 222

Tyr Ala Ser Gln Ser Ile Ser

fifteen

<210> 223

<211> 9

<212> Protein

<213> Mus musculus

<400> 223

Gln Gln Ser Asn Ser Trp Pro Tyr Thr

fifteen

<210> 224

<211> 5

<212> Protein

<213> Mus musculus

<400> 224

Asp Tyr Tyr Met Ser

fifteen

<210> 225

<211> 17

<212> Protein

<213> Mus musculus

<400> 225

Arg Asn Lys Ala Asn Gly Tyr Thr Thr Glu Tyr Ser Ala Ser Val Lys

1 5 10 15

gly

<210> 226

<211> 12

<212> Protein

<213> Mus musculus

<400> 226

Ala Arg Ala Pro Leu Leu Tyr Tyr Ala Met Asp Tyr

1 5 10

<210> 227

<211> 11

<212> Protein

<213> Mus musculus

<400> 227

Asn Val Ser Thr Ser Gly Tyr Ser Tyr Met His

1 5 10

<210> 228

<211> 7

<212> Protein

<213> Mus musculus

<400> 228

Leu Val Ser Asn Leu Glu Ser

fifteen

<210> 229

<211> 8

<212> Protein

<213> Mus musculus

<400> 229

Gln His Ile Arg Glu Leu Thr Arg

fifteen

<210> 230

<211> 5

<212> Protein

<213> Mus musculus

<400> 230

Ser Tyr Trp Met His

fifteen

<210> 231

<211> 17

<212> Protein

<213> Mus musculus

<400> 231

Met Ile Asp Pro Ser Asn Ser Glu Thr Arg Leu Asn Gln Lys Phe Lys

1 5 10 15

asp

<210> 232

<211> 12

<212> Protein

<213> Mus musculus

<400> 232

Ala Arg Gly Leu Arg His Tyr Trp Tyr Phe Asp Val

1 5 10

<210> 233

<211> 11

<212> Protein

<213> Mus musculus

<400> 233

Ser Val Ser Thr Ser Gly Tyr Ser Tyr Met His

1 5 10

<210> 234

<211> 7

<212> Protein

<213> Mus musculus

<400> 234

Leu Val Ser Asn Leu Glu Ser

fifteen

<210> 235

<211> 9

<212> Protein

<213> Mus musculus

<400> 235

Gln His Ile Arg Glu Leu Thr Arg Ser

fifteen

<210> 236

<211> 5

<212> Protein

<213> Mus musculus

<400> 236

Ser Tyr Gly Met Ser

fifteen

<210> 237

<211> 14

<212> Protein

<213> Mus musculus

<400> 237

Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Glu Trp Val Ala

1 5 10

<210> 238

<211> 11

<212> Protein

<213> Mus musculus

<400> 238

Leu Ala Ser Tyr Tyr Phe Asp Tyr Trp Gly Gln

1 5 10

<210> 239

<211> 15

<212> Protein

<213> Mus musculus

<400> 239

Thr Met Thr Cys Gln Ala Ser Gln Gly Thr Ser Ile Asn Leu Asn

1 5 10 15

<210> 240

<211> 7

<212> Protein

<213> Mus musculus

<400> 240

Gly Ala Ser Ser Leu Glu Asp

fifteen

<210> 241

<211> 11

<212> Protein

<213> Mus musculus

<400> 241

Leu Gln His Ser Tyr Leu Pro Pro Leu Thr Phe

1 5 10

<210> 242

<211> 5

<212> Protein

<213> Mus musculus

<400> 242

Thr Tyr Asp Leu His

fifteen

<210> 243

<211> 16

<212> Protein

<213> Mus musculus

<400> 243

Val Ile Trp Ser Gly Gly Ser Thr Asp Tyr Asn Ala Ala Phe Ile Ser

1 5 10 15

<210> 244

<211> 11

<212> Protein

<213> Mus musculus

<400> 244

Asn Tyr Gly Tyr Ser Ala Trp Phe Ala Tyr Trp

1 5 10

<210> 245

<211> 15

<212> Protein

<213> Mus musculus

<400> 245

Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser Asn

1 5 10 15

<210> 246

<211> 7

<212> Protein

<213> Mus musculus

<400> 246

Lys Val Ser Asn Arg Phe Ser

fifteen

<210> 247

<211> 9

<212> Protein

<213> Mus musculus

<400> 247

Phe Gln Gly Ser His Val Pro Leu Thr

fifteen

<210> 248

<211> 5

<212> Protein

<213> Mus musculus

<400> 248

Ala Tyr Ser Met His

fifteen

<210> 249

<211> 17

<212> Protein

<213> Mus musculus

<400> 249

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

1 5 10 15

gly

<210> 250

<211> 11

<212> Protein

<213> Mus musculus

<400> 250

Arg Ile Tyr Tyr Phe Gly Arg Gly Gly Phe Asp

1 5 10

<210> 251

<211> 15

<212> Protein

<213> Mus musculus

<400> 251

Ser Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser Asn

1 5 10 15

<210> 252

<211> 7

<212> Protein

<213> Mus musculus

<400> 252

Lys Val Ser Asn Arg Phe Ser

fifteen

<210> 253

<211> 9

<212> Protein

<213> Mus musculus

<400> 253

Phe Gln Gly Ser His Val Pro Tyr Thr

fifteen

<210> 254

<211> 5

<212> Protein

<213> Mus musculus

<400> 254

Asn Ser Trp Phe Asn

fifteen

<210> 255

<211> 19

<212> Protein

<213> Mus musculus

<400> 255

Glu Ile Arg Leu Thr Ser Asp Asn Tyr Ala Ile Tyr Tyr Ala Glu Ser

1 5 10 15

Val Lys Gly

<210> 256

<211> 11

<212> Protein

<213> Mus musculus

<400> 256

Pro Glu Thr Ala Arg Ala Thr Phe Ala Tyr Trp

1 5 10

<210> 257

<211> 15

<212> Protein

<213> Mus musculus

<400> 257

Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser Asn

1 5 10 15

<210> 258

<211> 7

<212> Protein

<213> Mus musculus

<400> 258

Lys Val Phe Asn Arg Phe Ser

fifteen

<210> 259

<211> 9

<212> Protein

<213> Mus musculus

<400> 259

Phe Gln Gly Ser His Val Pro Arg Thr

fifteen

<210> 260

<211> 5

<212> Protein

<213> Mus musculus

<400> 260

Ala Tyr Tyr Met His

fifteen

<210> 261

<211> 17

<212> Protein

<213> Mus musculus

<400> 261

Arg Val Asn Pro Asn Asn Gly Gly Thr Thr Tyr Asn Gln Lys Phe Lys

1 5 10 15

gly

<210> 262

<211> 11

<212> Protein

<213> Mus musculus

<400> 262

Arg Ile Tyr Tyr Gly Tyr Phe Asp Tyr Trp Gly

1 5 10

<210> 263

<211> 15

<212> Protein

<213> Mus musculus

<400> 263

Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn

1 5 10 15

<210> 264

<211> 7

<212> Protein

<213> Mus musculus

<400> 264

Val Ala Ser Asn Leu Glu Ser

fifteen

<210> 265

<211> 9

<212> Protein

<213> Mus musculus

<400> 265

Gln Gln Ser Asn Glu Asp Pro Tyr Thr

fifteen

<210> 266

<211> 4

<212> Protein

<213> Mus musculus

<400> 266

Asp Ile Tyr Met

one

<210> 267

<211> 17

<212> Protein

<213> Mus musculus

<400> 267

Lys Ile Asp Pro Ala Asn Gly Asn Thr Lys Tyr Asp Pro Lys Phe Gln

1 5 10 15

gly

<210> 268

<211> 11

<212> Protein

<213> Mus musculus

<400> 268

Thr Gly Asp Tyr Trp Gly Gln Gly Thr Thr Val

1 5 10

<210> 269

<211> 15

<212> Protein

<213> Mus musculus

<400> 269

Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser Arg Thr

1 5 10 15

<210> 270

<211> 7

<212> Protein

<213> Mus musculus

<400> 270

Trp Ala Ser Thr Arg Glu Ser

fifteen

<210> 271

<211> 9

<212> Protein

<213> Mus musculus

<400> 271

Arg Gln Ser Tyr Asn Leu Val Thr Phe

fifteen

<210> 272

<211> 5

<212> Protein

<213> Mus musculus

<400> 272

Ser Tyr Val Met His

fifteen

<210> 273

<211> 17

<212> Protein

<213> Mus musculus

<400> 273

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

1 5 10 15

gly

<210> 274

<211> 11

<212> Protein

<213> Mus musculus

<400> 274

Arg Tyr Tyr Tyr Gly Ser Ser Gly Gly Tyr Phe

1 5 10

<210> 275

<211> 15

<212> Protein

<213> Mus musculus

<400> 275

Arg Ala Ser Lys Ser Ile Ser Lys Tyr Leu Ala Trp Tyr Gln Glu

1 5 10 15

<210> 276

<211> 7

<212> Protein

<213> Mus musculus

<400> 276

Ser Gly Ser Thr Leu Gln Ser

fifteen

<210> 277

<211> 9

<212> Protein

<213> Mus musculus

<400> 277

Gln Gln His Asn Glu Tyr Pro Tyr Thr

fifteen

<210> 278

<211> 5

<212> Protein

<213> Mus musculus

<400> 278

Gly Tyr Phe Met Asn

fifteen

<210> 279

<211> 17

<212> Protein

<213> Mus musculus

<400> 279

Arg Ile Asn Pro Tyr Asn Gly Asp Thr Phe Tyr Asn Gln Lys Phe Lys

1 5 10 15

gly

<210> 280

<211> 11

<212> Protein

<213> Mus musculus

<400> 280

Arg Ile His Tyr Tyr Tyr Gly Ser Ser Tyr Tyr

1 5 10

<210> 281

<211> 15

<212> Protein

<213> Mus musculus

<400> 281

Arg Ala Ser Lys Ser Ile Ser Lys Tyr Leu Ala Trp Tyr Gln Glu

1 5 10 15

<210> 282

<211> 7

<212> Protein

<213> Mus musculus

<400> 282

Ser Gly Ser Thr Leu Gln Ser

fifteen

<210> 283

<211> 9

<212> Protein

<213> Mus musculus

<400> 283

Gln Gln His Asn Glu Tyr Pro Trp Thr

fifteen

<210> 284

<211> 5

<212> Protein

<213> Mus musculus

<400> 284

Glu Tyr Ile Ile His

fifteen

<210> 285

<211> 17

<212> Protein

<213> Mus musculus

<400> 285

Trp Phe Tyr Pro Gly Ser Gly Ser Ile Lys Tyr Asn Glu Lys Phe Lys

1 5 10 15

asp

<210> 286

<211> 11

<212> Protein

<213> Mus musculus

<400> 286

His Glu Val Tyr Tyr Asp Tyr Asp Lys Ser Met

1 5 10

<210> 287

<211> 15

<212> Protein

<213> Mus musculus

<400> 287

Leu Tyr Ser Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln

1 5 10 15

<210> 288

<211> 7

<212> Protein

<213> Mus musculus

<400> 288

Trp Ala Ser Thr Arg Glu Ser

fifteen

<210> 289

<211> 9

<212> Protein

<213> Mus musculus

<400> 289

Gln Gln Tyr Tyr Ser Tyr Pro Tyr Thr

fifteen

<210> 290

<211> 5

<212> Protein

<213> Mus musculus

<400> 290

Asn Tyr Leu Ile Glu

fifteen

<210> 291

<211> 19

<212> Protein

<213> Mus musculus

<400> 291

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

1 5 10 15

Gly Lys Ala

<210> 292

<211> 11

<212> Protein

<213> Mus musculus

<400> 292

Thr Gly Thr Asp Tyr Trp Gly Gln Gly Thr Thr

1 5 10

<210> 293

<211> 10

<212> Protein

<213> Mus musculus

<400> 293

Val Thr Ile Ser Cys Ser Ala Ser Gln Gly

1 5 10

<210> 294

<211> 7

<212> Protein

<213> Mus musculus

<400> 294

Tyr Thr Ser Ser Leu Arg Ser

fifteen

<210> 295

<211> 9

<212> Protein

<213> Mus musculus

<400> 295

Gln Gln Tyr Ser Lys Leu Pro Arg Thr

fifteen

<210> 296

<211> 12

<212> Protein

<213> Homo sapiens

<400> 296

Phe Thr Ser Gly Glu Lys Glu Gln Val Asp Glu Trp

1 5 10

<210> 297

<211> 16

<212> Protein

<213> Homo sapiens

<400> 297

Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu Leu Gln Tyr Val Leu

1 5 10 15

<210> 298

<211> 16

<212> Protein

<213> Homo sapiens

<400> 298

Val Glu Arg Val Phe Gln Ser Asn Tyr Phe Asp Ser Thr His Asn His

1 5 10 15

<210> 299

<211> 16

<212> Protein

<213> Homo sapiens

<400> 299

Phe Gln Ser Met Gln Thr Val Phe Asn Met Asn Ala Pro Val Pro Pro

1 5 10 15

<210> 300

<211> 5

<212> Protein

<213> Mus musculus

<400> 300

Thr Asn Ala Met Asn

fifteen

<210> 301

<211> 17

<212> Protein

<213> Mus musculus

<400> 301

Arg Ile Arg Ser Lys Ser Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser

1 5 10 15

Val

<210> 302

<211> 11

<212> Protein

<213> Mus musculus

<400> 302

Asp Trp Asp Gly Phe Leu Tyr Phe Asp Tyr Trp

1 5 10

<210> 303

<211> 112

<212> Protein

<213> Mus musculus

<400> 303

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

1 5 10 15

Ala Ser Gly Phe Thr Phe Asn Thr Asn Ala Met Asn Trp Val Arg Gln

20 25 30

Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Ser

35 40 45

Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr

50 55 60

Ile Ser Arg Asp Asp Ser Gln Ser Met Leu Tyr Leu Gln Met Asn Asn

65 70 75 80

Leu Lys Thr Glu Asp Thr Ala Met Tyr Tyr Cys Val Arg Asp Trp Asp

85 90 95

Gly Phe Leu Tyr Phe Asp Tyr Trp Ala Lys His His Leu Thr Leu Phe

100 105 110

<210> 304

<211> 15

<212> Protein

<213> Mus musculus

<400> 304

Ser Val Ser Thr Ser Gly Tyr Ser Tyr Met His Trp Asn Gln Gln

1 5 10 15

<210> 305

<211> 7

<212> Protein

<213> Mus musculus

<400> 305

Leu Val Ser Asn Leu Glu Ser

fifteen

<210> 306

<211> 9

<212> Protein

<213> Mus musculus

<400> 306

Gln His Ile Arg Glu Leu Thr Arg Ser

fifteen

<210> 307

<211> 104

<212> Protein

<213> Mus musculus

<400> 307

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

1 5 10 15

Ile Ser Tyr Arg Ala Ser Lys Ser Val Ser Thr Ser Gly Tyr Ser Tyr

20 25 30

Met His Trp Asn Gln Gln Lys Pro Gly Gln Pro Pro Arg Leu Leu Ile

35 40 45

Tyr Leu Val Ser Asn Leu Glu Ser Gly Val Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His Pro Val Glu Glu

65 70 75 80

Glu Asp Ala Ala Thr Tyr Tyr Cys Gln His Ile Arg Glu Leu Thr Arg

85 90 95

Ser Glu Gly Gly Pro Ser Trp Lys

100

<210> 308

<211> 14

<212> Protein

<213> Homo sapiens

<400> 308

Pro Pro Val Asn Glu Pro Glu Thr Leu Lys Gln Gln Asn Gln

1 5 10

<210> 309

<211> 12

<212> Protein

<213> Homo sapiens

<400> 309

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

1 5 10

<---

Claims (62)

1. Use of a combination of an antibody or fragment thereof with immunological reactivity to the extracellular region of the CAPRIN-1 protein present on the surface of cancer cells and having an amino acid sequence shown in any of the even-numbered SEQ ID NOs: 2 to 30, or an amino acid sequence having 80 % or more sequence identity with this amino acid sequence, and imiquimod together or separately in combination for the treatment and/or prevention of cancer expressing the CAPRIN-1 protein on the surface of the cell membrane. 2. Use according to claim 1, wherein the antibody or fragment thereof has immunological reactivity to a partial polypeptide of the CAPRIN-1 protein, a partial polypeptide with an amino acid sequence represented by any of SEQ ID NOs: 31 to 35, 296 to 299, 308 and 309 , or an amino acid sequence having 80% or more sequence identity with that amino acid sequence. 3. Use according to claim 1 or 2, wherein the antibody is a monoclonal antibody or a polyclonal antibody. 4. Application according to any one of paragraphs. 1-3, where the antibody or fragment thereof is any of the following from (A) to (M): (A) an antibody or fragment containing a heavy chain variable region with complementarity determining regions (CDR)1 of SEQ ID NO: 36, a CDR2 of SEQ ID NO: 37 and a CDR3 of SEQ ID NO: 38, and a light chain variable region of CDR1 with SEQ ID NO: 40, CDR2 of SEQ ID NO: 41 and CDR3 of SEQ ID NO: 42 and having immunological reactivity with the CAPRIN-1 protein; (B) an antibody or fragment containing a heavy chain variable region of CDR1 of SEQ ID NO: 44, CDR2 of SEQ ID NO: 45 and CDR3 of SEQ ID NO: 46, and a light chain variable region of CDR1 of SEQ ID NO: 48, CDR2 of SEQ ID NO: 49 and CDR3 of SEQ ID NO: 50 and having immunological reactivity with the CAPRIN-1 protein; (C) an antibody or fragment containing a heavy chain variable region of CDR1 of SEQ ID NO: 52, CDR2 of SEQ ID NO: 53 and CDR3 of SEQ ID NO: 54, and a light chain variable region of CDR1 of SEQ ID NO: 56, CDR2 of SEQ ID NO: 57 and CDR3 of SEQ ID NO: 58 and having immunological reactivity with the CAPRIN-1 protein; (D) an antibody or fragment containing the heavy chain variable region of CDR1 of SEQ ID NO: 60, CDR2 of SEQ ID NO: 61 and CDR3 of SEQ ID NO: 62 and the light chain variable region of CDR1 of SEQ ID NO: 64, CDR2 with SEQ ID NO: 65 and CDR3 with SEQ ID NO: 66 and having immunological reactivity with the CAPRIN-1 protein; (E) an antibody or fragment thereof comprising a heavy chain variable region of CDR1 of SEQ ID NO: 170, CDR2 of SEQ ID NO: 171 and CDR3 of SEQ ID NO: 172, and a light chain variable region of CDR1 of SEQ ID NO: 173 , CDR2 of SEQ ID NO: 174 and CDR3 of SEQ ID NO: 175 and having immunological reactivity with the CAPRIN-1 protein; (F) an antibody or fragment thereof comprising a heavy chain variable region of CDR1 of SEQ ID NO: 176, CDR2 of SEQ ID NO: 177 and CDR3 of SEQ ID NO: 178, and a light chain variable region of CDR1 of SEQ ID NO: 179 , CDR2 of SEQ ID NO: 180 and CDR3 of SEQ ID NO: 181 and having immunological reactivity with the CAPRIN-1 protein; (G) an antibody or fragment thereof comprising a heavy chain variable region of CDR1 of SEQ ID NO: 182, CDR2 of SEQ ID NO: 183, and CDR3 of SEQ ID NO: 184, and a light chain variable region of CDR1 of SEQ ID NO: 185, CDR2 of SEQ ID NO: 186 and CDR3 of SEQ ID NO: 187 and having immunological reactivity with the CAPRIN-1 protein; (H) an antibody or fragment thereof comprising a heavy chain variable region of CDR1 of SEQ ID NO: 188, CDR2 of SEQ ID NO: 189, and CDR3 of SEQ ID NO: 190, and a light chain variable region of CDR1 of SEQ ID NO: 191 , CDR2 of SEQ ID NO: 192 and CDR3 of SEQ ID NO: 193 and having immunological reactivity with the CAPRIN-1 protein; (I) an antibody or fragment thereof comprising a heavy chain variable region of CDR1 of SEQ ID NO: 146, CDR2 of SEQ ID NO: 147 and CDR3 of SEQ ID NO: 148, and a light chain variable region of CDR1 of SEQ ID NO: 149 , CDR2 of SEQ ID NO: 150 and CDR3 of SEQ ID NO: 151 and having immunological reactivity with the CAPRIN-1 protein; (J) an antibody or fragment thereof comprising a heavy chain variable region of CDR1 of SEQ ID NO: 272, CDR2 of SEQ ID NO: 273 and CDR3 of SEQ ID NO: 274, and a light chain variable region of CDR1 of SEQ ID NO: 275 , CDR2 of SEQ ID NO: 276 and CDR3 of SEQ ID NO: 277 and having immunological reactivity with the CAPRIN-1 protein; (K) An antibody or fragment thereof comprising a heavy chain variable region of CDR1 of SEQ ID NO: 290, CDR2 of SEQ ID NO: 291 and CDR3 of SEQ ID NO: 292, and a light chain variable region of CDR1 of SEQ ID NO: 293 , CDR2 of SEQ ID NO: 284 and CDR3 of SEQ ID NO: 295 and having immunological reactivity with the CAPRIN-1 protein; (L) an antibody or fragment thereof comprising a heavy chain variable region of CDR1 of SEQ ID NO: 301, CDR2 of SEQ ID NO: 302 and CDR3 of SEQ ID NO: 303, and a light chain variable region of CDR1 of SEQ ID NO: 305 , CDR2 of SEQ ID NO: 306 and CDR3 of SEQ ID NO: 307 and having immunological reactivity with the CAPRIN-1 protein; and (M) an antibody or fragment thereof comprising a heavy chain variable region of CDR1 of SEQ ID NO: 134, a CDR2 of SEQ ID NO: 135, and a CDR3 of SEQ ID NO: 136, and a light chain variable region of CDR1 of SEQ ID NO: 137 , CDR2 of SEQ ID NO: 138 and CDR3 of SEQ ID NO: 139 and having immunological reactivity with the CAPRIN-1 protein. 5. Application according to any one of paragraphs. 1-4, where the antibody or fragment thereof is any of the following from (a) to (al): (a) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 39 and a light chain variable region with the amino acid sequence of SEQ ID NO: 43; (b) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 47 and a light chain variable region with the amino acid sequence of SEQ ID NO: 51; (c) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 55 and a light chain variable region with the amino acid sequence of SEQ ID NO: 59; (d) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 63 and a light chain variable region with the amino acid sequence of SEQ ID NO: 67; (e) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 68 and a light chain variable region with the amino acid sequence of SEQ ID NO: 69; (f) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 70 and a light chain variable region with the amino acid sequence of SEQ ID NO: 71; (g) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 72 and a light chain variable region with the amino acid sequence of SEQ ID NO: 73; (h) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 74 and a light chain variable region with the amino acid sequence of SEQ ID NO: 75; (i) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 76 and a light chain variable region with the amino acid sequence of SEQ ID NO: 77; (j) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 78 and a light chain variable region with the amino acid sequence of SEQ ID NO: 79; (k) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 80 and a light chain variable region with the amino acid sequence of SEQ ID NO: 81; (l) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 82 and a light chain variable region with the amino acid sequence of SEQ ID NO: 83; (m) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 84 and a light chain variable region with the amino acid sequence of SEQ ID NO: 85; (n) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 86 and a light chain variable region with the amino acid sequence of SEQ ID NO: 87; (o) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 88 and a light chain variable region with the amino acid sequence of SEQ ID NO: 89; (p) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 90 and a light chain variable region with the amino acid sequence of SEQ ID NO: 91; (q) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 92 and a light chain variable region with the amino acid sequence of SEQ ID NO: 93; (r) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 94 and a light chain variable region with the amino acid sequence of SEQ ID NO: 95; (s) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 96 and a light chain variable region with the amino acid sequence of SEQ ID NO: 97; (t) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 98 and a light chain variable region with the amino acid sequence of SEQ ID NO: 99; (u) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 100 and a light chain variable region with the amino acid sequence of SEQ ID NO: 101; (v) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 102 and a light chain variable region with the amino acid sequence of SEQ ID NO: 103; (w) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 104 and a light chain variable region with the amino acid sequence of SEQ ID NO: 105; (x) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 106 and a light chain variable region with the amino acid sequence of SEQ ID NO: 107; (y) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 108 and a light chain variable region with the amino acid sequence of SEQ ID NO: 109; (z) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 110 and a light chain variable region with the amino acid sequence of SEQ ID NO: 111; (aa) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 112 and a light chain variable region with the amino acid sequence of SEQ ID NO: 113; (ab) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 114 and a light chain variable region with the amino acid sequence of SEQ ID NO: 115; (ac) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 116 and a light chain variable region with the amino acid sequence of SEQ ID NO: 117; (ad) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 118 and a light chain variable region with the amino acid sequence of SEQ ID NO: 119; (ae) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 120 and a light chain variable region with the amino acid sequence of SEQ ID NO: 121; (af) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 122 and a light chain variable region with the amino acid sequence of SEQ ID NO: 123; (ag) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 124 and a light chain variable region with the amino acid sequence of SEQ ID NO: 125; (ah) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 126 and a light chain variable region with the amino acid sequence of SEQ ID NO: 127; (ai) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 128 and a light chain variable region with the amino acid sequence of SEQ ID NO: 129; (aj) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 130 and a light chain variable region with the amino acid sequence of SEQ ID NO: 131; (ak) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 132 and a light chain variable region with the amino acid sequence of SEQ ID NO: 133; and (al) an antibody or fragment thereof comprising a heavy chain variable region with the amino acid sequence of SEQ ID NO: 300 and a light chain variable region with the amino acid sequence of SEQ ID NO: 304. 6. Application according to any one of paragraphs. 1-5, wherein the antibody is a human antibody, a humanized antibody, a chimeric antibody, or a single chain antibody. 7. Application according to any one of paragraphs. 1-6, where the malignant tumor is basal cell carcinoma, Paget's disease, skin cancer, breast cancer, kidney cancer, pancreatic cancer, colon cancer, lung cancer, brain tumor, gastric cancer, uterine cancer, ovarian cancer, cancer prostate cancer, bladder cancer, esophageal cancer, leukemia, lymphoma, liver cancer, gallbladder cancer, sarcoma, mastocytoma, adrenal cortex cancer, Ewing's tumor, Hodgkin's lymphoma, mesothelioma, multiple myeloma, testicular cancer, thyroid cancer, or head cancer, and neck. 8. Application according to any one of paragraphs. 1-7 wherein the dosage form of imiquimod is a transdermal formulation. 9. The use of imiquimod to increase the drug efficacy of a pharmaceutical composition for the treatment and / or prevention of a malignant tumor, containing as an active ingredient an antibody or its fragment with immunological reactivity to the extracellular region of the CAPRIN-1 protein present on the surface of malignant tumor cells and having an amino acid sequence, shown in any of the even numbered SEQ ID NOs: 2 to 30, or an amino acid sequence having 80% or more sequence identity with that amino acid sequence, wherein the cancer expresses the CAPRIN-1 protein on the surface of the cell membrane. 10. Use of an antibody or fragment thereof with immunological reactivity to the extracellular region of the CAPRIN-1 protein present on the surface of cancer cells and having an amino acid sequence shown in any of the even-numbered SEQ ID NOs: 2 to 30, or an amino acid sequence having 80% or more sequence identity with this amino acid sequence, to increase the drug efficacy of a pharmaceutical composition for the treatment and/or prevention of a malignant tumor containing imiquimod as an active ingredient, where the malignant tumor expresses the CAPRIN-1 protein on the surface of the cell membrane. 11. A method for treating and/or preventing cancer, comprising administering to an individual an antibody or fragment thereof having immunological reactivity to the extracellular region of the CAPRIN-1 protein present on the surface of cancer cells and having the amino acid sequence shown in any of the even-numbered SEQ ID NOs: 2 to 30, or an amino acid sequence having 80% or more sequence identity with that amino acid sequence, and imiquimod together or separately, wherein the cancer expresses the CAPRIN-1 protein on the cell membrane surface.