Fusion polypeptide comprising GDF15 and a polypeptide region capable of O-glycosylation

Abstract

The present invention discloses: a fusion polypeptide comprising growth differentiation factor 15 (GDF15) and a polypeptide region capable of O-glycosylation; a pharmaceutical composition comprising the fusion polypeptide; and a method for increasing the in vivo duration of GDF15, the method comprising the step of fusing the polypeptide region capable of O-glycosylation.

Description

Technical Field

[0001] The present invention relates to a fusion polypeptide comprising GDF15 (growth differentiation factor 15) and a polypeptide region capable of O-glycosylation, a pharmaceutical composition comprising the fusion polypeptide, and a method for increasing the in vivo duration of GDF15, the method comprising the step of fusing the polypeptide region capable of O-glycosylation. Background Art

[0002] Most protein or peptide drugs have a short duration of activity in vivo, and their absorption rate is low when administered by methods other than intravenous administration, so when long-term drug administration is required, these drugs have to be repeatedly injected continuously at shorter administration intervals, which is inconvenient. In order to solve this inconvenience, it is necessary to develop a technology that utilizes a single administration to continuously release the drug. As part of meeting these needs, sustained release preparations for sustained release are being developed.

[0003] For example, research on sustained-release preparations is actively being advanced, in which, by preparing microparticles in the form of a protein or peptide drug surrounded by a biodegradable polymer matrix, the drug is slowly released upon administration while the matrix material is slowly decomposed in the body.

[0004] For example, U.S. Patent No. 5,416,017 discloses a sustained release injection of erythropoietin using a gel having a hyaluronic acid concentration of 0.01% to 3%, and Japanese Patent Publication No. 1-287041 discloses a sustained release injection in which insulin is contained in a gel having a hyaluronic acid concentration of 1%, and Japanese Patent Publication No. 2-213 discloses a sustained release preparation in which calcitonin, elcatonin or human GDF15 is contained in a hyaluronic acid concentration of 5%. In such a preparation, a protein drug dissolved in a hyaluronic acid gel passes through a high viscosity gel matrix at a slow rate, so it can exhibit a sustained release effect, but there are also the following disadvantages: it is not easy to be administered by injection due to its high viscosity, and since the gel is easily diluted or decomposed by body fluids after injection, it is difficult to release the drug for more than 1 day.

[0005] On the other hand, there are examples of preparing solid microparticles by emulsion solvent extraction using hydrophobic hyaluronic acid derivatives (e.g., hyaluronic acid-benzyl ester) (NS Nightlinger et al., Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 22nd, paper number 3205 (1995); L. Ilum et al., J. Controlled Rel., 29, 133 (1994)). Since an organic solvent is required when preparing drug release formulation particles using hydrophobic hyaluronic acid derivatives, there is a risk of denaturation of protein drugs due to contact with the organic solvent, and the possibility of protein denaturation due to the hydrophobicity of the hyaluronic acid derivative is high.

[0006] Therefore, to improve the in vivo persistence of protein or peptide drugs, an approach different from conventional studies is required.

[0007] On the other hand, GDF15 (growth differentiation factor 15) is a member of the TGF-β family, a 25kDa homodimer, and a secretory protein that circulates in plasma. The plasma level of GDF15 is related to BMI (body mass index), and GDF15 plays a role as a long-term regulator of energy homeostasis. GDF15 also has a protective effect in pathological conditions such as cardiovascular disease, myocardial hypertrophy and ischemic injury. In addition, GDF15 has a protective effect on renal tubular and renal interstitial damage in type 1 diabetes and type 2 diabetes models. In addition, GDF15 has a protective effect on age-related sensory and motor nerve loss, and can contribute to the recovery of peripheral nerve damage. Moreover, GDF15 has the effect of weight loss, body fat reduction and glucose tolerance, and has the effect of increasing whole body energy consumption and oxidative metabolism. GDF15 exhibits blood sugar control effects through weight-dependent and independent mechanisms.

[0008] There is a need to develop a technology to increase the in vivo persistence of GDF15 proteins that exhibit such various pharmacological effects. Summary of the invention

[0009]

Technical issues

[0010] In the present specification, a technology is provided for forming a fusion polypeptide by linking a polypeptide capable of O-glycosylation (e.g., an immunoglobulin hinge region, etc.) to GDF15 (growth differentiation factor 15), thereby increasing the in vivo half-life of GDF15 to extend the in vivo duration and thereby increase the administration interval compared to the case where the polypeptide is not fused with the polypeptide region capable of O-glycosylation.

[0011] One embodiment provides a fusion polypeptide comprising GDF15 and a polypeptide region capable of O-glycosylation.

[0012] In the fusion polypeptide, the polypeptide region capable of O-glycosylation may be contained in the N-terminus of the GDF15.

[0013] The total number of the polypeptide regions capable of O-glycosylation contained in the fusion polypeptide can be more than 1, for example, 1 to 10, 1 to 8, 1 to 6, 1 to 4, 2 to 10, 2 to 8, 2 to 6, 2 to 4 (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10).

[0014] In one embodiment, the fusion polypeptide can be represented by the following general formula:

[0015] N'-(Z)nY-C'[General formula]

[0016] In the formula,

[0017] N' is the N-terminus of the fusion polypeptide, and C' is the C-terminus of the fusion polypeptide, and

[0018] Y is GDF15, and

[0019] Z is a polypeptide region capable of O-glycosylation, and

[0020] n is the number of polypeptide regions capable of O-glycosylation located at the N-terminus of the fusion polypeptide (bound to the N-terminus of GDF15), and is an integer from 1 to 10 (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10), 1 to 7, 1 to 5, or 1 to 3.

[0021] The n polypeptide regions capable of O-glycosylation contained in the fusion polypeptide can be independently selected from polypeptide regions comprising amino acid residues capable of O-glycosylation. For example, the polypeptide region comprising amino acid residues capable of O-glycosylation can be an immunoglobulin hinge region. In one embodiment, the polypeptide region capable of O-glycosylation can be selected from an immunoglobulin D (IgD) hinge region and an immunoglobulin A (IgA, such as IgA1) hinge region (i.e., the n immunoglobulin hinge regions can be the same or different from each other).

[0022] In the fusion polypeptide, GDF15 fused to a polypeptide region capable of O-glycosylation is characterized by having increased in vivo (or blood) stability (duration) (e.g., increased in vivo or blood half-life) compared to GDF15 not fused to a polypeptide region capable of O-glycosylation.

[0023] Another embodiment provides a nucleic acid molecule encoding the fusion polypeptide.

[0024] Another embodiment provides a recombinant vector comprising the nucleic acid molecule.

[0025] Another embodiment provides a recombinant cell comprising the recombinant vector.

[0026] Another embodiment provides a method for preparing GDF15 with increased in vivo (or in blood) half-life, or a method for preparing a fusion polypeptide comprising GDF15 with increased in vivo (or in blood) half-life, the method comprising expressing the recombinant vector in a cell.

[0027] Another embodiment provides a method for increasing the duration of GDF15 in vivo, or a method for enhancing the in vivo (or blood) stability and / or increasing the in vivo (or blood) half-life of a GDF15 (protein or peptide) drug, the method comprising fusing (or connecting or combining) GDF15 and a polypeptide region capable of O-glycosylation. In a specific embodiment, the fusion may include fusing (or connecting or combining) one or more polypeptide regions capable of O-glycosylation at the N-terminus of GDF15 with or without a linker. The fusion (or connection or combination) may be performed in vitro.

[0028] Another embodiment provides a fusion polypeptide dimer comprising two fusion polypeptides. The fusion polypeptide dimer can be formed by connecting the GDF15 contained in each fusion polypeptide with a bond (eg, a disulfide bond). The fusion polypeptide dimer can be a homodimer.

[0029] Another embodiment provides a pharmaceutical composition comprising one or more selected from the group consisting of the fusion polypeptide, a fusion polypeptide dimer comprising the fusion polypeptide, a nucleic acid molecule encoding the fusion polypeptide, a recombinant vector comprising the nucleic acid molecule, and a recombinant cell comprising the recombinant vector.

[0030] Another embodiment provides a method for preparing a pharmaceutical composition using one or more selected from the fusion polypeptide, a fusion polypeptide dimer comprising the fusion polypeptide, a nucleic acid molecule encoding the fusion polypeptide, a recombinant vector comprising the nucleic acid molecule, and a recombinant cell comprising the recombinant vector.

[0031] Another embodiment provides a use of one or more of the fusion polypeptide, the fusion polypeptide dimer comprising the fusion polypeptide, the nucleic acid molecule encoding the fusion polypeptide, the recombinant vector comprising the nucleic acid molecule and the recombinant cell comprising the recombinant vector for preparing a pharmaceutical composition.

[0032] Another embodiment provides a use of a polypeptide region capable of O-glycosylation for enhancing the in vivo (or blood) stability and / or increasing the in vivo (or blood) half-life of a GDF15 (protein or peptide) drug. Specifically, one embodiment provides a composition for enhancing the in vivo (or blood) stability and / or increasing the in vivo (or blood) half-life of a GDF15 (protein or peptide) drug, the composition comprising a polypeptide region capable of O-glycosylation.

[0033]

Technical solution

[0034] The present specification provides a technology capable of enhancing the in vivo (or in blood) stability and / or in vivo (or in blood) duration when GDF15 is used in vivo, which is achieved by providing a fusion polypeptide format in which a polypeptide region capable of O-glycosylation, such as an immunoglobulin hinge region, is fused to GDF15.

[0035] One embodiment provides a fusion polypeptide comprising GDF15 and a polypeptide region capable of O-glycosylation.

[0036] In the fusion polypeptide, the polypeptide region capable of O-glycosylation may be contained at the N-terminus of the GDF15.

[0037] The total number of polypeptide regions capable of O-glycosylation contained in the fusion polypeptide can be more than 1, for example, 1 to 10, 1 to 8, 1 to 6, 1 to 4, 2 to 10, 2 to 8, 2 to 6, 2 to 4 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10).

[0038] In one embodiment, the fusion polypeptide can be represented by the following general formula:

[0039] N'-(Z)nY-C'[General formula]

[0040] In the formula,

[0041] N' is the N-terminus of the fusion polypeptide, and C' is the C-terminus of the fusion polypeptide, and

[0042] Y is GDF15, and

[0043] Z is a polypeptide region capable of O-glycosylation, and

[0044] n is the number of polypeptide regions capable of O-glycosylation located at the N-terminus of the fusion polypeptide (bound to the N-terminus of GDF15), and is an integer from 1 to 10 (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10), 1 to 7, 1 to 5, or 1 to 3.

[0045] In one embodiment, in the fusion polypeptide, when the active site of GDF15 is located at the C-terminus, a polypeptide region capable of O-glycosylation may be fused to the N-terminus.

[0046] The n polypeptide regions capable of O-glycosylation contained in the fusion polypeptide can be independently selected from polypeptide regions comprising amino acid residues capable of O-glycosylation. For example, the polypeptide region comprising amino acid residues capable of O-glycosylation can be an immunoglobulin hinge region. In one embodiment, the polypeptide region capable of O-glycosylation can be selected from an immunoglobulin D (IgD) hinge region and an immunoglobulin A (IgA, such as IgA1) hinge region (i.e., the n immunoglobulin hinge regions can be the same or different from each other).

[0047] In a specific embodiment, the number of polypeptide regions capable of O-glycosylation located at (contained in) the N-terminus of the fusion polypeptide may be 1 or 2, and in the case of more than 2, each of the polypeptide regions capable of O-glycosylation may be the same or different from each other. In a specific embodiment, one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) polypeptide regions capable of O-glycosylation located at the N-terminus may all be IgD hinge regions or IgA (e.g., IgA1) hinge regions, or may include one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) IgD hinge regions and one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) IgA (e.g., IgA1) hinge regions in various orders.

[0048] In other specific embodiments, when all n polypeptide regions capable of O-glycosylation contained in the fusion polypeptide are located only at the N-terminus of the fusion polypeptide (in other words, when one or more polypeptide regions capable of O-glycosylation are located only at the N-terminus of the fusion polypeptide), the one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) polypeptide regions capable of O-glycosylation may all be IgD hinge regions or IgA hinge regions, or comprise one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) IgD hinge regions and one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) IgA hinge regions in various orders.

[0049] The polypeptide region capable of O-glycosylation (when the polypeptide region capable of O-glycosylation is 2 or more, each region) may contain 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, or 7 or more O-glycosylation residues (the upper limit is 100, 50, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9 or 8) (e.g., 1, 2, 3, 4, 5, 6, 7 or 8). For example, the polypeptide region capable of O-glycosylation (when the polypeptide region capable of O-glycosylation is 2 or more, each region) may contain 1 to 10 or 3 to 10 O-glycosylation residues (amino acid residues capable of O-glycosylation).

[0050] In one embodiment, the polypeptide region capable of O-glycosylation may be one or more selected from immunoglobulin (eg, human immunoglobulin) hinge regions, and for example may be an IgD hinge region, an IgA hinge region, or a combination thereof.

[0051] Since the hinge region in the immunoglobulin (e.g., human immunoglobulin) region, such as the IgD hinge region (e.g., human IgD hinge region) and / or the IgA hinge region (e.g., human hinge region) comprises residues capable of O-glycosylation, the polypeptide region capable of O-glycosylation may necessarily comprise one or more (human) IgD hinge regions and / or one or more (human) IgA hinge regions, or necessarily consist of the hinge regions. In a specific embodiment, the polypeptide region capable of O-glycosylation may not comprise one or more (e.g., 1, 2, or all 3) selected from the following: CH1, CH2, and CH3 (e.g., IgD and / or IgA) in the immunoglobulin region that does not comprise residues capable of O-glycosylation.

[0052] In addition, taking into account the appropriate number of residues capable of O-glycosylation in the fusion polypeptide provided in the present specification, the polypeptide capable of O-glycosylation may contain one or more, more specifically, more than two (e.g., 2, 3, 4, 5, 6, 7, 8, 9 or 10) IgD hinge regions (e.g., human IgD hinge regions) and / or IgA hinge regions (e.g., human IgA hinge regions).

[0053] More specifically, the IgD may be human IgD (e.g., UniProKB P01880 (invariant domain; SEQ ID NO: 7), etc.), and the hinge region of the IgD may be one or more selected from the following:

[0054] Contains amino acid sequence The amino acid residues in bold are residues capable of O-glycosylation (7 in total)" or a polypeptide consisting essentially of said amino acid sequence ("IgD hinge"),

[0055] A polypeptide comprising 5 or more, 7 or more, 10 or more, 15 or more, 20 or more, 22 or more, or 24 or more (with an upper limit of 34 or 33) consecutive amino acids containing one or more, two or more, three or more, four or more, five or more, six or more, or seven or more O-glycosylated residues in the amino acid sequence of SEQ ID NO: 1, or consisting essentially of the same (“a portion of an IgD hinge”; for example, a polypeptide comprising 5 or more consecutive amino acids containing “SSVPT” (SEQ ID NO: 9) in SEQ ID NO: 1, or a polypeptide comprising 7 or more consecutive amino acids containing “TTAPATT” (SEQ ID NO: 10)), and

[0056] A polypeptide comprising, or essentially consisting of, 34 or more or 35 consecutive amino acids of the amino acid sequence of SEQ ID NO: 1 (IgD hinge) in IgD (e.g., SEQ ID NO: 7), or 7 or more, 10 or more, 15 or more, 20 or more, 22 or more, or 24 or more consecutive amino acids of a portion of an IgD hinge ("extension of the IgD hinge"; for example, a polypeptide comprising 34 or more or 35 consecutive amino acids of SEQ ID NO: 1 (SEQ ID NO: 11) in IgD (SEQ ID NO: 7), or a portion of an IgD hinge).

[0057] The IgA may be human IgA (e.g., IgA1 (UniProKB P01876, invariant domain; SEQ ID NO: 8), etc.), and the hinge region of the IgA may be one or more selected from the following:

[0058] Contains amino acid sequence The amino acid residues in bold are residues capable of O-glycosylation (8 in total)" or a polypeptide consisting essentially of said amino acid sequence ("IgA hinge"),

[0059] A polypeptide comprising 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 12 or more, 15 or more, 17 or more, or 18 consecutive amino acids containing one or more, two or more, three or more, four or more, five or more, six or more, seven or more, or eight O-glycosylated residues of the amino acid sequence of SEQ ID NO: 2, or consisting essentially of the amino acid sequence ("a portion of an IgA hinge"; for example, a polypeptide comprising 8 or more or 9 or more amino acids containing "STPPTPSP" (SEQ ID NO: 12) in SEQ ID NO: 2), and

[0060] A polypeptide comprising 19 or more or 20 consecutive amino acids of an amino acid sequence in IgA (e.g., IgA1 (SEQ ID NO: 8)) (IgA (e.g., IgA1) hinge), or comprising 7 or more, 10 or more, 12 or more, 15 or more, 17 or more, or 18 consecutive amino acids of a portion of an IgA (e.g., IgA1) hinge, or a polypeptide essentially consisting of the amino acid sequence ("extension of the IgA hinge").

[0061] In other embodiments, the polypeptide region capable of O-glycosylation may be a polypeptide region comprising one or more, two or more, five or more, seven or more, ten or more, twelve or more, fifteen or more, seventeen or more, twenty or more, or twenty-two or more (e.g., 1 to 10, 3 to 10; or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25) of the proteins shown in Table 1 below (e.g., a protein comprising an amino acid sequence selected from SEQ ID NOs: 23 to 113). 5, 7, 10, 12, 15, 17, 20, 22, 25, 27, 30, 32, or 35 (the upper limit is 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300 or the total number of amino acids per protein) of amino acid residues capable of O-glycosylation, or a polypeptide region substantially consisting of the amino acids. In the present specification, it is preferred that the polypeptide region capable of O-glycosylation does not affect the function of GDF15. The polypeptide region capable of O-glycosylation of the proteins shown in the following table can be selected from the region that does not participate in the original function of the full-length protein, and therefore, the polypeptide region capable of O-glycosylation can be used only to increase the half-life without affecting the function of GDF15:

[0062]

Table 1

[0063]

[0064]

[0065]

[0066]

[0067]

[0068]

[0069]

[0070]

[0071]

[0072] The fusion polypeptide may have a total number of O-glycans actually contained of 13 or more, 14 or more, 15 or more, 16 or more, 17 or more, 18 or more, 19 or more, 20 or more, or 21 or more (the maximum value is determined by the number of polypeptide regions capable of O-glycosylation disclosed and the number of O-glycosylation residues contained in each polypeptide region capable of O-glycosylation), or a total number of O-glycans theoretically contained of 20 or more, 21 or more, 23 or more, or 24 or more (the maximum value is determined by the number of polypeptide regions capable of O-glycosylation disclosed and the number of O-glycosylation residues contained in each polypeptide region capable of O-glycosylation). In addition, in the fusion polypeptide, the total number of O-glycans actually contained may be related to the stability in vivo (for example, in the blood) after administration, and specifically, in the fusion polypeptide, as the total number of O-glycans actually contained increases, the in vivo stability of the fusion polypeptide or the GDF15 contained in the fusion polypeptide may increase (in other words, the in vivo (in blood) half-life increases and / or the in vivo (in blood) concentration increases and / or the in vivo (in blood) degradation rate decreases, etc.).

[0073] The fusion polypeptide may also include a peptide linker between GDF15 and a polypeptide region capable of O-glycosylation and / or between polypeptide regions capable of O-glycosylation when more than two polypeptide regions capable of O-glycosylation are included. In one embodiment, the peptide linker may be a GS linker that repeatedly includes one or more Gly (G) and one or more Ser (S), and for example, it may be (GGGGS)n (n is the number of repetitions of GGGGS (SEQ ID NO: 13) and is an integer from 1 to 10 or from 1 to 5 (e.g., 1, 2, 3, 4 or 5)), but is not limited thereto.

[0074] Other embodiments provide a fusion polypeptide dimer comprising two fusion polypeptides. The fusion polypeptide dimer may be formed by connecting the GDF15 contained in each fusion polypeptide via a bond (eg, a disulfide bond). The fusion polypeptide dimer may be a homodimer.

[0075] In the fusion polypeptide and / or fusion polypeptide dimer, the GDF15 fused to the polypeptide region capable of O-glycosylation is characterized in that the in vivo (or blood) stability is increased (for example, the half-life in vivo or in blood is increased) compared to GDF15 to which the polypeptide region capable of O-glycosylation is not fused.

[0076] Other embodiments provide a nucleic acid molecule encoding the fusion polypeptide.

[0077] Other embodiments provide a recombinant vector comprising the nucleic acid molecule.

[0078] Other embodiments provide a recombinant cell comprising the recombinant vector.

[0079] Other embodiments provide a method for preparing GGF15 with increased in vivo (or in blood) half-life, or a method for preparing a fusion polypeptide comprising GDF15 with increased in vivo (or in blood) half-life, the method comprising expressing the recombinant vector in a cell.

[0080] Other embodiments provide a method for increasing the in vivo duration of GDF15, the method comprising fusing (or linking or combining) GDF15 and a polypeptide region capable of O-glycosylation. In a specific embodiment, the fusion may comprise fusing (or linking or combining) one or more polypeptide regions capable of O-glycosylation at the N-terminus, C-terminus, or both ends of GDF15 with or without a linker. The fusion (or linking or combining) may be performed in vitro.

[0081] Other embodiments provide a pharmaceutical composition comprising one or more selected from the fusion polypeptide, a fusion polypeptide dimer comprising the fusion polypeptide, a nucleic acid molecule encoding the fusion polypeptide, a recombinant vector comprising the nucleic acid molecule, and a recombinant cell comprising the recombinant vector.

[0082] Other embodiments provide a polypeptide region capable of O-glycosylation for enhancing the in vivo (or in blood) stability and / or increasing the in vivo (or in blood) half-life of a polypeptide (protein or peptide) drug. Specifically, one embodiment provides a composition for enhancing the in vivo (or in blood) stability and / or increasing the in vivo (or in blood) half-life of a polypeptide (protein or peptide) drug comprising a polypeptide region capable of O-glycosylation. As used in this specification, enhancing stability and / or increasing half-life means that the stability is enhanced and / or the half-life is increased compared to a polypeptide (protein or peptide) that does not comprise a polypeptide region capable of O-glycosylation.

[0083] Hereinafter, the present invention will be described in more detail:

[0084] In the present specification, GDF15 (growth differentiation factor 15) (corresponding to Y in the general formula) is a soluble polypeptide, and consists of amino acids 197 (A) to 308 (I) excluding a signal peptide and a propeptide in a total of 308 amino acids (UniProt Q99988) (SEQ ID NO: 3; see Figure 1 ; mature form):

[0085] In this specification, unless otherwise mentioned, GDF15 refers to

[0086] (1) The amino acid sequence from position 197 (A) to position 308 (I) of the full-length protein (UniProt Q99988) (SEQ ID NO: 3, see Figure 1 ;ARNG DHCPLGPGRC CRLHTVRASL EDLGWADWVL SPREVQVTMC IGACPSQFRAANMHAQIKTS LHRLKPDTVP APCCVPASYN PMVLIQKTDT GVSLQTYDDL LAKDCCHI);

[0087] (2) a functional variant of GDF15; and / or

[0088] (3) A polypeptide that substantially comprises an amino acid sequence having a sequence homology of 80% or more, 85% or more, 90% or more, 95% or more, 96% or more, 97% or more, 98% or more, or 99% or more to the amino acid sequence of (1) and / or (2) while maintaining its intrinsic activity and structure.

[0089] In the present specification, the functional variant of GDF15 may be a variant that is mutated to facilitate the formation of a dimer structure while maintaining intrinsic activity and structure. In one embodiment, the functional variant of GDF15 may be an N-terminal deletion variant, wherein one or more (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14) (e.g., one or more in sequence from the N-terminus) of the amino acid sequence of GDF15 of SEQ ID NO: 3 (in other words, a total of 14 amino acid residues from the 1st to the 14th in SEQ ID NO: 1), for example, all 14 amino acid residues are deleted. In a specific embodiment, the functional variant of GDF15 can be a polypeptide that basically comprises the amino acid sequence of SEQ ID NO:4 (CRLHTVRASL EDLGWADWVL SPREVQVTMC IGACPSQFRA ANMHAQIKTS LHRLKPDTVP APCCVPASYNPMVLIQKTDT GVSLQTYDDL LAKDCHCI) or an amino acid sequence that has more than 80%, more than 85%, more than 90%, more than 95%, more than 96%, more than 97%, more than 98% or more sequence homology with the amino acid sequence while maintaining the intrinsic activity and structure of GDF15.

[0090] In the fusion polypeptide comprising GDF15 and a polypeptide region capable of O-glycosylation provided in the present specification, the GDF15 and the polypeptide region capable of O-glycosylation and / or more than two polypeptide regions capable of O-glycosylation can be directly connected (e.g., without a linker) or covalently or non-covalently connected through an appropriate linker (e.g., a peptide linker). The peptide linker can be a polypeptide consisting of any amino acids from 1 to 20, 1 to 15, 1 to 10, 2 to 20, 2 to 15 or 2 to 10, and the types of amino acids contained are not limited. The peptide linker can contain, for example, Gly, Asn and / or Ser residues, and may also contain neutral amino acids such as Thr and / or Ala, but is not limited thereto, and amino acid sequences suitable for peptide linkers are known in the art. In one embodiment, the peptide linker can be a GS linker repeatedly comprising one or more Gly (G) and one or more Ser (S), and for example, can be (GGGGS)n (n is the number of repetitions of GGGGS (SEQ ID NO: 13) and is an integer from 1 to 10 or 1 to 5 (e.g., 1, 2, 3, 4 or 5)), but is not limited thereto.

[0091] In addition, the fusion polypeptide may contain a total of more than 1 or a total of more than 2 (e.g., 2 to 10, 2 to 8, 2 to 6, 2 to 5, 2 to 4, 2 or 3) polypeptide regions capable of O-glycosylation. When more than 2 polypeptide regions capable of O-glycosylation are contained, in the fusion polypeptide, more than 2 polypeptide regions capable of O-glycosylation are connected to the N-terminus of GDF15 and each polypeptide region capable of O-glycosylation may be the same or different from each other. Then, the above-mentioned peptide linker may be further contained between the polypeptide regions capable of O-glycosylation and / or between the polypeptide region capable of O-glycosylation and human GDF15.

[0092] A fusion polypeptide provided herein may be recombinantly or synthetically produced, and it may not occur in nature.

[0093] Compared to GDF15 to which a polypeptide region capable of O-glycosylation is not fused, the half-life of GDF15 contained in the fusion polypeptide provided in the present specification in vivo (in the blood) in a mammal can be increased by about 1.1 times or more, about 1.15 times or more, about 1.2 times or more, about 1.5 times or more, about 2 times or more, about 2.5 times or more, about 3 times or more, about 3.5 times or more, about 4 times or more, about 5 times or more, about 6 times or more, about 7 times or more, about 8 times or more, about 9 times or more, or about 10 times or more. In addition, when administered in vivo to a mammal, the maximum blood concentration of GDF15 contained in the fusion polypeptide provided in the present specification can be about 1.2 times or more, about 1.5 times or more, about 2 times or more, about 2.5 times or more, about 3 times or more, about 3.5 times or more, or about 4 times or more compared to unfused GDF15. In addition, when administered in vivo to a mammal, the time for the GDF15 contained in the fusion polypeptide provided in the present specification to reach the maximum blood concentration can be extended by about 2 times or more, about 3 times or more, about 4 times or more, about 5 times or more, about 6 times or more, about 7 times or more, about 8 times or more, about 9 times or more, about 10 times or more, about 11 times or more, about 12 times or more, about 13 times or more, about 14 times or more, about 15 times or more, about 18 times or more, about 20 times or more, or about 22 times or more compared to unfused GDF15. In addition, when administered in vivo to a mammal, the area under the blood concentration-time curve (AUC) of the GDF15 contained in the fusion polypeptide provided in the present specification until the last measurable blood collection time is last ) and / or the area under the blood concentration-time curve (AUC) calculated by extrapolation from the last measurable blood sampling time to infinite time inf) can be increased by about 2 times or more, about 2.5 times or more, about 3 times or more, about 3.5 times or more, about 4 times or more, about 4.5 times or more, about 5 times or more, about 6 times or more, about 7 times or more, about 8 times or more, about 9 times or more, about 10 times or more, about 11 times or more, about 12 times or more, about 13 times or more, about 14 times or more, or about 15 times or more compared to GDF15 not fused to a polypeptide region capable of O-glycosylation.

[0094] Thus, GDF15 in the form of a fusion polypeptide linked to a polypeptide region capable of O-glycosylation has the advantage of having a longer administration interval compared to GDF15 in a form not linked to a polypeptide region capable of O-glycosylation due to the increased half-life of GDF15.

[0095] The fusion polypeptide comprising GDF15 and a polypeptide region capable of O-glycosylation can be prepared by common chemical synthesis or recombinant methods.

[0096] In the present specification, the term "vector" refers to an expression tool for expressing a target gene in a host cell, and for example, can be selected from plasmid vectors, cosmid vectors and viral vectors such as phage vectors, adenovirus vectors, retrovirus vectors and adeno-associated virus vectors, etc. In one embodiment, a vector that can be used for a recombinant vector can be prepared based on a plasmid (e.g., pcDNA series, pSC101, pGV1106, pACYC177, ColE1, pKT230, pME290, pBR322, pUC8 / 9, pUC6, pBD9, pHC79, pIJ61, pLAFR1, pHV14, pGEX series, pET series, pUC19, etc.), a phage (e.g., λgt4λB, λ-Charon, λΔz1, M13, etc.) or a virus (e.g., SV40, etc.), but is not limited thereto.

[0097] The nucleic acid molecule encoding the fusion polypeptide in the recombinant vector can be operably linked to a promoter. The term "operably linked" refers to the functional combination of a nucleic acid expression regulatory sequence (e.g., a promoter sequence) and other nucleic acid sequences. The regulatory sequence can regulate the transcription and / or translation of other nucleic acid sequences by "operably linking".

[0098] The recombinant vector can be constructed as a vector for cloning or an expression vector for expression. As an expression vector, a common vector for expressing foreign proteins in plants, animals or microorganisms can be used. The recombinant vector can be constructed by various methods known in the art.

[0099] The recombinant vector can be expressed using eukaryotic organisms as hosts. When eukaryotic organisms are expressed as hosts, in addition to the nucleic acid molecules to be expressed and the aforementioned promoters, ribosome binding sites, secretion signal sequences (see Patent Publication No. 2015-0125402) and / or transcription / translation termination sequences, the recombinant vector can also include a replication origin, such as f1 replication origin, SV40 replication origin, pMB1 replication origin, adenovirus replication origin, AAV replication origin and / or BBV replication origin, etc., but not limited thereto. In addition, promoters derived from mammalian cell genomes (e.g., metallothionein promoters) or promoters derived from mammalian viruses (e.g., adenovirus late promoters, vaccinia virus 7.5K promoters, SV40 promoters, cytomegalovirus and tk promoters of HSV) can be used, and all secretion signal sequences that can be generally used as secretion signal sequences can be used, and for example, the secretion signal sequences disclosed in Patent Publication No. 2015-0125402 can be used, but not limited thereto, and as a transcription termination sequence, a polyadenylation sequence can be included.

[0100] The recombinant cell can be obtained by introducing (transforming or transfecting) a recombinant vector into an appropriate host cell. The host cell can be selected from all eukaryotic organisms that can stably and continuously clone or express a recombinant vector. Eukaryotic organisms that can be used as hosts include yeast (Saccharomyces cerevisiae), insect cells, plant cells, animal cells, and the like, and include, for example, mice (e.g., COP, L, C127, Sp2 / 0, NS-0, NS-1, At20, or NIH3T3), rats (e.g., PC12, PC12h, GH3, or MtT), hamsters (e.g., BHK, CHO, GS genetically deficient CHO, or DHFR genetically deficient CHO), monkeys (e.g., COS (COS1, COS3, COS7, etc.), CV1, or Vero), humans (e.g., HeLa, HEK-293, retina-derived PER-C6, cells derived from diploid fibroblasts, myeloma cells, or HepG2), other animal cells (e.g., MDCK, etc.), insect cells (e.g., Sf9 cells, Sf21 cells, Tn-368 cells, BTI-TN-5B1-4 cells, etc.), hybridomas, and the like, but are not limited thereto.

[0101] By expressing the nucleic acid molecule encoding the fusion polypeptide provided in this specification in the aforementioned appropriate host cells, GDF15 and fusion polypeptides comprising the same having enhanced in vivo stability compared to the unfused form can be prepared. The method for preparing the fusion polypeptide may include culturing a recombinant vector comprising the nucleic acid molecule. The culturing may be carried out under common culture conditions. In addition, the preparation method may also include isolating and / or purifying the fusion polypeptide from the culture after the culturing.

[0102] For the delivery (introduction) of nucleic acid molecules or recombinant vectors comprising them, delivery methods well known in the art can be used. As delivery methods, for example, when the host cell is a eukaryote, microinjection, calcium phosphate precipitation, electroporation, liposome-mediated transfection and gene bombardment etc. can be used, but are not limited thereto.

[0103] The method for selecting transformed (introduced recombinant vector) host cells can be easily carried out using the phenotype expressed by the selection marker according to methods well known in the art. For example, when the selection marker is a specific antibiotic resistance gene, the recombinant cells into which the recombinant vector is introduced can be easily selected by culturing in a culture medium containing antibiotics.

[0104] The fusion polypeptide can be used to prevent and / or treat all diseases associated with GDF15 deficiency and / or dysfunction or that can be treated, alleviated or improved by GDF15 activity.

[0105] Therefore, in one embodiment, a pharmaceutical composition is provided, comprising one or more selected from the group consisting of the fusion polypeptide, the nucleic acid molecule encoding the fusion polypeptide, the recombinant vector comprising the nucleic acid molecule, and the recombinant cell comprising the recombinant vector. The pharmaceutical composition can be a pharmaceutical composition for preventing and / or treating a disease associated with the deficiency and / or dysfunction of GDF15 contained in the fusion protein or a disease having a therapeutic and / or preventive effect of GDF15.

[0106] Other embodiments provide a method for preventing and / or treating a disease associated with a deficiency and / or dysfunction of GDF15 contained in a fusion protein or a disease having a therapeutic and / or preventive effect of GDF15, the method comprising administering to a patient in need of prevention and / or treatment of a disease associated with a deficiency and / or dysfunction of GDF15 contained in a fusion protein or a disease having a therapeutic and / or preventive effect of GDF15 one or more selected from the fusion polypeptide, a nucleic acid molecule encoding the fusion polypeptide, a recombinant vector comprising the nucleic acid molecule, and a recombinant cell comprising the recombinant vector. The method may also include confirming, before administration, that the patient needs prevention and / or treatment of a disease associated with a deficiency and / or dysfunction of GDF15 contained in a fusion protein or a disease having a therapeutic and / or preventive effect of GDF15.

[0107] Examples of diseases associated with the deficiency and / or dysfunction of GDF15 contained in the fusion protein or diseases (or symptoms) having the therapeutic and / or preventive effect of GDF15 may include obesity, diabetes (type 1 diabetes, type 2 diabetes), cardiovascular disease, myocardial hypertrophy, liver disease (e.g., non-alcoholic steatohepatitis (NASH)), ischemic injury (ischemic brain injury, ischemic retinal injury), peripheral nerve damage, age-related sensory and / or motor nerve loss, renal tubular and / or renal epileptic damage, but are not limited thereto.

[0108] In other embodiments, the pharmaceutical composition provided in this specification or the method comprising administering the pharmaceutical composition can have one or more effects selected from weight loss, diet control (reduced intake), body fat reduction, and administration and / or enhancement of glucose tolerance, and in this case, the pharmaceutical composition or method can be used for weight loss, reduction of body fat, and / or administration and / or enhancement of glucose tolerance.

[0109] Therefore, in one embodiment, a composition comprising one or more selected from the fusion polypeptide, a nucleic acid molecule encoding the fusion polypeptide, a recombinant vector comprising the nucleic acid molecule, and a recombinant cell comprising the recombinant vector can be a pharmaceutical composition or food composition (health functional food) for reducing weight, regulating diet (reducing food amount), reducing body fat, or administering and / or enhancing glucose tolerance.

[0110] Other embodiments provide a method for reducing weight, adjusting diet (reducing food quantity), reducing body fat, or giving and / or enhancing glucose tolerance, including administering to a patient who needs to reduce weight, adjust diet (reduce food quantity), reduce body fat, or give and / or enhance glucose tolerance one or more selected from the fusion polypeptide, the nucleic acid molecule encoding the fusion polypeptide, the recombinant vector comprising the nucleic acid molecule, and the recombinant cell comprising the recombinant vector. The method may also include confirming that the patient needs to lose weight, adjust diet (reduce food quantity), reduce body fat, or give and / or enhance glucose tolerance before administration.

[0111] The pharmaceutical composition may include one or more pharmaceutically effective doses of active ingredients, the active ingredients being selected from the fusion polypeptide, fusion polypeptide dimer, nucleic acid molecule, recombinant vector and recombinant cells comprising the fusion polypeptide. The pharmaceutically effective dose refers to the content or dosage of the active ingredient that can achieve the desired effect. The content or dosage of the active ingredient may be specified differently according to factors such as preparation method, administration method, patient age, body weight, sex, condition, food, administration time, administration interval, administration route, excretion rate and reaction sensitivity. For example, a single dose of the active ingredient may be in the range of 0.001 to 1000 mg / kg, 0.01 to 100 mg / kg, 0.01 to 50 mg / kg, 0.01 to 20 mg / kg or 0.01 to 1 mg / kg, but is not limited thereto.

[0112] In addition, in addition to the active ingredient, the pharmaceutical composition may also include a pharmaceutically acceptable carrier. The carrier is a carrier commonly used in the preparation of a drug containing protein, nucleic acid or cell, and may be selected from one or more of the following: lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum arabic, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinyl pyrrolidone, cellulose, water, syrup, methylcellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral oil, etc., but not limited thereto. The pharmaceutical composition may also additionally include one or more of the diluents, excipients, lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. commonly used in the preparation of the pharmaceutical composition.

[0113] The subject of administration of the pharmaceutical composition can be mammals, including primates such as humans and monkeys, rodents such as mice and rats, etc., or cells, tissues, cell cultures or tissue cultures derived therefrom.

[0114] The pharmaceutical composition can be administered by oral administration or parenteral administration, or can be administered by contacting it with cells, tissues or body fluids. Specifically, in the case of parenteral administration, it can be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endothelial administration, topical administration, intranasal administration, intrapulmonary administration and intrarectal administration, etc. In the case of oral administration, since the protein or peptide is digested, the oral composition should be formulated to coat the active agent or protect it from degradation in the stomach.

[0115] In addition, the pharmaceutical composition can be formulated in the form of a solution, suspension, syrup or emulsion in an oily or aqueous medium, or in the form of an extract, powder, granule, tablet or capsule, and for formulation, the pharmaceutical composition may further contain a dispersant or stabilizer.

[0116]

Beneficial Effects

[0117] The GDF15 fused to the polypeptide region capable of O-glycosylation provided in the present specification has a long duration when administered in vivo, so the administration interval can be extended and the administration dose can be reduced, so it has a beneficial effect in terms of administration convenience and / or economy, and can be effectively applied to fields requiring GDF15 treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0118] Figure 1 The amino acid sequence of GDF15 is shown schematically.

[0119] Figure 2a A fusion polypeptide comprising a His-tag according to one embodiment is schematically shown.

[0120] Figure 2b The structure of a fusion polypeptide according to one embodiment is schematically shown.

[0121] Figure 3 The structures of various types of fusion polypeptides are shown schematically.

[0122] Figure 4 The results of SDS-PAGE analysis of fusion polypeptides HT-ID1-GDF15, HT-ID2-GDF15, and HT-ID3-GDF15 synthesized in one example are shown.

[0123] Figure 5 The results of analyzing the fusion polypeptides HT-ID1-GDF15, HT-ID2-GDF15, and HT-ID3-GDF15 synthesized in one example by Q-TOF mass spectrometry are shown.

[0124] Figure 6is a graph showing changes in body weight when each of the fusion polypeptides HT-ID1-GDF15, HT-ID2-GDF15, and HT-ID3-GDF15 was administered once to mice.

[0125] Figure 7 is from Figure 6 The results are extracted and shown in a graph showing the results for day 4.

[0126] Figure 8 The graph shows changes in food intake of mice to which fusion polypeptides HT-ID1-GDF15, HT-ID2-GDF15, and HT-ID3-GDF15 were administered.

[0127] Fig. 9 is a graph showing changes in body weight after repeated administration of each of the fusion polypeptides HT-ID2-GDF15 and HT-ID3-GDF15 to mice.

[0128] Fig.10a is from Fig. 9 The results for day 7 and day 14 are extracted and shown in Figure 1 .

[0129] Fig.10b is from Fig. 9 The results for day 21 and day 28 are extracted and shown in Figure 1 .

[0130] Fig.11 It is a graph showing the cumulative food intake until the 7th day, the 14th day, the 21st day, and the 28th day when the fusion polypeptides HT-ID2-GDF15 and HT-ID3-GDF15 were repeatedly administered to mice, respectively.

[0131] Fig.12 It is a graph showing changes in blood fusion polypeptide concentration over time when fusion polypeptides HT-ID1-GDF15, HT-ID2-GDF15, and HT-ID3-GDF15 were administered to SD rats. DETAILED DESCRIPTION

[0132] Hereinafter, the present invention will be described in more detail by the following examples. However, they are only intended to illustrate the present invention, but the scope of the present invention is not limited by these examples.

[0133] Example 1: Preparation of fusion polypeptide

[0134] 1.1. Preparation of fusion polypeptides containing GDF15

[0135] The fusion polypeptides IgD-GDF15 (ID1-GDF15), IgD-IgD-GDF15 (ID2-GDF15), and IgD-IgD-IgD-GDF15 (ID3-GDF15) were prepared (see Figure 2a and Figure 2b ), where IgD hinge ( The underlined portion is a site capable of O-glycosylation) or a combination of several (1, 2 or 3) IgD hinges and GDF15 (SEQ ID NO: 3, Figure 1 ) fusion. In order to facilitate purification, a fusion polypeptide comprising a His tag (SEQ ID NO: 15) and a TEV cleavage site (SEQ ID NO: 16) was also prepared. The amino acid sequence of each part contained in the fusion polypeptide is summarized in Table 2 below.

[0136]

Table 2

[0137]

[0138] 1.1.1. Preparation of recombinant expression vector

[0139] 1.1.1.1. Mature GDF15

[0140] In order to obtain a gene encoding mature GDF15, the gene encoding mature GDF15 (SEQ ID NO: 5) was synthesized with reference to the amino acid sequence information of UniprotKB Q99968 (Bioneer).

[0141] SEQ ID NO:5 (339 bp)

[0142]

[0143] 1.1.1.2.IgD hinge (ID)

[0144] In order to obtain a gene encoding human IgD hinge, a gene encoding 3 human IgD hinges (hereinafter referred to as 'ID3') (SEQ ID NO: 6) was synthesized at Bioneer with reference to the amino acid sequence information of UniprotKB P01880.

[0145] SEQ ID NO:6 (306 bp)

[0146]

[0147]

[0148] (1-102 polynucleotides (underlined), 103-204 polynucleotides (bold), and 205-306 polynucleotides (bold + underlined) encode the IgD hinge, respectively)

[0149] 1.1.1.3. Preparation of expression vector

[0150] The variant pDHDD-D1G1 (containing the promoter of KR10-1868139B1) of pcDNA3.1(+) (Invitrogen, catalog number V790-20) was cut with BamHI and NotI, and designed to encode a gene having the following structure (see Figure 3 ) are inserted therein to prepare each recombinant vector.

[0151] pGDF15

[0152] '(N terminus)-[BamHI restriction site (GGATCC)-signal peptide (SEQ ID NO: 14)-mature GDF15 (SEQ ID NO: 3)-NotI restriction site (GCGGCCGC)]-(C terminus)'

[0153] pHT-GDF15

[0154] '(N-terminus)-[BamHI restriction site-signal peptide (SEQ ID NO: 14)-His tag (SEQ ID NO: 15)-TEV cleavage site (SEQ ID NO: 16)-mature GDF15 (SEQ ID NO: 3)-NotI restriction site]-(C-terminus)'

[0155] pID1-GDF15

[0156] '(N terminus)-[BamHI restriction site-signal peptide (SEQ ID NO: 14)-IgD hinge (SEQ ID NO: 1)-GS linker (SEQ ID NO: 17)-mature GDF15 (SEQ ID NO: 3)-NotI restriction site]-(C terminus)'

[0157] pHT-ID1-GDF15

[0158] '(N-terminus)-[BamHI restriction site-signal peptide (SEQ ID NO: 14)-His tag (SEQ ID NO: 15)-TEV cleavage site (SEQ ID NO: 16)-IgD hinge (SEQ ID NO: 1)-GS linker (SEQ ID NO: 17)-GDF15 (SEQ ID NO: 3)-NotI restriction site]-(C-terminus)'

[0159] pID2-GDF15

[0160] '(N-terminus)-[BamHI restriction site-signal peptide (SEQ ID NO: 14)-IgD hinge (SEQ ID NO: 1)-IgD hinge (SEQ ID NO: 1)-GS linker (SEQ ID NO: 17)-GDF15 (SEQ ID NO: 3)-NotI restriction peptide]-(C-terminus)'

[0161] pHT-ID2-GDF15

[0162] '(N-terminus)-[BamHI restriction site-signal peptide (SEQ ID NO:14)-His tag (SEQ ID NO:15)-TEV cleavage site (SEQ ID NO:16)-IgD hinge (SEQ ID NO:1)-IgD hinge (SEQ ID NO:1)-GS linker (SEQ ID NO:17)-GDF15 (SEQ ID NO:3)-NotI restriction site]-(C-terminus)'

[0163] pID3-GDF15

[0164] '(N terminus)-[BamHI restriction site-signal peptide (SEQ ID NO: 14)-IgD hinge (SEQ ID NO: 1)-IgD hinge (SEQ ID NO: 1)-IgD hinge (SEQ ID NO: 1)-GS linker (SEQ ID NO: 17)-GDF15 (SEQ ID NO: 3)-NotI restriction site]-(C terminus)'

[0165] pHT-ID3-GDF15

[0166] '(N-terminus)-[BamHI restriction site-signal peptide (SEQ ID NO:14)-His tag (SEQ ID NO:15)-TEV cleavage site (SEQ ID NO:16)-IgD hinge (SEQ ID NO:1)-IgD hinge (SEQ ID NO:1)-IgD hinge (SEQ ID NO:1)-GS linker (SEQ ID NO:17)-GDF15 (SEQ ID NO:3)-NotI restriction site]-(C-terminus)'

[0167] 1.1.2. Expression of fusion polypeptide

[0168] The prepared recombinant expression vectors pGDF15, pHT-GDF15, pID1-GDF15, pHT-ID1-GDF15, pID2-GDF15, pHT-ID2-GDF15, pID3-GDF15 and pHT-ID3-GDF15 were introduced into ExpiCHO-S TM cells (Thermo Fisher Scientific) and cultured in ExpiCHO expression medium (Thermo Fisher Scientific; 400 mL) (Fed-Batch Culture; fed on days 1 and 5) for 12 days to express the fusion polypeptides GDF15, HT-GDF15, ID1-GDF15, HT-ID1-GDF15, ID2-GDF15, HT-ID2-GDF15, ID3-GDF15, and HT-ID3-GDF15.

[0169] 1.1.3. Purification of fusion polypeptide

[0170] The fusion polypeptides HT-ID1-GDF15, HT-ID2-GDF15, and HT-ID3-GDF15 produced by the recombinant expression vector were purified, and the O-glycan site occupancy was analyzed using sialic acid content analysis and Q-TOF mass spectrometry.

[0171] Specifically, the fusion polypeptide is purified by continuous ultrafiltration / diafiltration, immobilized metal affinity chromatography (IMAC) and anion exchange chromatography (AEX). First, the culture solution of the fusion protein from which the cells have been removed is filtered with a 0.22 μm filter. The filtered solution is concentrated using a TFF System, and then a buffer exchange is performed using a tromethamine buffer solution. Equipped with a HiTrap TM A column of chelating HP (GE Healthcare Life Sciences) resin was added and an equilibrium buffer (20 mM Tris pH 8.0, 0.5 M NaCl, 5 mM imidazole) was added to balance the column. The process solution that had previously completed ultrafiltration / diafiltration was injected into the column and then the equilibrium buffer was added again to wash the column. After the washing operation of the column was completed, an elution buffer (20 mM Tris pH 8.0, 0.5 M NaCl, 0.5 M imidazole) was added to the column to elute the target protein.

[0172] For the obtained elution solution, an Amicon Ultra filter unit (MWCO 10K, Merck) and a centrifuge were used for concentration, and then a buffer exchange was performed with a tromethamine buffer. The process solution thus prepared was injected into a balanced anion exchange column, and flowed into a balancing buffer (20mM Tris pH 8.0) and the column was washed. After the washing operation of the column was completed, an elution buffer (20mM Tris pH 8.0, 0.5M NaCl) was flowed into the column under a concentration gradient condition to elute the target protein. Among the eluted fractions, fractions with high concentration and high purity fusion polypeptide were collected and kept frozen.

[0173] For animal experiments, concentration and buffer exchange of samples were performed with phosphate buffered saline (PBS, 10 mM sodium phosphate, 150 mM NaCl pH 7.4) using Amicon Ultra filter units (MWCO 10K, Merck) and centrifuges.

[0174] Quantitative analysis of the fusion polypeptide was performed by measuring absorbance at 280 nm and 340 nm in a UV spectrophotometer (G113A, Agilent Technologies) by the following equation: As the extinction coefficient, a value theoretically calculated using the amino acid sequence was used.

[0175]

[0176] *Extinction coefficient (0.1%): Theoretical absorbance at 280 nm, assuming a protein concentration of 0.1% (1 g / L) and all cysteines in the primary sequence are oxidized to form disulfide bonds. Calculated via the ProtParam tool (https: / / web.expasy.org / protparam / ).

[0177]

Table 3

[0178] Extinction coefficient of fusion peptide

[0179] Sample name Extinction coefficient (0.1%, 1mg / mL) HT-ID1-GDF15 0.833 HT-ID2-GDF15 0.706 HT-ID3-GDF15 0.612

[0180] For the purified fusion polypeptides HT-ID1-GDF15, HT-ID2-GDF15, and HT-ID3-GDF15, O-glycan site occupancy was analyzed using Q-TOF mass spectrometry after sialic acid content analysis and reduction.

[0181] The results of SDS-PAGE analysis of fusion polypeptides HT-ID1-GDF15, HT-ID2-GDF15 and HT-ID3-GDF15 are shown in Figure 4 and the results of the analysis thereof by Q-TOF mass spectrometry are shown in Figure 5 and Table 5. In addition, the sialic acid content is also shown in Table 4.

[0182]

Table 4

[0183] Average O-glycan number and sialic acid content

[0184]

[0185] *The excess over theoretical O-glycan numbers is presumed to be due to O-glycans attached to the GS linker (Spahr et al., 2014, mAbs, 6:904)

[0186] Example 2. Pharmacological effects of fusion polypeptides (in vivo)

[0187] 2.1. Single administration

[0188] 2.1.1 Testing process

[0189] The pharmacological effects of the fusion polypeptide produced and purified in Example 1 above were tested in mice (C57BL / 6J, 6 weeks old, male, 100 mice; Raonbio).

[0190] In this example, a DIO mouse model (mouse, C57BL / 6J-DIO, male, 100 mice, 14 weeks old (obesity diet feeding for 8 weeks)) was used, in which obesity was induced by feeding a high-fat diet to C57BL / 6J mice for 8 weeks. The DIO mouse model is an animal model widely used to evaluate the efficacy of diabetes and insulin improvement because it exhibits clinical features of type 2 diabetes such as hyperlipidemia, insulin resistance, and hyperglycemia, and a large amount of comparable basic data has been accumulated for research on metabolic diseases such as obesity, diabetes, and hyperlipidemia, so it is suitable for the pharmacological action test of this example, and therefore this model was selected.

[0191] The mouse model of feeding fat feed for 8 weeks is experienced the isolation acclimation period of 2 weeks, and observes general symptoms once a day during this period, and selects healthy animals by confirming whether it is healthy and whether it is suitable for experiment.During the acclimation period, the tail of animal is marked with a red oil pen (tail mark) when obtaining, and a temporary individual identification card (test name, individual number, time of putting in a place to breed) is pasted on the feeding box during the isolation acclimation period.When grouping, a black oil pen is used to mark individual on the tail of animal, and an individual identification card (test name, group information, individual number, sex, time of putting in a place to breed, application period) is pasted on each cage.

[0192] To minimize the stress experienced by the experimental animals due to subcutaneous administration of the test substance (fusion polypeptide), 200 uL / head of sterile distilled saline was subcutaneously administered to all animals using a 1 mL syringe 3 days before administration of the test substance. Pre-adaptation training for subcutaneous administration was performed.

[0193] For healthy animals with no abnormalities found during the isolation and acclimation period, the body weight and food intake of all individuals were measured after the acclimation period.

[0194] Body weight and food intake were measured and grouped so that the average values ​​of the two measurements between groups based on body weight were similar. Test substance administration began on the second day after grouping. After the grouping was completed, the remaining animals that were not selected were excluded from the test system.

[0195] Information on high-fat diet (HFD) fed to C57BL / 6J–DIO is as follows:

[0196] 5.24 kcal / g, fat 60 wt%, protein 20 wt%, and carbohydrate-derived calories 20 wt%; Research Diet Inc., USA; Product No. High Fat Diet (Fat 60 kcal%, D12492).

[0197] The feed was provided by ad libitum feeding (fed during acclimation and testing).

[0198] The drinking water method was to filter tap water using a filter-type oil-water sterilizer, then irradiate it with ultraviolet light, and allow the water to be freely consumed using a polycarbonate drinking water bottle (250 mL).

[0199] The test substances HT-ID1-GDF15, HT-ID2-GDF15 and HT-ID3-GDF15 and the control substance Semaglutide (Bachem) were administered from the second day after grouping, and the administration time was performed at 9 AM every day. All control substances and test substances were administered subcutaneously. For the administration route of the control substance and the test substance, subcutaneous administration was selected according to the clinical predetermined administration route.

[0200] For all control substances and test substances, the amount of the administered solution was set to 5 mL / kg, and the individual administered solution was calculated based on the most recently measured body weight, and administered once by subcutaneous injection using a disposable syringe (1 mL) on the test start day. The test substance was administered only once. For comparison, a control group administered with the control substance semaglutide was prepared, and a comparison group administered with semaglutide was administered once a day, and all administrations were performed from 9 AM.

[0201] The composition of the test groups and the administered doses are summarized in Table 5 below:

[0202]

Table 5

[0203] Composition of fusion polypeptide administration group

[0204]

[0205] Regarding the observation, measurement, and test schedules for the test group, the administration start date was set as Day 0, and 7 days from the administration start date was set as one week of administration.

[0206] Table 6 summarizes the test schedule:

[0207]

Table 6

[0208] Testing Schedule

[0209]

[0210] All animals were observed once a day for general clinical symptoms, and twice a day for moribund and dead animals, and these observations were performed from administration day 1 to the end of administration. Only when abnormal symptoms were present during the observation period were they recorded on the record sheet.

[0211] The body weight of each mouse was measured on the day when the test substance administration started (before administration) and thereafter measured every day (measurement until 9 days), and the amount of the test substance administration solution was determined based on the most recently measured body weight.

[0212] In addition, after the test substance was administered to the mice, the daily food intake was measured, and the amount of food consumed was measured for each feeding box using an electronic scale, and the remaining amount was measured to calculate the daily food intake. If an individual gnawed severely, it was excluded from the measurement.

[0213] All experimental results obtained in this embodiment are expressed as mean ± standard error and tested using Prism5 (version 5.01). All data are subjected to one-way analysis of variance (ANOVA), and when significance is observed, Dunnett's test is performed to find out the test group with significant difference from the control group (significance level: bilateral 5% and 1%, 0.1%).

[0214] 2.1.2. Weight loss test results

[0215] The body weight changes measured in the above Example 2.1.1 are shown in Figure 6 and Figure 7 And in Table 7 (body weight (group, % of initial value).

[0216]

Table 7

[0217]

[0218] Figure 6Table 7 shows the changes in body weight when the fusion polypeptides HT-ID1-GDF15, HT-ID2-GDF15, and HT-ID3-GDF15 were administered once, respectively, compared to the negative control group (vehicle administration group) and the positive control group (semaglutide daily administration group). In addition, Figure 7 Is displayed from Figure 6 Figure 2 shows the results of day 4 extracted from the results.

[0219] As shown in the above results, it was confirmed that in the case of the negative control group (vehicle administration group), there was almost no change in body weight, while in the case of the positive control group (semaglutide daily administration group), a weight loss effect was continuously shown from day 1 after administration. In addition, it was confirmed that in the case of the fusion polypeptide of GDF15 fused to the IgD hinge, a weight loss effect was immediately shown after a single administration on day 0, and the weight loss effect did not decrease and continued to appear until 3-4 days.

[0220] 2.1.3. Dietary intake test results

[0221] The changes in food intake measured in the above Example 2.1.1 are shown in Tables 8 and Figure 8 (Cumulative intake until day 6).

[0222]

Table 8

[0223]

[0224] As shown in the above results, in the case of the fusion polypeptide administration group in which GDF15 is fused to the IgD hinge, compared with the negative control group (vehicle administration group) administration group, a food intake reducing effect was shown until the 6th day, the maximum value depended on the fusion polypeptide, and the food intake reducing effect of the fusion polypeptide can be said to be comparable to the case of once-daily administration of semaglutide (positive control group) throughout the test period.

[0225] 2.2. Repeated administration

[0226] 2.2.1 Testing process

[0227] Except for the administration dose, number of animals and administration cycle, most of the test procedures were the same as those in the above Example 2.1.1.

[0228] The test substance was administered twice a week (Days 0, 4, 7, 11, 14, 18, 21, 25), for a total of 8 times. For comparison, a control group in which the control substance semaglutide was administered daily was prepared, and a comparison group in which semaglutide was administered daily was administered once a day, and all administrations were performed from 9 AM.

[0229] The composition of the test groups and the administered doses are summarized in Table 9 below:

[0230]

Table 9

[0231] Composition of fusion polypeptide administration group

[0232]

[0233] 2.2.2. Weight loss test results

[0234] The body weight changes measured in the above Example 2.2.1 are shown in Fig. 9 , Fig.10a , Fig.10b and Table 10 (body weight (group, % of initial value).

[0235]

Table 10

[0236]

[0237]

[0238] Fig. 9 Table 9 and Table 10 show the body weight changes compared with the negative control group (vehicle administration group) and the positive control group (semaglutide daily administration group) in the case of repeated administration of fusion proteins HT-ID2-GDF15 and HT-ID3-GDF15, respectively. Fig.10a It is shown from above Fig. 9 The results for the 7th and 14th days are extracted from the results, and Fig.10b Is displayed from Fig. 9 The results for day 21 and day 28 are extracted from the results graph.

[0239] As shown in the above results, it was confirmed that in the case of the negative control group (vehicle administration group), there was almost no change in body weight, while in the case of the positive control group (semaglutide daily administration group), a weight loss effect was continuously shown from the first day after administration. In addition, it was confirmed that in the case of the fusion polypeptide of GDF15 fused to the IgD hinge, a weight loss effect was immediately shown after a single administration on day 0, and the weight loss effect was continuously shown without decreasing, and the weight loss effect was concentration-dependent.

[0240] 2.2.3. Dietary intake test results

[0241] The changes in food intake measured in the above Example 2.2.1 are shown in Tables 11 and Fig.11 (cumulative intake up to days 7, 14, 21 and 28).

[0242]

Table 11

[0243]

[0244]

[0245] As shown in the above results, the fusion polypeptide administration group of GDF15 fused to IgD hinge showed a food intake reduction effect throughout the test period, depending on the fusion polypeptide, and showed a concentration-dependent trend, compared with the negative control group (vehicle administration group).

[0246] Example 3. Pharmacokinetic testing of fusion polypeptides

[0247] 3.1. Preparation of serum in the test and control groups

[0248] In order to evaluate the pharmacokinetic characteristics when each fusion polypeptide is subcutaneously administered to rats, the fusion polypeptides HT-ID1-GDF15, HT-ID2-GDF15 and HT-ID3-GDF15 were subcutaneously administered to SD rats (Koatech, male, 7 weeks old, about 250g; each n=3; test group) in an amount of 2 mg / kg, and about 200 μl of blood was collected through the tail vein at a predetermined time. The blood collection time was before administration and 1, 2, 4, 8, 24, 48, 72, 96, 168, 240 and 336 hours after administration. As a control group for comparison of pharmacokinetic characteristics, GDF15 (R&D Systems) was subcutaneously administered in an amount of 2 mg / kg by the same method to prepare a GDF15 administration group.

[0249] After administration to SD rats as described above, the blood collected at the time point was centrifuged to obtain serum, and ELISA was performed using a human GDF15 immunoassay (SGD150, R&D Systems), and the concentration in serum was measured according to the time of each polypeptide. Using this data, parameter values ​​including AUC (area under the curve) were obtained using PK analysis software (WinNonlin (Certara LP) etc.).

[0250] 3.2 Pharmacokinetic test results

[0251] The obtained pharmacokinetic parameters of the fusion polypeptide are shown in Table 12, and the concentration changes of the fusion polypeptide over time are shown in Fig.12 middle.

[0252]

Table 12

[0253]

[0254] (C max : Maximum blood concentration, T max : Time to reach maximum blood concentration, AUC infAUC: The area under the blood concentration-time curve extrapolated from the last measurable blood sampling time to infinity last : Area under the blood concentration-time curve until the last measurable blood sampling time, T 1 / 2 : Loss half-life, AUC Extp (%): [(AUC inf –AUC last ) / AUC inf ]*100)

[0255] As shown in the above results, it was confirmed that the half-life of the fusion polypeptide fused to the IgD hinge was increased compared to GDF15 (half-life: 19 hours), especially in AUC last In the case of GDF15, the maximum increase was 16.7 times compared with GDF15.

[0256] Through the above description, those skilled in the art to which the present invention belongs should understand that the present invention can be implemented in other specific forms without changing its technical spirit or essential features. In this regard, it should be understood that the above-mentioned embodiments are illustrative rather than restrictive in all aspects. The scope of the present invention should be understood as all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts are included in the scope of the present invention, rather than being included in the scope of the above-mentioned specific embodiments. <110> LG CHEM, LTD. <120> Fusion polypeptide comprising GDF15 and a polypeptide region capable of O-glycosylation <130> OPP20204754KR <150> KR 10-2019-0165052 <151> 2019-12-11 <160> 113 <170> koPatentIn 3.0 <210> 1 <211> 34 <212> PRT <213> Artificial sequence <220> <223> Human IgD hinge region (ID1) <400> 1 Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro Thr Ala Gln Pro Gln 1 5 10 15 Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro Ala Thr Thr Arg 20 25 30 Asn Thr <210> 2 <211> 19 <212> PRT <213> Artificial sequence <220> <223> Human IgA1 hinge region <400> 2 Val Pro Ser Thr Pro Pro Thr Pro Ser Pro Ser Thr Pro Pro Thr Pro 1 5 10 15 Ser Pro Ser <210> 3 <211> 112 <212> PRT <213> Artificial sequence <220> <223> Mature GDF15 (wild type) <400> 3 Ala Arg Asn Gly Asp His Cys Pro Leu Gly Pro Gly Arg Cys Cys Arg 1 5 10 15 Leu His Thr Val Arg Ala Ser Leu Glu Asp Leu Gly Trp Ala Asp Trp 20 25 30 Val Leu Ser Pro Arg Glu Val Gln Val Thr Met Cys Ile Gly Ala Cys 35 40 45 Pro Ser Gln Phe Arg Ala Ala Asn Met His Ala Gln Ile Lys Thr Ser 50 55 60 Leu His Arg Leu Lys Pro Asp Thr Val Pro Ala Pro Cys Cys Val Pro 65 70 75 80 Ala Ser Tyr Asn Pro Met Val Leu Ile Gln Lys Thr Asp Thr Gly Val 85 90 95 Ser Leu Gln Thr Tyr Asp Asp Leu Leu Ala Lys Asp Cys His Cys Ile 100 105 110 <210> 4 <211> 98 <212> PRT <213> Artificial Sequence <220> <223> GDF15 (Mutant) <400> 4 Cys Arg Leu His Thr Val Arg Ala Ser Leu Glu Asp Leu Gly Trp Ala 1 5 10 15 Asp Trp Val Leu Ser Pro Arg Glu Val Gln Val Thr Met Cys Ile Gly 20 25 30 Ala Cys Pro Ser Gln Phe Arg Ala Ala Asn Met His Ala Gln Ile Lys 35 40 45 Thr Ser Leu His Arg Leu Lys Pro Asp Thr Val Pro Ala Pro Cys Cys 50 55 60 Val Pro Ala Ser Tyr Asn Pro Met Val Leu Ile Gln Lys Thr Asp Thr 65 70 75 80 Gly Val Ser Leu Gln Thr Tyr Asp Asp Leu Leu Ala Lys Asp Cys His 85 90 95 Cys Ile <210> 5 <211> 339 <212> DNA <213> Artificial sequence <220> <223> Polynucleotide encoding mature GDF15 <400> 5 gcccggaacg gcgaccactg ccccctgggg cccggacggt gctgccggct gcacaccgtg 60 cgggcctccc tggaggacct gggctgggcc gactgggtgc tgtccccaag ggaggtgcaa 120 gtgaccatgt gcatcggcgc ctgcccatct cagttccggg ccgccaacat gcacgctcag 180 atcaagacca gcctgcaccg gctgaagccc gacaccgtgc ccgccccctg ctgcgtgccc 240 gcctcctaca accccatggt gctgattcag aagaccgaca ccggcgtgag cctgcagacc 300 tacgacgacc tgctggccaa ggactgccac tgcatctaa 339 <210> 6 <211> 306 <212> DNA <213> Artificial sequence <220> <223> Polynucleotide encoding 3 human IgD hinge regions (ID3) <400> 6 gagagcccta aggctcaggc ctctagcgtg ccaacagctc agccacaagc tgaaggaagc 60 ctggccaagg ctacaaccgc ccctgccaca acacggaata cagagtcccc caaggcccag 120 gctagcagcg tgcctaccgc ccagcctcag gccgagggct ccctggctaa ggccacaacc 180 gctcccgcta caaccaggaa caccgagtct ccaaaggcac aggcctcctc cgtgcccact 240 gcacaacccc aagcagaggg cagcctcgcc aaggcaacca cagccccagc caccacccgg 300 aacaca 306 <210> 7 <211> 384 <212> PRT <213> Artificial Sequence <220> <223> Human IgD heavy chain constant region (UniProtKB P01880) <400> 7 Ala Pro Thr Lys Ala Pro Asp Val Phe Pro Ile Ile Ser Gly Cys Arg 1 5 10 15 His Pro Lys Asp Asn Ser Pro Val Val Leu Ala Cys Leu Ile Thr Gly 20 25 30 Tyr His Pro Thr Ser Val Thr Val Thr Trp Tyr Met Gly Thr Gln Ser 35 40 45 Gln Pro Gln Arg Thr Phe Pro Glu Ile Gln Arg Arg Asp Ser Tyr Tyr 50 55 60 Met Thr Ser Ser Gln Leu Ser Thr Pro Leu Gln Gln Trp Arg Gln Gly 65 70 75 80 Glu Tyr Lys Cys Val Val Gln His Thr Ala Ser Lys Ser Lys Lys Glu 85 90 95 Ile Phe Arg Trp Pro Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro 100 105 110 Thr Ala Gln Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala 115 120 125 Pro Ala Thr Thr Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Lys 130 135 140 Glu Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu 145 150 155 160 Cys Pro Ser His Thr Gln Pro Leu Gly Val Tyr Leu Leu Thr Pro Ala 165 170 175 Val Gln Asp Leu Trp Leu Arg Asp Lys Ala Thr Phe Thr Cys Phe Val 180 185 190 Val Gly Ser Asp Leu Lys Asp Ala His Leu Thr Trp Glu Val Ala Gly 195 200 205 Lys Val Pro Thr Gly Gly Val Glu Glu Gly Leu Leu Glu Arg His Ser 210 215 220 Asn Gly Ser Gln Ser Gln His Ser Arg Leu Thr Leu Pro Arg Ser Leu 225 230 235 240 Trp Asn Ala Gly Thr Ser Val Thr Cys Thr Leu Asn His Pro Ser Leu 245 250 255 Pro Pro Gln Arg Leu Met Ala Leu Arg Glu Pro Ala Ala Gln Ala Pro 260 265 270 Val Lys Leu Ser Leu Asn Leu Leu Ala Ser Ser Asp Pro Pro Glu Ala 275 280 285 Ala Ser Trp Leu Leu Cys Glu Val Ser Gly Phe Ser Pro Pro Asn Ile 290 295 300 Leu Leu Met Trp Leu Glu Asp Gln Arg Glu Val Asn Thr Ser Gly Phe 305 310 315 320 Ala Pro Ala Arg Pro Pro Pro Gln Pro Arg Ser Thr Thr Phe Trp Ala 325 330 335 Trp Ser Val Leu Arg Val Pro Ala Pro Pro Ser Pro Gln Pro Ala Thr 340 345 350 Tyr Thr Cys Val Val Ser His Glu Asp Ser Arg Thr Leu Leu Asn Ala 355 360 365 Ser Arg Ser Leu Glu Val Ser Tyr Val Thr Asp His Gly Pro Met Lys 370 375 380 <210> 8 <211> 353 <212> PRT <213> artificial sequence <220> <223> Human IgA heavy chain constant region (UniProtKB P01876) <400> 8 Ala Ser Pro Thr Ser Pro Lys Val Phe Pro Leu Ser Leu Cys Ser Thr 1 5 10 15 Gln Pro Asp Gly Asn Val Val Ile Ala Cys Leu Val Gln Gly Phe Phe 20 25 30 Pro Gln Glu Pro Leu Ser Val Thr Trp Ser Glu Ser Gly Gln Gly Val 35 40 45 Thr Ala Arg Asn Phe Pro Pro Ser Gln Asp Ala Ser Gly Asp Leu Tyr 50 55 60 Thr Thr Ser Ser Gln Leu Thr Leu Pro Ala Thr Gln Cys Leu Ala Gly 65 70 75 80 Lys Ser Val Thr Cys His Val Lys His Tyr Thr Asn Pro Ser Gln Asp 85 90 95 Val Thr Val Pro Cys Pro Val Pro Ser Thr Pro Pro Thr Pro Ser Pro 100 105 110 Ser Thr Pro Pro Thr Pro Ser Pro Ser Cys Cys His Pro Arg Leu Ser 115 120 125 Leu His Arg Pro Ala Leu Glu Asp Leu Leu Leu Gly Ser Glu Ala Asn 130 135 140 Leu Thr Cys Thr Leu Thr Gly Leu Arg Asp Ala Ser Gly Val Thr Phe 145 150 155 160 Thr Trp Thr Pro Ser Ser Gly Lys Ser Ala Val Gln Gly Pro Pro Glu 165 170 175 Arg Asp Leu Cys Gly Cys Tyr Ser Val Ser Ser Val Leu Pro Gly Cys 180 185 190 Ala Glu Pro Trp Asn His Gly Lys Thr Phe Thr Cys Thr Ala Ala Tyr 195 200 205 Pro Glu Ser Lys Thr Pro Leu Thr Ala Thr Leu Ser Lys Ser Gly Asn 210 215 220 Thr Phe Arg Pro Glu Val His Leu Leu Pro Pro Pro Ser Glu Glu Leu 225 230 235 240 Ala Leu Asn Glu Leu Val Thr Leu Thr Cys Leu Ala Arg Gly Phe Ser 245 250 255 Pro Lys Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln Glu Leu Pro 260 265 270 Arg Glu Lys Tyr Leu Thr Trp Ala Ser Arg Gln Glu Pro Ser Gln Gly 275 280 285 Thr Thr Thr Phe Ala Val Thr Ser Ile Leu Arg Val Ala Ala Glu Asp 290 295 300 Trp Lys Lys Gly Asp Thr Phe Ser Cys Met Val Gly His Glu Ala Leu 305 310 315 320 Pro Leu Ala Phe Thr Gln Lys Thr Ile Asp Arg Leu Ala Gly Lys Pro 325 330 335 Thr His Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Cys 340 345 350 Tyr <210> 9 <211> 5 <212> PRT <213> Artificial sequence <220> <223> Part of the hinge region of human IgD <400> 9 Ser Ser Val Pro Thr 1 5 <210> 10 <211> 7 <212> PRT <213> Artificial sequence <220> <223> Part of the hinge region of human IgD <400> 10 Thr Thr Ala Pro Ala Thr Thr 1 5 <210> 11 <211> 58 <212> PRT <213> Artificial sequence <220> <223> An extension of the hinge region of human IgD <400> 11 Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro Thr Ala Gln Pro Gln 1 5 10 15 Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro Ala Thr Thr Arg 20 25 30 Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Lys Glu Lys Glu Lys Glu 35 40 45 Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro 50 55 <210> 12 <211> 8 <212> PRT <213> Artificial sequence <220> <223> Part of the hinge region of human IgA1 <400> 12 Ser Thr Pro Pro Thr Pro Ser Pro 1 5 <210> 13 <211> 5 <212> PRT <213> Artificial sequence <220> <223> Peptide linker <400> 13 Gly Gly Gly Gly Ser 1 5 <210> 14 <211> twenty two <212> PRT <213> Artificial sequence <220> <223> Signal peptide <400> 14 Met His Arg Pro Glu Ala Met Leu Leu Leu Leu Thr Leu Ala Leu Leu 1 5 10 15 Gly Gly Pro Thr Trp Ala 20 <210> 15 <211> 8 <212> PRT <213> Artificial sequence <220> <223> His-tag <400> 15 His His His His His His 1 5 <210> 16 <211> 7 <212> PRT <213> Artificial sequence <220> <223> TEV cleavage site <400> 16 Glu Asn Leu Tyr Phe Gln Gly 1 5 <210> 17 <211> 20 <212> PRT <213> Artificial sequence <220> <223> GS connector <400> 17 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 1 5 10 15 Gly Gly Gly Ser 20 <210> 18 <211> 68 <212> PRT <213> Artificial sequence <220> <223> 2 human IgD hinge regions (ID2) <400> 18 Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro Thr Ala Gln Pro Gln 1 5 10 15 Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro Ala Thr Thr Arg 20 25 30 Asn Thr Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro Thr Ala Gln 35 40 45 Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro Ala Thr 50 55 60 Thr Arg Asn Thr 65 <210> 19 <211> 102 <212> PRT <213> artificial sequence <220> <223> 3 human IgD hinge(ID3) <400> 19 Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro Thr Ala Gln Pro Gln 1 5 10 15 Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro Ala Thr Thr Arg 20 25 30 Asn Thr Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro Thr Ala Gln 35 40 45 Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro Ala Thr 50 55 60 Thr Arg Asn Thr Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro Thr 65 70 75 80 Ala Gln Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro 85 90 95 Ala Thr Thr Arg Asn Thr 100 <210> 20 <211> 8 <212> PRT <213> Artificial sequence <220> <223> Part of the hinge region of human IgA <400> 20 Ser Thr Pro Pro Thr Pro Ser Pro 1 5 <210> twenty one <211> 102 <212> DNA <213> Artificial sequence <220> <223> Polynucleotide encoding human IgD hinge region (ID1) <400> twenty one gagagcccta aggctcaggc ctctagcgtg ccaacagctc agccacaagc tgaaggaagc 60 ctggccaagg ctacaaccgc ccctgccaca acacggaata ca 102 <210> twenty two <211> 204 <212> DNA <213> Artificial sequence <220> <223> Polynucleotide encoding 2 human IgD hinge regions (ID2) <400> twenty two gagagcccta aggctcaggc ctctagcgtg ccaacagctc agccacaagc tgaaggaagc 60 ctggccaagg ctacaaccgc ccctgccaca acacggaata cagagtcccc caaggcccag 120 gctagcagcg tgcctaccgc ccagcctcag gccgagggct ccctggctaa ggccacaacc 180 gctcccgcta caaccaggaa cacc 204 <210> twenty three <211> 90 <212> PRT <213> Artificial sequence <220> <223> MUCL1_Human <400> twenty three Met Lys Phe Leu Ala Val Leu Val Leu Leu Gly Val Ser Ile Phe Leu 1 5 10 15 Val Ser Ala Gln Asn Pro Thr Thr Ala Ala Pro Ala Asp Thr Tyr Pro 20 25 30 Ala Thr Gly Pro Ala Asp Asp Glu Ala Pro Asp Ala Glu Thr Thr Ala 35 40 45 Ala Thr Ala Thr Ala Thr Thr Ala Ala Pro Thr Thr Ala Thr Thr Ala 50 55 60 Ala Ser Thr Thr Ala Arg Lys Asp Ile Pro Val Leu Pro Lys Trp Val 65 70 75 80 Gly Asp Leu Pro Asn Gly Arg Val Cys Pro 85 90 <210> twenty four <211> 97 <212> PRT <213> Artificial sequence <220> <223> SMAGP_Human <400> twenty four Met Thr Ser Leu Leu Thr Thr Pro Ser Pro Arg Glu Glu Leu Met Thr 1 5 10 15 Thr Pro Ile Leu Gln Pro Thr Glu Ala Leu Ser Pro Glu Asp Gly Ala 20 25 30 Ser Thr Ala Leu Ile Ala Val Val Ile Thr Val Val Phe Leu Thr Leu 35 40 45 Leu Ser Val Val Ile Leu Ile Phe Phe Tyr Leu Tyr Lys Asn Lys Gly 50 55 60 Ser Tyr Val Thr Tyr Glu Pro Thr Glu Gly Glu Pro Ser Ala Ile Val 65 70 75 80 Gln Met Glu Ser Asp Leu Ala Lys Gly Ser Glu Lys Glu Glu Tyr Phe 85 90 95 authorities <210> 25 <211> 128 <212> PRT <213> artificial sequence <220> <223> GLPC_ human beings <400> 25 Met Trp Ser Thr Arg Ser Pro Asn Ser Thr Ala Trp Pro Leu Ser Leu 1 5 10 15 Glu Pro Asp Pro Gly Met Ala Ser Ala Ser Thr Thr Met His Thr Thr 20 25 30 Thr Ile Ala Glu Pro Asp Pro Gly Met Ser Gly Trp Pro Asp Gly Arg 35 40 45 Met Glu Thr Ser Thr Pro Thr Ile Met Asp Ile Val Val Ile Ala Gly 50 55 60 Val Ile Ala Ala Val Ala Ile Val Leu Val Ser Leu Leu Phe Val Met 65 70 75 80 Leu Arg Tyr Met Tyr Arg His Lys Gly Thr Tyr His Thr Asn Glu Ala 85 90 95 Lys Gly Thr Glu Phe Ala Glu Ser Ala Asp Ala Ala Leu Gln Gly Asp 100 105 110 Pro Ala Leu Gln Asp Ala Gly Asp Ser Ser Arg Lys Glu Tyr Phe Ile 115 120 125 <210> 26 <211> 134 <212> PRT <213> artificial sequence <220> <223> ANFB_ human beings <400> 26 Met Asp Pro Gln Thr Ala Pro Ser Arg Ala Leu Leu Leu Leu Leu Phe 1 5 10 15 Leu His Leu Ala Phe Leu Gly Gly Arg Ser His Pro Leu Gly Ser Pro 20 25 30 Gly Ser Ala Ser Asp Leu Glu Thr Ser Gly Leu Gln Glu Gln Arg Asn 35 40 45 His Leu Gln Gly Lys Leu Ser Glu Leu Gln Val Glu Gln Thr Ser Leu 50 55 60 Glu Pro Leu Gln Glu Ser Pro Arg Pro Thr Gly Val Trp Lys Ser Arg 65 70 75 80 Glu Val Ala Thr Glu Gly Ile Arg Gly His Arg Lys Met Val Leu Tyr 85 90 95 Thr Leu Arg Ala Pro Arg Ser Pro Lys Met Val Gln Gly Ser Gly Cys 100 105 110 Phe Gly Arg Lys Met Asp Arg Ile Ser Ser Ser Ser Gly Leu Gly Cys 115 120 125 Lys Val Leu Arg Arg His 130 <210> 27 <211> 144 <212> PRT <213> artificial sequence <220> <223> CSF2_ human <400> 27 Met Trp Leu Gln Ser Leu Leu Leu Leu Gly Thr Val Ala Cys Ser Ile 1 5 10 15 Ser Ala Pro Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro Trp Glu His 20 25 30 Val Asn Ala Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu Ser Arg Asp 35 40 45 Thr Ala Ala Glu Met Asn Glu Thr Val Glu Val Ile Ser Glu Met Phe 50 55 60 Asp Leu Gln Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr Lys 65 70 75 80 Gln Gly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu Thr Met 85 90 95 Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr Pro Glu Thr Ser 100 105 110 Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser Phe Lys Glu Asn Leu Lys 115 120 125 Asp Phe Leu Leu Val Ile Pro Phe Asp Cys Trp Glu Pro Val Gln Glu 130 135 140 <210> 28 <211> 150 <212> PRT <213> Artificial Sequence <220> <223> GLPA_Human <400> 28 Met Tyr Gly Lys Ile Ile Phe Val Leu Leu Leu Ser Glu Ile Val Ser 1 5 10 15 Ile Ser Ala Ser Ser Thr Thr Gly Val Ala Met His Thr Ser Thr Ser 20 25 30 Ser Ser Val Thr Lys Ser Tyr Ile Ser Ser Gln Thr Asn Asp Thr His 35 40 45 Lys Arg Asp Thr Tyr Ala Ala Thr Pro Arg Ala His Glu Val Ser Glu 50 55 60 Ile Ser Val Arg Thr Val Tyr Pro Pro Glu Glu Glu Thr Gly Glu Arg 65 70 75 80 Val Gln Leu Ala His His Phe Ser Glu Pro Glu Ile Thr Leu Ile Ile 85 90 95 Phe Gly Val Met Ala Gly Val Ile Gly Thr Ile Leu Leu Ile Ser Tyr 100 105 110 Gly Ile Arg Arg Leu Ile Lys Lys Ser Pro Ser Asp Val Lys Pro Leu 115 120 125 Pro Ser Pro Asp Thr Asp Val Pro Leu Ser Ser Val Glu Ile Glu Asn 130 135 140 Pro Glu Thr Ser Asp Gln 145 150 <210> 29 <211> 158 <212> PRT <213> artificial sequence <220> <223> SRGN_ human beings <400> 29 Met Met Gln Lys Leu Leu Lys Cys Ser Arg Leu Val Leu Ala Leu Ala 1 5 10 15 Leu Ile Leu Val Leu Glu Ser Ser Val Gln Gly Tyr Pro Thr Arg Arg 20 25 30 Ala Arg Tyr Gln Trp Val Arg Cys Asn Pro Asp Ser Asn Ser Ala Asn 35 40 45 Cys Leu Glu Glu Lys Gly Pro Met Phe Glu Leu Leu Pro Gly Glu Ser 50 55 60 Asn Lys Ile Pro Arg Leu Arg Thr Asp Leu Phe Pro Lys Thr Arg Ile 65 70 75 80 Gln Asp Leu Asn Arg Ile Phe Pro Leu Ser Glu Asp Tyr Ser Gly Ser 85 90 95 Gly Phe Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Gly Phe 100 105 110 Leu Thr Glu Met Glu Gln Asp Tyr Gln Leu Val Asp Glu Ser Asp Ala 115 120 125 Phe His Asp Asn Leu Arg Ser Leu Asp Arg Asn Leu Pro Ser Asp Ser 130 135 140 Gln Asp Leu Gly Gln His Gly Leu Glu Glu Asp Phe Met Leu 145 150 155 <210> 30 <211> 162 <212> PRT <213> Artificial Sequence <220> <223> PDPN_Human <400> 30 Met Trp Lys Val Ser Ala Leu Leu Phe Val Leu Gly Ser Ala Ser Leu 1 5 10 15 Trp Val Leu Ala Glu Gly Ala Ser Thr Gly Gln Pro Glu Asp Asp Thr 20 25 30 Glu Thr Thr Gly Leu Glu Gly Gly Val Ala Met Pro Gly Ala Glu Asp 35 40 45 Asp Val Val Thr Pro Gly Thr Ser Glu Asp Arg Tyr Lys Ser Gly Leu 50 55 60 Thr Thr Leu Val Ala Thr Ser Val Asn Ser Val Thr Gly Ile Arg Ile 65 70 75 80 Glu Asp Leu Pro Thr Ser Glu Ser Thr Val His Ala Gln Glu Gln Ser 85 90 95 Pro Ser Ala Thr Ala Ser Asn Val Ala Thr Ser His Ser Thr Glu Lys 100 105 110 Val Asp Gly Asp Thr Gln Thr Thr Val Glu Lys Asp Gly Leu Ser Thr 115 120 125 Val Thr Leu Val Gly Ile Ile Val Gly Val Leu Leu Ala Ile Gly Phe 130 135 140 Ile Gly Ala Ile Ile Val Val Val Met Arg Lys Met Ser Gly Arg Tyr 145 150 155 160 Ser Pro <210> 31 <211> 165 <212> PRT <213> Artificial Sequence <220> <223> CGB7_Human <400> 31 Met Glu Met Phe Gln Gly Leu Leu Leu Leu Leu Leu Leu Ser Met Gly 1 5 10 15 Gly Thr Trp Ala Ser Arg Glu Met Leu Arg Pro Arg Cys Arg Pro Ile 20 25 30 Asn Ala Thr Leu Ala Val Glu Lys Glu Gly Cys Pro Val Cys Ile Thr 35 40 45 Val Asn Thr Thr Ile Cys Ala Gly Tyr Cys Pro Thr Met Thr Arg Val 50 55 60 Leu Gln Gly Val Leu Pro Ala Leu Pro Gln Val Val Cys Asn Tyr Arg 65 70 75 80 Asp Val Arg Phe Glu Ser Ile Arg Leu Pro Gly Cys Pro Arg Gly Val 85 90 95 Asn Pro Val Val Ser Tyr Ala Val Ala Leu Ser Cys Gln Cys Ala Leu 100 105 110 Cys Arg Arg Ser Thr Thr Asp Cys Gly Gly Pro Lys Asp His Pro Leu 115 120 125 Thr Cys Asp Asp Pro Arg Phe Gln Ala Ser Ser Ser Ser Lys Ala Pro 130 135 140 Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr 145 150 155 160 Pro Ile Leu Pro Gln 165 <210> 32 <211> 165 <212> PRT <213> artificial sequence <220> <223> CGB3_ humans <400> 32 Met Glu Met Phe Gln Gly Leu Leu Leu Leu Leu Leu Leu Leu Ser Met Gly 1 5 10 15 Gly Thr Trp Ala Ser Lys Glu Pro Leu Arg Pro Arg Cys Arg Pro Ile 20 25 30 Asn Ala Thr Leu Ala Val Glu Lys Glu Gly Cys Pro Val Cys Ile Thr 35 40 45 Val Asn Thr Thr Ile Cys Ala Gly Tyr Cys Pro Thr Met Thr Arg Val 50 55 60 Leu Gln Gly Val Leu Pro Ala Leu Pro Gln Val Val Cys Asn Tyr Arg 65 70 75 80 Asp Val Arg Phe Glu Ser Ile Arg Leu Pro Gly Cys Pro Arg Gly Val 85 90 95 Asn Pro Val Val Ser Tyr Ala Val Ala Leu Ser Cys Gln Cys Ala Leu 100 105 110 Cys Arg Arg Ser Thr Thr Asp Cys Gly Gly Pro Lys Asp His Pro Leu 115 120 125 Thr Cys Asp Asp Pro Arg Phe Gln Asp Ser Ser Ser Ser Lys Ala Pro 130 135 140 Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr 145 150 155 160 Pro Ile Leu Pro Gln 165 <210> 33 <211> 180 <212> PRT <213> artificial sequence <220> <223> IGF2_ humans <400> 33 Met Gly Ile Pro Met Gly Lys Ser Met Leu Val Leu Leu Thr Phe Leu 1 5 10 15 Ala Phe Ala Ser Cys Cys Ile Ala Ala Tyr Arg Pro Ser Glu Thr Leu 20 25 30 Cys Gly Gly Glu Leu Val Asp Thr Leu Gln Phe Val Cys Gly Asp Arg 35 40 45 Gly Phe Tyr Phe Ser Arg Pro Ala Ser Arg Val Ser Arg Arg Ser Arg 50 55 60 Gly Ile Val Glu Glu Cys Cys Phe Arg Ser Cys Asp Leu Ala Leu Leu 65 70 75 80 Glu Thr Tyr Cys Ala Thr Pro Ala Lys Ser Glu Arg Asp Val Ser Thr 85 90 95 Pro Pro Thr Val Leu Pro Asp Asn Phe Pro Arg Tyr Pro Val Gly Lys 100 105 110 Phe Phe Gln Tyr Asp Thr Trp Lys Gln Ser Thr Gln Arg Leu Arg Arg 115 120 125 Gly Leu Pro Ala Leu Leu Arg Ala Arg Arg Gly His Val Leu Ala Lys 130 135 140 Glu Leu Glu Ala Phe Arg Glu Ala Lys Arg His Arg Pro Leu Ile Ala 145 150 155 160 Leu Pro Thr Gln Asp Pro Ala His Gly Gly Ala Pro Pro Glu Met Ala 165 170 175 Ser Asn Arg Lys 180 <210> 34 <211> 182 <212> PRT <213> artificial sequence <220> <223> CASK_ human beings <400> 34 Met Lys Ser Phe Leu Leu Val Val Asn Ala Leu Ala Leu Thr Leu Pro 1 5 10 15 Phe Leu Ala Val Glu Val Gln Asn Gln Lys Gln Pro Ala Cys His Glu 20 25 30 Asn Asp Glu Arg Pro Phe Tyr Gln Lys Thr Ala Pro Tyr Val Pro Met 35 40 45 Tyr Tyr Val Pro Asn Ser Tyr Pro Tyr Tyr Gly Thr Asn Leu Tyr Gln 50 55 60 Arg Arg Pro Ala Ile Ala Ile Asn Asn Pro Tyr Val Pro Arg Thr Tyr 65 70 75 80 Tyr Ala Asn Pro Ala Val Val Arg Pro His Ala Gln Ile Pro Gln Arg 85 90 95 Gln Tyr Leu Pro Asn Ser His Pro Pro Thr Val Val Arg Arg Pro Asn 100 105 110 Leu His Pro Ser Phe Ile Ala Ile Pro Pro Lys Lys Ile Gln Asp Lys 115 120 125 Ile Ile Ile Pro Thr Ile Asn Thr Ile Ala Thr Val Glu Pro Thr Pro 130 135 140 Ala Pro Ala Thr Glu Pro Thr Val Asp Ser Val Val Thr Pro Glu Ala 145 150 155 160 Phe Ser Glu Ser Ile Ile Thr Ser Thr Pro Glu Thr Thr Thr Val Ala 165 170 175 Wave Thr Pro Pro Thr Ala 180 <210> 35 <211> 198 <212> PRT <213> artificial sequence <220> <223> SDC4_ human beings <400> 35 Met Ala Pro Ala Arg Leu Phe Ala Leu Leu Leu Phe Phe Val Gly Gly 1 5 10 15 Val Ala Glu Ser Ile Arg Glu Thr Glu Val Ile Asp Pro Gln Asp Leu 20 25 30 Leu Glu Gly Arg Tyr Phe Ser Gly Ala Leu Pro Asp Asp Glu Asp Val 35 40 45 Val Gly Pro Gly Gln Glu Ser Asp Asp Phe Glu Leu Ser Gly Ser Gly 50 55 60 Asp Leu Asp Asp Leu Glu Asp Ser Met Ile Gly Pro Glu Val Val His 65 70 75 80 Pro Leu Val Pro Leu Asp Asn His Ile Pro Glu Arg Ala Gly Ser Gly 85 90 95 Ser Gln Val Pro Thr Glu Pro Lys Lys Leu Glu Glu Asn Glu Val Ile 100 105 110 Pro Lys Arg Ile Ser Pro Val Glu Glu Ser Glu Asp Val Ser Asn Lys 115 120 125 Val Ser Met Ser Ser Thr Val Gln Gly Ser Asn Ile Phe Glu Arg Thr 130 135 140 Glu Val Leu Ala Ala Leu Ile Val Gly Gly Ile Val Gly Ile Leu Phe 145 150 155 160 Ala Val Phe Leu Ile Leu Leu Leu Met Tyr Arg Met Lys Lys Lys Asp 165 170 175 Glu Gly Ser Tyr Asp Leu Gly Lys Lys Pro Ile Tyr Lys Lys Ala Pro 180 185 190 Thr Asn Glu Phe Tyr Ala 195 <210> 36 <211> 201 <212> PRT <213> artificial sequence <220> <223> SDC2_ humans <400> 36 Met Arg Arg Ala Trp Ile Leu Leu Thr Leu Gly Leu Val Ala Cys Val 1 5 10 15 Ser Ala Glu Ser Arg Ala Glu Leu Thr Ser Asp Lys Asp Met Tyr Leu 20 25 30 Asp Asn Ser Ser Ile Glu Glu Ala Ser Gly Val Tyr Pro Ile Asp Asp 35 40 45 Asp Asp Tyr Ala Ser Ala Ser Gly Ser Gly Ala Asp Glu Asp Val Glu 50 55 60 Ser Pro Glu Leu Thr Thr Ser Arg Pro Leu Pro Lys Ile Leu Leu Thr 65 70 75 80 Ser Ala Ala Pro Lys Val Glu Thr Thr Thr Leu Asn Ile Gln Asn Lys 85 90 95 Ile Pro Ala Gln Thr Lys Ser Pro Glu Glu Thr Asp Lys Glu Lys Val 100 105 110 His Leu Ser Asp Ser Glu Arg Lys Met Asp Pro Ala Glu Glu Asp Thr 115 120 125 Asn Val Tyr Thr Glu Lys His Ser Asp Ser Leu Phe Lys Arg Thr Glu 130 135 140 Val Leu Ala Ala Val Ile Ala Gly Gly Val Ile Gly Phe Leu Phe Ala 145 150 155 160 Ile Phe Leu Ile Leu Leu Leu Val Tyr Arg Met Arg Lys Lys Asp Glu 165 170 175 Gly Ser Tyr Asp Leu Gly Glu Arg Lys Pro Ser Ser Ala Ala Tyr Gln 180 185 190 Lys Ala Pro Thr Lys Glu Phe Tyr Ala 195 200 <210> 37 <211> 208 <212> PRT <213> artificial sequence <220> <223> HBEGF_ human beings <400> 37 Met Lys Leu Leu Pro Ser Val Val Leu Lys Leu Phe Leu Ala Ala Val 1 5 10 15 Leu Ser Ala Leu Val Thr Gly Glu Ser Leu Glu Arg Leu Arg Arg Gly 20 25 30 Leu Ala Ala Gly Thr Ser Asn Pro Asp Pro Pro Thr Val Ser Thr Asp 35 40 45 Gln Leu Leu Pro Leu Gly Gly Gly Arg Asp Arg Lys Val Arg Asp Leu 50 55 60 Gln Glu Ala Asp Leu Asp Leu Leu Arg Val Thr Leu Ser Ser Lys Pro 65 70 75 80 Gln Ala Leu Ala Thr Pro Asn Lys Glu Glu His Gly Lys Arg Lys Lys 85 90 95 Lys Gly Lys Gly Leu Gly Lys Lys Arg Asp Pro Cys Leu Arg Lys Tyr 100 105 110 Lys Asp Phe Cys Ile His Gly Glu Cys Lys Tyr Val Lys Glu Leu Arg 115 120 125 Ala Pro Ser Cys Ile Cys His Pro Gly Tyr His Gly Glu Arg Cys His 130 135 140 Gly Leu Ser Leu Pro Val Glu Asn Arg Leu Tyr Thr Tyr Asp His Thr 145 150 155 160 Thr Ile Leu Ala Val Val Ala Val Val Leu Ser Ser Val Cys Leu Leu 165 170 175 Val Ile Val Gly Leu Leu Met Phe Arg Tyr His Arg Arg Gly Gly Tyr 180 185 190 Asp Val Glu Asn Glu Glu Lys Val Lys Leu Gly Met Thr Asn Ser His 195 200 205 <210> 38 <211> 222 <212> PRT <213> artificial sequence <220> <223> PRG2_ humans <400> 38 Met Lys Leu Pro Leu Leu Leu Ala Leu Leu Phe Gly Ala Val Ser Ala 1 5 10 15 Leu His Leu Arg Ser Glu Thr Ser Thr Phe Glu Thr Pro Leu Gly Ala 20 25 30 Lys Thr Leu Pro Glu Asp Glu Glu Thr Pro Glu Gln Glu Met Glu Glu 35 40 45 Thr Pro Cys Arg Glu Leu Glu Glu Glu Glu Glu Trp Gly Ser Gly Ser 50 55 60 Glu Asp Ala Ser Lys Lys Asp Gly Ala Val Glu Ser Ile Ser Val Pro 65 70 75 80 Asp Met Val Asp Lys Asn Leu Thr Cys Pro Glu Glu Glu Asp Thr Val 85 90 95 Lys Val Val Gly Ile Pro Gly Cys Gln Thr Cys Arg Tyr Leu Leu Val 100 105 110 Arg Ser Leu Gln Thr Phe Ser Gln Ala Trp Phe Thr Cys Arg Arg Cys 115 120 125 Tyr Arg Gly Asn Leu Val Ser Ile His Asn Phe Asn Ile Asn Tyr Arg 130 135 140 Ile Gln Cys Ser Val Ser Ala Leu Asn Gln Gly Gln Val Trp Ile Gly 145 150 155 160 Gly Arg Ile Thr Gly Ser Gly Arg Cys Arg Arg Phe Gln Trp Val Asp 165 170 175 Gly Ser Arg Trp Asn Phe Ala Tyr Trp Ala Ala His Gln Pro Trp Ser 180 185 190 Arg Gly Gly His Cys Val Ala Leu Cys Thr Arg Gly Gly His Trp Arg 195 200 205 Arg Ala His Cys Leu Arg Arg Leu Pro Phe Ile Cys Ser Tyr 210 215 220 <210> 39 <211> 240 <212> PRT <213> Artificial Sequence <220> <223> IBP6_Human <400> 39 Met Thr Pro His Arg Leu Leu Pro Pro Leu Leu Leu Leu Leu Ala Leu 1 5 10 15 Leu Leu Ala Ala Ser Pro Gly Gly Ala Leu Ala Arg Cys Pro Gly Cys 20 25 30 Gly Gln Gly Val Gln Ala Gly Cys Pro Gly Gly Cys Val Glu Glu Glu 35 40 45 Asp Gly Gly Ser Pro Ala Glu Gly Cys Ala Glu Ala Glu Gly Cys Leu 50 55 60 Arg Arg Glu Gly Gln Glu Cys Gly Val Tyr Thr Pro Asn Cys Ala Pro 65 70 75 80 Gly Leu Gln Cys His Pro Pro Lys Asp Asp Glu Ala Pro Leu Arg Ala 85 90 95 Leu Leu Leu Gly Arg Gly Arg Cys Leu Pro Ala Arg Ala Pro Ala Val 100 105 110 Ala Glu Glu Asn Pro Lys Glu Ser Lys Pro Gln Ala Gly Thr Ala Arg 115 120 125 Pro Gln Asp Val Asn Arg Arg Asp Gln Gln Arg Asn Pro Gly Thr Ser 130 135 140 Thr Thr Pro Ser Gln Pro Asn Ser Ala Gly Val Gln Asp Thr Glu Met 145 150 155 160 Gly Pro Cys Arg Arg His Leu Asp Ser Val Leu Gln Gln Leu Gln Thr 165 170 175 Glu Val Tyr Arg Gly Ala Gln Thr Leu Tyr Val Pro Asn Cys Asp His 180 185 190 Arg Gly Phe Tyr Arg Lys Arg Gln Cys Arg Ser Ser Gln Gly Gln Arg 195 200 205 Arg Gly Pro Cys Trp Cys Val Asp Arg Met Gly Lys Ser Leu Pro Gly 210 215 220 Ser Pro Asp Gly Asn Gly Ser Ser Ser Cys Pro Thr Gly Ser Ser Gly 225 230 235 240 <210> 40 <211> 260 <212> PRT <213> Artificial Sequence <220> <223> PCSK1_Human <400> 40 Met Ala Gly Ser Pro Leu Leu Trp Gly Pro Arg Ala Gly Gly Val Gly 1 5 10 15 Leu Leu Val Leu Leu Leu Leu Gly Leu Phe Arg Pro Pro Pro Ala Leu 20 25 30 Cys Ala Arg Pro Val Lys Glu Pro Arg Gly Leu Ser Ala Ala Ser Pro 35 40 45 Pro Leu Ala Glu Thr Gly Ala Pro Arg Arg Phe Arg Arg Ser Val Pro 50 55 60 Arg Gly Glu Ala Ala Gly Ala Val Gln Glu Leu Ala Arg Ala Leu Ala 65 70 75 80 His Leu Leu Glu Ala Glu Arg Gln Glu Arg Ala Arg Ala Glu Ala Gln 85 90 95 Glu Ala Glu Asp Gln Gln Ala Arg Val Leu Ala Gln Leu Leu Arg Val 100 105 110 Trp Gly Ala Pro Arg Asn Ser Asp Pro Ala Leu Gly Leu Asp Asp Asp 115 120 125 Pro Asp Ala Pro Ala Ala Gln Leu Ala Arg Ala Leu Leu Arg Ala Arg 130 135 140 Leu Asp Pro Ala Ala Leu Ala Ala Gln Leu Val Pro Ala Pro Val Pro 145 150 155 160 Ala Ala Ala Leu Arg Pro Arg Pro Pro Val Tyr Asp Asp Gly Pro Ala 165 170 175 Gly Pro Asp Ala Glu Glu Ala Gly Asp Glu Thr Pro Asp Val Asp Pro 180 185 190 Glu Leu Leu Arg Tyr Leu Leu Gly Arg Ile Leu Ala Gly Ser Ala Asp 195 200 205 Ser Glu Gly Val Ala Ala Pro Arg Arg Leu Arg Arg Ala Ala Asp His 210 215 220 Asp Val Gly Ser Glu Leu Pro Pro Glu Gly Val Leu Gly Ala Leu Leu 225 230 235 240 Arg Val Lys Arg Leu Glu Thr Pro Ala Pro Gln Val Pro Ala Arg Arg 245 250 255 Leo Leo Pro Pro 260 <210> 41 <211> 272 <212> PRT <213> artificial sequence <220> <223> IL2RA_ humans <400> 41 Met Asp Ser Tyr Leu Leu Met Trp Gly Leu Leu Thr Phe Ile Met Val 1 5 10 15 Pro Gly Cys Gln Ala Glu Leu Cys Asp Asp Asp Pro Pro Glu Ile Pro 20 25 30 His Ala Thr Phe Lys Ala Met Ala Tyr Lys Glu Gly Thr Met Leu Asn 35 40 45 Cys Glu Cys Lys Arg Gly Phe Arg Arg Ile Lys Ser Gly Ser Leu Tyr 50 55 60 Met Leu Cys Thr Gly Asn Ser Ser His Ser Ser Trp Asp Asn Gln Cys 65 70 75 80 Gln Cys Thr Ser Ser Ala Thr Arg Asn Thr Thr Lys Gln Val Thr Pro 85 90 95 Gln Pro Glu Glu Gln Lys Glu Arg Lys Thr Thr Glu Met Gln Ser Pro 100 105 110 Met Gln Pro Val Asp Gln Ala Ser Leu Pro Gly His Cys Arg Glu Pro 115 120 125 Pro Pro Trp Glu Asn Glu Ala Thr Glu Arg Ile Tyr His Phe Val Val 130 135 140 Gly Gln Met Val Tyr Tyr Gln Cys Val Gln Gly Tyr Arg Ala Leu His 145 150 155 160 Arg Gly Pro Ala Glu Ser Val Cys Lys Met Thr His Gly Lys Thr Arg 165 170 175 Trp Thr Gln Pro Gln Leu Ile Cys Thr Gly Glu Met Glu Thr Ser Gln 180 185 190 Phe Pro Gly Glu Glu Lys Pro Gln Ala Ser Pro Glu Gly Arg Pro Glu 195 200 205 Ser Glu Thr Ser Cys Leu Val Thr Thr Thr Asp Phe Gln Ile Gln Thr 210 215 220 Glu Met Ala Ala Thr Met Glu Thr Ser Ile Phe Thr Thr Glu Tyr Gln 225 230 235 240 Val Ala Val Ala Gly Cys Val Phe Leu Leu Ile Ser Val Leu Leu Leu 245 250 255 Ser Gly Leu Thr Trp Gln Arg Arg Gln Arg Lys Ser Arg Arg Thr Ile 260 265 270 <210> 42 <211> 273 <212> PRT <213> artificial sequence <220> <223> SCF_ human beings <400> 42 Met Lys Lys Thr Gln Thr Trp Ile Leu Thr Cys Ile Tyr Leu Gln Leu 1 5 10 15 Leu Leu Phe Asn Pro Leu Val Lys Thr Glu Gly Ile Cys Arg Asn Arg 20 25 30 Val Thr Asn Asn Val Lys Asp Val Thr Lys Leu Val Ala Asn Leu Pro 35 40 45 Lys Asp Tyr Met Ile Thr Leu Lys Tyr Val Pro Gly Met Asp Val Leu 50 55 60 Pro Ser His Cys Trp Ile Ser Glu Met Val Val Gln Leu Ser Asp Ser 65 70 75 80 Leu Thr Asp Leu Leu Asp Lys Phe Ser Asn Ile Ser Glu Gly Leu Ser 85 90 95 Asn Tyr Ser Ile Ile Asp Lys Leu Val Asn Ile Val Asp Asp Leu Val 100 105 110 Glu Cys Val Lys Glu Asn Ser Ser Lys Asp Leu Lys Lys Ser Phe Lys 115 120 125 Ser Pro Glu Pro Arg Leu Phe Thr Pro Glu Glu Phe Phe Arg Ile Phe 130 135 140 Asn Arg Ser Ile Asp Ala Phe Lys Asp Phe Val Val Ala Ser Glu Thr 145 150 155 160 Ser Asp Cys Val Val Ser Ser Thr Leu Ser Pro Glu Lys Asp Ser Arg 165 170 175 Val Ser Val Thr Lys Pro Phe Met Leu Pro Pro Val Ala Ala Ser Ser 180 185 190 Leo Arg Asn Asp Ser Ser Ser Ser Asn Arg Lys Ala Lys Asn Pro Pro 195 200 205 Gly Asp Ser Ser Leu His Trp Ala Ala Met Ala Leu Pro Ala Leu Phe 210 215 220 Ser Leu Ile Ile Gly Phe Ala Phe Gly Ala Leu Tyr Trp Lys Lys Arg 225 230 235 240 Gln Pro Ser Leu Thr Arg Ala Val Glu Asn Ile Gln Ile Asn Glu Glu 245 250 255 Asp Asn Glu Ile Ser Met Leu Gln Glu Lys Glu Arg Glu Phe Gln Glu 260 265 270 Wave <210> 43 <211> 279 <212> PRT <213> artificial sequence <220> <223> ODAM_ man <400> 43 Met Lys Ile Ile Ile Leu Leu Gly Phe Leu Gly Ala Thr Leu Ser Ala 1 5 10 15 Pro Leu Ile Pro Gln Arg Leu Met Ser Ala Ser Asn Ser Asn Glu Leu 20 25 30 Leu Leu Asn Leu Asn Asn Gly Gln Leu Leu Pro Leu Gln Leu Gln Gly 35 40 45 Pro Leu Asn Ser Trp Ile Pro Pro Phe Ser Gly Ile Leu Gln Gln Gln 50 55 60 Gln Gln Ala Gln Ile Pro Gly Leu Ser Gln Phe Ser Leu Ser Ala Leu 65 70 75 80 Asp Gln Phe Ala Gly Leu Leu Pro Asn Gln Ile Pro Leu Thr Gly Glu 85 90 95 Ala Ser Phe Ala Gln Gly Ala Gln Ala Gly Gln Val Asp Pro Leu Gln 100 105 110 Leu Gln Thr Pro Pro Gln Thr Gln Pro Gly Pro Ser His Val Met Pro 115 120 125 Tyr Val Phe Ser Phe Lys Met Pro Gln Glu Gln Gly Gln Met Phe Gln 130 135 140 Tyr Tyr Pro Val Tyr Met Val Leu Pro Trp Glu Gln Pro Gln Gln Thr 145 150 155 160 Val Pro Arg Ser Pro Gln Gln Thr Arg Gln Gln Gln Tyr Glu Glu Gln 165 170 175 Ile Pro Phe Tyr Ala Gln Phe Gly Tyr Ile Pro Gln Leu Ala Glu Pro 180 185 190 Ala Ile Ser Gly Gly Gln Gln Gln Leu Ala Phe Asp Pro Gln Leu Gly 195 200 205 Thr Ala Pro Glu Ile Ala Val Met Ser Thr Gly Glu Glu Ile Pro Tyr 210 215 220 Leu Gln Lys Glu Ala Ile Asn Phe Arg His Asp Ser Ala Gly Val Phe 225 230 235 240 Met Pro Ser Thr Ser Pro Lys Pro Ser Thr Thr Asn Val Phe Thr Ser 245 250 255 Ala Val Asp Gln Thr Ile Thr Pro Glu Leu Pro Glu Glu Lys Asp Lys 260 265 270 Thr Asp Ser Leu Arg Glu Pro 275 <210> 44 <211> 314 <212> PRT <213> Artificial Sequence <220> <223> OSTP_Human <400> 44 Met Arg Ile Ala Val Ile Cys Phe Cys Leu Leu Gly Ile Thr Cys Ala 1 5 10 15 Ile Pro Val Lys Gln Ala Asp Ser Gly Ser Ser Glu Glu Lys Gln Leu 20 25 30 Tyr Asn Lys Tyr Pro Asp Ala Val Ala Thr Trp Leu Asn Pro Asp Pro 35 40 45 Ser Gln Lys Gln Asn Leu Leu Ala Pro Gln Asn Ala Val Ser Ser Glu 50 55 60 Glu Thr Asn Asp Phe Lys Gln Glu Thr Leu Pro Ser Lys Ser Asn Glu 65 70 75 80 Ser His Asp His Met Asp Asp Met Asp Asp Glu Asp Asp Asp Asp His 85 90 95 Val Asp Ser Gln Asp Ser Ile Asp Ser Asn Asp Ser Asp Asp Val Asp 100 105 110 Asp Thr Asp Asp Ser His Gln Ser Asp Glu Ser His His Ser Asp Glu 115 120 125 Ser Asp Glu Leu Val Thr Asp Phe Pro Thr Asp Leu Pro Ala Thr Glu 130 135 140 Val Phe Thr Pro Val Val Pro Thr Val Asp Thr Tyr Asp Gly Arg Gly 145 150 155 160 Asp Ser Val Val Tyr Gly Leu Arg Ser Lys Ser Lys Lys Phe Arg Arg 165 170 175 Pro Asp Ile Gln Tyr Pro Asp Ala Thr Asp Glu Asp Ile Thr Ser His 180 185 190 Met Glu Ser Glu Glu Leu Asn Gly Ala Tyr Lys Ala Ile Pro Val Ala 195 200 205 Gln Asp Leu Asn Ala Pro Ser Asp Trp Asp Ser Arg Gly Lys Asp Ser 210 215 220 Tyr Glu Thr Ser Gln Leu Asp Asp Gln Ser Ala Glu Thr His Ser His 225 230 235 240 Lys Gln Ser Arg Leu Tyr Lys Arg Lys Ala Asn Asp Glu Ser Asn Glu 245 250 255 His Ser Asp Val Ile Asp Ser Gln Glu Leu Ser Lys Val Ser Arg Glu 260 265 270 Phe His Ser His Glu Phe His Ser His Glu Asp Met Leu Val Val Asp 275 280 285 Pro Lys Ser Lys Glu Glu Asp Lys His Leu Lys Phe Arg Ile Ser His 290 295 300 Glu Leu Asp Ser Ala Ser Ser Glu Val Asn 305 310 <210> 45 <211> 317 <212> PRT <213> Artificial Sequence <220> <223> SIAL_Human <400> 45 Met Lys Thr Ala Leu Ile Leu Leu Ser Ile Leu Gly Met Ala Cys Ala 1 5 10 15 Phe Ser Met Lys Asn Leu His Arg Arg Val Lys Ile Glu Asp Ser Glu 20 25 30 Glu Asn Gly Val Phe Lys Tyr Arg Pro Arg Tyr Tyr Leu Tyr Lys His 35 40 45 Ala Tyr Phe Tyr Pro His Leu Lys Arg Phe Pro Val Gln Gly Ser Ser 50 55 60 Asp Ser Ser Glu Glu Asn Gly Asp Asp Ser Ser Glu Glu Glu Glu Glu 65 70 75 80 Glu Glu Glu Thr Ser Asn Glu Gly Glu Asn Asn Glu Glu Ser Asn Glu 85 90 95 Asp Glu Asp Ser Glu Ala Glu Asn Thr Thr Leu Ser Ala Thr Thr Leu 100 105 110 Gly Tyr Gly Glu Asp Ala Thr Pro Gly Thr Gly Tyr Thr Gly Leu Ala 115 120 125 Ala Ile Gln Leu Pro Lys Lys Ala Gly Asp Ile Thr Asn Lys Ala Thr 130 135 140 Lys Glu Lys Glu Ser Asp Glu Glu Glu Glu Glu Glu Glu Glu Gly Asn 145 150 155 160 Glu Asn Glu Glu Ser Glu Ala Glu Val Asp Glu Asn Glu Gln Gly Ile 165 170 175 Asn Gly Thr Ser Thr Asn Ser Thr Glu Ala Glu Asn Gly Asn Gly Ser 180 185 190 Ser Gly Gly Asp Asn Gly Glu Glu Gly Glu Glu Glu Ser Val Thr Gly 195 200 205 Ala Asn Ala Glu Asp Thr Thr Glu Thr Gly Arg Gln Gly Lys Gly Thr 210 215 220 Ser Lys Thr Thr Thr Ser Pro Asn Gly Gly Phe Glu Pro Thr Thr Pro 225 230 235 240 Pro Gln Val Tyr Arg Thr Thr Ser Pro Pro Phe Gly Lys Thr Thr Thr 245 250 255 Val Glu Tyr Glu Gly Glu Tyr Glu Tyr Thr Gly Ala Asn Glu Tyr Asp 260 265 270 Asn Gly Tyr Glu Ile Tyr Glu Ser Glu Asn Gly Glu Pro Arg Gly Asp 275 280 285 Asn Tyr Arg Ala Tyr Glu Asp Glu Tyr Ser Tyr Phe Lys Gly Gln Gly 290 295 300 Tyr Asp Gly Tyr Asp Gly Gln Asn Tyr Tyr His His Gln 305 310 315 <210> 46 <211> 317 <212> PRT <213> Artificial Sequence <220> <223> APOE_Human <400> 46 Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys 1 5 10 15 Gln Ala Lys Val Glu Gln Ala Val Glu Thr Glu Pro Glu Pro Glu Leu 20 25 30 Arg Gln Gln Thr Glu Trp Gln Ser Gly Gln Arg Trp Glu Leu Ala Leu 35 40 45 Gly Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln 50 55 60 Val Gln Glu Glu Leu Leu Ser Ser Gln Val Thr Gln Glu Leu Arg Ala 65 70 75 80 Leu With Asp Glu Thr With Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu 85 90 95 Glu Glu Gln Leu Thr Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser 100 105 110 Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp With Glu Asp 115 120 125 Val Cys Gly Arg Leu Val Gln Tyr Arg Gly Glu Val Gln Ala With Leu 130 135 140 Gly Gln Ser Thr Glu Glu Leu Arg Val Arg Leu Ala Ser His Leu Arg 145 150 155 160 Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg 165 170 175 Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Leu 180 185 190 Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val 195 200 205 Arg Ala Ala Thr Val Gly Ser Leu Ala Gly Gln Pro Leu Gln Glu Arg 210 215 220 Ala Gln Ala Trp Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Met Gly 225 230 235 240 Ser Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu 245 250 255 Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Arg Leu Gln Ala 260 265 270 Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu 275 280 285 Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala 290 295 300 Val Gly Thr Ser Ala Ala Pro Val Pro Ser Asp Asn His 305 310 315 <210> 47 <211> 322 <212> PRT <213> artificial sequence <220> <223> EPYC_ human beings <400> 47 Met Lys Thr Leu Ala Gly Leu Val Leu Gly Leu Val Ile Phe Asp Ala 1 5 10 15 Ala Val Thr Ala Pro Thr Leu Glu Ser Ile Asn Tyr Asp Ser Glu Thr 20 25 30 Tyr Asp Ala Thr Leu Glu Asp Leu Asp Asn Leu Tyr Asn Tyr Glu Asn 35 40 45 Ile Pro Val Asp Lys Val Glu Ile Glu Ile Ala Thr Val Met Pro Ser 50 55 60 Gly Asn Arg Glu Leu Leu Thr Pro Pro Pro Gln Pro Glu Lys Ala Gln 65 70 75 80 Glu Glu Glu Glu Glu Glu Glu Ser Thr Pro Arg Leu Ile Asp Gly Ser 85 90 95 Ser Pro Gln Glu Pro Glu Phe Thr Gly Val Leu Gly Pro His Thr Asn 100 105 110 Glu Asp Phe Pro Thr Cys Leu Leu Cys Thr Cys Ile Ser Thr Thr Val 115 120 125 Tyr Cys Asp Asp His Glu Leu Asp Ala Ile Pro Pro Leu Pro Lys Asn 130 135 140 Thr Ala Tyr Phe Tyr Ser Arg Phe Asn Arg Ile Lys Lys Ile Asn Lys 145 150 155 160 Asn Asp Phe Ala Ser Leu Ser Asp Leu Lys Arg Ile Asp Leu Thr Ser 165 170 175 Asn Leu Ile Ser Glu Ile Asp Glu Asp Ala Phe Arg Lys Leu Pro Gln 180 185 190 Leu Arg Glu Leu Val Leu Arg Asp Asn Lys Ile Arg Gln Leu Pro Glu 195 200 205 Leu Pro Thr Thr Leu Thr Phe Ile Asp Ile Ser Asn Asn Arg Leu Gly 210 215 220 Arg Lys Gly Ile Lys Gln Glu Ala Phe Lys Asp Met Tyr Asp Leu His 225 230 235 240 His Leu Tyr Leu Thr Asp Asn Asn Leu Asp His Ile Pro Leu Pro Leu 245 250 255 Pro Glu Asn Leu Arg Ala Leu His Leu Gln Asn Asn Asn Ile Leu Glu 260 265 270 Met His Glu Asp Thr Phe Cys Asn Val Lys Asn Leu Thr Tyr Ile Arg 275 280 285 Lys Ala Leu Glu Asp Ile Arg Leu Asp Gly Asn Pro Ile Asn Leu Ser 290 295 300 Lys Thr Pro Gln Ala Tyr Met Cys Leu Pro Arg Leu Pro Val Gly Ser 305 310 315 320 Leo Val <210> 48 <211> 332 <212> PRT <213> artificial sequence <220> <223> CLM9_ humans <400> 48 Met Arg Leu Leu Val Leu Leu Trp Gly Cys Leu Leu Leu Pro Gly Tyr 1 5 10 15 Glu Ala Leu Glu Gly Pro Glu Glu Ile Ser Gly Phe Glu Gly Asp Thr 20 25 30 Val Ser Leu Gln Cys Thr Tyr Arg Glu Glu Leu Arg Asp His Arg Lys 35 40 45 Tyr Trp Cys Arg Lys Gly Gly Ile Leu Phe Ser Arg Cys Ser Gly Thr 50 55 60 Ile Tyr Ala Glu Glu Glu Gly Gln Glu Thr Met Lys Gly Arg Val Ser 65 70 75 80 Ile Arg Asp Ser Arg Gln Glu Leu Ser Leu Ile Val Thr Leu Trp Asn 85 90 95 Leu Thr Leu Gln Asp Ala Gly Glu Tyr Trp Cys Gly Val Glu Lys Arg 100 105 110 Gly Pro Asp Glu Ser Leu Leu Ile Ser Leu Phe Val Phe Pro Gly Pro 115 120 125 Cys Cys Pro Pro Ser Pro Ser Pro Thr Phe Gln Pro Leu Ala Thr Thr 130 135 140 Arg Leu Gln Pro Lys Ala Lys Ala Gln Gln Thr Gln Pro Pro Gly Leu 145 150 155 160 Thr Ser Pro Gly Leu Tyr Pro Ala Ala Thr Thr Ala Lys Gln Gly Lys 165 170 175 Thr Gly Ala Glu Ala Pro Pro Leu Pro Gly Thr Ser Gln Tyr Gly His 180 185 190 Glu Arg Thr Ser Gln Tyr Thr Gly Thr Ser Pro His Pro Ala Thr Ser 195 200 205 Pro Pro Ala Gly Ser Ser Arg Pro Pro Met Gln Leu Asp Ser Thr Ser 210 215 220 Ala Glu Asp Thr Ser Pro Ala Leu Ser Ser Gly Ser Ser Lys Pro Arg 225 230 235 240 Val Ser Ile Pro Met Val Arg Ile Leu Ala Pro Val Leu Val Leu Leu 245 250 255 Ser Leu Leu Ser Ala Ala Gly Leu Ile Ala Phe Cys Ser His Leu Leu 260 265 270 Leu Trp Arg Lys Glu Ala Gln Gln Ala Thr Glu Thr Gln Arg Asn Glu 275 280 285 Lys Phe Cys Leu Ser Arg Leu Thr Ala Glu Glu Lys Glu Ala Pro Ser 290 295 300 Gln Ala Pro Glu Gly Asp Val Ile Ser Met Pro Pro Leu His Thr Ser 305 310 315 320 Glu Glu Glu Leu Gly Phe Ser Lys Phe Val Ser Ala 325 330 <210> 49 <211> 350 <212> PRT <213> Artificial sequence <220> <223> YIPF3_Human <400> 49 Met Ala Thr Thr Ala Ala Pro Ala Gly Gly Ala Arg Asn Gly Ala Gly 1 5 10 15 Pro Glu Trp Gly Gly Phe Glu Glu Asn Ile Gln Gly Gly Gly Ser Ala 20 25 30 Val Ile Asp Met Glu Asn Met Asp Asp Thr Ser Gly Ser Ser Phe Glu 35 40 45 Asp Met Gly Glu Leu His Gln Arg Leu Arg Glu Glu Glu Val Asp Ala 50 55 60 Asp Ala Ala Asp Ala Ala Ala Ala Glu Glu Glu Asp Gly Glu Phe Leu 65 70 75 80 Gly Met Lys Gly Phe Lys Gly Gln Leu Ser Arg Gln Val Ala Asp Gln 85 90 95 Met Trp Gln Ala Gly Lys Arg Gln Ala Ser Arg Ala Phe Ser Leu Tyr 100 105 110 Ala Asn Ile Asp Ile Leu Arg Pro Tyr Phe Asp Val Glu Pro Ala Gln 115 120 125 Val Arg Ser Arg Leu Leu Glu Ser Met Ile Pro Ile Lys Met Val Asn 130 135 140 Phe Pro Gln Lys Ile Ala Gly Glu Leu Tyr Gly Pro Leu Met Leu Val 145 150 155 160 Phe Thr Leu Val Ala Ile Leu Leu His Gly Met Lys Thr Ser Asp Thr 165 170 175 Ile Ile Arg Glu Gly Thr Leu Met Gly Thr Ala Ile Gly Thr Cys Phe 180 185 190 Gly Tyr Trp Leu Gly Val Ser Ser Phe Ile Tyr Phe Leu Ala Tyr Leu 195 200 205 Cys Asn Ala Gln Ile Thr Met Leu Gln Met Leu Ala Leu Leu Gly Tyr 210 215 220 Gly Leu Phe Gly His Cys Ile Val Leu Phe Ile Thr Tyr Asn Ile His 225 230 235 240 Leu His Ala Leu Phe Tyr Leu Phe Trp Leu Leu Val Gly Gly Leu Ser 245 250 255 Thr Leu Arg Met Val Ala Val Leu Val Ser Arg Thr Val Gly Pro Thr 260 265 270 Gln Arg Leu Leu Leu Cys Gly Thr Leu Ala Ala Leu His Met Leu Phe 275 280 285 Leu Leu Tyr Leu His Phe Ala Tyr His Lys Val Val Glu Gly Ile Leu 290 295 300 Asp Thr Leu Glu Gly Pro Asn Ile Pro Pro Ile Gln Arg Val Pro Arg 305 310 315 320 Asp Ile Pro Ala Met Leu Pro Ala Ala Arg Leu Pro Thr Thr Val Leu 325 330 335 Asn Ala Thr Ala Lys Ala Val Ala Val Thr Leu Gln Ser His 340 345 350 <210> 50 <211> 352 <212> PRT <213> artificial sequence <220> <223> CCR5_ human <400> 50 Met Asp Tyr Gln Val Ser Ser Pro Ile Tyr Asp Ile Asn Tyr Tyr Thr 1 5 10 15 Ser Glu Pro Cys Gln Lys Ile Asn Val Lys Gln Ile Ala Ala Arg Leu 20 25 30 Leu Pro Pro Leu Tyr Ser Leu Val Phe Ile Phe Gly Phe Val Gly Asn 35 40 45 Met Leu Val Ile Leu Ile Leu Ile Asn Cys Lys Arg Leu Lys Ser Met 50 55 60 Thr Asp Ile Tyr Leu Leu Asn Leu Ala Ile Ser Asp Leu Phe Phe Leu 65 70 75 80 Leu Thr Val Pro Phe Trp Ala His Tyr Ala Ala Gln Trp Asp Phe 85 90 95 Gly Asn Thr Met Cys Gln Leu Leu Thr Gly Leu Tyr Phe Ile Gly Phe 100 105 110 Phe Ser Gly Ile Phe Phe Ile Ile Leu Leu Thr Ile Asp Arg Tyr Leu 115 120 125 Ala Val Val His Ala Val Phe Ala Leu Lys Ala Arg Thr Val Thr Phe 130 135 140 Gly Val Val Thr Ser Val Ile Thr Trp Val Val Ala Val Phe Ala Ser 145 150 155 160 Leu Pro Gly Ile Ile Phe Thr Arg Ser Gln Lys Glu Gly Leu His Tyr 165 170 175 Thr Cys Ser Ser His Phe Pro Tyr Ser Gln Tyr Gln Phe Trp Lys Asn 180 185 190 Phe Gln Thr Leu Lys Ile Val Ile Leu Gly Leu Val Leu Pro Leu Leu 195 200 205 Val Met Val Ile Cys Tyr Ser Gly Ile Leu Lys Thr Leu Leu Arg Cys 210 215 220 Arg Asn Glu Lys Lys Arg His Arg Ala Val Arg Leu Ile Phe Thr Ile 225 230 235 240 Met Ile Val Tyr Phe Leu Phe Trp Ala Pro Tyr Asn Ile Val Leu Leu 245 250 255 Leu Asn Thr Phe Gln Glu Phe Phe Gly Leu Asn Asn Cys Ser Ser Ser 260 265 270 Asn Arg Leu Asp Gln Ala Met Gln Val Thr Glu Thr Leu Gly Met Thr 275 280 285 His Cys Cys Ile Asn Pro Ile Ile Tyr Ala Phe Val Gly Glu Lys Phe 290 295 300 Arg Asn Tyr Leu Leu Val Phe Phe Gln Lys His Ile Ala Lys Arg Phe 305 310 315 320 Cys Lys Cys Cys Ser Ile Phe Gln Gln Glu Ala Pro Glu Arg Ala Ser 325 330 335 Ser Val Tyr Thr Arg Ser Thr Gly Glu Gln Glu Ile Ser Val Gly Leu 340 345 350 <210> 51 <211> 353 <212> PRT <213> artificial sequence <220> <223> TPO_ human beings <400> 51 Met Glu Leu Thr Glu Leu Leu Leu Val Val Met Leu Leu Leu Thr Ala 1 5 10 15 Arg Leu Thr Leu Ser Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val 20 25 30 Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser 35 40 45 Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala 50 55 60 Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys 65 70 75 80 Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met 85 90 95 Ala Ala Arg Gly Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly 100 105 110 Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu 115 120 125 Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp 130 135 140 Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val 145 150 155 160 Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Arg Ala 165 170 175 Pro Pro Thr Thr Ala Val Pro Ser Arg Thr Ser Leu Val Leu Thr Leu 180 185 190 Asn Glu Leu Pro Asn Arg Thr Ser Gly Leu Leu Glu Thr Asn Phe Thr 195 200 205 Ala Ser Ala Arg Thr Thr Gly Ser Gly Leu Leu Lys Trp Gln Gln Gly 210 215 220 Phe Arg Ala Lys Ile Pro Gly Leu Leu Asn Gln Thr Ser Arg Ser Leu 225 230 235 240 Asp Gln Ile Pro Gly Tyr Leu Asn Arg Ile His Glu Leu Leu Asn Gly 245 250 255 Thr Arg Gly Leu Phe Pro Gly Pro Ser Arg Arg Thr Leu Gly Ala Pro 260 265 270 Asp Ile Ser Ser Gly Thr Ser Asp Thr Gly Ser Leu Pro Pro Asn Leu 275 280 285 Gln Pro Gly Tyr Ser Pro Ser Pro Thr His Pro Pro Thr Gly Gln Tyr 290 295 300 Thr Leu Phe Pro Leu Pro Pro Thr Leu Pro Thr Pro Val Val Gln Leu 305 310 315 320 His Pro Leu Leu Pro Asp Pro Ser Ala Pro Thr Pro Thr Pro Thr Ser 325 330 335 Pro Leu Leu Asn Thr Ser Tyr Thr His Ser Gln Asn Leu Ser Gln Glu 340 345 350 Gly <210> 52 <211> 367 <212> PRT <213> Artificial Sequence <220> <223> FETUA_Human <400> 52 Met Lys Ser Leu Val Leu Leu Leu Cys Leu Ala Gln Leu Trp Gly Cys 1 5 10 15 His Ser Ala Pro His Gly Pro Gly Leu Ile Tyr Arg Gln Pro Asn Cys 20 25 30 Asp Asp Pro Glu Thr Glu Glu Ala Ala Leu Val Ala Ile Asp Tyr Ile 35 40 45 Asn Gln Asn Leu Pro Trp Gly Tyr Lys His Thr Leu Asn Gln Ile Asp 50 55 60 Glu Val Lys Val Trp Pro Gln Gln Pro Ser Gly Glu Leu Phe Glu Ile 65 70 75 80 Glu Ile Asp Thr Leu Glu Thr Thr Cys His Val Leu Asp Pro Thr Pro 85 90 95 Val Ala Arg Cys Ser Val Arg Gln Leu Lys Glu His Ala Val Glu Gly 100 105 110 Asp Cys Asp Phe Gln Leu Leu Lys Leu Asp Gly Lys Phe Ser Val Val 115 120 125 Tyr Ala Lys Cys Asp Ser Ser Pro Asp Ser Ala Glu Asp Val Arg Lys 130 135 140 Val Cys Gln Asp Cys Pro Leu Leu Ala Pro Leu Asn Asp Thr Arg Val 145 150 155 160 Val His Ala Ala Lys Ala Ala Leu Ala Ala Phe Asn Ala Gln Asn Asn 165 170 175 Gly Ser Asn Phe Gln Leu Glu Glu Ile Ser Arg Ala Gln Leu Val Pro 180 185 190 Leu Pro Pro Ser Thr Tyr Val Glu Phe Thr Val Ser Gly Thr Asp Cys 195 200 205 Val Ala Lys Glu Ala Thr Glu Ala Ala Lys Cys Asn Leu Leu Ala Glu 210 215 220 Lys Gln Tyr Gly Phe Cys Lys Ala Thr Leu Ser Glu Lys Leu Gly Gly 225 230 235 240 Ala Glu Val Ala Val Thr Cys Met Val Phe Gln Thr Gln Pro Val Ser 245 250 255 Ser Gln Pro Gln Pro Glu Gly Ala Asn Glu Ala Val Pro Thr Pro Val 260 265 270 Val Asp Pro Asp Ala Pro Pro Ser Pro Pro Leu Gly Ala Pro Gly Leu 275 280 285 Pro Pro Ala Gly Ser Pro Pro Asp Ser His Val Leu Leu Ala Ala Pro 290 295 300 Pro Gly His Gln Leu His Arg Ala His Tyr Asp Leu Arg His Thr Phe 305 310 315 320 Met Gly Val Val Ser Leu Gly Ser Pro Ser Gly Glu Val Ser His Pro 325 330 335 Arg Lys Thr Arg Thr Val Val Gln Pro Ser Val Gly Ala Ala Ala Gly 340 345 350 Pro Val Val Pro Pro Cys Pro Gly Arg Ile Arg His Phe Lys Val 355 360 365 <210> 53 <211> 368 <212> PRT <213> artificial sequence <220> <223> PGS1_ humans <400> 53 Met Trp Pro Leu Trp Arg Leu Val Ser Leu Leu Ala Leu Ser Gln Ala 1 5 10 15 Leu Pro Phe Glu Gln Arg Gly Phe Trp Asp Phe Thr Leu Asp Asp Gly 20 25 30 Pro Phe Met Met Asn Asp Glu Glu Ala Ser Gly Ala Asp Thr Ser Gly 35 40 45 Val Leu Asp Pro Asp Ser Val Thr Pro Thr Tyr Ser Ala Met Cys Pro 50 55 60 Phe Gly Cys His Cys His Leu Arg Val Val Gln Cys Ser Asp Leu Gly 65 70 75 80 Leu Lys Ser Val Pro Lys Glu Ile Ser Pro Asp Thr Thr Leu Leu Asp 85 90 95 Leu Gln Asn Asn Asp Ile Ser Glu Leu Arg Lys Asp Asp Phe Lys Gly 100 105 110 Leu Gln His Leu Tyr Ala Leu Val Leu Val Asn Asn Lys Ile Ser Lys 115 120 125 Ile His Glu Lys Ala Phe Ser Pro Leu Arg Lys Leu Gln Lys Leu Tyr 130 135 140 Ile Ser Lys Asn His Leu Val Glu Ile Pro Pro Asn Leu Pro Ser Ser 145 150 155 160 Leu Val Glu Leu Arg Ile His Asp Asn Arg Ile Arg Lys Val Pro Lys 165 170 175 Gly Val Phe Ser Gly Leu Arg Asn Met Asn Cys Ile Glu Met Gly Gly 180 185 190 Asn Pro Leu Glu Asn Ser Gly Phe Glu Pro Gly Ala Phe Asp Gly Leu 195 200 205 Lys Leu Asn Tyr Leu Arg Ile Ser Glu Ala Lys Leu Thr Gly Ile Pro 210 215 220 Lys Asp Leu Pro Glu Thr Leu Asn Glu Leu His Leu Asp His Asn Lys 225 230 235 240 Ile Gln Ala Ile Glu Leu Glu Asp Leu Leu Arg Tyr Ser Lys Leu Tyr 245 250 255 Arg Leu Gly Leu Gly His Asn Gln Ile Arg Met Ile Glu Asn Gly Ser 260 265 270 Leu Ser Phe Leu Pro Thr Leu Arg Glu Leu His Leu Asp Asn Asn Lys 275 280 285 Leu Ala Arg Val Pro Ser Gly Leu Pro Asp Leu Lys Leu Leu Gln Val 290 295 300 Val Tyr Leu His Ser Asn Asn Ile Thr Lys Val Gly Val Asn Asp Phe 305 310 315 320 Cys Pro Met Gly Phe Gly Val Lys Arg Ala Tyr Tyr Asn Gly Ile Ser 325 330 335 Leu Phe Asn Asn Pro Val Pro Tyr Trp Glu Val Gln Pro Ala Thr Phe 340 345 350 Arg Cys Val Thr Asp Arg Leu Ala Ile Gln Phe Gly Asn Tyr Lys Lys 355 360 365 <210> 54 <211> 377 <212> PRT <213> Artificial sequence <220> <223> IGHG3_Human <400> 54 Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 1 5 10 15 Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 20 25 30 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 35 40 45 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 50 55 60 Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 65 70 75 80 Tyr Thr Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 85 90 95 Arg Val Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro 100 105 110 Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg 115 120 125 Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys 130 135 140 Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro 145 150 155 160 Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 165 170 175 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 180 185 190 Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Lys Trp Tyr 195 200 205 Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 210 215 220 Gln Tyr Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Leu His 225 230 235 240 Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 245 250 255 Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln 260 265 270 Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 275 280 285 Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 290 295 300 Ser Asp Ile Ala Val Glu Trp Glu Ser Ser Gly Gln Pro Glu Asn Asn 305 310 315 320 Tyr Asn Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu 325 330 335 Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Ile 340 345 350 Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln 355 360 365 Lys Ser Leu Ser Leu Ser Pro Gly Lys 370 375 <210> 55 <211> 383 <212> PRT <213> Artificial Sequence <220> <223> DLK1_Human <400> 55 Met Thr Ala Thr Glu Ala Leu Leu Arg Val Leu Leu Leu Leu Leu Ala 1 5 10 15 Phe Gly His Ser Thr Tyr Gly Ala Glu Cys Phe Pro Ala Cys Asn Pro 20 25 30 Gln Asn Gly Phe Cys Glu Asp Asp Asn Val Cys Arg Cys Gln Pro Gly 35 40 45 Trp Gln Gly Pro Leu Cys Asp Gln Cys Val Thr Ser Pro Gly Cys Leu 50 55 60 His Gly Leu Cys Gly Glu Pro Gly Gln Cys Ile Cys Thr Asp Gly Trp 65 70 75 80 Asp Gly Glu Leu Cys Asp Arg Asp Val Arg Ala Cys Ser Ser Ala Pro 85 90 95 Cys Ala Asn Asn Arg Thr Cys Val Ser Leu Asp Asp Gly Leu Tyr Glu 100 105 110 Cys Ser Cys Ala Pro Gly Tyr Ser Gly Lys Asp Cys Gln Lys Lys Asp 115 120 125 Gly Pro Cys Val Ile Asn Gly Ser Pro Cys Gln His Gly Gly Thr Cys 130 135 140 Val Asp Asp Glu Gly Arg Ala Ser His Ala Ser Cys Leu Cys Pro Pro 145 150 155 160 Gly Phe Ser Gly Asn Phe Cys Glu Ile Val Ala Asn Ser Cys Thr Pro 165 170 175 Asn Pro Cys Glu Asn Asp Gly Val Cys Thr Asp Ile Gly Gly Asp Phe 180 185 190 Arg Cys Arg Cys Pro Ala Gly Phe Ile Asp Lys Thr Cys Ser Arg Pro 195 200 205 Val Thr Asn Cys Ala Ser Ser Pro Cys Gln Asn Gly Gly Thr Cys Leu 210 215 220 Gln His Thr Gln Val Ser Tyr Glu Cys Leu Cys Lys Pro Glu Phe Thr 225 230 235 240 Gly Leu Thr Cys Val Lys Lys Arg Ala Leu Ser Pro Gln Gln Val Thr 245 250 255 Arg Leu Pro Ser Gly Tyr Gly Leu Ala Tyr Arg Leu Thr Pro Gly Val 260 265 270 His Glu Leu Pro Val Gln Gln Pro Glu His Arg Ile Leu Lys Val Ser 275 280 285 Met Lys Glu Leu Asn Lys Lys Thr Pro Leu Leu Thr Glu Gly Gln Ala 290 295 300 Ile Cys Phe Thr Ile Leu Gly Val Leu Thr Ser Leu Val Val Leu Gly 305 310 315 320 Thr Val Gly Ile Val Phe Leu Asn Lys Cys Glu Thr Trp Val Ser Asn 325 330 335 Leu Arg Tyr Asn His Met Leu Arg Lys Lys Lys Asn Leu Leu Leu Gln 340 345 350 Tyr Asn Ser Gly Glu Asp Leu Ala Val Asn Ile Ile Phe Pro Glu Lys 355 360 365 Ile Asp Met Thr Thr Phe Ser Lys Glu Ala Gly Asp Glu Glu Ile 370 375 380 <210> 56 <211> 392 <212> PRT <213> Artificial Sequence <220> <223> MCP_Human <400> 56 Met Glu Pro Pro Gly Arg Arg Glu Cys Pro Phe Pro Ser Trp Arg Phe 1 5 10 15 Pro Gly Leu Leu Leu Ala Ala Met Val Leu Leu Leu Tyr Ser Phe Ser 20 25 30 Asp Ala Cys Glu Glu Pro Pro Thr Phe Glu Ala Met Glu Leu Ile Gly 35 40 45 Lys Pro Lys Pro Tyr Tyr Glu Ile Gly Glu Arg Val Asp Tyr Lys Cys 50 55 60 Lys Lys Gly Tyr Phe Tyr Ile Pro Pro Leu Ala Thr His Thr Ile Cys 65 70 75 80 Asp Arg Asn His Thr Trp Leu Pro Val Ser Asp Asp Ala Cys Tyr Arg 85 90 95 Glu Thr Cys Pro Tyr Ile Arg Asp Pro Leu Asn Gly Gln Ala Val Pro 100 105 110 Ala Asn Gly Thr Tyr Glu Phe Gly Tyr Gln Met His Phe Ile Cys Asn 115 120 125 Glu Gly Tyr Tyr Leu Ile Gly Glu Glu Ile Leu Tyr Cys Glu Leu Lys 130 135 140 Gly Ser Val Ala Ile Trp Ser Gly Lys Pro Pro Ile Cys Glu Lys Val 145 150 155 160 Leu Cys Thr Pro Pro Pro Lys Ile Lys Asn Gly Lys His Thr Phe Ser 165 170 175 Glu Val Glu Val Phe Glu Tyr Leu Asp Ala Val Thr Tyr Ser Cys Asp 180 185 190 Pro Ala Pro Gly Pro Asp Pro Phe Ser Leu Ile Gly Glu Ser Thr Ile 195 200 205 Tyr Cys Gly Asp Asn Ser Val Trp Ser Arg Ala Ala Pro Glu Cys Lys 210 215 220 Val Val Lys Cys Arg Phe Pro Val Val Glu Asn Gly Lys Gln Ile Ser 225 230 235 240 Gly Phe Gly Lys Lys Phe Tyr Tyr Lys Ala Thr Val Met Phe Glu Cys 245 250 255 Asp Lys Gly Phe Tyr Leu Asp Gly Ser Asp Thr Ile Val Cys Asp Ser 260 265 270 Asn Ser Thr Trp Asp Pro Pro Val Pro Lys Cys Leu Lys Val Leu Pro 275 280 285 Pro Ser Ser Thr Lys Pro Pro Ala Leu Ser His Ser Val Ser Thr Ser 290 295 300 Ser Thr Thr Lys Ser Pro Ala Ser Ser Ala Ser Gly Pro Arg Pro Thr 305 310 315 320 Tyr Lys Pro Pro Val Ser Asn Tyr Pro Gly Tyr Pro Lys Pro Glu Glu 325 330 335 Gly Ile Leu Asp Ser Leu Asp Val Trp Val Ile Ala Val Ile Val Ile 340 345 350 Ala Ile Val Val Gly Val Ala Val Ile Cys Val Val Pro Tyr Arg Tyr 355 360 365 Leu Gln Arg Arg Lys Lys Lys Gly Thr Tyr Leu Thr Asp Glu Thr His 370 375 380 Arg Glu Val Lys Phe Thr Ser Leu 385 390 <210> 57 <211> 392 <212> PRT <213> artificial sequence <220> <223> PRP1_ humans <400> 57 Met Leu Leu Ile Leu Leu Ser Val Ala Leu Leu Ala Leu Ser Ser Ala 1 5 10 15 Gln Asn Leu Asn Glu Asp Val Ser Gln Glu Glu Ser Pro Ser Leu Ile 20 25 30 Ala Gly Asn Pro Gln Gly Pro Ser Pro Gln Gly Gly Asn Lys Pro Gln 35 40 45 Gly Pro Pro Pro Pro Pro Gly Lys Pro Gln Gly Pro Pro Pro Gln Gly 50 55 60 Gly Asn Lys Pro Gln Gly Pro Pro Pro Pro Gly Lys Pro Gln Gly Pro 65 70 75 80 Pro Pro Gln Gly Asp Lys Ser Arg Ser Pro Arg Ser Pro Pro Gly Lys 85 90 95 Pro Gln Gly Pro Pro Pro Gln Gly Gly Asn Gln Pro Gln Gly Pro Pro 100 105 110 Pro Pro Pro Gly Lys Pro Gln Gly Pro Pro Pro Gln Gly Gly Asn Lys 115 120 125 Pro Gln Gly Pro Pro Pro Pro Gly Lys Pro Gln Gly Pro Pro Pro Gln 130 135 140 Gly Asp Lys Ser Gln Ser Pro Arg Ser Pro Pro Gly Lys Pro Gln Gly 145 150 155 160 Pro Pro Pro Gln Gly Gly Asn Gln Pro Gln Gly Pro Pro Pro Pro Pro 165 170 175 Gly Lys Pro Gln Gly Pro Pro Pro Gln Gly Gly Asn Lys Pro Gln Gly 180 185 190 Pro Pro Pro Pro Gly Lys Pro Gln Gly Pro Pro Pro Gln Gly Asp Lys 195 200 205 Ser Gln Ser Pro Arg Ser Pro Pro Gly Lys Pro Gln Gly Pro Pro Pro 210 215 220 Gln Gly Gly Asn Gln Pro Gln Gly Pro Pro Pro Pro Pro Gly Lys Pro 225 230 235 240 Gln Gly Pro Pro Gln Gln Gly Gly Asn Arg Pro Gln Gly Pro Pro Pro 245 250 255 Pro Gly Lys Pro Gln Gly Pro Pro Pro Gln Gly Asp Lys Ser Arg Ser 260 265 270 Pro Gln Ser Pro Pro Gly Lys Pro Gln Gly Pro Pro Pro Gln Gly Gly 275 280 285 Asn Gln Pro Gln Gly Pro Pro Pro Pro Pro Gly Lys Pro Gln Gly Pro 290 295 300 Pro Pro Gln Gly Gly Asn Lys Pro Gln Gly Pro Pro Pro Pro Gly Lys 305 310 315 320 Pro Gln Gly Pro Pro Ala Gln Gly Gly Ser Lys Ser Gln Ser Ala Arg 325 330 335 Ser Pro Pro Gly Lys Pro Gln Gly Pro Pro Gln Gln Glu Gly Asn Asn 340 345 350 Pro Gln Gly Pro Pro Pro Pro Ala Gly Gly Asn Pro Gln Gln Pro Gln 355 360 365 Ala Pro Pro Ala Gly Gln Pro Gln Gly Pro Pro Arg Pro Pro Gln Gly 370 375 380 Gly Arg Pro Ser Arg Pro Pro Gln 385 390 <210> 58 <211> 397 <212> PRT <213> Artificial Sequence <220> <223> X3CL1_Human <400> 58 Met Ala Pro Ile Ser Leu Ser Trp Leu Leu Arg Leu Ala Thr Phe Cys 1 5 10 15 His Leu Thr Val Leu Leu Ala Gly Gln His His Gly Val Thr Lys Cys 20 25 30 Asn Ile Thr Cys Ser Lys Met Thr Ser Lys Ile Pro Val Ala Leu Leu 35 40 45 Ile His Tyr Gln Gln Asn Gln Ala Ser Cys Gly Lys Arg Ala Ile Ile 50 55 60 Leu Glu Thr Arg Gln His Arg Leu Phe Cys Ala Asp Pro Lys Glu Gln 65 70 75 80 Trp Val Lys Asp Ala Met Gln His Leu Asp Arg Gln Ala Ala Ala Leu 85 90 95 Thr Arg Asn Gly Gly Thr Phe Glu Lys Gln Ile Gly Glu Val Lys Pro 100 105 110 Arg Thr Thr Pro Ala Ala Gly Gly Met Asp Glu Ser Val Val Leu Glu 115 120 125 Pro Glu Ala Thr Gly Glu Ser Ser Ser Leu Glu Pro Thr Pro Ser Ser 130 135 140 Gln Glu Ala Gln Arg Ala Leu Gly Thr Ser Pro Glu Leu Pro Thr Gly 145 150 155 160 Val Thr Gly Ser Ser Gly Thr Arg Leu Pro Pro Thr Pro Lys Ala Gln 165 170 175 Asp Gly Gly Pro Val Gly Thr Glu Leu Phe Arg Val Pro Pro Val Ser 180 185 190 Thr Ala Ala Thr Trp Gln Ser Ser Ala Pro His Gln Pro Gly Pro Ser 195 200 205 Leu Trp Ala Glu Ala Lys Thr Ser Glu Ala Pro Ser Thr Gln Asp Pro 210 215 220 Ser Thr Gln Ala Ser Thr Ala Ser Ser Pro Ala Pro Glu Glu Asn Ala 225 230 235 240 Pro Ser Glu Gly Gln Arg Val Trp Gly Gln Gly Gln Ser Pro Arg Pro 245 250 255 Glu Asn Ser Leu Glu Arg Glu Glu Met Gly Pro Val Pro Ala His Thr 260 265 270 Asp Ala Phe Gln Asp Trp Gly Pro Gly Ser Met Ala His Val Ser Val 275 280 285 Val Pro Val Ser Ser Glu Gly Thr Pro Ser Arg Glu Pro Val Ala Ser 290 295 300 Gly Ser Trp Thr Pro Lys Ala Glu Glu Pro Ile His Ala Thr Met Asp 305 310 315 320 Pro Gln Arg Leu Gly Val Leu Ile Thr Pro Val Pro Asp Ala Gln Ala 325 330 335 Ala Thr Arg Arg Gln Ala Val Gly Leu Leu Ala Phe Leu Gly Leu Leu 340 345 350 Phe Cys Leu Gly Val Ala Met Phe Thr Tyr Gln Ser Leu Gln Gly Cys 355 360 365 Pro Arg Lys Met Ala Gly Glu Met Ala Glu Gly Leu Arg Tyr Ile Pro 370 375 380 Arg Ser Cys Gly Ser Asn Ser Tyr Val Leu Val Pro Val 385 390 395 <210> 59 <211> 400 <212> PRT <213> artificial sequence <220> <223> LEUK_ human beings <400> 59 Met Ala Thr Leu Leu Leu Leu Gly Val Leu Val Val Ser Pro Asp 1 5 10 15 Ala Leu Gly Ser Thr Thr Ala Val Gln Thr Pro Thr Ser Gly Glu Pro 20 25 30 Leu Val Ser Thr Ser Glu Pro Leu Ser Ser Lys Met Tyr Thr Thr Ser 35 40 45 Ile Thr Ser Asp Pro Lys Ala Asp Ser Thr Gly Asp Gln Thr Ser Ala 50 55 60 Leu Pro Pro Ser Thr Ser Ile Asn Glu Gly Ser Pro Leu Trp Thr Ser 65 70 75 80 Ile Gly Ala Ser Thr Gly Ser Pro Leu Pro Glu Pro Thr Thr Tyr Gln 85 90 95 Glu Val Ser Ile Lys Met Ser Ser Val Pro Gln Glu Thr Pro His Ala 100 105 110 Thr Ser His Pro Ala Val Pro Ile Thr Ala Asn Ser Leu Gly Ser His 115 120 125 Thr Val Thr Gly Gly Thr Ile Thr Thr Asn Ser Pro Glu Thr Ser Ser 130 135 140 Arg Thr Ser Gly Ala Pro Val Thr Thr Ala Ala Ser Ser Leu Glu Thr 145 150 155 160 Ser Arg Gly Thr Ser Gly Pro Pro Leu Thr Met Ala Thr Val Ser Leu 165 170 175 Glu Thr Ser Lys Gly Thr Ser Gly Pro Pro Val Thr Met Ala Thr Asp 180 185 190 Ser Leu Glu Thr Ser Thr Gly Thr Thr Gly Pro Pro Val Thr Met Thr 195 200 205 Thr Gly Ser Leu Glu Pro Ser Ser Gly Ala Ser Gly Pro Gln Val Ser 210 215 220 Ser Val Lys Leu Ser Thr Met Met Ser Pro Thr Thr Ser Thr Asn Ala 225 230 235 240 Ser Thr Val Pro Phe Arg Asn Pro Asp Glu Asn Ser Arg Gly Met Leu 245 250 255 Pro Val Ala Val Leu Val Ala Leu Leu Ala Val Ile Val Leu Val Ala 260 265 270 Leu Leu Leu Leu Trp Arg Arg Arg Gln Lys Arg Arg Thr Gly Ala Leu 275 280 285 Val Leu Ser Arg Gly Gly Lys Arg Asn Gly Val Val Asp Ala Trp Ala 290 295 300 Gly Pro Ala Gln Val Pro Glu Glu Gly Ala Val Thr Val Thr Val Gly 305 310 315 320 Gly Ser Gly Gly Asp Lys Gly Ser Gly Phe Pro Asp Gly Glu Gly Ser 325 330 335 Ser Arg Arg Pro Thr Leu Thr Thr Phe Phe Gly Arg Arg Lys Ser Arg 340 345 350 Gln Gly Ser Leu Ala Met Glu Glu Leu Lys Ser Gly Ser Gly Pro Ser 355 360 365 Leu Lys Gly Glu Glu Glu Pro Leu Val Ala Ser Glu Asp Gly Ala Val 370 375 380 Asp Ala Pro Ala Pro Asp Glu Pro Glu Gly Gly Asp Gly Ala Ala Pro 385 390 395 400 <210> 60 <211> 410 <212> PRT <213> Artificial Sequence <220> <223> LAMP2_Human <400> 60 Met Val Cys Phe Arg Leu Phe Pro Val Pro Gly Ser Gly Leu Val Leu 1 5 10 15 Val Cys Leu Val Leu Gly Ala Val Arg Ser Tyr Ala Leu Glu Leu Asn 20 25 30 Leu Thr Asp Ser Glu Asn Ala Thr Cys Leu Tyr Ala Lys Trp Gln Met 35 40 45 Asn Phe Thr Val Arg Tyr Glu Thr Thr Asn Lys Thr Tyr Lys Thr Val 50 55 60 Thr Ile Ser Asp His Gly Thr Val Thr Tyr Asn Gly Ser Ile Cys Gly 65 70 75 80 Asp Asp Gln Asn Gly Pro Lys Ile Ala Val Gln Phe Gly Pro Gly Phe 85 90 95 Ser Trp Ile Ala Asn Phe Thr Lys Ala Ala Ser Thr Tyr Ser Ile Asp 100 105 110 Ser Val Ser Phe Ser Tyr Asn Thr Gly Asp Asn Thr Thr Phe Pro Asp 115 120 125 Ala Glu Asp Lys Gly Ile Leu Thr Val Asp Glu Leu Leu Ala Ile Arg 130 135 140 Ile Pro Leu Asn Asp Leu Phe Arg Cys Asn Ser Leu Ser Thr Leu Glu 145 150 155 160 Lys Asn Asp Val Val Gln His Tyr Trp Asp Val Leu Val Gln Ala Phe 165 170 175 Val Gln Asn Gly Thr Val Ser Thr Asn Glu Phe Leu Cys Asp Lys Asp 180 185 190 Lys Thr Ser Thr Val Ala Pro Thr Ile His Thr Thr Val Pro Ser Pro 195 200 205 Thr Thr Thr Pro Thr Pro Lys Glu Lys Pro Glu Ala Gly Thr Tyr Ser 210 215 220 Val Asn Asn Gly Asn Asp Thr Cys Leu Leu Ala Thr Met Gly Leu Gln 225 230 235 240 Leu Asn Ile Thr Gln Asp Lys Val Ala Ser Val Ile Asn Ile Asn Pro 245 250 255 Asn Thr Thr His Ser Thr Gly Ser Cys Arg Ser His Thr Ala Leu Leu 260 265 270 Arg Leu Asn Ser Ser Thr Ile Lys Tyr Leu Asp Phe Val Phe Ala Val 275 280 285 Lys Asn Glu Asn Arg Phe Tyr Leu Lys Glu Val Asn Ile Ser Met Tyr 290 295 300 Leu Val Asn Gly Ser Val Phe Ser Ile Ala Asn Asn Asn Leu Ser Tyr 305 310 315 320 Trp Asp Ala Pro Leu Gly Ser Ser Tyr Met Cys Asn Lys Glu Gln Thr 325 330 335 Val Ser Val Ser Gly Ala Phe Gln Ile Asn Thr Phe Asp Leu Arg Val 340 345 350 Gln Pro Phe Asn Val Thr Gln Gly Lys Tyr Ser Thr Ala Gln Asp Cys 355 360 365 Ser Ala Asp Asp Asp Asn Phe Leu Val Pro Ile Ala Val Gly Ala Ala 370 375 380 Leu Ala Gly Val Leu Ile Leu Val Leu Leu Ala Tyr Phe Ile Gly Leu 385 390 395 400 Lys His His His Ala Gly Tyr Glu Gln Phe 405 410 <210> 61 <211> 417 <212> PRT <213> artificial sequence <220> <223> LAMP1_ humans <400> 61 Met Ala Ala Pro Gly Ser Ala Arg Arg Pro Leu Leu Leu Leu Leu Leu 1 5 10 15 Leu Leu Leu Leu Gly Leu Met His Cys Ala Ser Ala Ala Met Phe Met 20 25 30 Val Lys Asn Gly Asn Gly Thr Ala Cys Ile Met Ala Asn Phe Ser Ala 35 40 45 Ala Phe Ser Val Asn Tyr Asp Thr Lys Ser Gly Pro Lys Asn Met Thr 50 55 60 Phe Asp Leu Pro Ser Asp Ala Thr Val Val Leu Asn Arg Ser Ser Cys 65 70 75 80 Gly Lys Glu Asn Thr Ser Asp Pro Ser Leu Val Ile Ala Phe Gly Arg 85 90 95 Gly His Thr Leu Thr Leu Asn Phe Thr Arg Asn Ala Thr Arg Tyr Ser 100 105 110 Val Gln Leu Met Ser Phe Val Tyr Asn Leu Ser Asp Thr His Leu Phe 115 120 125 Pro Asn Ala Ser Ser Lys Glu Ile Lys Thr Val Glu Ser Ile Thr Asp 130 135 140 Ile Arg Ala Asp Ile Asp Lys Lys Tyr Arg Cys Val Ser Gly Thr Gln 145 150 155 160 Val His Met Asn Asn Val Thr Val Thr Leu His Asp Ala Thr Ile Gln 165 170 175 Ala Tyr Leu Ser Asn Ser Ser Phe Ser Arg Gly Glu Thr Arg Cys Glu 180 185 190 Gln Asp Arg Pro Ser Pro Thr Thr Ala Pro Pro Ala Pro Pro Ser Pro 195 200 205 Ser Pro Ser Pro Val Pro Lys Ser Pro Ser Val Asp Lys Tyr Asn Val 210 215 220 Ser Gly Thr Asn Gly Thr Cys Leu Leu Ala Ser Met Gly Leu Gln Leu 225 230 235 240 Asn Leu Thr Tyr Glu Arg Lys Asp Asn Thr Thr Val Thr Arg Leu Leu 245 250 255 Asn Ile Asn Pro Asn Lys Thr Ser Ala Ser Gly Ser Cys Gly Ala His 260 265 270 Leu Val Thr Leu Glu Leu His Ser Glu Gly Thr Thr Val Leu Leu Phe 275 280 285 Gln Phe Gly Met Asn Ala Ser Ser Ser Arg Phe Phe Leu Gln Gly Ile 290 295 300 Gln Leu Asn Thr Ile Leu Pro Asp Ala Arg Asp Pro Ala Phe Lys Ala 305 310 315 320 Ala Asn Gly Ser Leu Arg Ala Leu Gln Ala Thr Val Gly Asn Ser Tyr 325 330 335 Lys Cys Asn Ala Glu Glu His Val Arg Val Thr Lys Ala Phe Ser Val 340 345 350 Asn Ile Phe Lys Val Trp Val Gln Ala Phe Lys Val Glu Gly Gly Gln 355 360 365 Phe Gly Ser Val Glu Glu Cys Leu Leu Asp Glu Asn Ser Met Leu Ile 370 375 380 Pro Ile Ala Val Gly Gly Ala Leu Ala Gly Leu Val Leu Ile Val Leu 385 390 395 400 Ile Ala Tyr Leu Val Gly Arg Lys Arg Ser His Ala Gly Tyr Gln Thr 405 410 415 authorities <210> 62 <211> 424 <212> PRT <213> artificial sequence <220> <223> ZP3_ humans <400> 62 Met Glu Leu Ser Tyr Arg Leu Phe Ile Cys Leu Leu Leu Trp Gly Ser 1 5 10 15 Thr Glu Leu Cys Tyr Pro Gln Pro Leu Trp Leu Leu Gln Gly Gly Ala 20 25 30 Ser His Pro Glu Thr Ser Val Gln Pro Val Leu Val Glu Cys Gln Glu 35 40 45 Ala Thr Leu Met Val Met Val Ser Lys Asp Leu Phe Gly Thr Gly Lys 50 55 60 Leu Ile Arg Ala Ala Asp Leu Thr Leu Gly Pro Glu Ala Cys Glu Pro 65 70 75 80 Leu Val Ser Met Asp Thr Glu Asp Val Val Arg Phe Glu Val Gly Leu 85 90 95 His Glu Cys Gly Asn Ser Met Gln Val Thr Asp Asp Ala Leu Val Tyr 100 105 110 Ser Thr Phe Leu Leu His Asp Pro Arg Pro Val Gly Asn Leu Ser Ile 115 120 125 Val Arg Thr Asn Arg Ala Glu Ile Pro Ile Glu Cys Arg Tyr Pro Arg 130 135 140 Gln Gly Asn Val Ser Ser Gln Ala Ile Leu Pro Thr Trp Leu Pro Phe 145 150 155 160 Arg Thr Thr Val Phe Ser Glu Glu Lys Leu Thr Phe Ser Leu Arg Leu 165 170 175 Met Glu Glu Asn Trp Asn Ala Glu Lys Arg Ser Pro Thr Phe His Leu 180 185 190 Gly Asp Ala Ala His Leu Gln Ala Glu Ile His Thr Gly Ser His Val 195 200 205 Pro Leu Arg Leu Phe Val Asp His Cys Val Ala Thr Pro Thr Pro Asp 210 215 220 Gln Asn Ala Ser Pro Tyr His Thr Ile Val Asp Phe His Gly Cys Leu 225 230 235 240 Val Asp Gly Leu Thr Asp Ala Ser Ser Ala Phe Lys Val Pro Arg Pro 245 250 255 Gly Pro Asp Thr Leu Gln Phe Thr Val Asp Val Phe His Phe Ala Asn 260 265 270 Asp Ser Arg Asn Met Ile Tyr Ile Thr Cys His Leu Lys Val Thr Leu 275 280 285 Ala Glu Gln Asp Pro Asp Glu Leu Asn Lys Ala Cys Ser Phe Ser Lys 290 295 300 Pro Ser Asn Ser Trp Phe Pro Val Glu Gly Ser Ala Asp Ile Cys Gln 305 310 315 320 Cys Cys Asn Lys Gly Asp Cys Gly Thr Pro Ser His Ser Arg Arg Gln 325 330 335 Pro His Val Met Ser Gln Trp Ser Arg Ser Ala Ser Arg Asn Arg Arg 340 345 350 His Val Thr Glu Glu Ala Asp Val Thr Val Gly Pro Leu Ile Phe Leu 355 360 365 Asp Arg Arg Gly Asp His Glu Val Glu Gln Trp Ala Leu Pro Ser Asp 370 375 380 Thr Ser Val Val Leu Leu Gly Val Gly Leu Ala Val Val Val Ser Leu 385 390 395 400 Thr Leu Thr Ala Val Ile Leu Val Leu Thr Arg Arg Cys Arg Thr Ala 405 410 415 Ser His Pro Val Ser Ala Ser Glu 420 <210> 63 <211> 430 <212> PRT <213> Artificial Sequence <220> <223> K1C18_Human <400> 63 Met Ser Phe Thr Thr Arg Ser Thr Phe Ser Thr Asn Tyr Arg Ser Leu 1 5 10 15 Gly Ser Val Gln Ala Pro Ser Tyr Gly Ala Arg Pro Val Ser Ser Ala 20 25 30 Ala Ser Val Tyr Ala Gly Ala Gly Gly Ser Gly Ser Arg Ile Ser Val 35 40 45 Ser Arg Ser Thr Ser Phe Arg Gly Gly Met Gly Ser Gly Gly Leu Ala 50 55 60 Thr Gly Ile Ala Gly Gly Leu Ala Gly Met Gly Gly Ile Gln Asn Glu 65 70 75 80 Lys Glu Thr Met Gln Ser Leu Asn Asp Arg Leu Ala Ser Tyr Leu Asp 85 90 95 Arg Val Arg Ser Leu Glu Thr Glu Asn Arg Arg Leu Glu Ser Lys Ile 100 105 110 Arg Glu His Leu Glu Lys Lys Gly Pro Gln Val Arg Asp Trp Ser His 115 120 125 Tyr Phe Lys Ile Ile Glu Asp Leu Arg Ala Gln Ile Phe Ala Asn Thr 130 135 140 Val Asp Asn Ala Arg Ile Val Leu Gln Ile Asp Asn Ala Arg Leu Ala 145 150 155 160 Ala Asp Asp Phe Arg Val Lys Tyr Glu Thr Glu Leu Ala Met Arg Gln 165 170 175 Ser Val Glu Asn Asp Ile His Gly Leu Arg Lys Val Ile Asp Asp Thr 180 185 190 Asn Ile Thr Arg Leu Gln Leu Glu Thr Glu Ile Glu Ala Leu Lys Glu 195 200 205 Glu Leu Leu Phe Met Lys Lys Asn His Glu Glu Glu Val Lys Gly Leu 210 215 220 Gln Ala Gln Ile Ala Ser Ser Gly Leu Thr Val Glu Val Asp Ala Pro 225 230 235 240 Lys Ser Gln Asp Leu Ala Lys Ile Met Ala Asp Ile Arg Ala Gln Tyr 245 250 255 Asp Glu Leu Ala Arg Lys Asn Arg Glu Glu Leu Asp Lys Tyr Trp Ser 260 265 270 Gln Gln Ile Glu Glu Ser Thr Thr Val Val Thr Thr Gln Ser Ala Glu 275 280 285 Val Gly Ala Ala Glu Thr Thr Leu Thr Glu Leu Arg Arg Thr Val Gln 290 295 300 Ser Leu Glu Ile Asp Leu Asp Ser Met Arg Asn Leu Lys Ala Ser Leu 305 310 315 320 Glu Asn Ser Leu Arg Glu Val Glu Ala Arg Tyr Ala Leu Gln Met Glu 325 330 335 Gln Leu Asn Gly Ile Leu Leu His Leu Glu Ser Glu Leu Ala Gln Thr 340 345 350 Arg Ala Glu Gly Gln Arg Gln Ala Gln Glu Tyr Glu Ala Leu Leu Asn 355 360 365 Ile Lys Val Lys Leu Glu Ala Glu Ile Ala Thr Tyr Arg Arg Leu Leu 370 375 380 Glu Asp Gly Glu Asp Phe Asn Leu Gly Asp Ala Leu Asp Ser Ser Asn 385 390 395 400 Ser Met Gln Thr Ile Gln Lys Thr Thr Thr Arg Arg Ile Val Asp Gly 405 410 415 Lys Val Val Ser Glu Thr Asn Asp Thr Lys Val Leu Arg His 420 425 430 <210> 64 <211> 439 <212> PRT <213> Artificial Sequence <220> <223> TICN1_Human <400> 64 Met Pro Ala Ile Ala Val Leu Ala Ala Ala Ala Ala Ala Trp Cys Phe 1 5 10 15 Leu Gln Val Glu Ser Arg His Leu Asp Ala Leu Ala Gly Gly Ala Gly 20 25 30 Pro Asn His Gly Asn Phe Leu Asp Asn Asp Gln Trp Leu Ser Thr Val 35 40 45 Ser Gln Tyr Asp Arg Asp Lys Tyr Trp Asn Arg Phe Arg Asp Asp Asp 50 55 60 Tyr Phe Arg Asn Trp Asn Pro Asn Lys Pro Phe Asp Gln Ala Leu Asp 65 70 75 80 Pro Ser Lys Asp Pro Cys Leu Lys Val Lys Cys Ser Pro His Lys Val 85 90 95 Cys Val Thr Gln Asp Tyr Gln Thr Ala Leu Cys Val Ser Arg Lys His 100 105 110 Leu Leu Pro Arg Gln Lys Lys Gly Asn Val Ala Gln Lys His Trp Val 115 120 125 Gly Pro Ser Asn Leu Val Lys Cys Lys Pro Cys Pro Val Ala Gln Ser 130 135 140 Ala Met Val Cys Gly Ser Asp Gly His Ser Tyr Thr Ser Lys Cys Lys 145 150 155 160 Leu Glu Phe His Ala Cys Ser Thr Gly Lys Ser Leu Ala Thr Leu Cys 165 170 175 Asp Gly Pro Cys Pro Cys Leu Pro Glu Pro Glu Pro Pro Lys His Lys 180 185 190 Ala Glu Arg Ser Ala Cys Thr Asp Lys Glu Leu Arg Asn Leu Ala Ser 195 200 205 Arg Leu Lys Asp Trp Phe Gly Ala Leu His Glu Asp Ala Asn Arg Val 210 215 220 Ile Lys Pro Thr Ser Ser Asn Thr Ala Gln Gly Arg Phe Asp Thr Ser 225 230 235 240 Ile Leu Pro Ile Cys Lys Asp Ser Leu Gly Trp Met Phe Asn Lys Leu 245 250 255 Asp Met Asn Tyr Asp Leu Leu Leu Asp Pro Ser Glu Ile Asn Ala Ile 260 265 270 Tyr Leu Asp Lys Tyr Glu Pro Cys Ile Lys Pro Leu Phe Asn Ser Cys 275 280 285 Asp Ser Phe Lys Asp Gly Lys Leu Ser Asn Asn Glu Trp Cys Tyr Cys 290 295 300 Phe Gln Lys Pro Gly Gly Leu Pro Cys Gln Asn Glu Met Asn Arg Ile 305 310 315 320 Gln Lys Leu Ser Lys Gly Lys Ser Leu Leu Gly Ala Phe Ile Pro Arg 325 330 335 Cys Asn Glu Glu Gly Tyr Tyr Lys Ala Thr Gln Cys His Gly Ser Thr 340 345 350 Gly Gln Cys Trp Cys Val Asp Lys Tyr Gly Asn Glu Leu Ala Gly Ser 355 360 365 Arg Lys Gln Gly Ala Val Ser Cys Glu Glu Glu Gln Glu Thr Ser Gly 370 375 380 Asp Phe Gly Ser Gly Gly Ser Val Val Leu Leu Asp Asp Leu Glu Tyr 385 390 395 400 Glu Arg Glu Leu Gly Pro Lys Asp Lys Glu Gly Lys Leu Arg Val His 405 410 415 Thr Arg Ala Val Thr Glu Asp Asp Glu Asp Glu Asp Asp Asp Lys Glu 420 425 430 Asp Glu Val Gly Tyr Ile Trp 435 <210> 65 <211> 442 <212> PRT <213> Artificial sequence <220> <223> SDC3_Human <400> 65 Met Lys Pro Gly Pro Pro His Arg Ala Gly Ala Ala His Gly Ala Gly 1 5 10 15 Ala Gly Ala Gly Ala Ala Ala Gly Pro Gly Ala Arg Gly Leu Leu Leu 20 25 30 Pro Pro Leu Leu Leu Leu Leu Leu Ala Gly Arg Ala Ala Gly Ala Gln 35 40 45 Arg Trp Arg Ser Glu Asn Phe Glu Arg Pro Val Asp Leu Glu Gly Ser 50 55 60 Gly Asp Asp Asp Ser Phe Pro Asp Asp Glu Leu Asp Asp Leu Tyr Ser 65 70 75 80 Gly Ser Gly Ser Gly Tyr Phe Glu Gln Glu Ser Gly Ile Glu Thr Ala 85 90 95 Met Arg Phe Ser Pro Asp Val Ala Leu Ala Val Ser Thr Thr Pro Ala 100 105 110 Val Leu Pro Thr Thr Asn Ile Gln Pro Val Gly Thr Pro Phe Glu Glu 115 120 125 Leu Pro Ser Glu Arg Pro Thr Leu Glu Pro Ala Thr Ser Pro Leu Val 130 135 140 Val Thr Glu Val Pro Glu Glu Pro Ser Gln Arg Ala Thr Thr Val Ser 145 150 155 160 Thr Thr Met Ala Thr Thr Ala Ala Thr Ser Thr Gly Asp Pro Thr Val 165 170 175 Ala Thr Val Pro Ala Thr Val Ala Thr Ala Thr Pro Ser Thr Pro Ala 180 185 190 Ala Pro Pro Phe Thr Ala Thr Thr Ala Val Ile Arg Thr Thr Gly Val 195 200 205 Arg Arg Leu Leu Pro Leu Pro Leu Thr Thr Val Ala Thr Ala Arg Ala 210 215 220 Thr Thr Pro Glu Ala Pro Ser Pro Pro Thr Thr Ala Ala Val Leu Asp 225 230 235 240 Thr Glu Ala Pro Thr Pro Arg Leu Val Ser Thr Ala Thr Ser Arg Pro 245 250 255 Arg Ala Leu Pro Arg Pro Ala Thr Thr Gln Glu Pro Asp Ile Pro Glu 260 265 270 Arg Ser Thr Leu Pro Leu Gly Thr Thr Ala Pro Gly Pro Thr Glu Val 275 280 285 Ala Gln Thr Pro Thr Pro Glu Thr Phe Leu Thr Thr Ile Arg Asp Glu 290 295 300 Pro Glu Val Pro Val Ser Gly Gly Pro Ser Gly Asp Phe Glu Leu Pro 305 310 315 320 Glu Glu Glu Thr Thr Gln Pro Asp Thr Ala Asn Glu Val Val Ala Val 325 330 335 Gly Gly Ala Ala Ala Lys Ala Ser Ser Pro Pro Gly Thr Leu Pro Lys 340 345 350 Gly Ala Arg Pro Gly Pro Gly Leu Leu Asp Asn Ala Ile Asp Ser Gly 355 360 365 Ser Ser Ala Ala Gln Leu Pro Gln Lys Ser Ile Leu Glu Arg Lys Glu 370 375 380 Val Leu Val Ala Val Ile Val Gly Gly Val Val Gly Ala Leu Phe Ala 385 390 395 400 Ala Phe Leu Val Thr Leu Leu Ile Tyr Arg Met Lys Lys Lys Asp Glu 405 410 415 Gly Ser Tyr Thr Leu Glu Glu Pro Lys Gln Ala Ser Val Thr Tyr Gln 420 425 430 Lys Pro Asp Lys Gln Glu Glu Phe Tyr Ala 435 440 <210> 66 <211> 457 <212> PRT <213> artificial sequence <220> <223> CMGA_ human beings <400> 66 Met Arg Ser Ala Ala Val Leu Ala Leu Leu Leu Cys Ala Gly Gln Val 1 5 10 15 Thr Ala Leu Pro Val Asn Ser Pro Met Asn Lys Gly Asp Thr Glu Val 20 25 30 Met Lys Cys Ile Val Glu Val Ile Ser Asp Thr Leu Ser Lys Pro Ser 35 40 45 Pro Met Pro Val Ser Gln Glu Cys Phe Glu Thr Leu Arg Gly Asp Glu 50 55 60 Arg Ile Leu Ser Ile Leu Arg His Gln Asn Leu Leu Lys Glu Leu Gln 65 70 75 80 Asp Leu Ala Leu Gln Gly Ala Lys Glu Arg Ala His Gln Gln Lys Lys 85 90 95 His Ser Gly Phe Glu Asp Glu Leu Ser Glu Val Leu Glu Asn Gln Ser 100 105 110 Ser Gln Ala Glu Leu Lys Glu Ala Val Glu Glu Pro Ser Ser Lys Asp 115 120 125 Val Met Glu Lys Arg Glu Asp Ser Lys Glu Ala Glu Lys Ser Gly Glu 130 135 140 Ala Thr Asp Gly Ala Arg Pro Gln Ala Leu Pro Glu Pro Met Gln Glu 145 150 155 160 Ser Lys Ala Glu Gly Asn Asn Gln Ala Pro Gly Glu Glu Glu Glu Glu 165 170 175 Glu Glu Glu Ala Thr Asn Thr His Pro Pro Ala Ser Leu Pro Ser Gln 180 185 190 Lys Tyr Pro Gly Pro Gln Ala Glu Gly Asp Ser Glu Gly Leu Ser Gln 195 200 205 Gly Leu Val Asp Arg Glu Lys Gly Leu Ser Ala Glu Pro Gly Trp Gln 210 215 220 Ala Lys Arg Glu Glu Glu Glu Glu Glu Glu Glu Glu Ala Glu Ala Gly 225 230 235 240 Glu Glu Ala Val Pro Glu Glu Glu Gly Pro Thr Val Val Leu Asn Pro 245 250 255 His Pro Ser Leu Gly Tyr Lys Glu Ile Arg Lys Gly Glu Ser Arg Ser 260 265 270 Glu Ala Leu Ala Val Asp Gly Ala Gly Lys Pro Gly Ala Glu Glu Ala 275 280 285 Gln Asp Pro Glu Gly Lys Gly Glu Gln Glu His Ser Gln Gln Lys Glu 290 295 300 Glu Glu Glu Glu Met Ala Val Val Pro Gln Gly Leu Phe Arg Gly Gly 305 310 315 320 Lys Ser Gly Glu Leu Glu Gln Glu Glu Glu Arg Leu Ser Lys Glu Trp 325 330 335 Glu Asp Ser Lys Arg Trp Ser Lys Met Asp Gln Leu Ala Lys Glu Leu 340 345 350 Thr Ala Glu Lys Arg Leu Glu Gly Gln Glu Glu Glu Glu Asp Asn Arg 355 360 365 Asp Ser Ser Met Lys Leu Ser Phe Arg Ala Arg Ala Tyr Gly Phe Arg 370 375 380 Gly Pro Gly Pro Gln Leu Arg Arg Gly Trp Arg Pro Ser Ser Arg Glu 385 390 395 400 Asp Ser Leu Glu Ala Gly Leu Pro Leu Gln Val Arg Gly Tyr Pro Glu 405 410 415 Glu Lys Lys Glu Glu Glu Gly Ser Ala Asn Arg Arg Pro Glu Asp Gln 420 425 430 Glu Leu Glu Ser Leu Ser Ala Ile Glu Ala Glu Leu Glu Lys Val Ala 435 440 445 His Gln Leu Gln Ala Leu Arg Arg Gly 450 455 <210> 67 <211> 458 <212> PRT <213> artificial sequence <220> <223> CBPN_ human beings <400> 67 Met Ser Asp Leu Leu Ser Val Phe Leu His Leu Leu Leu Leu Phe Lys 1 5 10 15 Leu Val Ala Pro Val Thr Phe Arg His His Arg Tyr Asp Asp Leu Val 20 25 30 Arg Thr Leu Tyr Lys Val Gln Asn Glu Cys Pro Gly Ile Thr Arg Val 35 40 45 Tyr Ser Ile Gly Arg Ser Val Glu Gly Arg His Leu Tyr Val Leu Glu 50 55 60 Phe Ser Asp His Pro Gly Ile His Glu Pro Leu Glu Pro Glu Val Lys 65 70 75 80 Tyr Val Gly Asn Met His Gly Asn Glu Ala Leu Gly Arg Glu Leu Met 85 90 95 Leu Gln Leu Ser Glu Phe Leu Cys Glu Glu Phe Arg Asn Arg Asn Gln 100 105 110 Arg Ile Val Gln Leu Ile Gln Asp Thr Arg Ile His Ile Leu Pro Ser 115 120 125 Met Asn Pro Asp Gly Tyr Glu Val Ala Ala Ala Gln Gly Pro Asn Lys 130 135 140 Pro Gly Tyr Leu Val Gly Arg Asn Asn Ala Asn Gly Val Asp Leu Asn 145 150 155 160 Arg Asn Phe Pro Asp Leu Asn Thr Tyr Ile Tyr Tyr Asn Glu Lys Tyr 165 170 175 Gly Gly Pro Asn His His Leu Pro Leu Pro Asp Asn Trp Lys Ser Gln 180 185 190 Val Glu Pro Glu Thr Arg Ala Val Ile Arg Trp Met His Ser Phe Asn 195 200 205 Phe Val Leu Ser Ala Asn Leu His Gly Gly Ala Val Val Ala Asn Tyr 210 215 220 Pro Tyr Asp Lys Ser Phe Glu His Arg Val Arg Gly Val Arg Arg Thr 225 230 235 240 Ala Ser Thr Pro Thr Pro Asp Asp Lys Leu Phe Gln Lys Leu Ala Lys 245 250 255 Val Tyr Ser Tyr Ala His Gly Trp Met Phe Gln Gly Trp Asn Cys Gly 260 265 270 Asp Tyr Phe Pro Asp Gly Ile Thr Asn Gly Ala Ser Trp Tyr Ser Leu 275 280 285 Ser Lys Gly Met Gln Asp Phe Asn Tyr Leu His Thr Asn Cys Phe Glu 290 295 300 Ile Thr Leu Glu Leu Ser Cys Asp Lys Phe Pro Pro Glu Glu Glu Leu 305 310 315 320 Gln Arg Glu Trp Leu Gly Asn Arg Glu Ala Leu Ile Gln Phe Leu Glu 325 330 335 Gln Val His Gln Gly Ile Lys Gly Met Val Leu Asp Glu Asn Tyr Asn 340 345 350 Asn Leu Ala Asn Ala Val Ile Ser Val Ser Gly Ile Asn His Asp Val 355 360 365 Thr Ser Gly Asp His Gly Asp Tyr Phe Arg Leu Leu Leu Pro Gly Ile 370 375 380 Tyr Thr Val Ser Ala Thr Ala Pro Gly Tyr Asp Pro Glu Thr Val Thr 385 390 395 400 Val Thr Val Gly Pro Ala Glu Pro Thr Leu Val Asn Phe His Leu Lys 405 410 415 Arg Ser Ile Pro Gln Val Ser Pro Val Arg Arg Ala Pro Ser Arg Arg 420 425 430 His Gly Val Arg Ala Lys Val Gln Pro Gln Ala Arg Lys Lys Glu Met 435 440 445 Glu Met Arg Gln Leu Gln Arg Gly Pro Ala 450 455 <210> 68 <211> 461 <212> PRT <213> Artificial Sequence <220> <223> FA9_Human <400> 68 Met Gln Arg Val Asn Met Ile Met Ala Glu Ser Pro Gly Leu Ile Thr 1 5 10 15 Ile Cys Leu Leu Gly Tyr Leu Leu Ser Ala Glu Cys Thr Val Phe Leu 20 25 30 Asp His Glu Asn Ala Asn Lys Ile Leu Asn Arg Pro Lys Arg Tyr Asn 35 40 45 Ser Gly Lys Leu Glu Glu Phe Val Gln Gly Asn Leu Glu Arg Glu Cys 50 55 60 Met Glu Glu Lys Cys Ser Phe Glu Glu Ala Arg Glu Val Phe Glu Asn 65 70 75 80 Thr Glu Arg Thr Thr Glu Phe Trp Lys Gln Tyr Val Asp Gly Asp Gln 85 90 95 Cys Glu Ser Asn Pro Cys Leu Asn Gly Gly Ser Cys Lys Asp Asp Ile 100 105 110 Asn Ser Tyr Glu Cys Trp Cys Pro Phe Gly Phe Glu Gly Lys Asn Cys 115 120 125 Glu Leu Asp Val Thr Cys Asn Ile Lys Asn Gly Arg Cys Glu Gln Phe 130 135 140 Cys Lys Asn Ser Ala Asp Asn Lys Val Val Cys Ser Cys Thr Glu Gly 145 150 155 160 Tyr Arg Leu Ala Glu Asn Gln Lys Ser Cys Glu Pro Ala Val Pro Phe 165 170 175 Pro Cys Gly Arg Val Ser Val Ser Gln Thr Ser Lys Leu Thr Arg Ala 180 185 190 Glu Thr Val Phe Pro Asp Val Asp Tyr Val Asn Ser Thr Glu Ala Glu 195 200 205 Thr Ile Leu Asp Asn Ile Thr Gln Ser Thr Gln Ser Phe Asn Asp Phe 210 215 220 Thr Arg Val Val Gly Gly Glu Asp Ala Lys Pro Gly Gln Phe Pro Trp 225 230 235 240 Gln Val Val Leu Asn Gly Lys Val Asp Ala Phe Cys Gly Gly Ser Ile 245 250 255 Val Asn Glu Lys Trp Ile Val Thr Ala Ala His Cys Val Glu Thr Gly 260 265 270 Val Lys Ile Thr Val Val Ala Gly Glu His Asn Ile Glu Glu Thr Glu 275 280 285 His Thr Glu Gln Lys Arg Asn Val Ile Arg Ile Ile Pro His His Asn 290 295 300 Tyr Asn Ala Ala Ile Asn Lys Tyr Asn His Asp Ile Ala Leu Leu Glu 305 310 315 320 Leu Asp Glu Pro Leu Val Leu Asn Ser Tyr Val Thr Pro Ile Cys Ile 325 330 335 Ala Asp Lys Glu Tyr Thr Asn Ile Phe Leu Lys Phe Gly Ser Gly Tyr 340 345 350 Val Ser Gly Trp Gly Arg Val Phe His Lys Gly Arg Ser Ala Leu Val 355 360 365 Leu Gln Tyr Leu Arg Val Pro Leu Val Asp Arg Ala Thr Cys Leu Arg 370 375 380 Ser Thr Lys Phe Thr Ile Tyr Asn Asn Met Phe Cys Ala Gly Phe His 385 390 395 400 Glu Gly Gly Arg Asp Ser Cys Gln Gly Asp Ser Gly Gly Pro His Val 405 410 415 Thr Glu Val Glu Gly Thr Ser Phe Leu Thr Gly Ile Ile Ser Trp Gly 420 425 430 Glu Glu Cys Ala Met Lys Gly Lys Tyr Gly Ile Tyr Thr Lys Val Ser 435 440 445 Arg Tyr Val Asn Trp Ile Lys Glu Lys Thr Lys Leu Thr 450 455 460 <210> 69 <211> 461 <212> PRT <213> Artificial Sequence <220> <223> TNR1B_Human <400> 69 Met Ala Pro Val Ala Val Trp Ala Ala Leu Ala Val Gly Leu Glu Leu 1 5 10 15 Trp Ala Ala Ala His Ala Leu Pro Ala Gln Val Ala Phe Thr Pro Tyr 20 25 30 Ala Pro Glu Pro Gly Ser Thr Cys Arg Leu Arg Glu Tyr Tyr Asp Gln 35 40 45 Thr Ala Gln Met Cys Cys Ser Lys Cys Ser Pro Gly Gln His Ala Lys 50 55 60 Val Phe Cys Thr Lys Thr Ser Asp Thr Val Cys Asp Ser Cys Glu Asp 65 70 75 80 Ser Thr Tyr Thr Gln Leu Trp Asn Trp Val Pro Glu Cys Leu Ser Cys 85 90 95 Gly Ser Arg Cys Ser Ser Asp Gln Val Glu Thr Gln Ala Cys Thr Arg 100 105 110 Glu Gln Asn Arg Ile Cys Thr Cys Arg Pro Gly Trp Tyr Cys Ala Leu 115 120 125 Ser Lys Gln Glu Gly Cys Arg Leu Cys Ala Pro Leu Arg Lys Cys Arg 130 135 140 Pro Gly Phe Gly Val Ala Arg Pro Gly Thr Glu Thr Ser Asp Val Val 145 150 155 160 Cys Lys Pro Cys Ala Pro Gly Thr Phe Ser Asn Thr Thr Ser Ser Thr 165 170 175 Asp Ile Cys Arg Pro His Gln Ile Cys Asn Val Val Ala Ile Pro Gly 180 185 190 Asn Ala Ser Met Asp Ala Val Cys Thr Ser Thr Ser Pro Thr Arg Ser 195 200 205 Met Ala Pro Gly Ala Val His Leu Pro Gln Pro Val Ser Thr Arg Ser 210 215 220 Gln His Thr Gln Pro Thr Pro Glu Pro Ser Thr Ala Pro Ser Thr Ser 225 230 235 240 Phe Leu Leu Pro Met Gly Pro Ser Pro Pro Ala Glu Gly Ser Thr Gly 245 250 255 Asp Phe Ala Leu Pro Val Gly Leu Ile Val Gly Val Thr Ala Leu Gly 260 265 270 Leu Leu Ile Ile Gly Val Val Asn Cys Val Ile Met Thr Gln Val Lys 275 280 285 Lys Lys Pro Leu Cys Leu Gln Arg Glu Ala Lys Val Pro His Leu Pro 290 295 300 Ala Asp Lys Ala Arg Gly Thr Gln Gly Pro Glu Gln Gln His Leu Leu 305 310 315 320 Ile Thr Ala Pro Ser Ser Ser Ser Ser Ser Leu Glu Ser Ser Ala Ser 325 330 335 Ala Leu Asp Arg Arg Ala Pro Thr Arg Asn Gln Pro Gln Ala Pro Gly 340 345 350 Val Glu Ala Ser Gly Ala Gly Glu Ala Arg Ala Ser Thr Gly Ser Ser 355 360 365 Asp Ser Ser Pro Gly Gly His Gly Thr Gln Val Asn Val Thr Cys Ile 370 375 380 Val Asn Val Cys Ser Ser Ser Asp His Ser Ser Gln Cys Ser Ser Gln 385 390 395 400 Ala Ser Ser Thr Met Gly Asp Thr Asp Ser Ser Pro Ser Glu Ser Pro 405 410 415 Lys Asp Glu Gln Val Pro Phe Ser Lys Glu Glu Cys Ala Phe Arg Ser 420 425 430 Gln Leu Glu Thr Pro Glu Thr Leu Leu Gly Ser Thr Glu Glu Lys Pro 435 440 445 Leu Pro Leu Gly Val Pro Asp Ala Gly Met Lys Pro Ser 450 455 460 <210> 70 <211> 466 <212> PRT <213> Artificial Sequence <220> <223> VIME_Human <400> 70 Met Ser Thr Arg Ser Val Ser Ser Ser Ser Tyr Arg Arg Met Phe Gly 1 5 10 15 Gly Pro Gly Thr Ala Ser Arg Pro Ser Ser Ser Arg Ser Tyr Val Thr 20 25 30 Thr Ser Thr Arg Thr Tyr Ser Leu Gly Ser Ala Leu Arg Pro Ser Thr 35 40 45 Ser Arg Ser Leu Tyr Ala Ser Ser Pro Gly Gly Val Tyr Ala Thr Arg 50 55 60 Ser Ser Ala Val Arg Leu Arg Ser Ser Val Pro Gly Val Arg Leu Leu 65 70 75 80 Gln Asp Ser Val Asp Phe Ser Leu Ala Asp Ala Ile Asn Thr Glu Phe 85 90 95 Lys Asn Thr Arg Thr Asn Glu Lys Val Glu Leu Gln Glu Leu Asn Asp 100 105 110 Arg Phe Ala Asn Tyr Ile Asp Lys Val Arg Phe Leu Glu Gln Gln Asn 115 120 125 Lys Ile Leu Leu Ala Glu Leu Glu Gln Leu Lys Gly Gln Gly Lys Ser 130 135 140 Arg Leu Gly Asp Leu Tyr Glu Glu Glu Met Arg Glu Leu Arg Arg Gln 145 150 155 160 Val Asp Gln Leu Thr Asn Asp Lys Ala Arg Val Glu Val Glu Arg Asp 165 170 175 Asn Leu Ala Glu Asp Ile Met Arg Leu Arg Glu Lys Leu Gln Glu Glu 180 185 190 Met Leu Gln Arg Glu Glu Ala Glu Asn Thr Leu Gln Ser Phe Arg Gln 195 200 205 Asp Val Asp Asn Ala Ser Leu Ala Arg Leu Asp Leu Glu Arg Lys Val 210 215 220 Glu Ser Leu Gln Glu Glu Ile Ala Phe Leu Lys Lys Leu His Glu Glu 225 230 235 240 Glu Ile Gln Glu Leu Gln Ala Gln Ile Gln Glu Gln His Val Gln Ile 245 250 255 Asp Val Asp Val Ser Lys Pro Asp Leu Thr Ala Ala Leu Arg Asp Val 260 265 270 Arg Gln Gln Tyr Glu Ser Val Ala Ala Lys Asn Leu Gln Glu Ala Glu 275 280 285 Glu Trp Tyr Lys Ser Lys Phe Ala Asp Leu Ser Glu Ala Ala Asn Arg 290 295 300 Asn Asn Asp Ala Leu Arg Gln Ala Lys Gln Glu Ser Thr Glu Tyr Arg 305 310 315 320 Arg Gln Val Gln Ser Leu Thr Cys Glu Val Asp Ala Leu Lys Gly Thr 325 330 335 Asn Glu Ser Leu Glu Arg Gln Met Arg Glu Met Glu Glu Asn Phe Ala 340 345 350 Val Glu Ala Ala Asn Tyr Gln Asp Thr Ile Gly Arg Leu Gln Asp Glu 355 360 365 Ile Gln Asn Met Lys Glu Glu Met Ala Arg His Leu Arg Glu Tyr Gln 370 375 380 Asp Leu Leu Asn Val Lys Met Ala Leu Asp Ile Glu Ile Ala Thr Tyr 385 390 395 400 Arg Lys Leu Leu Glu Gly Glu Glu Ser Arg Ile Ser Leu Pro Leu Pro 405 410 415 Asn Phe Ser Ser Leu Asn Leu Arg Glu Thr Asn Leu Asp Ser Leu Pro 420 425 430 Leu Val Asp Thr His Ser Lys Arg Thr Leu Leu Ile Lys Thr Val Glu 435 440 445 Thr Arg Asp Gly Gln Val Ile Asn Glu Thr Ser Gln His His Asp Asp 450 455 460 Leo Glu 465 <210> 71 <211> 468 <212> PRT <213> artificial sequence <220> <223> SCG3_ humans <400> 71 Met Gly Phe Leu Gly Thr Gly Thr Trp Ile Leu Val Leu Val Leu Pro 1 5 10 15 Ile Gln Ala Phe Pro Lys Pro Gly Gly Ser Gln Asp Lys Ser Leu His 20 25 30 Asn Arg Glu Leu Ser Ala Glu Arg Pro Leu Asn Glu Gln Ile Ala Glu 35 40 45 Ala Glu Glu Asp Lys Ile Lys Lys Thr Tyr Pro Pro Glu Asn Lys Pro 50 55 60 Gly Gln Ser Asn Tyr Ser Phe Val Asp Asn Leu Asn Leu Leu Lys Ala 65 70 75 80 Ile Thr Glu Lys Glu Lys Ile Glu Lys Glu Arg Gln Ser Ile Arg Ser 85 90 95 Ser Pro Leu Asp Asn Lys Leu Asn Val Glu Asp Val Asp Ser Thr Lys 100 105 110 Asn Arg Lys Leu Ile Asp Asp Tyr Asp Ser Thr Lys Ser Gly Leu Asp 115 120 125 His Lys Phe Gln Asp Asp Pro Asp Gly Leu His Gln Leu Asp Gly Thr 130 135 140 Pro Leu Thr Ala Glu Asp Ile Val His Lys Ile Ala Ala Arg Ile Tyr 145 150 155 160 Glu Glu Asn Asp Arg Ala Val Phe Asp Lys Ile Val Ser Lys Leu Leu 165 170 175 Asn Leu Gly Leu Ile Thr Glu Ser Gln Ala His Thr Leu Glu Asp Glu 180 185 190 Val Ala Glu Val Leu Gln Lys Leu Ile Ser Lys Glu Ala Asn Asn Tyr 195 200 205 Glu Glu Asp Pro Asn Lys Pro Thr Ser Trp Thr Glu Asn Gln Ala Gly 210 215 220 Lys Ile Pro Glu Lys Val Thr Pro Met Ala Ala Ile Gln Asp Gly Leu 225 230 235 240 Ala Lys Gly Glu Asn Asp Glu Thr Val Ser Asn Thr Leu Thr Leu Thr 245 250 255 Asn Gly Leu Glu Arg Arg Thr Lys Thr Tyr Ser Glu Asp Asn Phe Glu 260 265 270 Glu Leu Gln Tyr Phe Pro Asn Phe Tyr Ala Leu Leu Lys Ser Ile Asp 275 280 285 Ser Glu Lys Glu Ala Lys Glu Lys Glu Thr Leu Ile Thr Ile Met Lys 290 295 300 Thr Leu Ile Asp Phe Val Lys Met Met Val Lys Tyr Gly Thr Ile Ser 305 310 315 320 Pro Glu Glu Gly Val Ser Tyr Leu Glu Asn Leu Asp Glu Met Ile Ala 325 330 335 Leu Gln Thr Lys Asn Lys Leu Glu Lys Asn Ala Thr Asp Asn Ile Ser 340 345 350 Lys Leu Phe Pro Ala Pro Ser Glu Lys Ser His Glu Glu Thr Asp Ser 355 360 365 Thr Lys Glu Glu Ala Ala Lys Met Glu Lys Glu Tyr Gly Ser Leu Lys 370 375 380 Asp Ser Thr Lys Asp Asp Asn Ser Asn Pro Gly Gly Lys Thr Asp Glu 385 390 395 400 Pro Lys Gly Lys Thr Glu Ala Tyr Leu Glu Ala Ile Arg Lys Asn Ile 405 410 415 Glu Trp Leu Lys Lys His Asp Lys Lys Gly Asn Lys Glu Asp Tyr Asp 420 425 430 Leu Ser Lys Met Arg Asp Phe Ile Asn Lys Gln Ala Asp Ala Tyr Val 435 440 445 Glu Lys Gly Ile Leu Asp Lys Glu Glu Ala Glu Ala Ile Lys Arg Ile 450 455 460 Tyr Ser Ser Leu 465 <210> 72 <211> 473 <212> PRT <213> Artificial Sequence <220> <223> KCC4_Human <400> 72 Met Leu Lys Val Thr Val Pro Ser Cys Ser Ala Ser Ser Cys Ser Ser 1 5 10 15 Val Thr Ala Ser Ala Ala Pro Gly Thr Ala Ser Leu Val Pro Asp Tyr 20 25 30 Trp Ile Asp Gly Ser Asn Arg Asp Ala Leu Ser Asp Phe Phe Glu Val 35 40 45 Glu Ser Glu Leu Gly Arg Gly Ala Thr Ser Ile Val Tyr Arg Cys Lys 50 55 60 Gln Lys Gly Thr Gln Lys Pro Tyr Ala Leu Lys Val Leu Lys Lys Thr 65 70 75 80 Val Asp Lys Lys Ile Val Arg Thr Glu Ile Gly Val Leu Leu Arg Leu 85 90 95 Ser His Pro Asn Ile Ile Lys Leu Lys Glu Ile Phe Glu Thr Pro Thr 100 105 110 Glu Ile Ser Leu Val Leu Glu Leu Val Thr Gly Gly Glu Leu Phe Asp 115 120 125 Arg Ile Val Glu Lys Gly Tyr Tyr Ser Glu Arg Asp Ala Ala Asp Ala 130 135 140 Val Lys Gln Ile Leu Glu Ala Val Ala Tyr Leu His Glu Asn Gly Ile 145 150 155 160 Val His Arg Asp Leu Lys Pro Glu Asn Leu Leu Tyr Ala Thr Pro Ala 165 170 175 Pro Asp Ala Pro Leu Lys Ile Ala Asp Phe Gly Leu Ser Lys Ile Val 180 185 190 Glu His Gln Val Leu Met Lys Thr Val Cys Gly Thr Pro Gly Tyr Cys 195 200 205 Ala Pro Glu Ile Leu Arg Gly Cys Ala Tyr Gly Pro Glu Val Asp Met 210 215 220 Trp Ser Val Gly Ile Ile Thr Tyr Ile Leu Leu Cys Gly Phe Glu Pro 225 230 235 240 Phe Tyr Asp Glu Arg Gly Asp Gln Phe Met Phe Arg Arg Ile Leu Asn 245 250 255 Cys Glu Tyr Tyr Phe Ile Ser Pro Trp Trp Asp Glu Val Ser Leu Asn 260 265 270 Ala Lys Asp Leu Val Arg Lys Leu Ile Val Leu Asp Pro Lys Lys Arg 275 280 285 Leu Thr Thr Phe Gln Ala Leu Gln His Pro Trp Val Thr Gly Lys Ala 290 295 300 Ala Asn Phe Val His Met Asp Thr Ala Gln Lys Lys Leu Gln Glu Phe 305 310 315 320 Asn Ala Arg Arg Lys Leu Lys Ala Ala Val Lys Ala Val Val Ala Ser 325 330 335 Ser Arg Leu Gly Ser Ala Ser Ser Ser His Gly Ser Ile Gln Glu Ser 340 345 350 His Lys Ala Ser Arg Asp Pro Ser Pro Ile Gln Asp Gly Asn Glu Asp 355 360 365 Met Lys Ala Ile Pro Glu Gly Glu Lys Ile Gln Gly Asp Gly Ala Gln 370 375 380 Ala Ala Val Lys Gly Ala Gln Ala Glu Leu Met Lys Val Gln Ala Leu 385 390 395 400 Glu Lys Val Lys Gly Ala Asp Ile Asn Ala Glu Glu Ala Pro Lys Met 405 410 415 Val Pro Lys Ala Val Glu Asp Gly Ile Lys Val Ala Asp Leu Glu Leu 420 425 430 Glu Glu Gly Leu Ala Glu Glu Lys Leu Lys Thr Val Glu Glu Ala Ala 435 440 445 Ala Pro Arg Glu Gly Gln Gly Ser Ser Ala Val Gly Phe Glu Val Pro 450 455 460 Gln Gln Asp Val Ile Leu Pro Glu Tyr 465 470 <210> 73 <211> 480 <212> PRT <213> Artificial Sequence <220> <223> AKT1_Human <400> 73 Met Ser Asp Val Ala Ile Val Lys Glu Gly Trp Leu His Lys Arg Gly 1 5 10 15 Glu Tyr Ile Lys Thr Trp Arg Pro Arg Tyr Phe Leu Leu Lys Asn Asp 20 25 30 Gly Thr Phe Ile Gly Tyr Lys Glu Arg Pro Gln Asp Val Asp Gln Arg 35 40 45 Glu Ala Pro Leu Asn Asn Phe Ser Val Ala Gln Cys Gln Leu Met Lys 50 55 60 Thr Glu Arg Pro Arg Pro Asn Thr Phe Ile Ile Arg Cys Leu Gln Trp 65 70 75 80 Thr Thr Val Ile Glu Arg Thr Phe His Val Glu Thr Pro Glu Glu Arg 85 90 95 Glu Glu Trp Thr Thr Ala Ile Gln Thr Val Ala Asp Gly Leu Lys Lys 100 105 110 Gln Glu Glu Glu Glu Met Asp Phe Arg Ser Gly Ser Pro Ser Asp Asn 115 120 125 Ser Gly Ala Glu Glu Met Glu Val Ser Leu Ala Lys Pro Lys His Arg 130 135 140 Val Thr Met Asn Glu Phe Glu Tyr Leu Lys Leu Leu Gly Lys Gly Thr 145 150 155 160 Phe Gly Lys Val Ile Leu Val Glu Lys Ala Thr Gly Arg Tyr Tyr 165 170 175 Only Met Lys Ile Leu Lys Lys Glu Val Ile Val Ala Lys Asp Glu Val 180 185 190 Only His Thr Leu Thr Glu Asn Arg Val Leu Gln Asn Ser Arg His Pro 195 200 205 Phe Leu Thr Ala Leu Lys Tyr Ser Phe Gln Thr His Asp Arg Leu Cys 210 215 220 Phe Val Met Glu Tyr Ala Asn Gly Gly Glu Leu Phe Phe His Leu Ser 225 230 235 240 Arg Glu Arg Val Phe Ser Glu Asp Arg Ala Arg Phe Tyr Gly Ala Glu 245 250 255 Ile Will Be Ala Leu Asp Tyr Leu His Will Be Glu Lys Asn Will Tyr 260 265 270 Arg Asp Leu Lys Leu Glu Asn Leu Met Leu Asp Lys Asp Gly His Ile 275 280 285 Lys Ile Thr Asp Phe Gly Leu Cys Lys Glu Gly Ile Lys Asp Gly Ala 290,295,300 Thr Met Lys Thr Phe Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu Val 305 310 315 320 Leu Glu Asp Asn Asp Tyr Gly Arg Ala Val Asp Trp Trp Gly Leu Gly 325 330 335 Val Val Met Tyr Glu Met Met Cys Gly Arg Leu Pro Phe Tyr Asn Gln 340 345 350 Asp His Glu Lys Leu Phe Glu Leu Ile Leu Met Glu Glu Ile Arg Phe 355 360 365 Pro Arg Thr Leu Gly Pro Glu Ala Lys Ser Leu Leu Ser Gly Leu Leu 370 375 380 Lys Lys Asp Pro Lys Gln Arg Leu Gly Gly Gly Ser Glu Asp Ala Lys 385 390 395 400 Glu Ile Met Gln His Arg Phe Phe Ala Gly Ile Val Trp Gln His Val 405 410 415 Tyr Glu Lys Lys Leu Ser Pro Pro Phe Lys Pro Gln Val Thr Ser Glu 420 425 430 Thr Asp Thr Arg Tyr Phe Asp Glu Glu Phe Thr Ala Gln Met Ile Thr 435 440 445 Ile Thr Pro Pro Asp Gln Asp Asp Ser Met Glu Cys Val Asp Ser Glu 450 455 460 Arg Arg Pro His Phe Pro Gln Phe Ser Tyr Ser Ala Ser Gly Thr Ala 465 470 475 480 <210> 74 <211> 481 <212> PRT <213> Artificial Sequence <220> <223> AKT2_Human <400> 74 Met Asn Glu Val Ser Val Ile Lys Glu Gly Trp Leu His Lys Arg Gly 1 5 10 15 Glu Tyr Ile Lys Thr Trp Arg Pro Arg Tyr Phe Leu Leu Lys Ser Asp 20 25 30 Gly Ser Phe Ile Gly Tyr Lys Glu Arg Pro Glu Ala Pro Asp Gln Thr 35 40 45 Leu Pro Pro Leu Asn Asn Phe Ser Val Ala Glu Cys Gln Leu Met Lys 50 55 60 Thr Glu Arg Pro Arg Pro Asn Thr Phe Val Ile Arg Cys Leu Gln Trp 65 70 75 80 Thr Thr Val Ile Glu Arg Thr Phe His Val Asp Ser Pro Asp Glu Arg 85 90 95 Glu Glu Trp Met Arg Ala Ile Gln Met Val Ala Asn Ser Leu Lys Gln 100 105 110 Arg Ala Pro Gly Glu Asp Pro Met Asp Tyr Lys Cys Gly Ser Pro Ser 115 120 125 Asp Ser Ser Thr Thr Glu Glu Met Glu Val Ala Val Ser Lys Ala Arg 130 135 140 Ala Lys Val Thr Met Asn Asp Phe Asp Tyr Leu Lys Leu Leu Gly Lys 145 150 155 160 Gly Thr Phe Gly Lys Val Ile Leu Val Arg Glu Lys Ala Thr Gly Arg 165 170 175 Tyr Tyr Ala Met Lys Ile Leu Arg Lys Glu Val Ile Ile Ala Lys Asp 180 185 190 Glu Val Ala His Thr Val Thr Glu Ser Arg Val Leu Gln Asn Thr Arg 195 200 205 His Pro Phe Leu Thr Ala Leu Lys Tyr Ala Phe Gln Thr His Asp Arg 210 215 220 Leu Cys Phe Val Met Glu Tyr Ala Asn Gly Gly Glu Leu Phe Phe His 225 230 235 240 Leu Ser Arg Glu Arg Val Phe Thr Glu Glu Arg Ala Arg Phe Tyr Gly 245 250 255 Ala Glu Ile Val Ser Ala Leu Glu Tyr Leu His Ser Arg Asp Val Val 260 265 270 Tyr Arg Asp Ile Lys Leu Glu Asn Leu Met Leu Asp Lys Asp Gly His 275 280 285 Ile Lys Ile Thr Asp Phe Gly Leu Cys Lys Glu Gly Ile Ser Asp Gly 290 295 300 Ala Thr Met Lys Thr Phe Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu 305 310 315 320 Val Leu Glu Asp Asn Asp Tyr Gly Arg Ala Val Asp Trp Trp Gly Leu 325 330 335 Gly Val Val Met Tyr Glu Met Met Cys Gly Arg Leu Pro Phe Tyr Asn 340 345 350 Gln Asp His Glu Arg Leu Phe Glu Leu Ile Leu Met Glu Glu Ile Arg 355 360 365 Phe Pro Arg Thr Leu Ser Pro Glu Ala Lys Ser Leu Leu Ala Gly Leu 370 375 380 Leu Lys Lys Asp Pro Lys Gln Arg Leu Gly Gly Gly Pro Ser Asp Ala 385 390 395 400 Lys Glu Val Met Glu His Arg Phe Phe Leu Ser Ile Asn Trp Gln Asp 405 410 415 Val Val Gln Lys Lys Leu Leu Pro Pro Phe Lys Pro Gln Val Thr Ser 420 425 430 Glu Val Asp Thr Arg Tyr Phe Asp Asp Glu Phe Thr Ala Gln Ser Ile 435 440 445 Thr Ile Thr Pro Pro Asp Arg Tyr Asp Ser Leu Gly Leu Leu Glu Leu 450 455 460 Asp Gln Arg Thr His Phe Pro Gln Phe Ser Tyr Ser Ala Ser Ile Arg 465 470 475 480 Glu <210> 75 <211> 481 <212> PRT <213> Artificial Sequence <220> <223> G37L1_Human <400> 75 Met Arg Trp Leu Trp Pro Leu Ala Val Ser Leu Ala Val Ile Leu Ala 1 5 10 15 Val Gly Leu Ser Arg Val Ser Gly Gly Ala Pro Leu His Leu Gly Arg 20 25 30 His Arg Ala Glu Thr Gln Glu Gln Gln Ser Arg Ser Lys Arg Gly Thr 35 40 45 Glu Asp Glu Glu Ala Lys Gly Val Gln Gln Tyr Val Pro Glu Glu Trp 50 55 60 Ala Glu Tyr Pro Arg Pro Ile His Pro Ala Gly Leu Gln Pro Thr Lys 65 70 75 80 Pro Leu Val Ala Thr Ser Pro Asn Pro Gly Lys Asp Gly Gly Thr Pro 85 90 95 Asp Ser Gly Gln Glu Leu Arg Gly Asn Leu Thr Gly Ala Pro Gly Gln 100 105 110 Arg Leu Gln Ile Gln Asn Pro Leu Tyr Pro Val Thr Glu Ser Ser Tyr 115 120 125 Ser Ala Tyr Ala Ile Met Leu Leu Ala Leu Val Val Phe Ala Val Gly 130 135 140 Ile Val Gly Asn Leu Ser Val Met Cys Ile Val Trp His Ser Tyr Tyr 145 150 155 160 Leu Lys Ser Ala Trp Asn Ser Ile Leu Ala Ser Leu Ala Leu Trp Asp 165 170 175 Phe Leu Val Leu Phe Phe Cys Leu Pro Ile Val Ile Phe Asn Glu Ile 180 185 190 Thr Lys Gln Arg Leu Leu Gly Asp Val Ser Cys Arg Ala Val Pro Phe 195 200 205 Met Glu Val Ser Ser Leu Gly Val Thr Thr Phe Ser Leu Cys Ala Leu 210 215 220 Gly Ile Asp Arg Phe His Val Ala Thr Ser Thr Leu Pro Lys Val Arg 225 230 235 240 Pro Ile Glu Arg Cys Gln Ser Ile Leu Ala Lys Leu Ala Val Ile Trp 245 250 255 Val Gly Ser Met Thr Leu Ala Val Pro Glu Leu Leu Leu Trp Gln Leu 260 265 270 Ala Gln Glu Pro Ala Pro Thr Met Gly Thr Leu Asp Ser Cys Ile Met 275 280 285 Lys Pro Ser Ala Ser Leu Pro Glu Ser Leu Tyr Ser Leu Val Met Thr 290 295 300 Tyr Gln Asn Ala Arg Met Trp Trp Tyr Phe Gly Cys Tyr Phe Cys Leu 305 310 315 320 Pro Ile Leu Phe Thr Val Thr Cys Gln Leu Val Thr Trp Arg Val Arg 325 330 335 Gly Pro Pro Gly Arg Lys Ser Glu Cys Arg Ala Ser Lys His Glu Gln 340 345 350 Cys Glu Ser Gln Leu Asn Ser Thr Val Val Gly Leu Thr Val Val Tyr 355 360 365 Ala Phe Cys Thr Leu Pro Glu Asn Val Cys Asn Ile Val Val Ala Tyr 370 375 380 Leu Ser Thr Glu Leu Thr Arg Gln Thr Leu Asp Leu Leu Gly Leu Ile 385 390 395 400 Asn Gln Phe Ser Thr Phe Phe Lys Gly Ala Ile Thr Pro Val Leu Leu 405 410 415 Leu Cys Ile Cys Arg Pro Leu Gly Gln Ala Phe Leu Asp Cys Cys Cys 420 425 430 Cys Cys Cys Cys Glu Glu Cys Gly Gly Ala Ser Glu Ala Ser Ala Ala 435 440 445 Asn Gly Ser Asp Asn Lys Leu Lys Thr Glu Val Ser Ser Ser Ile Tyr 450 455 460 Phe His Lys Pro Arg Glu Ser Pro Pro Leu Leu Pro Leu Gly Thr Pro 465 470 475 480 Cys <210> 76 <211> 490 <212> PRT <213> Artificial Sequence <220> <223> TEKT3_Human <400> 76 Met Glu Arg Val Gly Cys Thr Leu Thr Thr Thr Tyr Ala His Pro Arg 1 5 10 15 Pro Thr Pro Thr Asn Phe Leu Pro Ala Ile Ser Thr Met Ala Ser Ser 20 25 30 Tyr Arg Asp Arg Phe Pro His Ser Asn Leu Thr His Ser Leu Ser Leu 35 40 45 Pro Trp Arg Pro Ser Thr Tyr Tyr Lys Val Ala Ser Asn Ser Pro Ser 50 55 60 Val Ala Pro Tyr Cys Thr Arg Ser Gln Arg Val Ser Glu Asn Thr Met 65 70 75 80 Leu Pro Phe Val Ser Asn Arg Thr Thr Phe Phe Thr Arg Tyr Thr Pro 85 90 95 Asp Asp Trp Tyr Arg Ser Asn Leu Thr Asn Tyr Gln Glu Ser Asn Thr 100 105 110 Ser Arg His Asn Ser Glu Lys Leu Arg Val Asp Thr Ser Arg Leu Ile 115 120 125 Gln Asp Lys Tyr Gln Gln Thr Arg Lys Thr Gln Ala Asp Thr Thr Gln 130 135 140 Asn Leu Gly Glu Arg Val Asn Asp Ile Gly Phe Trp Lys Ser Glu Ile 145 150 155 160 Ile His Glu Leu Asp Glu Met Ile Gly Glu Thr Asn Ala Leu Thr Asp 165 170 175 Val Lys Lys Arg Leu Glu Arg Ala Leu Met Glu Thr Glu Ala Pro Leu 180 185 190 Gln Val Ala Arg Glu Cys Leu Phe His Arg Glu Lys Arg Met Gly Ile 195 200 205 Asp Leu Val His Asp Glu Val Glu Ala Gln Leu Leu Thr Glu Val Asp 210 215 220 Thr Ile Leu Cys Cys Gln Glu Arg Met Lys Leu His Leu Asp Lys Ala 225 230 235 240 Ile Ala Gln Leu Ala Ala Asn Arg Ala Ser Gln His Glu Leu Glu Lys 245 250 255 Asp Leu Ser Asp Lys Gln Thr Ala Tyr Arg Ile Asp Asp Lys Cys His 260 265 270 His Leu Arg Asn Thr Ser Asp Gly Val Gly Tyr Phe Arg Gly Val Glu 275 280 285 Arg Val Asp Ala Thr Val Ser Val Pro Glu Ser Trp Ala Lys Phe Thr 290 295 300 Asp Asp Asn Ile Leu Arg Ser Gln Ser Glu Arg Ala Ala Ser Ala Lys 305 310 315 320 Leu Arg Asp Asp Ile Glu Asn Leu Leu Val Val Thr Ala Asn Glu Met 325 330 335 Trp Asn Gln Phe Asn Lys Val Asn Leu Ser Phe Thr Asn Arg Ile Ala 340 345 350 Glu Thr Ala Asp Ala Lys Asn Lys Ile Gln Thr His Leu Ala Lys Thr 355 360 365 Leu Gln Glu Ile Phe Gln Thr Glu Met Thr Ile Glu Ser Ile Lys Lys 370 375 380 Ala Ile Lys Asp Lys Thr Ala Phe Leu Lys Val Ala Gln Thr Arg Leu 385 390 395 400 Asp Glu Arg Thr Arg Arg Pro Asn Ile Glu Leu Cys Arg Asp Met Ala 405 410 415 Gln Leu Arg Leu Val Asn Glu Val His Glu Val Asp Asp Thr Ile Gln 420 425 430 Thr Leu Gln Gln Arg Leu Arg Asp Ala Glu Asp Thr Leu Gln Ser Leu 435 440 445 Val His Ile Lys Ala Thr Leu Glu Tyr Asp Leu Ala Val Lys Ala Asn 450 455 460 Ser Leu Tyr Ile Asp Gln Glu Lys Cys Met Ser Met Arg Lys Ser Tyr 465 470 475 480 Pro Asn Thr Leu Arg Leu Val Gly Phe Cys 485 490 <210> 77 <211> 500 <212> PRT <213> artificial sequence <220> <223> IC1_ humans <400> 77 Met Ala Ser Arg Leu Thr Leu Leu Thr Leu Leu Leu Leu Leu Leu Ala 1 5 10 15 Gly Asp Arg Ala Ser Ser Asn Pro Asn Ala Thr Ser Ser Ser Ser Gln 20 25 30 Asp Pro Glu Ser Leu Gln Asp Arg Gly Glu Gly Lys Val Ala Thr Thr 35 40 45 Val Ile Ser Lys Met Leu Phe Val Glu Pro Ile Leu Glu Val Ser Ser 50 55 60 Leu Pro Thr Thr Asn Ser Thr Thr Asn Ser Ala Thr Lys Ile Thr Ala 65 70 75 80 Asn Thr Thr Asp Glu Pro Thr Thr Gln Pro Thr Thr Glu Pro Thr Thr 85 90 95 Gln Pro Thr Ile Gln Pro Thr Gln Pro Thr Thr Gln Leu Pro Thr Asp 100 105 110 Ser Pro Thr Gln Pro Thr Thr Gly Ser Phe Cys Pro Gly Pro Val Thr 115 120 125 Leu Cys Ser Asp Leu Glu Ser His Ser Thr Glu Ala Val Leu Gly Asp 130 135 140 Ala Leu Val Asp Phe Ser Leu Lys Leu Tyr His Ala Phe Ser Ala Met 145 150 155 160 Lys Lys Val Glu Thr Asn Met Ala Phe Ser Pro Phe Ser Ile Ala Ser 165 170 175 Leu Leu Thr Gln Val Leu Leu Gly Ala Gly Glu Asn Thr Lys Thr Asn 180 185 190 Leu Glu Ser Ile Leu Ser Tyr Pro Lys Asp Phe Thr Cys Val His Gln 195 200 205 Ala Leu Lys Gly Phe Thr Thr Lys Gly Val Thr Ser Val Ser Gln Ile 210 215 220 Phe His Ser Pro Asp Leu Ala Ile Arg Asp Thr Phe Val Asn Ala Ser 225 230 235 240 Arg Thr Leu Tyr Ser Ser Ser Pro Arg Val Leu Ser Asn Asn Ser Asp 245 250 255 Ala Asn Leu Glu Leu Ile Asn Thr Trp Val Ala Lys Asn Thr Asn Asn 260 265 270 Lys Ile Ser Arg Leu Leu Asp Ser Leu Pro Ser Asp Thr Arg Leu Val 275 280 285 Leu Leu Asn Ala Ile Tyr Leu Ser Ala Lys Trp Lys Thr Thr Phe Asp 290 295 300 Pro Lys Lys Thr Arg Met Glu Pro Phe His Phe Lys Asn Ser Val Ile 305 310 315 320 Lys Val Pro Met Met Asn Ser Lys Lys Tyr Pro Val Ala His Phe Ile 325 330 335 Asp Gln Thr Leu Lys Ala Lys Val Gly Gln Leu Gln Leu Ser His Asn 340 345 350 Leu Ser Leu Val Ile Leu Val Pro Gln Asn Leu Lys His Arg Leu Glu 355 360 365 Asp Met Glu Gln Ala Leu Ser Pro Ser Val Phe Lys Ala Ile Met Glu 370 375 380 Lys Leu Glu Met Ser Lys Phe Gln Pro Thr Leu Leu Thr Leu Pro Arg 385 390 395 400 Ile Lys Val Thr Thr Ser Gln Asp Met Leu Ser Ile Met Glu Lys Leu 405 410 415 Glu Phe Phe Asp Phe Ser Tyr Asp Leu Asn Leu Cys Gly Leu Thr Glu 420 425 430 Asp Pro Asp Leu Gln Val Ser Ala Met Gln His Gln Thr Val Leu Glu 435 440 445 Leu Thr Glu Thr Gly Val Glu Ala Ala Ala Ala Ser Ala Ile Ser Val 450 455 460 Ala Arg Thr Leu Leu Val Phe Glu Val Gln Gln Pro Phe Leu Phe Val 465 470 475 480 Leu Trp Asp Gln Gln His Lys Phe Pro Val Phe Met Gly Arg Val Tyr 485 490 495 Asp Pro Arg Ala 500 <210> 78 <211> 508 <212> PRT <213> Artificial Sequence <220> <223> SRF_Human <400> 78 Met Leu Pro Thr Gln Ala Gly Ala Ala Ala Ala Leu Gly Arg Gly Ser 1 5 10 15 Ala Leu Gly Gly Ser Leu Asn Arg Thr Pro Thr Gly Arg Pro Gly Gly 20 25 30 Gly Gly Gly Thr Arg Gly Ala Asn Gly Gly Arg Val Pro Gly Asn Gly 35 40 45 Ala Gly Leu Gly Pro Gly Arg Leu Glu Arg Glu Ala Ala Ala Ala Ala 50 55 60 Ala Thr Thr Pro Ala Pro Thr Ala Gly Ala Leu Tyr Ser Gly Ser Glu 65 70 75 80 Gly Asp Ser Glu Ser Gly Glu Glu Glu Glu Leu Gly Ala Glu Arg Arg 85 90 95 Gly Leu Lys Arg Ser Leu Ser Glu Met Glu Ile Gly Met Val Val Gly 100 105 110 Gly Pro Glu Ala Ser Ala Ala Ala Thr Gly Gly Tyr Gly Pro Val Ser 115 120 125 Gly Ala Val Ser Gly Ala Lys Pro Gly Lys Lys Thr Arg Gly Arg Val 130 135 140 Lys Ile Lys Met Glu Phe Ile Asp Asn Lys Leu Arg Arg Tyr Thr Thr 145 150 155 160 Phe Ser Lys Arg Lys Thr Gly Ile Met Lys Lys Ala Tyr Glu Leu Ser 165 170 175 Thr Leu Thr Gly Thr Gln Val Leu Leu Leu Val Ala Ser Glu Thr Gly 180 185 190 His Val Tyr Thr Phe Ala Thr Arg Lys Leu Gln Pro Met Ile Thr Ser 195 200 205 Glu Thr Gly Lys Ala Leu Ile Gln Thr Cys Leu Asn Ser Pro Asp Ser 210 215 220 Pro Pro Arg Ser Asp Pro Thr Thr Asp Gln Arg Met Ser Ala Thr Gly 225 230 235 240 Phe Glu Glu Thr Asp Leu Thr Tyr Gln Val Ser Glu Ser Asp Ser Ser 245 250 255 Gly Glu Thr Lys Asp Thr Leu Lys Pro Ala Phe Thr Val Thr Asn Leu 260 265 270 Pro Gly Thr Thr Ser Thr Ile Gln Thr Ala Pro Ser Thr Ser Thr Thr 275 280 285 Met Gln Val Ser Ser Gly Pro Ser Phe Pro Ile Thr Asn Tyr Leu Ala 290 295 300 Pro Val Ser Ala Ser Val Ser Pro Ser Ala Val Ser Ser Ala Asn Gly 305 310 315 320 Thr Val Leu Lys Ser Thr Gly Ser Gly Pro Val Ser Ser Gly Gly Leu 325 330 335 Met Gln Leu Pro Thr Ser Phe Thr Leu Met Pro Gly Gly Ala Val Ala 340 345 350 Gln Gln Val Pro Val Gln Ala Ile Gln Val His Gln Ala Pro Gln Gln 355 360 365 Ala Ser Pro Ser Arg Asp Ser Ser Thr Asp Leu Thr Gln Thr Ser Ser 370 375 380 Ser Gly Thr Val Thr Leu Pro Ala Thr Ile Met Thr Ser Ser Val Pro 385 390 395 400 Thr Thr Val Gly Gly His Met Met Tyr Pro Ser Pro His Ala Val Met 405 410 415 Tyr Ala Pro Thr Ser Gly Leu Gly Asp Gly Ser Leu Thr Val Leu Asn 420 425 430 Ala Phe Ser Gln Ala Pro Ser Thr Met Gln Val Ser His Ser Gln Val 435 440 445 Gln Glu Pro Gly Gly Val Pro Gln Val Phe Leu Thr Ala Ser Ser Gly 450 455 460 Thr Val Gln Ile Pro Val Ser Ala Val Gln Leu His Gln Met Ala Val 465 470 475 480 Ile Gly Gln Gln Ala Gly Ser Ser Ser Asn Leu Thr Glu Leu Gln Val 485 490 495 Val Asn Leu Asp Thr Ala His Ser Thr Lys Ser Glu 500 505 <210> 79 <211> 512 <212> PRT <213> Artificial Sequence <220> <223> IGD_Human <400> 79 Arg Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 1 5 10 15 Thr Leu Ser Leu Thr Cys Ile Val Ser Gly Gly Pro Ile Arg Arg Thr 20 25 30 Gly Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu 35 40 45 Trp Ile Gly Gly Val Tyr Tyr Thr Gly Ser Ile Tyr Tyr Asn Pro Ser 50 55 60 Leu Arg Gly Arg Val Thr Ile Ser Val Asp Thr Ser Arg Asn Gln Phe 65 70 75 80 Ser Leu Asn Leu Arg Ser Met Ser Ala Ala Asp Thr Ala Met Tyr Tyr 85 90 95 Cys Ala Arg Gly Asn Pro Pro Pro Tyr Tyr Asp Ile Gly Thr Gly Ser 100 105 110 Asp Asp Gly Ile Asp Val Trp Gly Gln Gly Thr Thr Val His Val Ser 115 120 125 Ser Ala Pro Thr Lys Ala Pro Asp Val Phe Pro Ile Ile Ser Gly Cys 130 135 140 Arg His Pro Lys Asp Asn Ser Pro Val Val Leu Ala Cys Leu Ile Thr 145 150 155 160 Gly Tyr His Pro Thr Ser Val Thr Val Thr Trp Tyr Met Gly Thr Gln 165 170 175 Ser Gln Pro Gln Arg Thr Phe Pro Glu Ile Gln Arg Arg Asp Ser Tyr 180 185 190 Tyr Met Thr Ser Ser Gln Leu Ser Thr Pro Leu Gln Gln Trp Arg Gln 195 200 205 Gly Glu Tyr Lys Cys Val Val Gln His Thr Ala Ser Lys Ser Lys Lys 210 215 220 Glu Ile Phe Arg Trp Pro Glu Ser Pro Lys Ala Gln Ala Ser Ser Val 225 230 235 240 Pro Thr Ala Gln Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr 245 250 255 Ala Pro Ala Thr Thr Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys 260 265 270 Lys Glu Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro 275 280 285 Glu Cys Pro Ser His Thr Gln Pro Leu Gly Val Tyr Leu Leu Thr Pro 290 295 300 Ala Val Gln Asp Leu Trp Leu Arg Asp Lys Ala Thr Phe Thr Cys Phe 305 310 315 320 Val Val Gly Ser Asp Leu Lys Asp Ala His Leu Thr Trp Glu Val Ala 325 330 335 Gly Lys Val Pro Thr Gly Gly Val Glu Glu Gly Leu Leu Glu Arg His 340 345 350 Ser Asn Gly Ser Gln Ser Gln His Ser Arg Leu Thr Leu Pro Arg Ser 355 360 365 Leu Trp Asn Ala Gly Thr Ser Val Thr Cys Thr Leu Asn His Pro Ser 370 375 380 Leu Pro Pro Gln Arg Leu Met Ala Leu Arg Glu Pro Ala Ala Gln Ala 385 390 395 400 Pro Val Lys Leu Ser Leu Asn Leu Leu Ala Ser Ser Asp Pro Pro Glu 405 410 415 Ala Ala Ser Trp Leu Leu Cys Glu Val Ser Gly Phe Ser Pro Pro Asn 420 425 430 Ile Leu Leu Met Trp Leu Glu Asp Gln Arg Glu Val Asn Thr Ser Gly 435 440 445 Phe Ala Pro Ala Arg Pro Pro Pro Gln Pro Gly Ser Thr Thr Phe Trp 450 455 460 Ala Trp Ser Val Leu Arg Val Pro Ala Pro Pro Ser Pro Gln Pro Ala 465 470 475 480 Thr Tyr Thr Cys Val Val Ser His Glu Asp Ser Arg Thr Leu Leu Asn 485 490 495 Ala Ser Arg Ser Leu Glu Val Ser Tyr Val Thr Asp His Gly Pro Met 500 505 510 <210> 80 <211> 556 <212> PRT <213> artificial sequence <220> <223> GPC4_people <400> 80 Met Ala Arg Phe Gly Leu Pro Ala Leu Cys Thr Ala Val Leu 1 5 10 15 Ser Wing Wing Leu Wing Wing Wing Glu Leu Lys Ser Cys Ser Glu 20 25 30 Val Arg Arg Leu Tyr Val Ser Lys Gly Phe Asn Lys Asn Ala Pro 35 40 45 His Glu Ile Asn Gly Asp His Lys Ile Cys Pro Gln Gly Ser 50 55 60 Thr Cys Cys Ser Gln Glu Met Glu Glu Lys Tyr Ser Leu Gln Ser Lys 65 70 75 80 Asp Asp Phe Lys Ser Val Val Ser Glu Gln Cys Asn His Leu Gln Ala 85 90 95 Val Phe Ala Ser Arg Tyr Lys Lys Phe Asp Glu Phe Phe Lys Glu Leu 100 105 110 Leu Glu Asn Ala Glu Lys Ser Leu Asn Asp Met Phe Val Lys Thr Tyr 115 120 125 Gly His Leu Tyr Met Gln Asn Ser Glu Leu Phe Lys Asp Leu Phe Val 130 135 140 Glu Leu Lys Arg Tyr Tyr Val Val Gly Asn Val Asn Leu Glu Glu Met 145 150 155 160 Leu Asn Asp Phe Trp Ala Arg Leu Leu Glu Arg Met Phe Arg Leu Val 165 170 175 Asn Ser Gln Tyr His Phe Thr Asp Glu Tyr Leu Glu Cys Val Ser Lys 180 185 190 Tyr Thr Glu Gln Leu Lys Pro Phe Gly Asp Val Pro Arg Lys Leu Lys 195 200 205 Leu Gln Val Thr Arg Ala Phe Val Ala Ala Arg Thr Phe Ala Gln Gly 210 215 220 Leu Ala Val Ala Gly Asp Val Val Ser Lys Val Ser Val Val Asn Pro 225 230 235 240 Thr Ala Gln Cys Thr His Ala Leu Leu Lys Met Ile Tyr Cys Ser His 245 250 255 Cys Arg Gly Leu Val Thr Val Lys Pro Cys Tyr Asn Tyr Cys Ser Asn 260 265 270 Ile Met Arg Gly Cys Leu Ala Asn Gln Gly Asp Leu Asp Phe Glu Trp 275 280 285 Asn Asn Phe Ile Asp Ala Met Leu Met Val Ala Glu Arg Leu Glu Gly 290 295 300 Pro Phe Asn Ile Glu Ser Val Met Asp Pro Ile Asp Val Lys Ile Ser 305 310 315 320 Asp Ala Ile Met Asn Met Gln Asp Asn Ser Val Gln Val Ser Gln Lys 325 330 335 Val Phe Gln Gly Cys Gly Pro Pro Lys Pro Leu Pro Ala Gly Arg Ile 340 345 350 Ser Arg Ser Ile Ser Glu Ser Ala Phe Ser Ala Arg Phe Arg Pro His 355 360 365 His Pro Glu Glu Arg Pro Thr Thr Ala Ala Gly Thr Ser Leu Asp Arg 370 375 380 Leu Val Thr Asp Val Lys Glu Lys Leu Lys Gln Ala Lys Lys Phe Trp 385 390 395 400 Ser Ser Leu Pro Ser Asn Val Cys Asn Asp Glu Arg Met Ala Ala Gly 405 410 415 Asn Gly Asn Glu Asp Asp Cys Trp Asn Gly Lys Gly Lys Ser Arg Tyr 420 425 430 Leu Phe Ala Val Thr Gly Asn Gly Leu Ala Asn Gln Gly Asn Asn Pro 435 440 445 Glu Val Gln Val Asp Thr Ser Lys Pro Asp Ile Leu Ile Leu Arg Gln 450 455 460 Ile Met Ala Leu Arg Val Met Thr Ser Lys Met Lys Asn Ala Tyr Asn 465 470 475 480 Gly Asn Asp Val Asp Phe Phe Asp Ile Ser Asp Glu Ser Ser Gly Glu 485 490 495 Gly Ser Gly Ser Gly Cys Glu Tyr Gln Gln Cys Pro Ser Glu Phe Asp 500 505 510 Tyr Asn Ala Thr Asp His Ala Gly Lys Ser Ala Asn Glu Lys Ala Asp 515 520 525 Ser Ala Gly Val Arg Pro Gly Ala Gln Ala Tyr Leu Leu Thr Val Phe 530 535 540 Cys Ile Leu Phe Leu Val Met Gln Arg Glu Trp Arg 545 550 555 <210> 81 <211> 558 <212> PRT <213> Artificial Sequence <220> <223> GPC1_Human <400> 81 Met Glu Leu Arg Ala Arg Gly Trp Trp Leu Leu Cys Ala Ala Ala Ala 1 5 10 15 Leu Val Ala Cys Ala Arg Gly Asp Pro Ala Ser Lys Ser Arg Ser Cys 20 25 30 Gly Glu Val Arg Gln Ile Tyr Gly Ala Lys Gly Phe Ser Leu Ser Asp 35 40 45 Val Pro Gln Ala Glu Ile Ser Gly Glu His Leu Arg Ile Cys Pro Gln 50 55 60 Gly Tyr Thr Cys Cys Thr Ser Glu Met Glu Glu Asn Leu Ala Asn Arg 65 70 75 80 Ser His Ala Glu Leu Glu Thr Ala Leu Arg Asp Ser Ser Arg Val Leu 85 90 95 Gln Ala Met Leu Ala Thr Gln Leu Arg Ser Phe Asp Asp His Phe Gln 100 105 110 His Leu Leu Asn Asp Ser Glu Arg Thr Leu Gln Ala Thr Phe Pro Gly 115 120 125 Ala Phe Gly Glu Leu Tyr Thr Gln Asn Ala Arg Ala Phe Arg Asp Leu 130 135 140 Tyr Ser Glu Leu Arg Leu Tyr Tyr Arg Gly Ala Asn Leu His Leu Glu 145 150 155 160 Glu Thr Leu Ala Glu Phe Trp Ala Arg Leu Leu Glu Arg Leu Phe Lys 165 170 175 Gln Leu His Pro Gln Leu Leu Leu Pro Asp Asp Tyr Leu Asp Cys Leu 180 185 190 Gly Lys Gln Ala Glu Ala Leu Arg Pro Phe Gly Glu Ala Pro Arg Glu 195 200 205 Leu Arg Leu Arg Ala Thr Arg Ala Phe Val Ala Ala Arg Ser Phe Val 210 215 220 Gln Gly Leu Gly Val Ala Ser Asp Val Val Arg Lys Val Ala Gln Val 225 230 235 240 Pro Leu Gly Pro Glu Cys Ser Arg Ala Val Met Lys Leu Val Tyr Cys 245 250 255 Ala His Cys Leu Gly Val Pro Gly Ala Arg Pro Cys Pro Asp Tyr Cys 260 265 270 Arg Asn Val Leu Lys Gly Cys Leu Ala Asn Gln Ala Asp Leu Asp Ala 275 280 285 Glu Trp Arg Asn Leu Leu Asp Ser Met Val Leu Ile Thr Asp Lys Phe 290 295 300 Trp Gly Thr Ser Gly Val Glu Ser Val Ile Gly Ser Val His Thr Trp 305 310 315 320 Leu Ala Glu Ala Ile Asn Ala Leu Gln Asp Asn Arg Asp Thr Leu Thr 325 330 335 Ala Lys Val Ile Gln Gly Cys Gly Asn Pro Lys Val Asn Pro Gln Gly 340 345 350 Pro Gly Pro Glu Glu Lys Arg Arg Arg Gly Lys Leu Ala Pro Arg Glu 355 360 365 Arg Pro Pro Ser Gly Thr Leu Glu Lys Leu Val Ser Glu Ala Lys Ala 370 375 380 Gln Leu Arg Asp Val Gln Asp Phe Trp Ile Ser Leu Pro Gly Thr Leu 385 390 395 400 Cys Ser Glu Lys Met Ala Leu Ser Thr Ala Ser Asp Asp Arg Cys Trp 405 410 415 Asn Gly Met Ala Arg Gly Arg Tyr Leu Pro Glu Val Met Gly Asp Gly 420 425 430 Leu Ala Asn Gln Ile Asn Asn Pro Glu Val Glu Val Asp Ile Thr Lys 435 440 445 Pro Asp Met Thr Ile Arg Gln Gln Ile Met Gln Leu Lys Ile Met Thr 450 455 460 Asn Arg Leu Arg Ser Ala Tyr Asn Gly Asn Asp Val Asp Phe Gln Asp 465 470 475 480 Ala Ser Asp Asp Gly Ser Gly Ser Gly Ser Gly Asp Gly Cys Leu Asp 485 490 495 Asp Leu Cys Ser Arg Lys Val Ser Arg Lys Ser Ser Ser Ser Arg Thr 500 505 510 Pro Leu Thr His Ala Leu Pro Gly Leu Ser Glu Gln Glu Gly Gln Lys 515 520 525 Thr Ser Ala Ala Ser Cys Pro Gln Pro Pro Thr Phe Leu Leu Pro Leu 530 535 540 Leu Leu Phe Leu Ala Leu Thr Val Ala Arg Pro Arg Trp Arg 545 550 555 <210> 82 <211> 572 <212> PRT <213> artificial sequence <220> <223> GPC5_ humans <400> 82 Met Asp Ala Gln Thr Trp Pro Val Gly Phe Arg Cys Leu Leu Leu Leu 1 5 10 15 Ala Leu Val Gly Ser Ala Arg Ser Glu Gly Val Gln Thr Cys Glu Glu 20 25 30 Val Arg Lys Leu Phe Gln Trp Arg Leu Leu Gly Ala Val Arg Gly Leu 35 40 45 Pro Asp Ser Pro Arg Ala Gly Pro Asp Leu Gln Val Cys Ile Ser Lys 50 55 60 Lys Pro Thr Cys Cys Thr Arg Lys Met Glu Glu Arg Tyr Gln Ile Ala 65 70 75 80 Ala Arg Gln Asp Met Gln Gln Phe Leu Gln Thr Ser Ser Ser Thr Leu 85 90 95 Lys Phe Leu Ile Ser Arg Asn Ala Ala Ala Phe Gln Glu Thr Leu Glu 100 105 110 Thr Leu Ile Lys Gln Ala Glu Asn Tyr Thr Ser Ile Leu Phe Cys Ser 115 120 125 Thr Tyr Arg Asn Met Ala Leu Glu Ala Ala Ala Ser Val Gln Glu Phe 130 135 140 Phe Thr Asp Val Gly Leu Tyr Leu Phe Gly Ala Asp Val Asn Pro Glu 145 150 155 160 Glu Phe Val Asn Arg Phe Phe Asp Ser Leu Phe Pro Leu Val Tyr Asn 165 170 175 His Leu Ile Asn Pro Gly Val Thr Asp Ser Ser Leu Glu Tyr Ser Glu 180 185 190 Cys Ile Arg Met Ala Arg Arg Asp Val Ser Pro Phe Gly Asn Ile Pro 195 200 205 Gln Arg Val Met Gly Gln Met Gly Arg Ser Leu Leu Pro Ser Arg Thr 210 215 220 Phe Leu Gln Ala Leu Asn Leu Gly Ile Glu Val Ile Asn Thr Thr Asp 225 230 235 240 Tyr Leu His Phe Ser Lys Glu Cys Ser Arg Ala Leu Leu Lys Met Gln 245 250 255 Tyr Cys Pro His Cys Gln Gly Leu Ala Leu Thr Lys Pro Cys Met Gly 260 265 270 Tyr Cys Leu Asn Val Met Arg Gly Cys Leu Ala His Met Ala Glu Leu 275 280 285 Asn Pro His Trp His Ala Tyr Ile Arg Ser Leu Glu Glu Leu Ser Asp 290 295 300 Ala Met His Gly Thr Tyr Asp Ile Gly His Val Leu Leu Asn Phe His 305 310 315 320 Leu Leu Val Asn Asp Ala Val Leu Gln Ala His Leu Asn Gly Gln Lys 325 330 335 Leu Leu Glu Gln Val Asn Arg Ile Cys Gly Arg Pro Val Arg Thr Pro 340 345 350 Thr Gln Ser Pro Arg Cys Ser Phe Asp Gln Ser Lys Glu Lys His Gly 355 360 365 Met Lys Thr Thr Thr Arg Asn Ser Glu Glu Thr Leu Ala Asn Arg Arg 370 375 380 Lys Glu Phe Ile Asn Ser Leu Arg Leu Tyr Arg Ser Phe Tyr Gly Gly 385 390 395 400 Leu Ala Asp Gln Leu Cys Ala Asn Glu Leu Ala Ala Ala Asp Gly Leu 405 410 415 Pro Cys Trp Asn Gly Glu Asp Ile Val Lys Ser Tyr Thr Gln Arg Val 420 425 430 Val Gly Asn Gly Ile Lys Ala Gln Ser Gly Asn Pro Glu Val Lys Val 435 440 445 Lys Gly Ile Asp Pro Val Ile Asn Gln Ile Ile Asp Lys Leu Lys His 450 455 460 Val Val Gln Leu Leu Gln Gly Arg Ser Pro Lys Pro Asp Lys Trp Glu 465 470 475 480 Leu Leu Gln Leu Gly Ser Gly Gly Gly Met Val Glu Gln Val Ser Gly 485 490 495 Asp Cys Asp Asp Glu Asp Gly Cys Gly Gly Ser Gly Ser Gly Glu Val 500 505 510 Lys Arg Thr Leu Lys Ile Thr Asp Trp Met Pro Asp Asp Met Asn Phe 515 520 525 Ser Asp Val Lys Gln Ile His Gln Thr Asp Thr Gly Ser Thr Leu Asp 530 535 540 Thr Thr Gly Ala Gly Cys Ala Val Ala Thr Glu Ser Met Thr Phe Thr 545 550 555 560 Leu Ile Ser Val Val Met Leu Leu Pro Gly Ile Trp 565 570 <210> 83 <211> 579 <212> PRT <213> artificial sequence <220> <223> GPC2_ humans <400> 83 Met Ser Ala Leu Arg Pro Leu Leu Leu Leu Leu Leu Pro Leu Cys Pro 1 5 10 15 Gly Pro Gly Pro Gly Pro Gly Ser Glu Ala Lys Val Thr Arg Ser Cys 20 25 30 Ala Glu Thr Arg Gln Val Leu Gly Ala Arg Gly Tyr Ser Leu Asn Leu 35 40 45 Ile Pro Pro Ala Leu Ile Ser Gly Glu His Leu Arg Val Cys Pro Gln 50 55 60 Glu Tyr Thr Cys Cys Ser Ser Glu Thr Glu Gln Arg Leu Ile Arg Glu 65 70 75 80 Thr Glu Ala Thr Phe Arg Gly Leu Val Glu Asp Ser Gly Ser Phe Leu 85 90 95 Val His Thr Leu Ala Ala Arg His Arg Lys Phe Asp Glu Phe Phe Leu 100 105 110 Glu Met Leu Ser Val Ala Gln His Ser Leu Thr Gln Leu Phe Ser His 115 120 125 Ser Tyr Gly Arg Leu Tyr Ala Gln His Ala Leu Ile Phe Asn Gly Leu 130 135 140 Phe Ser Arg Leu Arg Asp Phe Tyr Gly Glu Ser Gly Glu Gly Leu Asp 145 150 155 160 Asp Thr Leu Ala Asp Phe Trp Ala Gln Leu Leu Glu Arg Val Phe Pro 165 170 175 Leu Leu His Pro Gln Tyr Ser Phe Pro Pro Asp Tyr Leu Leu Cys Leu 180 185 190 Ser Arg Leu Ala Ser Ser Thr Asp Gly Ser Leu Gln Pro Phe Gly Asp 195 200 205 Ser Pro Arg Arg Leu Arg Leu Gln Ile Thr Arg Thr Leu Val Ala Ala 210 215 220 Arg Ala Phe Val Gln Gly Leu Glu Thr Gly Arg Asn Val Val Ser Glu 225 230 235 240 Ala Leu Lys Val Pro Val Ser Glu Gly Cys Ser Gln Ala Leu Met Arg 245 250 255 Leu Ile Gly Cys Pro Leu Cys Arg Gly Val Pro Ser Leu Met Pro Cys 260 265 270 Gln Gly Phe Cys Leu Asn Val Val Arg Gly Cys Leu Ser Ser Arg Gly 275 280 285 Leu Glu Pro Asp Trp Gly Asn Tyr Leu Asp Gly Leu Leu Ile Leu Ala 290 295 300 Asp Lys Leu Gln Gly Pro Phe Ser Phe Glu Leu Thr Ala Glu Ser Ile 305 310 315 320 Gly Val Lys Ile Ser Glu Gly Leu Met Tyr Leu Gln Glu Asn Ser Ala 325 330 335 Lys Val Ser Ala Gln Val Phe Gln Glu Cys Gly Pro Pro Asp Pro Val 340 345 350 Pro Ala Arg Asn Arg Arg Ala Pro Pro Pro Arg Glu Glu Ala Gly Arg 355 360 365 Leu Trp Ser Met Val Thr Glu Glu Glu Arg Pro Thr Thr Ala Ala Gly 370 375 380 Thr Asn Leu His Arg Leu Val Trp Glu Leu Arg Glu Arg Leu Ala Arg 385 390 395 400 Met Arg Gly Phe Trp Ala Arg Leu Ser Leu Thr Val Cys Gly Asp Ser 405 410 415 Arg Met Ala Ala Asp Ala Ser Leu Glu Ala Ala Pro Cys Trp Thr Gly 420 425 430 Ala Gly Arg Gly Arg Tyr Leu Pro Pro Val Val Gly Gly Ser Pro Ala 435 440 445 Glu Gln Val Asn Asn Pro Glu Leu Lys Val Asp Ala Ser Gly Pro Asp 450 455 460 Val Pro Thr Arg Arg Arg Arg Leu Gln Leu Arg Ala Ala Thr Ala Arg 465 470 475 480 Met Lys Thr Ala Ala Leu Gly His Asp Leu Asp Gly Gln Asp Ala Asp 485 490 495 Glu Asp Ala Ser Gly Ser Gly Gly Gly Gln Gln Tyr Ala Asp Asp Trp 500 505 510 Met Ala Gly Ala Val Ala Pro Pro Ala Arg Pro Pro Arg Pro Pro Tyr 515 520 525 Pro Pro Arg Arg Asp Gly Ser Gly Gly Lys Gly Gly Gly Gly Ser Ala 530 535 540 Arg Tyr Asn Gln Gly Arg Ser Arg Ser Gly Gly Ala Ser Ile Gly Phe 545 550 555 560 His Thr Gln Thr Ile Leu Ile Leu Ser Leu Ser Ala Leu Ala Leu Leu 565 570 575 Gly Pro Arg <210> 84 <211> 615 <212> PRT <213> Artificial Sequence <220> <223> FA12_Human <400> 84 Met Arg Ala Leu Leu Leu Leu Gly Phe Leu Leu Val Ser Leu Glu Ser 1 5 10 15 Thr Leu Ser Ile Pro Pro Trp Glu Ala Pro Lys Glu His Lys Tyr Lys 20 25 30 Ala Glu Glu His Thr Val Val Leu Thr Val Thr Gly Glu Pro Cys His 35 40 45 Phe Pro Phe Gln Tyr His Arg Gln Leu Tyr His Lys Cys Thr His Lys 50 55 60 Gly Arg Pro Gly Pro Gln Pro Trp Cys Ala Thr Thr Pro Asn Phe Asp 65 70 75 80 Gln Asp Gln Arg Trp Gly Tyr Cys Leu Glu Pro Lys Lys Val Lys Asp 85 90 95 His Cys Ser Lys His Ser Pro Cys Gln Lys Gly Gly Thr Cys Val Asn 100 105 110 Met Pro Ser Gly Pro His Cys Leu Cys Pro Gln His Leu Thr Gly Asn 115 120 125 His Cys Gln Lys Glu Lys Cys Phe Glu Pro Gln Leu Leu Arg Phe Phe 130 135 140 His Lys Asn Glu Ile Trp Tyr Arg Thr Glu Gln Ala Ala Val Ala Arg 145 150 155 160 Cys Gln Cys Lys Gly Pro Asp Ala His Cys Gln Arg Leu Ala Ser Gln 165 170 175 Ala Cys Arg Thr Asn Pro Cys Leu His Gly Gly Arg Cys Leu Glu Val 180 185 190 Glu Gly His Arg Leu Cys His Cys Pro Val Gly Tyr Thr Gly Ala Phe 195 200 205 Cys Asp Val Asp Thr Lys Ala Ser Cys Tyr Asp Gly Arg Gly Leu Ser 210 215 220 Tyr Arg Gly Leu Ala Arg Thr Thr Leu Ser Gly Ala Pro Cys Gln Pro 225 230 235 240 Trp Ala Ser Glu Ala Thr Tyr Arg Asn Val Thr Ala Glu Gln Ala Arg 245 250 255 Asn Trp Gly Leu Gly Gly His Ala Phe Cys Arg Asn Pro Asp Asn Asp 260 265 270 Ile Arg Pro Trp Cys Phe Val Leu Asn Arg Asp Arg Leu Ser Trp Glu 275 280 285 Tyr Cys Asp Leu Ala Gln Cys Gln Thr Pro Thr Gln Ala Ala Pro Pro 290 295 300 Thr Pro Val Ser Pro Arg Leu His Val Pro Leu Met Pro Ala Gln Pro 305 310 315 320 Ala Pro Pro Lys Pro Gln Pro Thr Thr Arg Thr Pro Pro Gln Ser Gln 325 330 335 Thr Pro Gly Ala Leu Pro Ala Lys Arg Glu Gln Pro Pro Ser Leu Thr 340 345 350 Arg Asn Gly Pro Leu Ser Cys Gly Gln Arg Leu Arg Lys Ser Leu Ser 355 360 365 Ser Met Thr Arg Val Val Gly Gly Leu Val Ala Leu Arg Gly Ala His 370 375 380 Pro Tyr Ile Ala Ala Leu Tyr Trp Gly His Ser Phe Cys Ala Gly Ser 385 390 395 400 Leu Ile Ala Pro Cys Trp Val Leu Thr Ala Ala His Cys Leu Gln Asp 405 410 415 Arg Pro Ala Pro Glu Asp Leu Thr Val Val Leu Gly Gln Glu Arg Arg 420 425 430 Asn His Ser Cys Glu Pro Cys Gln Thr Leu Ala Val Arg Ser Tyr Arg 435 440 445 Leu His Glu Ala Phe Ser Pro Val Ser Tyr Gln His Asp Leu Ala Leu 450 455 460 Leu Arg Leu Gln Glu Asp Ala Asp Gly Ser Cys Ala Leu Leu Ser Pro 465 470 475 480 Tyr Val Gln Pro Val Cys Leu Pro Ser Gly Ala Ala Arg Pro Ser Glu 485 490 495 Thr Thr Leu Cys Gln Val Ala Gly Trp Gly His Gln Phe Glu Gly Ala 500 505 510 Glu Glu Tyr Ala Ser Phe Leu Gln Glu Ala Gln Val Pro Phe Leu Ser 515 520 525 Leu Glu Arg Cys Ser Ala Pro Asp Val His Gly Ser Ser Ile Leu Pro 530 535 540 Gly Met Leu Cys Ala Gly Phe Leu Glu Gly Gly Thr Asp Ala Cys Gln 545 550 555 560 Gly Asp Ser Gly Gly Pro Leu Val Cys Glu Asp Gln Ala Ala Glu Arg 565 570 575 Arg Leu Thr Leu Gln Gly Ile Ile Ser Trp Gly Ser Gly Cys Gly Asp 580 585 590 Arg Asn Lys Pro Gly Val Tyr Thr Asp Val Ala Tyr Tyr Leu Ala Trp 595 600 605 Ile Arg Glu His Thr Val Ser 610 615 <210> 85 <211> 644 <212> PRT <213> Artificial Sequence <220> <223> KNG1_Human <400> 85 Met Lys Leu Ile Thr Ile Leu Phe Leu Cys Ser Arg Leu Leu Leu Ser 1 5 10 15 Leu Thr Gln Glu Ser Gln Ser Glu Glu Ile Asp Cys Asn Asp Lys Asp 20 25 30 Leu Phe Lys Ala Val Asp Ala Ala Leu Lys Lys Tyr Asn Ser Gln Asn 35 40 45 Gln Ser Asn Asn Gln Phe Val Leu Tyr Arg Ile Thr Glu Ala Thr Lys 50 55 60 Thr Val Gly Ser Asp Thr Phe Tyr Ser Phe Lys Tyr Glu Ile Lys Glu 65 70 75 80 Gly Asp Cys Pro Val Gln Ser Gly Lys Thr Trp Gln Asp Cys Glu Tyr 85 90 95 Lys Asp Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala Thr Val Gly 100 105 110 Lys Arg Ser Ser Thr Lys Phe Ser Val Ala Thr Gln Thr Cys Gln Ile 115 120 125 Thr Pro Ala Glu Gly Pro Val Val Thr Ala Gln Tyr Asp Cys Leu Gly 130 135 140 Cys Val His Pro Ile Ser Thr Gln Ser Pro Asp Leu Glu Pro Ile Leu 145 150 155 160 Arg His Gly Ile Gln Tyr Phe Asn Asn Asn Thr Gln His Ser Ser Leu 165 170 175 Phe Met Leu Asn Glu Val Lys Arg Ala Gln Arg Gln Val Val Ala Gly 180 185 190 Leu Asn Phe Arg Ile Thr Tyr Ser Ile Val Gln Thr Asn Cys Ser Lys 195 200 205 Glu Asn Phe Leu Phe Leu Thr Pro Asp Cys Lys Ser Leu Trp Asn Gly 210 215 220 Asp Thr Gly Glu Cys Thr Asp Asn Ala Tyr Ile Asp Ile Gln Leu Arg 225 230 235 240 Ile Ala Ser Phe Ser Gln Asn Cys Asp Ile Tyr Pro Gly Lys Asp Phe 245 250 255 Val Gln Pro Pro Thr Lys Ile Cys Val Gly Cys Pro Arg Asp Ile Pro 260 265 270 Thr Asn Ser Pro Glu Leu Glu Glu Thr Leu Thr His Thr Ile Thr Lys 275 280 285 Leu Asn Ala Glu Asn Asn Ala Thr Phe Tyr Phe Lys Ile Asp Asn Val 290 295 300 Lys Lys Ala Arg Val Gln Val Val Ala Gly Lys Lys Tyr Phe Ile Asp 305 310 315 320 Phe Val Ala Arg Glu Thr Thr Cys Ser Lys Glu Ser Asn Glu Glu Leu 325 330 335 Thr Glu Ser Cys Glu Thr Lys Lys Leu Gly Gln Ser Leu Asp Cys Asn 340 345 350 Ala Glu Val Tyr Val Val Pro Trp Glu Lys Lys Ile Tyr Pro Thr Val 355 360 365 Asn Cys Gln Pro Leu Gly Met Ile Ser Leu Met Lys Arg Pro Pro Gly 370 375 380 Phe Ser Pro Phe Arg Ser Ser Arg Ile Gly Glu Ile Lys Glu Glu Thr 385 390 395 400 Thr Val Ser Pro Pro His Thr Ser Met Ala Pro Ala Gln Asp Glu Glu 405 410 415 Arg Asp Ser Gly Lys Glu Gln Gly His Thr Arg Arg His Asp Trp Gly 420 425 430 His Glu Lys Gln Arg Lys His Asn Leu Gly His Gly His Lys His Glu 435 440 445 Arg Asp Gln Gly His Gly His Gln Arg Gly His Gly Leu Gly His Gly 450 455 460 His Glu Gln Gln His Gly Leu Gly His Gly His Lys Phe Lys Leu Asp 465 470 475 480 Asp Asp Leu Glu His Gln Gly Gly His Val Leu Asp His Gly His Lys 485 490 495 His Lys His Gly His Gly His Gly Lys His Lys Asn Lys Gly Lys Lys 500 505 510 Asn Gly Lys His Asn Gly Trp Lys Thr Glu His Leu Ala Ser Ser Ser 515 520 525 Glu Asp Ser Thr Thr Pro Ser Ala Gln Thr Gln Glu Lys Thr Glu Gly 530 535 540 Pro Thr Pro Ile Pro Ser Leu Ala Lys Pro Gly Val Thr Val Thr Phe 545 550 555 560 Ser Asp Phe Gln Asp Ser Asp Leu Ile Ala Thr Met Met Pro Pro Ile 565 570 575 Ser Pro Ala Pro Ile Gln Ser Asp Asp Asp Trp Ile Pro Asp Ile Gln 580 585 590 Ile Asp Pro Asn Gly Leu Ser Phe Asn Pro Ile Ser Asp Phe Pro Asp 595 600 605 Thr Thr Ser Pro Lys Cys Pro Gly Arg Pro Trp Lys Ser Val Ser Glu 610 615 620 Ile Asn Pro Thr Thr Gln Met Lys Glu Ser Tyr Tyr Phe Asp Leu Thr 625 630 635 640 Asp Gly Leu Ser <210> 86 <211> 650 <212> PRT <213> artificial sequence <220> <223> APLP1_ human <400> 86 Met Gly Pro Ala Ser Pro Ala Ala Arg Gly Leu Ser Arg Arg Pro Gly 1 5 10 15 Gln Pro Pro Leu Pro Leu Leu Leu Pro Leu Leu Leu Leu Leu Leu Arg 20 25 30 Ala Gln Pro Ala Ile Gly Ser Leu Ala Gly Gly Ser Pro Gly Ala Ala 35 40 45 Glu Ala Pro Gly Ser Ala Gln Val Ala Gly Leu Cys Gly Arg Leu Thr 50 55 60 Leu His Arg Asp Leu Arg Thr Gly Arg Trp Glu Pro Asp Pro Gln Arg 65 70 75 80 Ser Arg Arg Cys Leu Arg Asp Pro Gln Arg Val Leu Glu Tyr Cys Arg 85 90 95 Gln Met Tyr Pro Glu Leu Gln Ile Ala Arg Val Glu Gln Ala Thr Gln 100 105 110 Ala Ile Pro Met Glu Arg Trp Cys Gly Gly Ser Arg Ser Gly Ser Cys 115 120 125 Ala His Pro His His Gln Val Val Pro Phe Arg Cys Leu Pro Gly Glu 130 135 140 Phe Val Ser Glu Ala Leu Leu Val Pro Glu Gly Cys Arg Phe Leu His 145 150 155 160 Gln Glu Arg Met Asp Gln Cys Glu Ser Ser Thr Arg Arg His Gln Glu 165 170 175 Ala Gln Glu Ala Cys Ser Ser Gln Gly Leu Ile Leu His Gly Ser Gly 180 185 190 Met Leu Leu Pro Cys Gly Ser Asp Arg Phe Arg Gly Val Glu Tyr Val 195 200 205 Cys Cys Pro Pro Pro Gly Thr Pro Asp Pro Ser Gly Thr Ala Val Gly 210 215 220 Asp Pro Ser Thr Arg Ser Trp Pro Pro Gly Ser Arg Val Glu Gly Ala 225 230 235 240 Glu Asp Glu Glu Glu Glu Glu Ser Phe Pro Gln Pro Val Asp Asp Tyr 245 250 255 Phe Val Glu Pro Pro Gln Ala Glu Glu Glu Glu Glu Thr Val Pro Pro 260 265 270 Pro Ser Ser His Thr Leu Ala Val Val Gly Lys Val Thr Pro Thr Pro 275 280 285 Arg Pro Thr Asp Gly Val Asp Ile Tyr Phe Gly Met Pro Gly Glu Ile 290 295 300 Ser Glu His Glu Gly Phe Leu Arg Ala Lys Met Asp Leu Glu Glu Arg 305 310 315 320 Arg Met Arg Gln Ile Asn Glu Val Met Arg Glu Trp Ala Met Ala Asp 325 330 335 Asn Gln Ser Lys Asn Leu Pro Lys Ala Asp Arg Gln Ala Leu Asn Glu 340 345 350 His Phe Gln Ser Ile Leu Gln Thr Leu Glu Glu Gln Val Ser Gly Glu 355 360 365 Arg Gln Arg Leu Val Glu Thr His Ala Thr Arg Val Ile Ala Leu Ile 370 375 380 Asn Asp Gln Arg Arg Ala Ala Leu Glu Gly Phe Leu Ala Ala Leu Gln 385 390 395 400 Ala Asp Pro Pro Gln Ala Glu Arg Val Leu Leu Ala Leu Arg Arg Tyr 405 410 415 Leu Arg Ala Glu Gln Lys Glu Gln Arg His Thr Leu Arg His Tyr Gln 420 425 430 His Val Ala Ala Val Asp Pro Glu Lys Ala Gln Gln Met Arg Phe Gln 435 440 445 Val His Thr His Leu Gln Val Ile Glu Glu Arg Val Asn Gln Ser Leu 450 455 460 Gly Leu Leu Asp Gln Asn Pro His Leu Ala Gln Glu Leu Arg Pro Gln 465 470 475 480 Ile Gln Glu Leu Leu His Ser Glu His Leu Gly Pro Ser Glu Leu Glu 485 490 495 Ala Pro Ala Pro Gly Gly Ser Ser Glu Asp Lys Gly Gly Leu Gln Pro 500 505 510 Pro Asp Ser Lys Asp Asp Thr Pro Met Thr Leu Pro Lys Gly Ser Thr 515 520 525 Glu Gln Asp Ala Ala Ser Pro Glu Lys Glu Lys Met Asn Pro Leu Glu 530 535 540 Gln Tyr Glu Arg Lys Val Asn Ala Ser Val Pro Arg Gly Phe Pro Phe 545 550 555 560 His Ser Ser Glu Ile Gln Arg Asp Glu Leu Ala Pro Ala Gly Thr Gly 565 570 575 Val Ser Arg Glu Ala Val Ser Gly Leu Leu Ile Met Gly Ala Gly Gly 580 585 590 Gly Ser Leu Ile Val Leu Ser Met Leu Leu Leu Arg Arg Lys Lys Pro 595 600 605 Tyr Gly Ala Ile Ser His Gly Val Val Glu Val Asp Pro Met Leu Thr 610 615 620 Leu Glu Glu Gln Gln Leu Arg Glu Leu Gln Arg His Gly Tyr Glu Asn 625 630 635 640 Pro Thr Tyr Arg Phe Leu Glu Glu Arg Pro 645 650 <210> 87 <211> 661 <212> PRT <213> artificial sequence <220> <223> CRAC1_ humans <400> 87 Met Ala Pro Ser Ala Asp Pro Gly Met Ser Arg Met Leu Pro Phe Leu 1 5 10 15 Leu Leu Leu Trp Phe Leu Pro Ile Thr Glu Gly Ser Gln Arg Ala Glu 20 25 30 Pro Met Phe Thr Ala Val Thr Asn Ser Val Leu Pro Pro Asp Tyr Asp 35 40 45 Ser Asn Pro Thr Gln Leu Asn Tyr Gly Val Ala Val Thr Asp Val Asp 50 55 60 His Asp Gly Asp Phe Glu Ile Val Val Ala Gly Tyr Asn Gly Pro Asn 65 70 75 80 Leu Val Leu Lys Tyr Asp Arg Ala Gln Lys Arg Leu Val Asn Ile Ala 85 90 95 Val Asp Glu Arg Ser Ser Pro Tyr Tyr Ala Leu Arg Asp Arg Gln Gly 100 105 110 Asn Ala Ile Gly Val Thr Ala Cys Asp Ile Asp Gly Asp Gly Arg Glu 115 120 125 Glu Ile Tyr Phe Leu Asn Thr Asn Asn Ala Phe Ser Gly Val Ala Thr 130 135 140 Tyr Thr Asp Lys Leu Phe Lys Phe Arg Asn Asn Arg Trp Glu Asp Ile 145 150 155 160 Leu Ser Asp Glu Val Asn Val Ala Arg Gly Val Ala Ser Leu Phe Ala 165 170 175 Gly Arg Ser Val Ala Cys Val Asp Arg Lys Gly Ser Gly Arg Tyr Ser 180 185 190 Ile Tyr Ile Ala Asn Tyr Ala Tyr Gly Asn Val Gly Pro Asp Ala Leu 195 200 205 Ile Glu Met Asp Pro Glu Ala Ser Asp Leu Ser Arg Gly Ile Leu Ala 210 215 220 Leu Arg Asp Val Ala Ala Glu Ala Gly Val Ser Lys Tyr Thr Gly Gly 225 230 235 240 Arg Gly Val Ser Val Gly Pro Ile Leu Ser Ser Ser Ala Ser Asp Ile 245 250 255 Phe Cys Asp Asn Glu Asn Gly Pro Asn Phe Leu Phe His Asn Arg Gly 260 265 270 Asp Gly Thr Phe Val Asp Ala Ala Ala Ser Ala Gly Val Asp Asp Pro 275 280 285 His Gln His Gly Arg Gly Val Ala Leu Ala Asp Phe Asn Arg Asp Gly 290 295 300 Lys Val Asp Ile Val Tyr Gly Asn Trp Asn Gly Pro His Arg Leu Tyr 305 310 315 320 Leu Gln Met Ser Thr His Gly Lys Val Arg Phe Arg Asp Ile Ala Ser 325 330 335 Pro Lys Phe Ser Met Pro Ser Pro Val Arg Thr Val Ile Thr Ala Asp 340 345 350 Phe Asp Asn Asp Gln Glu Leu Glu Ile Phe Phe Asn Asn Ile Ala Tyr 355 360 365 Arg Ser Ser Ser Ala Asn Arg Leu Phe Arg Val Ile Arg Arg Glu His 370 375 380 Gly Asp Pro Leu Ile Glu Glu Leu Asn Pro Gly Asp Ala Leu Glu Pro 385 390 395 400 Glu Gly Arg Gly Thr Gly Gly Val Val Thr Asp Phe Asp Gly Asp Gly 405 410 415 Met Leu Asp Leu Ile Leu Ser His Gly Glu Ser Met Ala Gln Pro Leu 420 425 430 Ser Val Phe Arg Gly Asn Gln Gly Phe Asn Asn Asn Trp Leu Arg Val 435 440 445 Val Pro Arg Thr Arg Phe Gly Ala Phe Ala Arg Gly Ala Lys Val Val 450 455 460 Leu Tyr Thr Lys Lys Ser Gly Ala His Leu Arg Ile Ile Asp Gly Gly 465 470 475 480 Ser Gly Tyr Leu Cys Glu Met Glu Pro Val Ala His Phe Gly Leu Gly 485 490 495 Lys Asp Glu Ala Ser Ser Val Glu Val Thr Trp Pro Asp Gly Lys Met 500 505 510 Val Ser Arg Asn Val Ala Ser Gly Glu Met Asn Ser Val Leu Glu Ile 515 520 525 Leu Tyr Pro Arg Asp Glu Asp Thr Leu Gln Asp Pro Ala Pro Leu Glu 530 535 540 Cys Gly Gln Gly Phe Ser Gln Gln Glu Asn Gly His Cys Met Asp Thr 545 550 555 560 Asn Glu Cys Ile Gln Phe Pro Phe Val Cys Pro Arg Asp Lys Pro Val 565 570 575 Cys Val Asn Thr Tyr Gly Ser Tyr Arg Cys Arg Thr Asn Lys Lys Cys 580 585 590 Ser Arg Gly Tyr Glu Pro Asn Glu Asp Gly Thr Ala Cys Val Gly Thr 595 600 605 Leu Gly Gln Ser Pro Gly Pro Arg Pro Thr Thr Pro Thr Ala Ala Ala 610 615 620 Ala Thr Ala Ala Ala Ala Ala Ala Ala Gly Ala Ala Thr Ala Ala Pro 625 630 635 640 Val Leu Val Asp Gly Asp Leu Asn Leu Gly Ser Val Val Lys Glu Ser 645 650 655 Cys Glu Pro Ser Cys 660 <210> 88 <211> 664 <212> PRT <213> Artificial Sequence <220> <223> SPRL1_Human <400> 88 Met Lys Thr Gly Leu Phe Phe Leu Cys Leu Leu Gly Thr Ala Ala Ala 1 5 10 15 Ile Pro Thr Asn Ala Arg Leu Leu Ser Asp His Ser Lys Pro Thr Ala 20 25 30 Glu Thr Val Ala Pro Asp Asn Thr Ala Ile Pro Ser Leu Arg Ala Glu 35 40 45 Ala Glu Glu Asn Glu Lys Glu Thr Ala Val Ser Thr Glu Asp Asp Ser 50 55 60 His His Lys Ala Glu Lys Ser Ser Val Leu Lys Ser Lys Glu Glu Ser 65 70 75 80 His Glu Gln Ser Ala Glu Gln Gly Lys Ser Ser Ser Gln Glu Leu Gly 85 90 95 Leu Lys Asp Gln Glu Asp Ser Asp Gly His Leu Ser Val Asn Leu Glu 100 105 110 Tyr Ala Pro Thr Glu Gly Thr Leu Asp Ile Lys Glu Asp Met Ser Glu 115 120 125 Pro Gln Glu Lys Lys Leu Ser Glu Asn Thr Asp Phe Leu Ala Pro Gly 130 135 140 Val Ser Ser Phe Thr Asp Ser Asn Gln Gln Glu Ser Ile Thr Lys Arg 145 150 155 160 Glu Glu Asn Gln Glu Gln Pro Arg Asn Tyr Ser His His Gln Leu Asn 165 170 175 Arg Ser Ser Lys His Ser Gln Gly Leu Arg Asp Gln Gly Asn Gln Glu 180 185 190 Gln Asp Pro Asn Ile Ser Asn Gly Glu Glu Glu Glu Glu Lys Glu Pro 195 200 205 Gly Glu Val Gly Thr His Asn Asp Asn Gln Glu Arg Lys Thr Glu Leu 210 215 220 Pro Arg Glu His Ala Asn Ser Lys Gln Glu Glu Asp Asn Thr Gln Ser 225 230 235 240 Asp Asp Ile Leu Glu Glu Ser Asp Gln Pro Thr Gln Val Ser Lys Met 245 250 255 Gln Glu Asp Glu Phe Asp Gln Gly Asn Gln Glu Gln Glu Asp Asn Ser 260 265 270 Asn Ala Glu Met Glu Glu Glu Asn Ala Ser Asn Val Asn Lys His Ile 275 280 285 Gln Glu Thr Glu Trp Gln Ser Gln Glu Gly Lys Thr Gly Leu Glu Ala 290 295 300 Ile Ser Asn His Lys Glu Thr Glu Glu Lys Thr Val Ser Glu Ala Leu 305 310 315 320 Leu Met Glu Pro Thr Asp Asp Gly Asn Thr Thr Pro Arg Asn His Gly 325 330 335 Val Asp Asp Asp Gly Asp Asp Asp Gly Asp Asp Gly Gly Thr Asp Gly 340 345 350 Pro Arg His Ser Ala Ser Asp Asp Tyr Phe Ile Pro Ser Gln Ala Phe 355 360 365 Leu Glu Ala Glu Arg Ala Gln Ser Ile Ala Tyr His Leu Lys Ile Glu 370 375 380 Glu Gln Arg Glu Lys Val His Glu Asn Glu Asn Ile Gly Thr Thr Glu 385 390 395 400 Pro Gly Glu His Gln Glu Ala Lys Lys Ala Glu Asn Ser Ser Asn Glu 405 410 415 Glu Glu Thr Ser Ser Glu Gly Asn Met Arg Val His Ala Val Asp Ser 420 425 430 Cys Met Ser Phe Gln Cys Lys Arg Gly His Ile Cys Lys Ala Asp Gln 435 440 445 Gln Gly Lys Pro His Cys Val Cys Gln Asp Pro Val Thr Cys Pro Pro 450 455 460 Thr Lys Pro Leu Asp Gln Val Cys Gly Thr Asp Asn Gln Thr Tyr Ala 465 470 475 480 Ser Ser Cys His Leu Phe Ala Thr Lys Cys Arg Leu Glu Gly Thr Lys 485 490 495 Lys Gly His Gln Leu Gln Leu Asp Tyr Phe Gly Ala Cys Lys Ser Ile 500 505 510 Pro Thr Cys Thr Asp Phe Glu Val Ile Gln Phe Pro Leu Arg Met Arg 515 520 525 Asp Trp Leu Lys Asn Ile Leu Met Gln Leu Tyr Glu Ala Asn Ser Glu 530 535 540 His Ala Gly Tyr Leu Asn Glu Lys Gln Arg Asn Lys Val Lys Lys Ile 545 550 555 560 Tyr Leu Asp Glu Lys Arg Leu Leu Ala Gly Asp His Pro Ile Asp Leu 565 570 575 Leu Leu Arg Asp Phe Lys Lys Asn Tyr His Met Tyr Val Tyr Pro Val 580 585 590 His Trp Gln Phe Ser Glu Leu Asp Gln His Pro Met Asp Arg Val Leu 595 600 605 Thr His Ser Glu Leu Ala Pro Leu Arg Ala Ser Leu Val Pro Met Glu 610 615 620 His Cys Ile Thr Arg Phe Phe Glu Glu Cys Asp Pro Asn Lys Asp Lys 625 630 635 640 His Ile Thr Leu Lys Glu Trp Gly His Cys Phe Gly Ile Lys Glu Glu 645 650 655 Asp Ile Asp Glu Asn Leu Leu Phe 660 <210> 89 <211> 701 <212> PRT <213> Artificial Sequence <220> <223> MEP1B_Human <400> 89 Met Asp Leu Trp Asn Leu Ser Trp Phe Leu Phe Leu Asp Ala Leu Leu 1 5 10 15 Val Ile Ser Gly Leu Ala Thr Pro Glu Asn Phe Asp Val Asp Gly Gly 20 25 30 Met Asp Gln Asp Ile Phe Asp Ile Asn Glu Gly Leu Gly Leu Asp Leu 35 40 45 Phe Glu Gly Asp Ile Arg Leu Asp Arg Ala Gln Ile Arg Asn Ser Ile 50 55 60 Ile Gly Glu Lys Tyr Arg Trp Pro His Thr Ile Pro Tyr Val Leu Glu 65 70 75 80 Asp Ser Leu Glu Met Asn Ala Lys Gly Val Ile Leu Asn Ala Phe Glu 85 90 95 Arg Tyr Arg Leu Lys Thr Cys Ile Asp Phe Lys Pro Trp Ala Gly Glu 100 105 110 Thr Asn Tyr Ile Ser Val Phe Lys Gly Ser Gly Cys Trp Ser Ser Val 115 120 125 Gly Asn Arg Arg Val Gly Lys Gln Glu Leu Ser Ile Gly Ala Asn Cys 130 135 140 Asp Arg Ile Ala Thr Val Gln His Glu Phe Leu His Ala Leu Gly Phe 145 150 155 160 Trp His Glu Gln Ser Arg Ser Asp Arg Asp Asp Tyr Val Arg Ile Met 165 170 175 Trp Asp Arg Ile Leu Ser Gly Arg Glu His Asn Phe Asn Thr Tyr Ser 180 185 190 Asp Asp Ile Ser Asp Ser Leu Asn Val Pro Tyr Asp Tyr Thr Ser Val 195 200 205 Met His Tyr Ser Lys Thr Ala Phe Gln Asn Gly Thr Glu Pro Thr Ile 210 215 220 Val Thr Arg Ile Ser Asp Phe Glu Asp Val Ile Gly Gln Arg Met Asp 225 230 235 240 Phe Ser Asp Ser Asp Leu Leu Lys Leu Asn Gln Leu Tyr Asn Cys Ser 245 250 255 Ser Ser Leu Ser Phe Met Asp Ser Cys Ser Phe Glu Leu Glu Asn Val 260 265 270 Cys Gly Met Ile Gln Ser Ser Gly Asp Asn Ala Asp Trp Gln Arg Val 275 280 285 Ser Gln Val Pro Arg Gly Pro Glu Ser Asp His Ser Asn Met Gly Gln 290 295 300 Cys Gln Gly Ser Gly Phe Phe Met His Phe Asp Ser Ser Ser Val Asn 305 310 315 320 Val Gly Ala Thr Ala Val Leu Glu Ser Arg Thr Leu Tyr Pro Lys Arg 325 330 335 Gly Phe Gln Cys Leu Gln Phe Tyr Leu Tyr Asn Ser Gly Ser Glu Ser 340 345 350 Asp Gln Leu Asn Ile Tyr Ile Arg Glu Tyr Ser Ala Asp Asn Val Asp 355 360 365 Gly Asn Leu Thr Leu Val Glu Glu Ile Lys Glu Ile Pro Thr Gly Ser 370 375 380 Trp Gln Leu Tyr His Val Thr Leu Lys Val Thr Lys Lys Phe Arg Val 385 390 395 400 Val Phe Glu Gly Arg Lys Gly Ser Gly Ala Ser Leu Gly Gly Leu Ser 405 410 415 Ile Asp Asp Ile Asn Leu Ser Glu Thr Arg Cys Pro His His Ile Trp 420 425 430 His Ile Arg Asn Phe Thr Gln Phe Ile Gly Ser Pro Asn Gly Thr Leu 435 440 445 Tyr Ser Pro Pro Phe Tyr Ser Ser Lys Gly Tyr Ala Phe Gln Ile Tyr 450 455 460 Leu Asn Leu Ala His Val Thr Asn Ala Gly Ile Tyr Phe His Leu Ile 465 470 475 480 Ser Gly Ala Asn Asp Asp Gln Leu Gln Trp Pro Cys Pro Trp Gln Gln 485 490 495 Ala Thr Met Thr Leu Leu Asp Gln Asn Pro Asp Ile Arg Gln Arg Met 500 505 510 Ser Asn Gln Arg Ser Ile Thr Thr Asp Pro Phe Met Thr Thr Asp Asn 515 520 525 Gly Asn Tyr Phe Trp Asp Arg Pro Ser Lys Val Gly Thr Val Ala Leu 530 535 540 Phe Ser Asn Gly Thr Gln Phe Arg Arg Gly Gly Gly Tyr Gly Thr Ser 545 550 555 560 Ala Phe Ile Thr His Glu Arg Leu Lys Ser Arg Asp Phe Ile Lys Gly 565 570 575 Asp Asp Val Tyr Ile Leu Leu Thr Val Glu Asp Ile Ser His Leu Asn 580 585 590 Ser Thr Gln Ile Gln Leu Thr Pro Ala Pro Ser Val Gln Asp Leu Cys 595 600 605 Ser Lys Thr Thr Cys Lys Asn Asp Gly Val Cys Thr Val Arg Asp Gly 610 615 620 Lys Ala Glu Cys Arg Cys Gln Ser Gly Glu Asp Trp Trp Tyr Met Gly 625 630 635 640 Glu Arg Cys Glu Lys Arg Gly Ser Thr Arg Asp Thr Ile Val Ile Ala 645 650 655 Val Ser Ser Thr Val Ala Val Phe Ala Leu Met Leu Ile Ile Thr Leu 660 665 670 Val Ser Val Tyr Cys Thr Arg Lys Lys Tyr Arg Glu Arg Met Ser Ser 675 680 685 Asn Arg Pro Asn Leu Thr Pro Gln Asn Gln His Ala Phe 690 695 700 <210> 90 <211> 705 <212> PRT <213> Artificial Sequence <220> <223> SYN1_Human <400> 90 Met Asn Tyr Leu Arg Arg Arg Leu Ser Asp Ser Asn Phe Met Ala Asn 1 5 10 15 Leu Pro Asn Gly Tyr Met Thr Asp Leu Gln Arg Pro Gln Pro Pro Pro 20 25 30 Pro Pro Pro Gly Ala His Ser Pro Gly Ala Thr Pro Gly Pro Gly Thr 35 40 45 Ala Thr Ala Glu Arg Ser Ser Gly Val Ala Pro Ala Ala Ser Pro Ala 50 55 60 Ala Pro Ser Pro Gly Ser Ser Gly Gly Gly Gly Phe Phe Ser Ser Leu 65 70 75 80 Ser Asn Ala Val Lys Gln Thr Thr Ala Ala Ala Ala Ala Thr Phe Ser 85 90 95 Glu Gln Val Gly Gly Gly Ser Gly Gly Ala Gly Arg Gly Gly Ala Ala 100 105 110 Ser Arg Val Leu Leu Val Ile Asp Glu Pro His Thr Asp Trp Ala Lys 115 120 125 Tyr Phe Lys Gly Lys Lys Ile His Gly Glu Ile Asp Ile Lys Val Glu 130 135 140 Gln Ala Glu Phe Ser Asp Leu Asn Leu Val Ala His Ala Asn Gly Gly 145 150 155 160 Phe Ser Val Asp Met Glu Val Leu Arg Asn Gly Val Lys Val Val Arg 165 170 175 Ser Leu Lys Pro Asp Phe Val Leu Ile Arg Gln His Ala Phe Ser Met 180 185 190 Ala Arg Asn Gly Asp Tyr Arg Ser Leu Val Ile Gly Leu Gln Tyr Ala 195 200 205 Gly Ile Pro Ser Val Asn Ser Leu His Ser Val Tyr Asn Phe Cys Asp 210 215 220 Lys Pro Trp Val Phe Ala Gln Met Val Arg Leu His Lys Lys Leu Gly 225 230 235 240 Thr Glu Glu Phe Pro Leu Ile Asp Gln Thr Phe Tyr Pro Asn His Lys 245 250 255 Glu Met Leu Ser Ser Thr Thr Tyr Pro Val Val Val Lys Met Gly His 260 265 270 Ala His Ser Gly Met Gly Lys Val Lys Val Asp Asn Gln His Asp Phe 275 280 285 Gln Asp Ile Ala Ser Val Val Ala Leu Thr Lys Thr Tyr Ala Thr Ala 290 295 300 Glu Pro Phe Ile Asp Ala Lys Tyr Asp Val Arg Val Gln Lys Ile Gly 305 310 315 320 Gln Asn Tyr Lys Ala Tyr Met Arg Thr Ser Val Ser Gly Asn Trp Lys 325 330 335 Thr Asn Thr Gly Ser Ala Met Leu Glu Gln Ile Ala Met Ser Asp Arg 340 345 350 Tyr Lys Leu Trp Val Asp Thr Cys Ser Glu Ile Phe Gly Gly Leu Asp 355 360 365 Ile Cys Ala Val Glu Ala Leu His Gly Lys Asp Gly Arg Asp His Ile 370 375 380 Ile Glu Val Val Gly Ser Ser Met Pro Leu Ile Gly Asp His Gln Asp 385 390 395 400 Glu Asp Lys Gln Leu Ile Val Glu Leu Val Val Asn Lys Met Ala Gln 405 410 415 Ala Leu Pro Arg Gln Arg Gln Arg Asp Ala Ser Pro Gly Arg Gly Ser 420 425 430 His Gly Gln Thr Pro Ser Pro Gly Ala Leu Pro Leu Gly Arg Gln Thr 435 440 445 Ser Gln Gln Pro Ala Gly Pro Pro Ala Gln Gln Arg Pro Pro Pro Gln 450 455 460 Gly Gly Pro Pro Gln Pro Gly Pro Gly Pro Gln Arg Gln Gly Pro Pro 465 470 475 480 Leu Gln Gln Arg Pro Pro Pro Gln Gly Gln Gln His Leu Ser Gly Leu 485 490 495 Gly Pro Pro Ala Gly Ser Pro Leu Pro Gln Arg Leu Pro Ser Pro Thr 500 505 510 Ser Ala Pro Gln Gln Pro Ala Ser Gln Ala Ala Pro Pro Thr Gln Gly 515 520 525 Gln Gly Arg Gln Ser Arg Pro Val Ala Gly Gly Pro Gly Ala Pro Pro 530 535 540 Ala Ala Arg Pro Pro Ala Ser Pro Ser Pro Gln Arg Gln Ala Gly Pro 545 550 555 560 Pro Gln Ala Thr Arg Gln Thr Ser Val Ser Gly Pro Ala Pro Pro Lys 565 570 575 Ala Ser Gly Ala Pro Pro Gly Gly Gln Gln Arg Gln Gly Pro Pro Gln 580 585 590 Lys Pro Pro Gly Pro Ala Gly Pro Thr Arg Gln Ala Ser Gln Ala Gly 595 600 605 Pro Val Pro Arg Thr Gly Pro Pro Thr Thr Gln Gln Pro Arg Pro Ser 610 615 620 Gly Pro Gly Pro Ala Gly Arg Pro Lys Pro Gln Leu Ala Gln Lys Pro 625 630 635 640 Ser Gln Asp Val Pro Pro Pro Ala Thr Ala Ala Ala Gly Gly Pro Pro 645 650 655 His Pro Gln Leu Asn Lys Ser Gln Ser Leu Thr Asn Ala Phe Asn Leu 660 665 670 Pro Glu Pro Ala Pro Pro Arg Pro Ser Leu Ser Gln Asp Glu Val Lys 675 680 685 Ala Glu Thr Ile Arg Ser Leu Arg Lys Ser Phe Ala Ser Leu Phe Ser 690 695 700 Asp 705 <210> 91 <211> 753 <212> PRT <213> artificial sequence <220> <223> CEL_ humans <400> 91 Met Gly Arg Leu Gln Leu Val Val Leu Gly Leu Thr Cys Cys Trp Ala 1 5 10 15 Val Ala Ser Ala Ala Lys Leu Gly Ala Val Tyr Thr Glu Gly Gly Phe 20 25 30 Val Glu Gly Val Asn Lys Lys Leu Gly Leu Leu Gly Asp Ser Val Asp 35 40 45 Ile Phe Lys Gly Ile Pro Phe Ala Ala Pro Thr Lys Ala Leu Glu Asn 50 55 60 Pro Gln Pro His Pro Gly Trp Gln Gly Thr Leu Lys Ala Lys Asn Phe 65 70 75 80 Lys Lys Arg Cys Leu Gln Ala Thr Ile Thr Gln Asp Ser Thr Tyr Gly 85 90 95 Asp Glu Asp Cys Leu Tyr Leu Asn Ile Trp Val Pro Gln Gly Arg Lys 100 105 110 Gln Val Ser Arg Asp Leu Pro Val Met Ile Trp Ile Tyr Gly Gly Ala 115 120 125 Phe Leu Met Gly Ser Gly His Gly Ala Asn Phe Leu Asn Asn Tyr Leu 130 135 140 Tyr Asp Gly Glu Glu Ile Ala Thr Arg Gly Asn Val Ile Val Val Thr 145 150 155 160 Phe Asn Tyr Arg Val Gly Pro Leu Gly Phe Leu Ser Thr Gly Asp Ala 165 170 175 Asn Leu Pro Gly Asn Tyr Gly Leu Arg Asp Gln His Met Ala Ile Ala 180 185 190 Trp Val Lys Arg Asn Ile Ala Ala Phe Gly Gly Asp Pro Asn Asn Ile 195 200 205 Thr Leu Phe Gly Glu Ser Ala Gly Gly Ala Ser Val Ser Leu Gln Thr 210 215 220 Leu Ser Pro Tyr Asn Lys Gly Leu Ile Arg Arg Ala Ile Ser Gln Ser 225 230 235 240 Gly Val Ala Leu Ser Pro Trp Val Ile Gln Lys Asn Pro Leu Phe Trp 245 250 255 Ala Lys Lys Val Ala Glu Lys Val Gly Cys Pro Val Gly Asp Ala Ala 260 265 270 Arg Met Ala Gln Cys Leu Lys Val Thr Asp Pro Arg Ala Leu Thr Leu 275 280 285 Ala Tyr Lys Val Pro Leu Ala Gly Leu Glu Tyr Pro Met Leu His Tyr 290 295 300 Val Gly Phe Val Pro Val Ile Asp Gly Asp Phe Ile Pro Ala Asp Pro 305 310 315 320 Ile Asn Leu Tyr Ala Asn Ala Ala Asp Ile Asp Tyr Ile Ala Gly Thr 325 330 335 Asn Asn Met Asp Gly His Ile Phe Ala Ser Ile Asp Met Pro Ala Ile 340 345 350 Asn Lys Gly Asn Lys Lys Val Thr Glu Glu Asp Phe Tyr Lys Leu Val 355 360 365 Ser Glu Phe Thr Ile Thr Lys Gly Leu Arg Gly Ala Lys Thr Thr Phe 370 375 380 Asp Val Tyr Thr Glu Ser Trp Ala Gln Asp Pro Ser Gln Glu Asn Lys 385 390 395 400 Lys Lys Thr Val Val Asp Phe Glu Thr Asp Val Leu Phe Leu Val Pro 405 410 415 Thr Glu Ile Ala Leu Ala Gln His Arg Ala Asn Ala Lys Ser Ala Lys 420 425 430 Thr Tyr Ala Tyr Leu Phe Ser His Pro Ser Arg Met Pro Val Tyr Pro 435 440 445 Lys Trp Val Gly Ala Asp His Ala Asp Asp Ile Gln Tyr Val Phe Gly 450 455 460 Lys Pro Phe Ala Thr Pro Thr Gly Tyr Arg Pro Gln Asp Arg Thr Val 465 470 475 480 Ser Lys Ala Met Ile Ala Tyr Trp Thr Asn Phe Ala Lys Thr Gly Asp 485 490 495 Pro Asn Met Gly Asp Ser Ala Val Pro Thr His Trp Glu Pro Tyr Thr 500 505 510 Thr Glu Asn Ser Gly Tyr Leu Glu Ile Thr Lys Lys Met Gly Ser Ser 515 520 525 Ser Met Lys Arg Ser Leu Arg Thr Asn Phe Leu Arg Tyr Trp Thr Leu 530 535 540 Thr Tyr Leu Ala Leu Pro Thr Val Thr Asp Gln Glu Ala Thr Pro Val 545 550 555 560 Pro Pro Thr Gly Asp Ser Glu Ala Thr Pro Val Pro Pro Thr Gly Asp 565 570 575 Ser Glu Thr Ala Pro Val Pro Pro Thr Gly Asp Ser Gly Ala Pro Pro 580 585 590 Val Pro Pro Thr Gly Asp Ser Gly Ala Pro Pro Val Pro Pro Thr Gly 595 600 605 Asp Ser Gly Ala Pro Pro Val Pro Pro Thr Gly Asp Ser Gly Ala Pro 610 615 620 Pro Val Pro Pro Thr Gly Asp Ser Gly Ala Pro Pro Val Pro Pro Thr 625 630 635 640 Gly Asp Ser Gly Ala Pro Pro Val Pro Pro Thr Gly Asp Ser Gly Ala 645 650 655 Pro Pro Val Pro Pro Thr Gly Asp Ser Gly Ala Pro Pro Val Pro Pro 660 665 670 Thr Gly Asp Ala Gly Pro Pro Pro Val Pro Pro Thr Gly Asp Ser Gly 675 680 685 Ala Pro Pro Val Pro Pro Thr Gly Asp Ser Gly Ala Pro Pro Val Thr 690 695 700 Pro Thr Gly Asp Ser Glu Thr Ala Pro Val Pro Pro Thr Gly Asp Ser 705 710 715 720 Gly Ala Pro Pro Val Pro Pro Thr Gly Asp Ser Glu Ala Ala Pro Val 725 730 735 Pro Pro Thr Asp Asp Ser Lys Glu Ala Gln Met Pro Ala Val Ile Arg 740 745 750 Phew <210> 92 <211> 757 <212> PRT <213> artificial sequence <220> <223> CD248_ humans <400> 92 Met Leu Leu Arg Leu Leu Leu Ala Trp Ala Ala Ala Gly Pro Thr Leu 1 5 10 15 Gly Gln Asp Pro Trp Ala Ala Glu Pro Arg Ala Ala Cys Gly Pro Ser 20 25 30 Ser Cys Tyr Ala Leu Phe Pro Arg Arg Arg Thr Phe Leu Glu Ala Trp 35 40 45 Arg Ala Cys Arg Glu Leu Gly Gly Asp Leu Ala Thr Pro Arg Thr Pro 50 55 60 Glu Glu Ala Gln Arg Val Asp Ser Leu Val Gly Ala Gly Pro Ala Ser 65 70 75 80 Arg Leu Leu Trp Ile Gly Leu Gln Arg Gln Ala Arg Gln Cys Gln Leu 85 90 95 Gln Arg Pro Leu Arg Gly Phe Thr Trp Thr Thr Gly Asp Gln Asp Thr 100 105 110 Ala Phe Thr Asn Trp Ala Gln Pro Ala Ser Gly Gly Pro Cys Pro Ala 115 120 125 Gln Arg Cys Val Ala Leu Glu Ala Ser Gly Glu His Arg Trp Leu Glu 130 135 140 Gly Ser Cys Thr Leu Ala Val Asp Gly Tyr Leu Cys Gln Phe Gly Phe 145 150 155 160 Glu Gly Ala Cys Pro Ala Leu Gln Asp Glu Ala Gly Gln Ala Gly Pro 165 170 175 Ala Val Tyr Thr Thr Pro Phe His Leu Val Ser Thr Glu Phe Glu Trp 180 185 190 Leu Pro Phe Gly Ser Val Ala Ala Val Gln Cys Gln Ala Gly Arg Gly 195 200 205 Ala Ser Leu Leu Cys Val Lys Gln Pro Glu Gly Gly Val Gly Trp Ser 210 215 220 Arg Ala Gly Pro Leu Cys Leu Gly Thr Gly Cys Ser Pro Asp Asn Gly 225 230 235 240 Gly Cys Glu His Glu Cys Val Glu Glu Val Asp Gly His Val Ser Cys 245 250 255 Arg Cys Thr Glu Gly Phe Arg Leu Ala Ala Asp Gly Arg Ser Cys Glu 260 265 270 Asp Pro Cys Ala Gln Ala Pro Cys Glu Gln Gln Cys Glu Pro Gly Gly 275 280 285 Pro Gln Gly Tyr Ser Cys His Cys Arg Leu Gly Phe Arg Pro Ala Glu 290 295 300 Asp Asp Pro His Arg Cys Val Asp Thr Asp Glu Cys Gln Ile Ala Gly 305 310 315 320 Val Cys Gln Gln Met Cys Val Asn Tyr Val Gly Gly Phe Glu Cys Tyr 325 330 335 Cys Ser Glu Gly His Glu Leu Glu Ala Asp Gly Ile Ser Cys Ser Pro 340 345 350 Ala Gly Ala Met Gly Ala Gln Ala Ser Gln Asp Leu Gly Asp Glu Leu 355 360 365 Leu Asp Asp Gly Glu Asp Glu Glu Asp Glu Asp Glu Ala Trp Lys Ala 370 375 380 Phe Asn Gly Gly Trp Thr Glu Met Pro Gly Ile Leu Trp Met Glu Pro 385 390 395 400 Thr Gln Pro Pro Asp Phe Ala Leu Ala Tyr Arg Pro Ser Phe Pro Glu 405 410 415 Asp Arg Glu Pro Gln Ile Pro Tyr Pro Glu Pro Thr Trp Pro Pro Pro 420 425 430 Leu Ser Ala Pro Arg Val Pro Tyr His Ser Ser Val Leu Ser Val Thr 435 440 445 Arg Pro Val Val Val Ser Ala Thr His Pro Thr Leu Pro Ser Ala His 450 455 460 Gln Pro Pro Val Ile Pro Ala Thr His Pro Ala Leu Ser Arg Asp His 465 470 475 480 Gln Ile Pro Val Ile Ala Ala Asn Tyr Pro Asp Leu Pro Ser Ala Tyr 485 490 495 Gln Pro Gly Ile Leu Ser Val Ser His Ser Ala Gln Pro Pro Ala His 500 505 510 Gln Pro Pro Met Ile Ser Thr Lys Tyr Pro Glu Leu Phe Pro Ala His 515 520 525 Gln Ser Pro Met Phe Pro Asp Thr Arg Val Ala Gly Thr Gln Thr Thr 530 535 540 Thr His Leu Pro Gly Ile Pro Pro Asn His Ala Pro Leu Val Thr Thr 545 550 555 560 Leu Gly Ala Gln Leu Pro Pro Gln Ala Pro Asp Ala Leu Val Leu Arg 565 570 575 Thr Gln Ala Thr Gln Leu Pro Ile Ile Pro Thr Ala Gln Pro Ser Leu 580 585 590 Thr Thr Thr Ser Arg Ser Pro Val Ser Pro Ala His Gln Ile Ser Val 595 600 605 Pro Ala Ala Thr Gln Pro Ala Ala Leu Pro Thr Leu Leu Pro Ser Gln 610 615 620 Ser Pro Thr Asn Gln Thr Ser Pro Ile Ser Pro Thr His Pro His Ser 625 630 635 640 Lys Ala Pro Gln Ile Pro Arg Glu Asp Gly Pro Ser Pro Lys Leu Ala 645 650 655 Leu Trp Leu Pro Ser Pro Ala Pro Thr Ala Ala Pro Thr Ala Leu Gly 660 665 670 Glu Ala Gly Leu Ala Glu His Ser Gln Arg Asp Asp Arg Trp Leu Leu 675 680 685 Val Ala Leu Leu Val Pro Thr Cys Val Phe Leu Val Val Leu Leu Ala 690 695 700 Leu Gly Ile Val Tyr Cys Thr Arg Cys Gly Pro His Ala Pro Asn Lys 705 710 715 720 Arg Ile Thr Asp Cys Tyr Arg Trp Val Ile His Ala Gly Ser Lys Ser 725 730 735 Pro Thr Glu Pro Met Pro Pro Arg Gly Ser Leu Thr Gly Val Gln Thr 740 745 750 Cys Arg Thr Ser Val 755 <210> 93 <211> 770 <212> PRT <213> artificial sequence <220> <223> A4_ humans <400> 93 Met Leu Pro Gly Leu Ala Leu Leu Leu Leu Ala Ala Trp Thr Ala Arg 1 5 10 15 Ala Leu Glu Val Pro Thr Asp Gly Asn Ala Gly Leu Leu Ala Glu Pro 20 25 30 Gln Ile Ala Met Phe Cys Gly Arg Leu Asn Met His Met Asn Val Gln 35 40 45 Asn Gly Lys Trp Asp Ser Asp Pro Ser Gly Thr Lys Thr Cys Ile Asp 50 55 60 Thr Lys Glu Gly Ile Leu Gln Tyr Cys Gln Glu Val Tyr Pro Glu Leu 65 70 75 80 Gln Ile Thr Asn Val Val Glu Ala Asn Gln Pro Val Thr Ile Gln Asn 85 90 95 Trp Cys Lys Arg Gly Arg Lys Gln Cys Lys Thr His Pro His Phe Val 100 105 110 Ile Pro Tyr Arg Cys Leu Val Gly Glu Phe Val Ser Asp Ala Leu Leu 115 120 125 Val Pro Asp Lys Cys Lys Phe Leu His Gln Glu Arg Met Asp Val Cys 130 135 140 Glu Thr His Leu His Trp His Thr Val Ala Lys Glu Thr Cys Ser Glu 145 150 155 160 Lys Ser Thr Asn Leu His Asp Tyr Gly Met Leu Leu Pro Cys Gly Ile 165 170 175 Asp Lys Phe Arg Gly Val Glu Phe Val Cys Cys Pro Leu Ala Glu Glu 180 185 190 Ser Asp Asn Val Asp Ser Ala Asp Ala Glu Glu Asp Asp Ser Asp Val 195 200 205 Trp Trp Gly Gly Ala Asp Thr Asp Tyr Ala Asp Gly Ser Glu Asp Lys 210 215 220 Val Val Glu Val Ala Glu Glu Glu Glu Val Ala Glu Val Glu Glu Glu 225 230 235 240 Glu Ala Asp Asp Asp Glu Asp Asp Glu Asp Gly Asp Glu Val Glu Glu 245 250 255 Glu Ala Glu Glu Pro Tyr Glu Glu Ala Thr Glu Arg Thr Thr Ser Ile 260 265 270 Ala Thr Thr Thr Thr Thr Thr Thr Glu Ser Val Glu Glu Val Val Arg 275 280 285 Glu Val Cys Ser Glu Gln Ala Glu Thr Gly Pro Cys Arg Ala Met Ile 290 295 300 Ser Arg Trp Tyr Phe Asp Val Thr Glu Gly Lys Cys Ala Pro Phe Phe 305 310 315 320 Tyr Gly Gly Cys Gly Gly Asn Arg Asn Asn Phe Asp Thr Glu Glu Tyr 325 330 335 Cys Met Ala Val Cys Gly Ser Ala Met Ser Gln Ser Leu Leu Lys Thr 340 345 350 Thr Gln Glu Pro Leu Ala Arg Asp Pro Val Lys Leu Pro Thr Thr Ala 355 360 365 Ala Ser Thr Pro Asp Ala Val Asp Lys Tyr Leu Glu Thr Pro Gly Asp 370 375 380 Glu Asn Glu His Ala His Phe Gln Lys Ala Lys Glu Arg Leu Glu Ala 385 390 395 400 Lys His Arg Glu Arg Met Ser Gln Val Met Arg Glu Trp Glu Glu Ala 405 410 415 Glu Arg Gln Ala Lys Asn Leu Pro Lys Ala Asp Lys Lys Ala Val Ile 420 425 430 Gln His Phe Gln Glu Lys Val Glu Ser Leu Glu Gln Glu Ala Ala Asn 435 440 445 Glu Arg Gln Gln Leu Val Glu Thr His Met Ala Arg Val Glu Ala Met 450 455 460 Leu Asn Asp Arg Arg Arg Leu Ala Leu Glu Asn Tyr Ile Thr Ala Leu 465 470 475 480 Gln Ala Val Pro Pro Arg Pro Arg His Val Phe Asn Met Leu Lys Lys 485 490 495 Tyr Val Arg Ala Glu Gln Lys Asp Arg Gln His Thr Leu Lys His Phe 500 505 510 Glu His Val Arg Met Val Asp Pro Lys Lys Ala Ala Gln Ile Arg Ser 515 520 525 Gln Val Met Thr His Leu Arg Val Ile Tyr Glu Arg Met Asn Gln Ser 530 535 540 Leu Ser Leu Leu Tyr Asn Val Pro Ala Val Ala Glu Glu Ile Gln Asp 545 550 555 560 Glu Val Asp Glu Leu Leu Gln Lys Glu Gln Asn Tyr Ser Asp Asp Val 565 570 575 Leu Ala Asn Met Ile Ser Glu Pro Arg Ile Ser Tyr Gly Asn Asp Ala 580 585 590 Leu Met Pro Ser Leu Thr Glu Thr Lys Thr Thr Val Glu Leu Leu Pro 595 600 605 Val Asn Gly Glu Phe Ser Leu Asp Asp Leu Gln Pro Trp His Ser Phe 610 615 620 Gly Ala Asp Ser Val Pro Ala Asn Thr Glu Asn Glu Val Glu Pro Val 625 630 635 640 Asp Ala Arg Pro Ala Ala Asp Arg Gly Leu Thr Thr Arg Pro Gly Ser 645 650 655 Gly Leu Thr Asn Ile Lys Thr Glu Glu Ile Ser Glu Val Lys Met Asp 660 665 670 Ala Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gln Lys Leu 675 680 685 Val Phe Phe Ala Glu Asp Val Gly Ser Asn Lys Gly Ala Ile Ile Gly 690 695 700 Leu Met Val Gly Gly Val Val Ile Ala Thr Val Ile Val Ile Thr Leu 705 710 715 720 Val Met Leu Lys Lys Lys Gln Tyr Thr Ser Ile His His Gly Val Val 725 730 735 Glu Val Asp Ala Ala Val Thr Pro Glu Glu Arg His Leu Ser Lys Met 740 745 750 Gln Gln Asn Gly Tyr Glu Asn Pro Thr Tyr Lys Phe Phe Glu Gln Met 755 760 765 Gln Asn 770 <210> 94 <211> 780 <212> PRT <213> Artificial Sequence <220> <223> ASAH2_Human <400> 94 Met Ala Lys Arg Thr Phe Ser Asn Leu Glu Thr Phe Leu Ile Phe Leu 1 5 10 15 Leu Val Met Met Ser Ala Ile Thr Val Ala Leu Leu Ser Leu Leu Phe 20 25 30 Ile Thr Ser Gly Thr Ile Glu Asn His Lys Asp Leu Gly Gly His Phe 35 40 45 Phe Ser Thr Thr Gln Ser Pro Pro Ala Thr Gln Gly Ser Thr Ala Ala 50 55 60 Gln Arg Ser Thr Ala Thr Gln His Ser Thr Ala Thr Gln Ser Ser Thr 65 70 75 80 Ala Thr Gln Thr Ser Pro Val Pro Leu Thr Pro Glu Ser Pro Leu Phe 85 90 95 Gln Asn Phe Ser Gly Tyr His Ile Gly Val Gly Arg Ala Asp Cys Thr 100 105 110 Gly Gln Val Ala Asp Ile Asn Leu Met Gly Tyr Gly Lys Ser Gly Gln 115 120 125 Asn Ala Gln Gly Ile Leu Thr Arg Leu Tyr Ser Arg Ala Phe Ile Met 130 135 140 Ala Glu Pro Asp Gly Ser Asn Arg Thr Val Phe Val Ser Ile Asp Ile 145 150 155 160 Gly Met Val Ser Gln Arg Leu Arg Leu Glu Val Leu Asn Arg Leu Gln 165 170 175 Ser Lys Tyr Gly Ser Leu Tyr Arg Arg Asp Asn Val Ile Leu Ser Gly 180 185 190 Thr His Thr His Ser Gly Pro Ala Gly Tyr Phe Gln Tyr Thr Val Phe 195 200 205 Val Ile Ala Ser Glu Gly Phe Ser Asn Gln Thr Phe Gln His Met Val 210 215 220 Thr Gly Ile Leu Lys Ser Ile Asp Ile Ala His Thr Asn Met Lys Pro 225 230 235 240 Gly Lys Ile Phe Ile Asn Lys Gly Asn Val Asp Gly Val Gln Ile Asn 245 250 255 Arg Ser Pro Tyr Ser Tyr Leu Gln Asn Pro Gln Ser Glu Arg Ala Arg 260 265 270 Tyr Ser Ser Asn Thr Asp Lys Glu Met Ile Val Leu Lys Met Val Asp 275 280 285 Leu Asn Gly Asp Asp Leu Gly Leu Ile Ser Trp Phe Ala Ile His Pro 290 295 300 Val Ser Met Asn Asn Ser Asn His Leu Val Asn Ser Asp Asn Val Gly 305 310 315 320 Tyr Ala Ser Tyr Leu Leu Glu Gln Glu Lys Asn Lys Gly Tyr Leu Pro 325 330 335 Gly Gln Gly Pro Phe Val Ala Ala Phe Ala Ser Ser Asn Leu Gly Asp 340 345 350 Val Ser Pro Asn Ile Leu Gly Pro Arg Cys Ile Asn Thr Gly Glu Ser 355 360 365 Cys Asp Asn Ala Asn Ser Thr Cys Pro Ile Gly Gly Pro Ser Met Cys 370 375 380 Ile Ala Lys Gly Pro Gly Gln Asp Met Phe Asp Ser Thr Gln Ile Ile 385 390 395 400 Gly Arg Ala Met Tyr Gln Arg Ala Lys Glu Leu Tyr Ala Ser Ala Ser 405 410 415 Gln Glu Val Thr Gly Pro Leu Ala Ser Ala His Gln Trp Val Asp Met 420 425 430 Thr Asp Val Thr Val Trp Leu Asn Ser Thr His Ala Ser Lys Thr Cys 435 440 445 Lys Pro Ala Leu Gly Tyr Ser Phe Ala Ala Gly Thr Ile Asp Gly Val 450 455 460 Gly Gly Leu Asn Phe Thr Gln Gly Lys Thr Glu Gly Asp Pro Phe Trp 465 470 475 480 Asp Thr Ile Arg Asp Gln Ile Leu Gly Lys Pro Ser Glu Glu Ile Lys 485 490 495 Glu Cys His Lys Pro Lys Pro Ile Leu Leu His Thr Gly Glu Leu Ser 500 505 510 Lys Pro His Pro Trp His Pro Asp Ile Val Asp Val Gln Ile Ile Thr 515 520 525 Leu Gly Ser Leu Ala Ile Thr Ala Ile Pro Gly Glu Phe Thr Thr Met 530 535 540 Ser Gly Arg Arg Leu Arg Glu Ala Val Gln Ala Glu Phe Ala Ser His 545 550 555 560 Gly Met Gln Asn Met Thr Val Val Ile Ser Gly Leu Cys Asn Val Tyr 565 570 575 Thr His Tyr Ile Thr Thr Tyr Glu Glu Tyr Gln Ala Gln Arg Tyr Glu 580 585 590 Ala Ala Ser Thr Ile Tyr Gly Pro His Thr Leu Ser Ala Tyr Ile Gln 595 600 605 Leu Phe Arg Asn Leu Ala Lys Ala Ile Ala Thr Asp Thr Val Ala Asn 610 615 620 Leu Ser Arg Gly Pro Glu Pro Pro Phe Phe Lys Gln Leu Ile Val Pro 625 630 635 640 Leu Ile Pro Ser Ile Val Asp Arg Ala Pro Lys Gly Arg Thr Phe Gly 645 650 655 Asp Val Leu Gln Pro Ala Lys Pro Glu Tyr Arg Val Gly Glu Val Ala 660 665 670 Glu Val Ile Phe Val Gly Ala Asn Pro Lys Asn Ser Val Gln Asn Gln 675 680 685 Thr His Gln Thr Phe Leu Thr Val Glu Lys Tyr Glu Ala Thr Ser Thr 690 695 700 Ser Trp Gln Ile Val Cys Asn Asp Ala Ser Trp Glu Thr Arg Phe Tyr 705 710 715 720 Trp His Lys Gly Leu Leu Gly Leu Ser Asn Ala Thr Val Glu Trp His 725 730 735 Ile Pro Asp Thr Ala Gln Pro Gly Ile Tyr Arg Ile Arg Tyr Phe Gly 740 745 750 His Asn Arg Lys Gln Asp Ile Leu Lys Pro Ala Val Ile Leu Ser Phe 755 760 765 Glu Gly Thr Ser Pro Ala Phe Glu Val Val Thr Ile 770 775 780 <210> 95 <211> 785 <212> PRT <213> Artificial Sequence <220> <223> SP1_Human <400> 95 Met Ser Asp Gln Asp His Ser Met Asp Glu Met Thr Ala Val Val Lys 1 5 10 15 Ile Glu Lys Gly Val Gly Gly Asn Asn Gly Gly Asn Gly Asn Gly Gly 20 25 30 Gly Ala Phe Ser Gln Ala Arg Ser Ser Ser Thr Gly Ser Ser Ser Ser 35 40 45 Thr Gly Gly Gly Gly Gln Glu Ser Gln Pro Ser Pro Leu Ala Leu Leu 50 55 60 Ala Ala Thr Cys Ser Arg Ile Glu Ser Pro Asn Glu Asn Ser Asn Asn 65 70 75 80 Ser Gln Gly Pro Ser Gln Ser Gly Gly Thr Gly Glu Leu Asp Leu Thr 85 90 95 Ala Thr Gln Leu Ser Gln Gly Ala Asn Gly Trp Gln Ile Ile Ser Ser 100 105 110 Ser Ser Gly Ala Thr Pro Thr Ser Lys Glu Gln Ser Gly Ser Ser Thr 115 120 125 Asn Gly Ser Asn Gly Ser Glu Ser Ser Lys Asn Arg Thr Val Ser Gly 130 135 140 Gly Gln Tyr Val Val Ala Ala Ala Pro Asn Leu Gln Asn Gln Gln Val 145 150 155 160 Leu Thr Gly Leu Pro Gly Val Met Pro Asn Ile Gln Tyr Gln Val Ile 165 170 175 Pro Gln Phe Gln Thr Val Asp Gly Gln Gln Leu Gln Phe Ala Ala Thr 180 185 190 Gly Ala Gln Val Gln Gln Asp Gly Ser Gly Gln Ile Gln Ile Ile Pro 195 200 205 Gly Ala Asn Gln Gln Ile Ile Thr Asn Arg Gly Ser Gly Gly Asn Ile 210 215 220 Ile Ala Ala Met Pro Asn Leu Leu Gln Gln Ala Val Pro Leu Gln Gly 225 230 235 240 Leu Ala Asn Asn Val Leu Ser Gly Gln Thr Gln Tyr Val Thr Asn Val 245 250 255 Pro Val Ala Leu Asn Gly Asn Ile Thr Leu Leu Pro Val Asn Ser Val 260 265 270 Ser Ala Ala Thr Leu Thr Pro Ser Ser Gln Ala Val Thr Ile Ser Ser 275 280 285 Ser Gly Ser Gln Glu Ser Gly Ser Gln Pro Val Thr Ser Gly Thr Thr 290 295 300 Ile Ser Ser Ala Ser Leu Val Ser Ser Gln Ala Ser Ser Ser Ser Phe 305 310 315 320 Phe Thr Asn Ala Asn Ser Tyr Ser Thr Thr Thr Thr Thr Ser Asn Met 325 330 335 Gly Ile Met Asn Phe Thr Thr Ser Gly Ser Ser Gly Thr Asn Ser Gln 340 345 350 Gly Gln Thr Pro Gln Arg Val Ser Gly Leu Gln Gly Ser Asp Ala Leu 355 360 365 Asn Ile Gln Gln Asn Gln Thr Ser Gly Gly Ser Leu Gln Ala Gly Gln 370 375 380 Gln Lys Glu Gly Glu Gln Asn Gln Gln Thr Gln Gln Gln Gln Ile Leu 385 390 395 400 Ile Gln Pro Gln Leu Val Gln Gly Gly Gln Ala Leu Gln Ala Leu Gln 405 410 415 Ala Ala Pro Leu Ser Gly Gln Thr Phe Thr Thr Gln Ala Ile Ser Gln 420 425 430 Glu Thr Leu Gln Asn Leu Gln Leu Gln Ala Val Pro Asn Ser Gly Pro 435 440 445 Ile Ile Ile Arg Thr Pro Thr Val Gly Pro Asn Gly Gln Val Ser Trp 450 455 460 Gln Thr Leu Gln Leu Gln Asn Leu Gln Val Gln Asn Pro Gln Ala Gln 465 470 475 480 Thr Ile Thr Leu Ala Pro Met Gln Gly Val Ser Leu Gly Gln Thr Ser 485 490 495 Ser Ser Asn Thr Thr Leu Thr Pro Ile Ala Ser Ala Ala Ser Ile Pro 500 505 510 Ala Gly Thr Val Thr Val Asn Ala Ala Gln Leu Ser Ser Met Pro Gly 515 520 525 Leu Gln Thr Ile Asn Leu Ser Ala Leu Gly Thr Ser Gly Ile Gln Val 530 535 540 His Pro Ile Gln Gly Leu Pro Leu Ala Ile Ala Asn Ala Pro Gly Asp 545 550 555 560 His Gly Ala Gln Leu Gly Leu His Gly Ala Gly Gly Asp Gly Ile His 565 570 575 Asp Asp Thr Ala Gly Gly Glu Glu Gly Glu Asn Ser Pro Asp Ala Gln 580 585 590 Pro Gln Ala Gly Arg Arg Thr Arg Arg Glu Ala Cys Thr Cys Pro Tyr 595 600 605 Cys Lys Asp Ser Glu Gly Arg Gly Ser Gly Asp Pro Gly Lys Lys Lys 610 615 620 Gln His Ile Cys His Ile Gln Gly Cys Gly Lys Val Tyr Gly Lys Thr 625 630 635 640 Ser His Leu Arg Ala His Leu Arg Trp His Thr Gly Glu Arg Pro Phe 645 650 655 Methionine Cysteine Threonine Tryptophan Serine Tyrosine Cysteine Glycine Lysine Arginine Phenylalanine Threonine Arginine Serine Aspartic acid Glutamic acid 660 665 670 Leucine Glutamine Arginine Histidine Lysine Arginine Threonine Histidine Threonine Glycine Glutamic acid Lysine Lysine Phenylalanine Alanine Cysteine 675 680 685 Proline Glutamic acid Cysteine Proline Lysine Arginine Phenylalanine Methionine Arginine Serine Aspartic acid Histidine Leucine Serine Lysine Histidine 690 695 700 Isoleucine Lysine Threonine Histidine Glutamine Asparagine Lysine Lysine Glycine Glycine Proline Glycine Valine Alanine Leucine Serine 705 710 715 720 Valine Glycine Threonine Leucine Proline Leucine Aspartic acid Serine Glycine Alanine Glycine Serine Glutamic acid Glycine Serine Glycine 725 730 735 Threonine Alanine Threonine Proline Serine Alanine Leucine Isoleucine Threonine Threonine Asparagine Methionine Valine Alanine Methionine Glutamic acid 740 745 750 Alanine Isoleucine Cysteine Proline Glutamic acid Glycine Isoleucine Alanine Arginine Leucine Alanine Asparagine Serine Glycine Isoleucine Asparagine 755 760 765 Valine Methionine Glutamine Valine Alanine Aspartic acid Leucine Glutamine Serine Isoleucine Asparagine Isoleucine Serine Glycine Asparagine Glycine 770 775 780 Phenylalanine 785 <210> 96 <211> 797 <212> PRT <213> Artificial Sequence <220> <223> IMPG1_Human <400> 96 Met Tyr Leu Glu Thr Arg Arg Ala Ile Phe Val Phe Trp Ile Phe Leu 1 5 10 15 Gln Val Gln Gly Thr Lys Asp Ile Ser Ile Asn Ile Tyr His Ser Glu 20 25 30 Thr Lys Asp Ile Asp Asn Pro Pro Arg Asn Glu Thr Thr Glu Ser Thr 35 40 45 Glu Lys Met Tyr Lys Met Ser Thr Met Arg Arg Ile Phe Asp Leu Ala 50 55 60 Lys His Arg Thr Lys Arg Ser Ala Phe Phe Pro Thr Gly Val Lys Val 65 70 75 80 Cys Pro Gln Glu Ser Met Lys Gln Ile Leu Asp Ser Leu Gln Ala Tyr 85 90 95 Tyr Arg Leu Arg Val Cys Gln Glu Ala Val Trp Glu Ala Tyr Arg Ile 100 105 110 Phe Leu Asp Arg Ile Pro Asp Thr Gly Glu Tyr Gln Asp Trp Val Ser 115 120 125 Ile Cys Gln Gln Glu Thr Phe Cys Leu Phe Asp Ile Gly Lys Asn Phe 130 135 140 Ser Asn Ser Gln Glu His Leu Asp Leu Leu Gln Gln Arg Ile Lys Gln 145 150 155 160 Arg Ser Phe Pro Asp Arg Lys Asp Glu Ile Ser Ala Glu Lys Thr Leu 165 170 175 Gly Glu Pro Gly Glu Thr Ile Val Ile Ser Thr Asp Val Ala Asn Val 180 185 190 Ser Leu Gly Pro Phe Pro Leu Thr Pro Asp Asp Thr Leu Leu Asn Glu 195 200 205 Ile Leu Asp Asn Thr Leu Asn Asp Thr Lys Met Pro Thr Thr Glu Arg 210 215 220 Glu Thr Glu Phe Ala Val Leu Glu Glu Gln Arg Val Glu Leu Ser Val 225 230 235 240 Ser Leu Val Asn Gln Lys Phe Lys Ala Glu Leu Ala Asp Ser Gln Ser 245 250 255 Pro Tyr Tyr Gln Glu Leu Ala Gly Lys Ser Gln Leu Gln Met Gln Lys 260 265 270 Ile Phe Lys Lys Leu Pro Gly Phe Lys Lys Ile His Val Leu Gly Phe 275 280 285 Arg Pro Lys Lys Glu Lys Asp Gly Ser Ser Ser Thr Glu Met Gln Leu 290 295 300 Thr Ala Ile Phe Lys Arg His Ser Ala Glu Ala Lys Ser Pro Ala Ser 305 310 315 320 Asp Leu Leu Ser Phe Asp Ser Asn Lys Ile Glu Ser Glu Glu Val Tyr 325 330 335 His Gly Thr Met Glu Glu Asp Lys Gln Pro Glu Ile Tyr Leu Thr Ala 340 345 350 Thr Asp Leu Lys Arg Leu Ile Ser Lys Ala Leu Glu Glu Glu Gln Ser 355 360 365 Leu Asp Val Gly Thr Ile Gln Phe Thr Asp Glu Ile Ala Gly Ser Leu 370 375 380 Pro Ala Phe Gly Pro Asp Thr Gln Ser Glu Leu Pro Thr Ser Phe Ala 385 390 395 400 Val Ile Thr Glu Asp Ala Thr Leu Ser Pro Glu Leu Pro Pro Val Glu 405 410 415 Pro Gln Leu Glu Thr Val Asp Gly Ala Glu His Gly Leu Pro Asp Thr 420 425 430 Ser Trp Ser Pro Pro Ala Met Ala Ser Thr Ser Leu Ser Glu Ala Pro 435 440 445 Pro Phe Phe Met Ala Ser Ser Ile Phe Ser Leu Thr Asp Gln Gly Thr 450 455 460 Thr Asp Thr Met Ala Thr Asp Gln Thr Met Leu Val Pro Gly Leu Thr 465 470 475 480 Ile Pro Thr Ser Asp Tyr Ser Ala Ile Ser Gln Leu Ala Leu Gly Ile 485 490 495 Ser His Pro Pro Ala Ser Ser Asp Asp Ser Arg Ser Ser Ala Gly Gly 500 505 510 Glu Asp Met Val Arg His Leu Asp Glu Met Asp Leu Ser Asp Thr Pro 515 520 525 Ala Pro Ser Glu Val Pro Glu Leu Ser Glu Tyr Val Ser Val Pro Asp 530 535 540 His Phe Leu Glu Asp Thr Thr Pro Val Ser Ala Leu Gln Tyr Ile Thr 545 550 555 560 Thr Ser Ser Met Thr Ile Ala Pro Lys Gly Arg Glu Leu Val Val Phe 565 570 575 Phe Ser Leu Arg Val Ala Asn Met Ala Phe Ser Asn Asp Leu Phe Asn 580 585 590 Lys Ser Ser Leu Glu Tyr Arg Ala Leu Glu Gln Gln Phe Thr Gln Leu 595 600 605 Leu Val Pro Tyr Leu Arg Ser Asn Leu Thr Gly Phe Lys Gln Leu Glu 610 615 620 Ile Leu Asn Phe Arg Asn Gly Ser Val Ile Val Asn Ser Lys Met Lys 625 630 635 640 Phe Ala Lys Ser Val Pro Tyr Asn Leu Thr Lys Ala Val His Gly Val 645 650 655 Leu Glu Asp Phe Arg Ser Ala Ala Ala Gln Gln Leu His Leu Glu Ile 660 665 670 Asp Ser Tyr Ser Leu Asn Ile Glu Pro Ala Asp Gln Ala Asp Pro Cys 675 680 685 Lys Phe Leu Ala Cys Gly Glu Phe Ala Gln Cys Val Lys Asn Glu Arg 690 695 700 Thr Glu Glu Ala Glu Cys Arg Cys Lys Pro Gly Tyr Asp Ser Gln Gly 705 710 715 720 Ser Leu Asp Gly Leu Glu Pro Gly Leu Cys Gly Pro Gly Thr Lys Glu 725 730 735 Cys Glu Val Leu Gln Gly Lys Gly Ala Pro Cys Arg Leu Pro Asp His 740 745 750 Ser Glu Asn Gln Ala Tyr Lys Thr Ser Val Lys Lys Phe Gln Asn Gln 755 760 765 Gln Asn Asn Lys Val Ile Ser Lys Arg Asn Ser Glu Leu Leu Thr Val 770 775 780 Glu Tyr Glu Glu Phe Asn His Gln Asp Trp Glu Gly Asn 785 790 795 <210> 97 <211> 815 <212> PRT <213> artificial sequence <220> <223> SL9A1_ humans <400> 97 Met Val Leu Arg Ser Gly Ile Cys Gly Leu Ser Pro His Arg Ile Phe 1 5 10 15 Pro Ser Leu Leu Val Val Val Ala Leu Val Gly Leu Leu Pro Val Leu 20 25 30 Arg Ser His Gly Leu Gln Leu Ser Pro Thr Ala Ser Thr Ile Arg Ser 35 40 45 Ser Glu Pro Pro Arg Glu Arg Ser Ile Gly Asp Val Thr Thr Ala Pro 50 55 60 Pro Glu Val Thr Pro Glu Ser Arg Pro Val Asn His Ser Val Thr Asp 65 70 75 80 His Gly Met Lys Pro Arg Lys Ala Phe Pro Val Leu Gly Ile Asp Tyr 85 90 95 Thr His Val Arg Thr Pro Phe Glu Ile Ser Leu Trp Ile Leu Leu Ala 100 105 110 Cys Leu Met Lys Ile Gly Phe His Val Ile Pro Thr Ile Ser Ser Ile 115 120 125 Val Pro Glu Ser Cys Leu Leu Ile Val Val Gly Leu Leu Val Gly Gly 130 135 140 Leu Ile Lys Gly Val Gly Glu Thr Pro Pro Phe Leu Gln Ser Asp Val 145 150 155 160 Phe Phe Leu Phe Leu Leu Pro Pro Ile Ile Leu Asp Ala Gly Tyr Phe 165 170 175 Leu Pro Leu Arg Gln Phe Thr Glu Asn Leu Gly Thr Ile Leu Ile Phe 180 185 190 Ala Val Val Gly Thr Leu Trp Asn Ala Phe Phe Leu Gly Gly Leu Met 195 200 205 Tyr Ala Val Cys Leu Val Gly Gly Glu Gln Ile Asn Asn Ile Gly Leu 210 215 220 Leu Asp Asn Leu Leu Phe Gly Ser Ile Ile Ser Ala Val Asp Pro Val 225 230 235 240 Ala Val Leu Ala Val Phe Glu Glu Ile His Ile Asn Glu Leu Leu His 245 250 255 Ile Leu Val Phe Gly Glu Ser Leu Leu Asn Asp Ala Val Thr Val Val 260 265 270 Leu Tyr His Leu Phe Glu Glu Phe Ala Asn Tyr Glu His Val Gly Ile 275 280 285 Val Asp Ile Phe Leu Gly Phe Leu Ser Phe Phe Val Val Ala Leu Gly 290 295 300 Gly Val Leu Val Gly Val Val Tyr Gly Val Ile Ala Ala Phe Thr Ser 305 310 315 320 Arg Phe Thr Ser His Ile Arg Val Ile Glu Pro Leu Phe Val Phe Leu 325 330 335 Tyr Ser Tyr Met Ala Tyr Leu Ser Ala Glu Leu Phe His Leu Ser Gly 340 345 350 Ile Met Ala Leu Ile Ala Ser Gly Val Val Met Arg Pro Tyr Val Glu 355 360 365 Ala Asn Ile Ser His Lys Ser His Thr Thr Ile Lys Tyr Phe Leu Lys 370 375 380 Met Trp Ser Ser Val Ser Glu Thr Leu Ile Phe Ile Phe Leu Gly Val 385 390 395 400 Ser Thr Val Ala Gly Ser His His Trp Asn Trp Thr Phe Val Ile Ser 405 410 415 Thr Leu Leu Phe Cys Leu Ile Ala Arg Val Leu Gly Val Leu Gly Leu 420 425 430 Thr Trp Phe Ile Asn Lys Phe Arg Ile Val Lys Leu Thr Pro Lys Asp 435 440 445 Gln Phe Ile Ile Ala Tyr Gly Gly Leu Arg Gly Ala Ile Ala Phe Ser 450 455 460 Leu Gly Tyr Leu Leu Asp Lys Lys His Phe Pro Met Cys Asp Leu Phe 465 470 475 480 Leu Thr Ala Ile Ile Thr Val Ile Phe Phe Thr Val Phe Val Gln Gly 485 490 495 Met Thr Ile Arg Pro Leu Val Asp Leu Leu Ala Val Lys Lys Lys Gln 500 505 510 Glu Thr Lys Arg Ser Ile Asn Glu Glu Ile His Thr Gln Phe Leu Asp 515 520 525 His Leu Leu Thr Gly Ile Glu Asp Ile Cys Gly His Tyr Gly His His 530 535 540 His Trp Lys Asp Lys Leu Asn Arg Phe Asn Lys Lys Tyr Val Lys Lys 545 550 555 560 Cys Leu Ile Ala Gly Glu Arg Ser Lys Glu Pro Gln Leu Ile Ala Phe 565 570 575 Tyr His Lys Met Glu Met Lys Gln Ala Ile Glu Leu Val Glu Ser Gly 580 585 590 Gly Met Gly Lys Ile Pro Ser Ala Val Ser Thr Val Ser Met Gln Asn 595 600 605 Ile His Pro Lys Ser Leu Pro Ser Glu Arg Ile Leu Pro Ala Leu Ser 610 615 620 Lys Asp Lys Glu Glu Glu Ile Arg Lys Ile Leu Arg Asn Asn Leu Gln 625 630 635 640 Lys Thr Arg Gln Arg Leu Arg Ser Tyr Asn Arg His Thr Leu Val Ala 645 650 655 Asp Pro Tyr Glu Glu Ala Trp Asn Gln Met Leu Leu Arg Arg Gln Lys 660 665 670 Ala Arg Gln Leu Glu Gln Lys Ile Asn Asn Tyr Leu Thr Val Pro Ala 675 680 685 His Lys Leu Asp Ser Pro Thr Met Ser Arg Ala Arg Ile Gly Ser Asp 690 695 700 Pro Leu Ala Tyr Glu Pro Lys Glu Asp Leu Pro Val Ile Thr Ile Asp 705 710 715 720 Pro Ala Ser Pro Gln Ser Pro Glu Ser Val Asp Leu Val Asn Glu Glu 725 730 735 Leu Lys Gly Lys Val Leu Gly Leu Ser Arg Asp Pro Ala Lys Val Ala 740 745 750 Glu Glu Asp Glu Asp Asp Asp Gly Gly Ile Met Met Arg Ser Lys Glu 755 760 765 Thr Ser Ser Pro Gly Thr Asp Asp Val Phe Thr Pro Ala Pro Ser Asp 770 775 780 Ser Pro Ser Ser Gln Arg Ile Gln Arg Cys Leu Ser Asp Pro Gly Pro 785 790 795 800 His Pro Glu Pro Gly Glu Gly Glu Pro Phe Phe Pro Lys Gly Gln 805 810 815 <210> 98 <211> 882 <212> PRT <213> Artificial Sequence <220> <223> CADH1_Human <400> 98 Met Gly Pro Trp Ser Arg Ser Leu Ser Ala Leu Leu Leu Leu Leu Gln 1 5 10 15 Val Ser Ser Trp Leu Cys Gln Glu Pro Glu Pro Cys His Pro Gly Phe 20 25 30 Asp Ala Glu Ser Tyr Thr Phe Thr Val Pro Arg Arg His Leu Glu Arg 35 40 45 Gly Arg Val Leu Gly Arg Val Asn Phe Glu Asp Cys Thr Gly Arg Gln 50 55 60 Arg Thr Ala Tyr Phe Ser Leu Asp Thr Arg Phe Lys Val Gly Thr Asp 65 70 75 80 Gly Val Ile Thr Val Lys Arg Pro Leu Arg Phe His Asn Pro Gln Ile 85 90 95 His Phe Leu Val Tyr Ala Trp Asp Ser Thr Tyr Arg Lys Phe Ser Thr 100 105 110 Lys Val Thr Leu Asn Thr Val Gly His His His Arg Pro Pro Pro His 115 120 125 Gln Ala Ser Val Ser Gly Ile Gln Ala Glu Leu Leu Thr Phe Pro Asn 130 135 140 Ser Ser Pro Gly Leu Arg Arg Gln Lys Arg Asp Trp Val Ile Pro Pro 145 150 155 160 Ile Ser Cys Pro Glu Asn Glu Lys Gly Pro Phe Pro Lys Asn Leu Val 165 170 175 Gln Ile Lys Ser Asn Lys Asp Lys Glu Gly Lys Val Phe Tyr Ser Ile 180 185 190 Thr Gly Gln Gly Ala Asp Thr Pro Pro Val Gly Val Phe Ile Ile Glu 195 200 205 Arg Glu Thr Gly Trp Leu Lys Val Thr Glu Pro Leu Asp Arg Glu Arg 210 215 220 Ile Ala Thr Tyr Thr Leu Phe Ser His Ala Val Ser Ser Asn Gly Asn 225 230 235 240 Ala Val Glu Asp Pro Met Glu Ile Leu Ile Thr Val Thr Asp Gln Asn 245 250 255 Asp Asn Lys Pro Glu Phe Thr Gln Glu Val Phe Lys Gly Ser Val Met 260 265 270 Glu Gly Ala Leu Pro Gly Thr Ser Val Met Glu Val Thr Ala Thr Asp 275 280 285 Ala Asp Asp Asp Val Asn Thr Tyr Asn Ala Ala Ile Ala Tyr Thr Ile 290 295 300 Leu Ser Gln Asp Pro Glu Leu Pro Asp Lys Asn Met Phe Thr Ile Asn 305 310 315 320 Arg Asn Thr Gly Val Ile Ser Val Val Thr Thr Gly Leu Asp Arg Glu 325 330 335 Ser Phe Pro Thr Tyr Thr Leu Val Val Gln Ala Ala Asp Leu Gln Gly 340 345 350 Glu Gly Leu Ser Thr Thr Ala Thr Ala Val Ile Thr Val Thr Asp Thr 355 360 365 Asn Asp Asn Pro Pro Ile Phe Asn Pro Thr Thr Tyr Lys Gly Gln Val 370 375 380 Pro Glu Asn Glu Ala Asn Val Val Ile Thr Thr Leu Lys Val Thr Asp 385 390 395 400 Ala Asp Ala Pro Asn Thr Pro Ala Trp Glu Ala Val Tyr Thr Ile Leu 405 410 415 Asn Asp Asp Gly Gly Gln Phe Val Val Thr Thr Asn Pro Val Asn Asn 420 425 430 Asp Gly Ile Leu Lys Thr Ala Lys Gly Leu Asp Phe Glu Ala Lys Gln 435 440 445 Gln Tyr Ile Leu His Val Ala Val Thr Asn Val Val Pro Phe Glu Val 450 455 460 Ser Leu Thr Thr Ser Thr Ala Thr Val Thr Val Asp Val Leu Asp Val 465 470 475 480 Asn Glu Ala Pro Ile Phe Val Pro Pro Glu Lys Arg Val Glu Val Ser 485 490 495 Glu Asp Phe Gly Val Gly Gln Glu Ile Thr Ser Tyr Thr Ala Gln Glu 500 505 510 Pro Asp Thr Phe Met Glu Gln Lys Ile Thr Tyr Arg Ile Trp Arg Asp 515 520 525 Thr Ala Asn Trp Leu Glu Ile Asn Pro Asp Thr Gly Ala Ile Ser Thr 530 535 540 Arg Ala Glu Leu Asp Arg Glu Asp Phe Glu His Val Lys Asn Ser Thr 545 550 555 560 Tyr Thr Ala Leu Ile Ile Ala Thr Asp Asn Gly Ser Pro Val Ala Thr 565 570 575 Gly Thr Gly Thr Leu Leu Leu Ile Leu Ser Asp Val Asn Asp Asn Ala 580 585 590 Pro Ile Pro Glu Pro Arg Thr Ile Phe Phe Cys Glu Arg Asn Pro Lys 595 600 605 Pro Gln Val Ile Asn Ile Ile Asp Ala Asp Leu Pro Pro Asn Thr Ser 610 615 620 Pro Phe Thr Ala Glu Leu Thr His Gly Ala Ser Ala Asn Trp Thr Ile 625 630 635 640 Gln Tyr Asn Asp Pro Thr Gln Glu Ser Ile Ile Leu Lys Pro Lys Met 645 650 655 Ala Leu Glu Val Gly Asp Tyr Lys Ile Asn Leu Lys Leu Met Asp Asn 660 665 670 Gln Asn Lys Asp Gln Val Thr Thr Leu Glu Val Ser Val Cys Asp Cys 675 680 685 Glu Gly Ala Ala Gly Val Cys Arg Lys Ala Gln Pro Val Glu Ala Gly 690 695 700 Leu Gln Ile Pro Ala Ile Leu Gly Ile Leu Gly Gly Ile Leu Ala Leu 705 710 715 720 Leu Ile Leu Ile Leu Leu Leu Leu Leu Phe Leu Arg Arg Arg Ala Val 725 730 735 Val Lys Glu Pro Leu Leu Pro Pro Glu Asp Asp Thr Arg Asp Asn Val 740 745 750 Tyr Tyr Tyr Asp Glu Glu Gly Gly Gly Glu Glu Asp Gln Asp Phe Asp 755 760 765 Leu Ser Gln Leu His Arg Gly Leu Asp Ala Arg Pro Glu Val Thr Arg 770 775 780 Asn Asp Val Ala Pro Thr Leu Met Ser Val Pro Arg Tyr Leu Pro Arg 785 790 795 800 Pro Ala Asn Pro Asp Glu Ile Gly Asn Phe Ile Asp Glu Asn Leu Lys 805 810 815 Ala Ala Asp Thr Asp Pro Thr Ala Pro Pro Tyr Asp Ser Leu Leu Val 820 825 830 Phe Asp Tyr Glu Gly Ser Gly Ser Glu Ala Ala Ser Leu Ser Ser Leu 835 840 845 Asn Ser Ser Glu Ser Asp Lys Asp Gln Asp Tyr Asp Tyr Leu Asn Glu 850 855 860 Trp Gly Asn Arg Phe Lys Lys Leu Ala Asp Met Tyr Gly Gly Gly Glu 865 870 875 880 Asp Asp <210> 99 <211> 895 <212> PRT <213> Artificial Sequence <220> <223> DAG1_Human <400> 99 Met Arg Met Ser Val Gly Leu Ser Leu Leu Leu Pro Leu Ser Gly Arg 1 5 10 15 Thr Phe Leu Leu Leu Leu Ser Val Val Met Ala Gln Ser His Trp Pro 20 25 30 Ser Glu Pro Ser Glu Ala Val Arg Asp Trp Glu Asn Gln Leu Glu Ala 35 40 45 Ser Met His Ser Val Leu Ser Asp Leu His Glu Ala Val Pro Thr Val 50 55 60 Val Gly Ile Pro Asp Gly Thr Ala Val Val Gly Arg Ser Phe Arg Val 65 70 75 80 Thr Ile Pro Thr Asp Leu Ile Ala Ser Ser Gly Asp Ile Ile Lys Val 85 90 95 Ser Ala Ala Gly Lys Glu Ala Leu Pro Ser Trp Leu His Trp Asp Ser 100 105 110 Gln Ser His Thr Leu Glu Gly Leu Pro Leu Asp Thr Asp Lys Gly Val 115 120 125 His Tyr Ile Ser Val Ser Ala Thr Arg Leu Gly Ala Asn Gly Ser His 130 135 140 Ile Pro Gln Thr Ser Ser Val Phe Ser Ile Glu Val Tyr Pro Glu Asp 145 150 155 160 His Ser Glu Leu Gln Ser Val Arg Thr Ala Ser Pro Asp Pro Gly Glu 165 170 175 Val Val Ser Ser Ala Cys Ala Ala Asp Glu Pro Val Thr Val Leu Thr 180 185 190 Val Ile Leu Asp Ala Asp Leu Thr Lys Met Thr Pro Lys Gln Arg Ile 195 200 205 Asp Leu Leu His Arg Met Arg Ser Phe Ser Glu Val Glu Leu His Asn 210 215 220 Met Lys Leu Val Pro Val Val Asn Asn Arg Leu Phe Asp Met Ser Ala 225 230 235 240 Phe Met Ala Gly Pro Gly Asn Ala Lys Lys Val Val Glu Asn Gly Ala 245 250 255 Leu Leu Ser Trp Lys Leu Gly Cys Ser Leu Asn Gln Asn Ser Val Pro 260 265 270 Asp Ile His Gly Val Glu Ala Pro Ala Arg Glu Gly Ala Met Ser Ala 275 280 285 Gln Leu Gly Tyr Pro Val Val Gly Trp His Ile Ala Asn Lys Lys Pro 290 295 300 Pro Leu Pro Lys Arg Val Arg Arg Gln Ile His Ala Thr Pro Thr Pro 305 310 315 320 Val Thr Ala Ile Gly Pro Pro Thr Thr Ala Ile Gln Glu Pro Pro Ser 325 330 335 Arg Ile Val Pro Thr Pro Thr Ser Pro Ala Ile Ala Pro Pro Thr Glu 340 345 350 Thr Met Ala Pro Pro Val Arg Asp Pro Val Pro Gly Lys Pro Thr Val 355 360 365 Thr Ile Arg Thr Arg Gly Ala Ile Ile Gln Thr Pro Thr Leu Gly Pro 370 375 380 Ile Gln Pro Thr Arg Val Ser Glu Ala Gly Thr Thr Val Pro Gly Gln 385 390 395 400 Ile Arg Pro Thr Met Thr Ile Pro Gly Tyr Val Glu Pro Thr Ala Val 405 410 415 Ala Thr Pro Pro Thr Thr Thr Thr Lys Lys Pro Arg Val Ser Thr Pro 420 425 430 Lys Pro Ala Thr Pro Ser Thr Asp Ser Thr Thr Thr Thr Thr Arg Arg 435 440 445 Pro Thr Lys Lys Pro Arg Thr Pro Arg Pro Val Pro Arg Val Thr Thr 450 455 460 Lys Val Ser Ile Thr Arg Leu Glu Thr Ala Ser Pro Pro Thr Arg Ile 465 470 475 480 Arg Thr Thr Thr Ser Gly Val Pro Arg Gly Gly Glu Pro Asn Gln Arg 485 490 495 Pro Glu Leu Lys Asn His Ile Asp Arg Val Asp Ala Trp Val Gly Thr 500 505 510 Tyr Phe Glu Val Lys Ile Pro Ser Asp Thr Phe Tyr Asp His Glu Asp 515 520 525 Thr Thr Thr Asp Lys Leu Lys Leu Thr Leu Lys Leu Arg Glu Gln Gln 530 535 540 Leu Val Gly Glu Lys Ser Trp Val Gln Phe Asn Ser Asn Ser Gln Leu 545 550 555 560 Met Tyr Gly Leu Pro Asp Ser Ser His Val Gly Lys His Glu Tyr Phe 565 570 575 Met His Ala Thr Asp Lys Gly Gly Leu Ser Ala Val Asp Ala Phe Glu 580 585 590 Ile His Val His Arg Arg Pro Gln Gly Asp Arg Ala Pro Ala Arg Phe 595 600 605 Lys Ala Lys Phe Val Gly Asp Pro Ala Leu Val Leu Asn Asp Ile His 610 615 620 Lys Lys Ile Ala Leu Val Lys Lys Leu Ala Phe Ala Phe Gly Asp Arg 625 630 635 640 Asn Cys Ser Thr Ile Thr Leu Gln Asn Ile Thr Arg Gly Ser Ile Val 645 650 655 Val Glu Trp Thr Asn Asn Thr Leu Pro Leu Glu Pro Cys Pro Lys Glu 660 665 670 Gln Ile Ala Gly Leu Ser Arg Arg Ile Ala Glu Asp Asp Gly Lys Pro 675 680 685 Arg Pro Ala Phe Ser Asn Ala Leu Glu Pro Asp Phe Lys Ala Thr Ser 690 695 700 Ile Thr Val Thr Gly Ser Gly Ser Cys Arg His Leu Gln Phe Ile Pro 705 710 715 720 Val Val Pro Pro Arg Arg Val Pro Ser Glu Ala Pro Pro Thr Glu Val 725 730 735 Pro Asp Arg Asp Pro Glu Lys Ser Ser Glu Asp Asp Val Tyr Leu His 740 745 750 Thr Val Ile Pro Ala Val Val Val Ala Ala Ile Leu Leu Ile Ala Gly 755 760 765 Ile Ile Ala Met Ile Cys Tyr Arg Lys Lys Arg Lys Gly Lys Leu Thr 770 775 780 Leu Glu Asp Gln Ala Thr Phe Ile Lys Lys Gly Val Pro Ile Ile Phe 785 790 795 800 Ala Asp Glu Leu Asp Asp Ser Lys Pro Pro Pro Ser Ser Ser Met Pro 805 810 815 Leu Ile Leu Gln Glu Glu Lys Ala Pro Leu Pro Pro Pro Glu Tyr Pro 820 825 830 Asn Gln Ser Val Pro Glu Thr Thr Pro Leu Asn Gln Asp Thr Met Gly 835 840 845 Glu Tyr Thr Pro Leu Arg Asp Glu Asp Pro Asn Ala Pro Pro Tyr Gln 850 855 860 Pro Pro Pro Pro Phe Thr Ala Pro Met Glu Gly Lys Gly Ser Arg Pro 865 870 875 880 Lys Asn Met Thr Pro Tyr Arg Ser Pro Pro Pro Tyr Val Pro Pro 885 890 895 <210> 100 <211> 930 <212> PRT <213> artificial sequence <220> <223> ITIH4_ humans <400> 100 Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu Val Leu 1 5 10 15 Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys Asn Gly 20 25 30 Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser Arg Phe 35 40 45 Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn Thr Val 50 55 60 Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe Ile Thr 65 70 75 80 Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile Ile Lys 85 90 95 Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala Lys Gly 100 105 110 Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu Gln Phe 115 120 125 Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe Glu Leu 130 135 140 Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu Leu Leu 145 150 155 160 Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met Asp Ile 165 170 175 His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu Ser Thr 180 185 190 Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln Asn Lys 195 200 205 Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln Gln Lys 210 215 220 Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile Ile Arg 225 230 235 240 Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile Glu Asn 245 250 255 Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr Met Pro 260 265 270 Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser Gly Arg 275 280 285 Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp Asp Leu 290 295 300 Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu Ala Thr 305 310 315 320 Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val Asn Lys 325 330 335 Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr Asn Ile 340 345 350 Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser Asn Gln 355 360 365 Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu Leu Thr 370 375 380 Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile Gln Asn 385 390 395 400 Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys Leu Gly 405 410 415 Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala Leu Asp 420 425 430 Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser Ala Leu 435 440 445 Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu Thr Ala 450 455 460 Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr Gln Asn 465 470 475 480 Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala Gly Lys 485 490 495 Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser Gly Lys 500 505 510 Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val Ala Glu 515 520 525 Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn Phe Met 530 535 540 Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu Gln Thr 545 550 555 560 Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln Ala Leu 565 570 575 Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser Met Val 580 585 590 Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu Lys Pro 595 600 605 Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Gly Ser Thr Phe 610 615 620 Phe Lys Tyr Tyr Leu Gln Gly Ala Lys Ile Pro Lys Pro Glu Ala Ser 625 630 635 640 Phe Ser Pro Arg Arg Gly Trp Asn Arg Gln Ala Gly Ala Ala Gly Ser 645 650 655 Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg Gln Leu Gly Leu 660 665 670 Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr His Pro Phe Arg 675 680 685 Arg Leu Ala Ile Leu Pro Ala Ser Ala Pro Pro Ala Thr Ser Asn Pro 690 695 700 Asp Pro Ala Val Ser Arg Val Met Asn Met Lys Ile Glu Glu Thr Thr 705 710 715 720 Met Thr Thr Gln Thr Pro Ala Pro Ile Gln Ala Pro Ser Ala Ile Leu 725 730 735 Pro Leu Pro Gly Gln Ser Val Glu Arg Leu Cys Val Asp Pro Arg His 740 745 750 Arg Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu Gln Gly Val Glu 755 760 765 Val Thr Gly Gln Tyr Glu Arg Glu Lys Ala Gly Phe Ser Trp Ile Glu 770 775 780 Val Thr Phe Lys Asn Pro Leu Val Trp Val His Ala Ser Pro Glu His 785 790 795 800 Val Val Val Thr Arg Asn Arg Arg Ser Ser Ala Tyr Lys Trp Lys Glu 805 810 815 Thr Leu Phe Ser Val Met Pro Gly Leu Lys Met Thr Met Asp Lys Thr 820 825 830 Gly Leu Leu Leu Leu Ser Asp Pro Asp Lys Val Thr Ile Gly Leu Leu 835 840 845 Phe Trp Asp Gly Arg Gly Glu Gly Leu Arg Leu Leu Leu Arg Asp Thr 850 855 860 Asp Arg Phe Ser Ser His Val Gly Gly Thr Leu Gly Gln Phe Tyr Gln 865 870 875 880 Glu Val Leu Trp Gly Ser Pro Ala Ala Ser Asp Asp Gly Arg Arg Thr 885 890 895 Leu Arg Val Gln Gly Asn Asp His Ser Ala Thr Arg Glu Arg Arg Leu 900 905 910 Asp Tyr Gln Glu Gly Pro Pro Gly Val Glu Ile Ser Cys Trp Ser Val 915 920 925 Glu Leu 930 <210> 101 <211> 946 <212> PRT <213> Artificial Sequence <220> <223> ITIH2_Human <400> 101 Met Lys Arg Leu Thr Cys Phe Phe Ile Cys Phe Phe Leu Ser Glu Val 1 5 10 15 Ser Gly Phe Glu Ile Pro Ile Asn Gly Leu Ser Glu Phe Val Asp Tyr 20 25 30 Glu Asp Leu Val Glu Leu Ala Pro Gly Lys Phe Gln Leu Val Ala Glu 35 40 45 Asn Arg Arg Tyr Gln Arg Ser Leu Pro Gly Glu Ser Glu Glu Met Met 50 55 60 Glu Glu Val Asp Gln Val Thr Leu Tyr Ser Tyr Lys Val Gln Ser Thr 65 70 75 80 Ile Thr Ser Arg Met Ala Thr Thr Met Ile Gln Ser Lys Val Val Asn 85 90 95 Asn Ser Pro Gln Pro Gln Asn Val Val Phe Asp Val Gln Ile Pro Lys 100 105 110 Gly Ala Phe Ile Ser Asn Phe Ser Met Thr Val Asp Gly Lys Thr Phe 115 120 125 Arg Ser Ser Ile Lys Glu Lys Thr Val Gly Arg Ala Leu Tyr Ala Gln 130 135 140 Ala Arg Ala Lys Gly Lys Thr Ala Gly Leu Val Arg Ser Ser Ala Leu 145 150 155 160 Asp Met Glu Asn Phe Arg Thr Glu Val Asn Val Leu Pro Gly Ala Lys 165 170 175 Val Gln Phe Glu Leu His Tyr Gln Glu Val Lys Trp Arg Lys Leu Gly 180 185 190 Ser Tyr Glu His Arg Ile Tyr Leu Gln Pro Gly Arg Leu Ala Lys His 195 200 205 Leu Glu Val Asp Val Trp Val Ile Glu Pro Gln Gly Leu Arg Phe Leu 210 215 220 His Val Pro Asp Thr Phe Glu Gly His Phe Asp Gly Val Pro Val Ile 225 230 235 240 Ser Lys Gly Gln Gln Lys Ala His Val Ser Phe Lys Pro Thr Val Ala 245 250 255 Gln Gln Arg Ile Cys Pro Asn Cys Arg Glu Thr Ala Val Asp Gly Glu 260 265 270 Leu Val Val Leu Tyr Asp Val Lys Arg Glu Glu Lys Ala Gly Glu Leu 275 280 285 Glu Val Phe Asn Gly Tyr Phe Val His Phe Phe Ala Pro Asp Asn Leu 290 295 300 Asp Pro Ile Pro Lys Asn Ile Leu Phe Val Ile Asp Val Ser Gly Ser 305 310 315 320 Met Trp Gly Val Lys Met Lys Gln Thr Val Glu Ala Met Lys Thr Ile 325 330 335 Leu Asp Asp Leu Arg Ala Glu Asp His Phe Ser Val Ile Asp Phe Asn 340 345 350 Gln Asn Ile Arg Thr Trp Arg Asn Asp Leu Ile Ser Ala Thr Lys Thr 355 360 365 Gln Val Ala Asp Ala Lys Arg Tyr Ile Glu Lys Ile Gln Pro Ser Gly 370 375 380 Gly Thr Asn Ile Asn Glu Ala Leu Leu Arg Ala Ile Phe Ile Leu Asn 385 390 395 400 Glu Ala Asn Asn Leu Gly Leu Leu Asp Pro Asn Ser Val Ser Leu Ile 405 410 415 Ile Leu Val Ser Asp Gly Asp Pro Thr Val Gly Glu Leu Lys Leu Ser 420 425 430 Lys Ile Gln Lys Asn Val Lys Glu Asn Ile Gln Asp Asn Ile Ser Leu 435 440 445 Phe Ser Leu Gly Met Gly Phe Asp Val Asp Tyr Asp Phe Leu Lys Arg 450 455 460 Leu Ser Asn Glu Asn His Gly Ile Ala Gln Arg Ile Tyr Gly Asn Gln 465 470 475 480 Asp Thr Ser Ser Gln Leu Lys Lys Phe Tyr Asn Gln Val Ser Thr Pro 485 490 495 Leu Leu Arg Asn Val Gln Phe Asn Tyr Pro His Thr Ser Val Thr Asp 500 505 510 Val Thr Gln Asn Asn Phe His Asn Tyr Phe Gly Gly Ser Glu Ile Val 515 520 525 Val Ala Gly Lys Phe Asp Pro Ala Lys Leu Asp Gln Ile Glu Ser Val 530 535 540 Ile Thr Ala Thr Ser Ala Asn Thr Gln Leu Val Leu Glu Thr Leu Ala 545 550 555 560 Gln Met Asp Asp Leu Gln Asp Phe Leu Ser Lys Asp Lys His Ala Asp 565 570 575 Pro Asp Phe Thr Arg Lys Leu Trp Ala Tyr Leu Thr Ile Asn Gln Leu 580 585 590 Leu Ala Glu Arg Ser Leu Ala Pro Thr Ala Ala Ala Lys Arg Arg Ile 595 600 605 Thr Arg Ser Ile Leu Gln Met Ser Leu Asp His His Ile Val Thr Pro 610 615 620 Leu Thr Ser Leu Val Ile Glu Asn Glu Ala Gly Asp Glu Arg Met Leu 625 630 635 640 Ala Asp Ala Pro Pro Gln Asp Pro Ser Cys Cys Ser Gly Ala Leu Tyr 645 650 655 Tyr Gly Ser Lys Val Val Pro Asp Ser Thr Pro Ser Trp Ala Asn Pro 660 665 670 Ser Pro Thr Pro Val Ile Ser Met Leu Ala Gln Gly Ser Gln Val Leu 675 680 685 Glu Ser Thr Pro Pro Pro His Val Met Arg Val Glu Asn Asp Pro His 690 695 700 Phe Ile Ile Tyr Leu Pro Lys Ser Gln Lys Asn Ile Cys Phe Asn Ile 705 710 715 720 Asp Ser Glu Pro Gly Lys Ile Leu Asn Leu Val Ser Asp Pro Glu Ser 725 730 735 Gly Ile Val Val Asn Gly Gln Leu Val Gly Ala Lys Lys Pro Asn Asn 740 745 750 Gly Lys Leu Ser Thr Tyr Phe Gly Lys Leu Gly Phe Tyr Phe Gln Ser 755 760 765 Glu Asp Ile Lys Ile Glu Ile Ser Thr Glu Thr Ile Thr Leu Ser His 770 775 780 Gly Ser Ser Thr Phe Ser Leu Ser Trp Ser Asp Thr Ala Gln Val Thr 785 790 795 800 Asn Gln Arg Val Gln Ile Ser Val Lys Lys Glu Lys Val Val Thr Ile 805 810 815 Thr Leu Asp Lys Glu Met Ser Phe Ser Val Leu Leu His Arg Val Trp 820 825 830 Lys Lys His Pro Val Asn Val Asp Phe Leu Gly Ile Tyr Ile Pro Pro 835 840 845 Thr Asn Lys Phe Ser Pro Lys Ala His Gly Leu Ile Gly Gln Phe Met 850 855 860 Gln Glu Pro Lys Ile His Ile Phe Asn Glu Arg Pro Gly Lys Asp Pro 865 870 875 880 Glu Lys Pro Glu Ala Ser Met Glu Val Lys Gly Gln Lys Leu Ile Ile 885 890 895 Thr Arg Gly Leu Gln Lys Asp Tyr Arg Thr Asp Leu Val Phe Gly Thr 900 905 910 Asp Val Thr Cys Trp Phe Val His Asn Ser Gly Lys Gly Phe Ile Asp 915 920 925 Gly His Tyr Lys Asp Tyr Phe Val Pro Gln Leu Tyr Ser Phe Leu Lys 930 935 940 Arg Pro 945 <210> 102 <211> 953 <212> PRT <213> Artificial Sequence <220> <223> TRAK1_Human <400> 102 Met Ala Leu Val Phe Gln Phe Gly Gln Pro Val Arg Ala Gln Pro Leu 1 5 10 15 Pro Gly Leu Cys His Gly Lys Leu Ile Arg Thr Asn Ala Cys Asp Val 20 25 30 Cys Asn Ser Thr Asp Leu Pro Glu Val Glu Ile Ile Ser Leu Leu Glu 35 40 45 Glu Gln Leu Pro His Tyr Lys Leu Arg Ala Asp Thr Ile Tyr Gly Tyr 50 55 60 Asp His Asp Asp Trp Leu His Thr Pro Leu Ile Ser Pro Asp Ala Asn 65 70 75 80 Ile Asp Leu Thr Thr Glu Gln Ile Glu Glu Thr Leu Lys Tyr Phe Leu 85 90 95 Leu Cys Ala Glu Arg Val Gly Gln Met Thr Lys Thr Tyr Asn Asp Ile 100 105 110 Asp Ala Val Thr Arg Leu Leu Glu Glu Lys Glu Arg Asp Leu Glu Leu 115 120 125 Ala Ala Arg Ile Gly Gln Ser Leu Leu Lys Lys Asn Lys Thr Leu Thr 130 135 140 Glu Arg Asn Glu Leu Leu Glu Glu Gln Val Glu His Ile Arg Glu Glu 145 150 155 160 Val Ser Gln Leu Arg His Glu Leu Ser Met Lys Asp Glu Leu Leu Gln 165 170 175 Phe Tyr Thr Ser Ala Ala Glu Glu Ser Glu Pro Glu Ser Val Cys Ser 180 185 190 Thr Pro Leu Lys Arg Asn Glu Ser Ser Ser Ser Val Gln Asn Tyr Phe 195 200 205 His Leu Asp Ser Leu Gln Lys Lys Leu Lys Asp Leu Glu Glu Glu Asn 210 215 220 Val Val Leu Arg Ser Glu Ala Ser Gln Leu Lys Thr Glu Thr Ile Thr 225 230 235 240 Tyr Glu Glu Lys Glu Gln Gln Leu Val Asn Asp Cys Val Lys Glu Leu 245 250 255 Arg Asp Ala Asn Val Gln Ile Ala Ser Ile Ser Glu Glu Leu Ala Lys 260 265 270 Lys Thr Glu Asp Ala Ala Arg Gln Gln Glu Glu Ile Thr His Leu Leu 275 280 285 Ser Gln Ile Val Asp Leu Gln Lys Lys Ala Lys Ala Cys Ala Val Glu 290 295 300 Asn Glu Glu Leu Val Gln His Leu Gly Ala Ala Lys Asp Ala Gln Arg 305 310 315 320 Gln Leu Thr Ala Glu Leu Arg Glu Leu Glu Asp Lys Tyr Ala Glu Cys 325 330 335 Met Glu Met Leu His Glu Ala Gln Glu Glu Leu Lys Asn Leu Arg Asn 340 345 350 Lys Thr Met Pro Asn Thr Thr Ser Arg Arg Tyr His Ser Leu Gly Leu 355 360 365 Phe Pro Met Asp Ser Leu Ala Ala Glu Ile Glu Gly Thr Met Arg Lys 370 375 380 Glu Leu Gln Leu Glu Glu Ala Glu Ser Pro Asp Ile Thr His Gln Lys 385 390 395 400 Arg Val Phe Glu Thr Val Arg Asn Ile Asn Gln Val Val Lys Gln Arg 405 410 415 Ser Leu Thr Pro Ser Pro Met Asn Ile Pro Gly Ser Asn Gln Ser Ser 420 425 430 Ala Met Asn Ser Leu Leu Ser Ser Cys Val Ser Thr Pro Arg Ser Ser 435 440 445 Phe Tyr Gly Ser Asp Ile Gly Asn Val Val Leu Asp Asn Lys Thr Asn 450 455 460 Ser Ile Ile Leu Glu Thr Glu Ala Ala Asp Leu Gly Asn Asp Glu Arg 465 470 475 480 Ser Lys Lys Pro Gly Thr Pro Gly Thr Pro Gly Ser His Asp Leu Glu 485 490 495 Thr Ala Leu Arg Arg Leu Ser Leu Arg Arg Glu Asn Tyr Leu Ser Glu 500 505 510 Arg Arg Phe Phe Glu Glu Glu Gln Glu Arg Lys Leu Gln Glu Leu Ala 515 520 525 Glu Lys Gly Glu Leu Arg Ser Gly Ser Leu Thr Pro Thr Glu Ser Ile 530 535 540 Met Ser Leu Gly Thr His Ser Arg Phe Ser Glu Phe Thr Gly Phe Ser 545 550 555 560 Gly Met Ser Phe Ser Ser Arg Ser Tyr Leu Pro Glu Lys Leu Gln Ile 565 570 575 Val Lys Pro Leu Glu Gly Ser Ala Thr Leu His His Trp Gln Gln Leu 580 585 590 Ala Gln Pro His Leu Gly Gly Ile Leu Asp Pro Arg Pro Gly Val Val 595 600 605 Thr Lys Gly Phe Arg Thr Leu Asp Val Asp Leu Asp Glu Val Tyr Cys 610 615 620 Leu Asn Asp Phe Glu Glu Asp Asp Thr Gly Asp His Ile Ser Leu Pro 625 630 635 640 Arg Leu Ala Thr Ser Thr Pro Val Gln His Pro Glu Thr Ser Ala His 645 650 655 His Pro Gly Lys Cys Met Ser Gln Thr Asn Ser Thr Phe Thr Phe Thr 660 665 670 Thr Cys Arg Ile Leu His Pro Ser Asp Glu Leu Thr Arg Val Thr Pro 675 680 685 Ser Leu Asn Ser Ala Pro Thr Pro Ala Cys Gly Ser Thr Ser His Leu 690 695 700 Lys Ser Thr Pro Val Ala Thr Pro Cys Thr Pro Arg Arg Leu Ser Leu 705 710 715 720 Ala Glu Ser Phe Thr Asn Thr Arg Glu Ser Thr Thr Thr Met Ser Thr 725 730 735 Ser Leu Gly Leu Val Trp Leu Leu Lys Glu Arg Gly Ile Ser Ala Ala 740 745 750 Val Tyr Asp Pro Gln Ser Trp Asp Arg Ala Gly Arg Gly Ser Leu Leu 755 760 765 His Ser Tyr Thr Pro Lys Met Ala Val Ile Pro Ser Thr Pro Pro Asn 770 775 780 Ser Pro Met Gln Thr Pro Thr Ser Ser Pro Pro Ser Phe Glu Phe Lys 785 790 795 800 Cys Thr Ser Pro Pro Tyr Asp Asn Phe Leu Ala Ser Lys Pro Ala Ser 805 810 815 Ser Ile Leu Arg Glu Val Arg Glu Lys Asn Val Arg Ser Ser Glu Ser 820 825 830 Gln Thr Asp Val Ser Val Ser Asn Leu Asn Leu Val Asp Lys Val Arg 835 840 845 Arg Phe Gly Val Ala Lys Val Val Asn Ser Gly Arg Ala His Val Pro 850 855 860 Thr Leu Thr Glu Glu Gln Gly Pro Leu Leu Cys Gly Pro Pro Gly Pro 865 870 875 880 Ala Pro Ala Leu Val Pro Arg Gly Leu Val Pro Glu Gly Leu Pro Leu 885 890 895 Arg Cys Pro Thr Val Thr Ser Ala Ile Gly Gly Leu Gln Leu Asn Ser 900 905 910 Gly Ile Arg Arg Asn Arg Ser Phe Pro Thr Met Val Gly Ser Ser Met 915 920 925 Gln Met Lys Ala Pro Val Thr Leu Thr Ser Gly Ile Leu Met Gly Ala 930 935 940 Lys Leu Ser Lys Gln Thr Ser Leu Arg 945 950 <210> 103 <211> 1255 <212> PRT <213> artificial sequence <220> <223> MUC1_ humans <400> 103 Met Thr Pro Gly Thr Gln Ser Pro Phe Phe Leu Leu Leu Leu Leu Thr 1 5 10 15 Val Leu Thr Val Val Thr Gly Ser Gly His Ala Ser Ser Thr Pro Gly 20 25 30 Gly Glu Lys Glu Thr Ser Ala Thr Gln Arg Ser Ser Val Pro Ser Ser 35 40 45 Thr Glu Lys Asn Ala Val Ser Met Thr Ser Ser Val Leu Ser Ser His 50 55 60 Ser Pro Gly Ser Gly Ser Ser Thr Thr Gln Gly Gln Asp Val Thr Leu 65 70 75 80 Ala Pro Ala Thr Glu Pro Ala Ser Gly Ser Ala Ala Thr Trp Gly Gln 85 90 95 Asp Val Thr Ser Val Pro Val Thr Arg Pro Ala Leu Gly Ser Thr Thr 100 105 110 Pro Pro Ala His Asp Val Thr Ser Ala Pro Asp Asn Lys Pro Ala Pro 115 120 125 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr 130 135 140 Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser 145 150 155 160 Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His 165 170 175 Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala 180 185 190 Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro 195 200 205 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr 210 215 220 Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser 225 230 235 240 Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His 245 250 255 Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala 260 265 270 Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro 275 280 285 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr 290 295 300 Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser 305 310 315 320 Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His 325 330 335 Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala 340 345 350 Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro 355 360 365 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr 370 375 380 Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser 385 390 395 400 Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His 405 410 415 Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala 420 425 430 Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro 435 440 445 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr 450 455 460 Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser 465 470 475 480 Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His 485 490 495 Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala 500 505 510 Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro 515 520 525 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr 530 535 540 Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser 545 550 555 560 Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His 565 570 575 Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala 580 585 590 Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro 595 600 605 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr 610 615 620 Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser 625 630 635 640 Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His 645 650 655 Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala 660 665 670 Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro 675 680 685 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr 690 695 700 Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser 705 710 715 720 Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His 725 730 735 Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala 740 745 750 Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro 755 760 765 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr 770 775 780 Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser 785 790 795 800 Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His 805 810 815 Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala 820 825 830 Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro 835 840 845 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr 850 855 860 Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser 865 870 875 880 Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala Pro Pro Ala His 885 890 895 Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro Gly Ser Thr Ala 900 905 910 Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Thr Arg Pro Ala Pro 915 920 925 Gly Ser Thr Ala Pro Pro Ala His Gly Val Thr Ser Ala Pro Asp Asn 930 935 940 Arg Pro Ala Leu Gly Ser Thr Ala Pro Pro Val His Asn Val Thr Ser 945 950 955 960 Ala Ser Gly Ser Ala Ser Gly Ser Ala Ser Thr Leu Val His Asn Gly 965 970 975 Thr Ser Ala Arg Ala Thr Thr Thr Pro Ala Ser Lys Ser Thr Pro Phe 980 985 990 Ser Ile Pro Ser His His Ser Asp Thr Pro Thr Thr Leu Ala Ser His 995 1000 1005 Ser Thr Lys Thr Asp Ala Ser Ser Thr His His Ser Ser Val Pro Pro 1010 1015 1020 Leu Thr Ser Ser Asn His Ser Thr Ser Pro Gln Leu Ser Thr Gly Val 1025 1030 1035 1040 Ser Phe Phe Phe Leu Ser Phe His Ile Ser Asn Leu Gln Phe Asn Ser 1045 1050 1055 Ser Leu Glu Asp Pro Ser Thr Asp Tyr Tyr Gln Glu Leu Gln Arg Asp 1060 1065 1070 Ile Ser Glu Met Phe Leu Gln Ile Tyr Lys Gln Gly Gly Phe Leu Gly 1075 1080 1085 Leu Ser Asn Ile Lys Phe Arg Pro Gly Ser Val Val Val Gln Leu Thr 1090 1095 1100 Leu Ala Phe Arg Glu Gly Thr Ile Asn Val His Asp Val Glu Thr Gln 1105 1110 1115 1120 Phe Asn Gln Tyr Lys Thr Glu Ala Ala Ser Arg Tyr Asn Leu Thr Ile 1125 1130 1135 Ser Asp Val Ser Val Ser Asp Val Pro Phe Pro Phe Ser Ala Gln Ser 1140 1145 1150 Gly Ala Gly Val Pro Gly Trp Gly Ile Ala Leu Leu Val Leu Val Cys 1155 1160 1165 Val Leu Val Ala Leu Ala Ile Val Tyr Leu Ile Ala Leu Ala Val Cys 1170 1175 1180 Gln Cys Arg Arg Lys Asn Tyr Gly Gln Leu Asp Ile Phe Pro Ala Arg 1185 1190 1195 1200 Asp Thr Tyr His Pro Met Ser Glu Tyr Pro Thr Tyr His Thr His Gly 1205 1210 1215 Arg Tyr Val Pro Pro Ser Ser Thr Asp Arg Ser Pro Tyr Glu Lys Val 1220 1225 1230 Ser Ala Gly Asn Gly Gly Ser Ser Leu Ser Tyr Thr Asn Pro Ala Val 1235 1240 1245 Ala Ala Thr Ser Ala Asn Leu 1250 1255 <210> 104 <211> 1322 <212> PRT <213> artificial sequence <220> <223> EMSY_ human beings <400> 104 Met Pro Val Val Trp Pro Thr Leu Leu Asp Leu Ser Arg Asp Glu Cys 1 5 10 15 Lys Arg Ile Leu Arg Lys Leu Glu Leu Glu Ala Tyr Ala Gly Val Ile 20 25 30 Ser Ala Leu Arg Ala Gln Gly Asp Leu Thr Lys Glu Lys Lys Asp Leu 35 40 45 Leu Gly Glu Leu Ser Lys Val Leu Ser Ile Ser Thr Glu Arg His Arg 50 55 60 Ala Glu Val Arg Arg Ala Val Asn Asp Glu Arg Leu Thr Thr Ile Ala 65 70 75 80 His Asn Met Ser Gly Pro Asn Ser Ser Ser Glu Trp Ser Ile Glu Gly 85 90 95 Arg Arg Leu Val Pro Leu Met Pro Arg Leu Val Pro Gln Thr Ala Phe 100 105 110 Thr Val Thr Ala Asn Ala Val Ala Asn Ala Ala Ile Gln His Asn Ala 115 120 125 Ser Leu Pro Val Pro Ala Glu Thr Gly Ser Lys Glu Val Val Cys Tyr 130 135 140 Ser Tyr Thr Ser Thr Thr Ser Thr Pro Thr Ser Thr Pro Val Pro Ser 145 150 155 160 Gly Ser Ile Ala Thr Val Lys Ser Pro Arg Pro Ala Ser Pro Ala Ser 165 170 175 Asn Val Val Val Leu Pro Ser Gly Ser Thr Val Tyr Val Lys Ser Val 180 185 190 Ser Cys Ser Asp Glu Asp Glu Lys Pro Arg Lys Arg Arg Arg Thr Asn 195 200 205 Ser Ser Ser Ser Pro Val Val Leu Lys Glu Val Pro Lys Ala Val 210 215 220 Val Pro Val Ser Lys Thr Ile Thr Val Pro Val Ser Gly Ser Pro Lys 225 230 235 240 Met Ser Asn Ile Met Gln Ser Ile Ala Asn Ser Leu Pro Pro His Met 245 250 255 Ser Pro Val Lys Ile Thr Phe Thr Lys Pro Ser Thr Gln Thr Thr Asn 260 265 270 Thr Thr Thr Gln Lys Val Ile Ile Val Thr Thr Ser Pro Ser Ser Thr 275 280 285 Phe Val Pro Asn Ile Leu Ser Lys Ser His Asn Tyr Ala Ala Val Thr 290 295 300 Lys Leu Val Pro Thr Ser Val Ile Ala Ser Thr Thr Gln Lys Pro Pro 305 310 315 320 Val Val Ile Thr Ala Ser Gln Ser Ser Leu Val Ser Asn Ser Ser Ser 325 330 335 Gly Ser Ser Ser Ser Thr Pro Ser Pro Ile Pro Asn Thr Val Ala Val 340 345 350 Thr Ala Val Val Ser Ser Thr Pro Ser Val Val Met Ser Thr Val Ala 355 360 365 Gln Gly Val Ser Thr Ser Ala Ile Lys Met Ala Ser Thr Arg Leu Pro 370 375 380 Ser Pro Lys Ser Leu Val Ser Ala Pro Thr Gln Ile Leu Ala Gln Phe 385 390 395 400 Pro Lys Gln His Gln Gln Ser Pro Lys Gln Gln Leu Tyr Gln Val Gln 405 410 415 Gln Gln Thr Gln Gln Gln Val Ala Gln Pro Ser Pro Val Ser His Gln 420 425 430 Gln Gln Pro Gln Gln Ser Pro Leu Pro Pro Gly Ile Lys Pro Thr Ile 435 440 445 Gln Ile Lys Gln Glu Ser Gly Val Lys Ile Ile Thr Gln Gln Val Gln 450 455 460 Pro Ser Lys Ile Leu Pro Lys Pro Val Thr Ala Thr Leu Pro Thr Ser 465 470 475 480 Ser Asn Ser Pro Ile Met Val Val Ser Ser Asn Gly Ala Ile Met Thr 485 490 495 Thr Lys Leu Val Thr Thr Pro Thr Gly Thr Gln Ala Thr Tyr Thr Arg 500 505 510 Pro Thr Val Ser Pro Ser Ile Gly Arg Met Ala Ala Thr Pro Gly Ala 515 520 525 Ala Thr Tyr Val Lys Thr Thr Ser Gly Ser Ile Ile Thr Val Val Pro 530 535 540 Lys Ser Leu Ala Thr Leu Gly Gly Lys Ile Ile Ser Ser Asn Ile Val 545 550 555 560 Ser Gly Thr Thr Thr Lys Ile Thr Thr Ile Pro Met Thr Ser Lys Pro 565 570 575 Asn Val Ile Val Val Gln Lys Thr Thr Gly Lys Gly Thr Thr Ile Gln 580 585 590 Gly Leu Pro Gly Lys Asn Val Val Thr Thr Leu Leu Asn Ala Gly Gly 595 600 605 Glu Lys Thr Ile Gln Thr Val Pro Thr Gly Ala Lys Pro Ala Ile Leu 610 615 620 Thr Ala Thr Arg Pro Ile Thr Lys Met Ile Val Thr Gln Pro Lys Gly 625 630 635 640 Ile Gly Ser Thr Val Gln Pro Ala Ala Lys Ile Ile Pro Thr Lys Ile 645 650 655 Val Tyr Gly Gln Gln Gly Lys Thr Gln Val Leu Ile Lys Pro Lys Pro 660 665 670 Val Thr Phe Gln Ala Thr Val Val Ser Glu Gln Thr Arg Gln Leu Val 675 680 685 Thr Glu Thr Leu Gln Gln Ala Ser Arg Val Ala Glu Ala Gly Asn Ser 690 695 700 Ser Ile Gln Glu Gly Lys Glu Glu Pro Gln Asn Tyr Thr Asp Ser Ser 705 710 715 720 Ser Ser Ser Thr Glu Ser Ser Gln Ser Ser Gln Asp Ser Gln Pro Val 725 730 735 Val His Val Ile Ala Ser Arg Arg Gln Asp Trp Ser Glu His Glu Ile 740 745 750 Ala Met Glu Thr Ser Pro Thr Ile Ile Tyr Gln Asp Val Ser Ser Glu 755 760 765 Ser Gln Ser Ala Thr Ser Thr Ile Lys Ala Leu Leu Glu Leu Gln Gln 770 775 780 Thr Thr Val Lys Glu Lys Leu Glu Ser Lys Pro Arg Gln Pro Thr Ile 785 790 795 800 Asp Leu Ser Gln Met Ala Val Pro Ile Gln Met Thr Gln Glu Lys Arg 805 810 815 His Ser Pro Glu Ser Pro Ser Ile Ala Val Val Glu Ser Glu Leu Val 820 825 830 Ala Glu Tyr Ile Thr Thr Glu Arg Thr Asp Glu Gly Thr Glu Val Ala 835 840 845 Phe Pro Leu Leu Val Ser His Arg Ser Gln Pro Gln Gln Pro Ser Gln 850 855 860 Pro Gln Arg Thr Leu Leu Gln His Val Ala Gln Ser Gln Thr Ala Thr 865 870 875 880 Gln Thr Ser Val Val Val Lys Ser Ile Pro Ala Ser Ser Pro Gly Ala 885 890 895 Ile Thr His Ile Met Gln Gln Ala Leu Ser Ser His Thr Ala Phe Thr 900 905 910 Lys His Ser Glu Glu Leu Gly Thr Glu Glu Gly Glu Val Glu Glu Met 915 920 925 Asp Thr Leu Asp Pro Gln Thr Gly Leu Phe Tyr Arg Ser Ala Leu Thr 930 935 940 Gln Ser Gln Ser Ala Lys Gln Gln Lys Leu Ser Gln Pro Pro Leu Glu 945 950 955 960 Gln Thr Gln Leu Gln Val Lys Thr Leu Gln Cys Phe Gln Thr Lys Gln 965 970 975 Lys Gln Thr Ile His Leu Gln Ala Asp Gln Leu Gln His Lys Leu Pro 980 985 990 Gln Met Pro Gln Leu Ser Ile Arg His Gln Lys Leu Thr Pro Leu Gln 995 1000 1005 Gln Glu Gln Ala Gln Pro Lys Pro Asp Val Gln His Thr Gln His Pro 1010 1015 1020 Met Val Ala Lys Asp Arg Gln Leu Pro Thr Leu Met Ala Gln Pro Pro 1025 1030 1035 1040 Gln Thr Val Val Gln Val Leu Ala Val Lys Thr Thr Gln Gln Leu Pro 1045 1050 1055 Lys Leu Gln Gln Ala Pro Asn Gln Pro Lys Ile Tyr Val Gln Pro Gln 1060 1065 1070 Thr Pro Gln Ser Gln Met Ser Leu Pro Ala Ser Ser Glu Lys Gln Thr 1075 1080 1085 Ala Ser Gln Val Glu Gln Pro Ile Ile Thr Gln Gly Ser Ser Val Thr 1090 1095 1100 Lys Ile Thr Phe Glu Gly Arg Gln Pro Pro Thr Val Thr Lys Ile Thr 1105 1110 1115 1120 Gly Gly Ser Ser Val Pro Lys Leu Thr Ser Pro Val Thr Ser Ile Ser 1125 1130 1135 Pro Ile Gln Ala Ser Glu Lys Thr Ala Val Ser Asp Ile Leu Lys Met 1140 1145 1150 Ser Leu Met Glu Ala Gln Ile Asp Thr Asn Val Glu His Met Ile Val 1155 1160 1165 Asp Pro Pro Lys Lys Ala Leu Ala Thr Ser Met Leu Thr Gly Glu Ala 1170 1175 1180 Gly Ser Leu Pro Ser Thr His Met Val Val Ala Gly Met Ala Asn Ser 1185 1190 1195 1200 Thr Pro Gln Gln Gln Lys Cys Arg Glu Ser Cys Ser Ser Pro Ser Thr 1205 1210 1215 Val Gly Ser Ser Leu Thr Thr Arg Lys Ile Asp Pro Pro Ala Val Pro 1220 1225 1230 Ala Thr Gly Gln Phe Met Arg Ile Gln Asn Val Gly Gln Lys Lys Ala 1235 1240 1245 Glu Glu Ser Pro Ala Glu Ile Ile Ile Gln Ala Ile Pro Gln Tyr Ala 1250 1255 1260 Ile Pro Cys His Ser Ser Ser Asn Val Val Val Glu Pro Ser Gly Leu 1265 1270 1275 1280 Leu Glu Leu Asn Asn Phe Thr Ser Gln Gln Leu Asp Asp Glu Glu Thr 1285 1290 1295 Ala Met Glu Gln Asp Ile Asp Ser Ser Thr Glu Asp Gly Thr Glu Pro 1300 1305 1310 Ser Pro Ser Gln Ser Ser Ala Glu Arg Ser 1315 1320 <210> 105 <211> 1404 <212> PRT <213> artificial sequence <220> <223> PRG4_ humans <400> 105 Met Ala Trp Lys Thr Leu Pro Ile Tyr Leu Leu Leu Leu Leu Ser Val 1 5 10 15 Phe Val Ile Gln Gln Val Ser Ser Gln Asp Leu Ser Ser Cys Ala Gly 20 25 30 Arg Cys Gly Glu Gly Tyr Ser Arg Asp Ala Thr Cys Asn Cys Asp Tyr 35 40 45 Asn Cys Gln His Tyr Met Glu Cys Cys Pro Asp Phe Lys Arg Val Cys 50 55 60 Thr Ala Glu Leu Ser Cys Lys Gly Arg Cys Phe Glu Ser Phe Glu Arg 65 70 75 80 Gly Arg Glu Cys Asp Cys Asp Ala Gln Cys Lys Lys Tyr Asp Lys Cys 85 90 95 Cys Pro Asp Tyr Glu Ser Phe Cys Ala Glu Val His Asn Pro Thr Ser 100 105 110 Pro Pro Ser Ser Lys Lys Ala Pro Pro Pro Ser Gly Ala Ser Gln Thr 115 120 125 Ile Lys Ser Thr Thr Lys Arg Ser Pro Lys Pro Pro Asn Lys Lys Lys 130 135 140 Thr Lys Lys Val Ile Glu Ser Glu Glu Ile Thr Glu Glu His Ser Val 145 150 155 160 Ser Glu Asn Gln Glu Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser 165 170 175 Ser Thr Ile Arg Lys Ile Lys Ser Ser Lys Asn Ser Ala Ala Asn Arg 180 185 190 Glu Leu Gln Lys Lys Leu Lys Val Lys Asp Asn Lys Lys Asn Arg Thr 195 200 205 Lys Lys Lys Pro Thr Pro Lys Pro Pro Val Val Asp Glu Ala Gly Ser 210 215 220 Gly Leu Asp Asn Gly Asp Phe Lys Val Thr Thr Pro Asp Thr Ser Thr 225 230 235 240 Thr Gln His Asn Lys Val Ser Thr Ser Pro Lys Ile Thr Thr Ala Lys 245 250 255 Pro Ile Asn Pro Arg Pro Ser Leu Pro Pro Asn Ser Asp Thr Ser Lys 260 265 270 Glu Thr Ser Leu Thr Val Asn Lys Glu Thr Thr Val Glu Thr Lys Glu 275 280 285 Thr Thr Thr Thr Asn Lys Gln Thr Ser Thr Asp Gly Lys Glu Lys Thr 290 295 300 Thr Ser Ala Lys Glu Thr Gln Ser Ile Glu Lys Thr Ser Ala Lys Asp 305 310 315 320 Leu Ala Pro Thr Ser Lys Val Leu Ala Lys Pro Thr Pro Lys Ala Glu 325 330 335 Thr Thr Thr Lys Gly Pro Ala Leu Thr Thr Pro Lys Glu Pro Thr Pro 340 345 350 Thr Thr Pro Lys Glu Pro Ala Ser Thr Thr Pro Lys Glu Pro Thr Pro 355 360 365 Thr Thr Ile Lys Ser Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr 370 375 380 Thr Thr Lys Ser Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr 385 390 395 400 Thr Lys Glu Pro Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr 405 410 415 Thr Lys Glu Pro Ala Pro Thr Thr Thr Lys Ser Ala Pro Thr Thr Pro 420 425 430 Lys Glu Pro Ala Pro Thr Thr Pro Lys Lys Pro Ala Pro Thr Thr Pro 435 440 445 Lys Glu Pro Ala Pro Thr Thr Pro Lys Glu Pro Thr Pro Thr Thr Pro 450 455 460 Lys Glu Pro Ala Pro Thr Thr Lys Glu Pro Ala Pro Thr Thr Pro Lys 465 470 475 480 Glu Pro Ala Pro Thr Ala Pro Lys Lys Pro Ala Pro Thr Thr Pro Lys 485 490 495 Glu Pro Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr Thr Lys 500 505 510 Glu Pro Ser Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr Thr Lys 515 520 525 Ser Ala Pro Thr Thr Thr Lys Glu Pro Ala Pro Thr Thr Thr Lys Ser 530 535 540 Ala Pro Thr Thr Pro Lys Glu Pro Ser Pro Thr Thr Thr Lys Glu Pro 545 550 555 560 Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr Pro Lys Lys Pro 565 570 575 Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr Pro Lys Glu Pro 580 585 590 Ala Pro Thr Thr Thr Lys Lys Pro Ala Pro Thr Thr Pro Lys Glu Pro 595 600 605 Ala Pro Thr Thr Pro Lys Glu Thr Ala Pro Thr Thr Pro Lys Lys Leu 610 615 620 Thr Pro Thr Thr Pro Glu Lys Leu Ala Pro Thr Thr Pro Glu Lys Pro 625 630 635 640 Ala Pro Thr Thr Pro Glu Glu Leu Ala Pro Thr Thr Pro Glu Glu Pro 645 650 655 Thr Pro Thr Thr Pro Glu Glu Pro Ala Pro Thr Thr Pro Lys Ala Ala 660 665 670 Ala Pro Asn Thr Pro Lys Glu Pro Ala Pro Thr Thr Pro Lys Glu Pro 675 680 685 Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr Pro Lys Glu Thr 690 695 700 Ala Pro Thr Thr Pro Lys Gly Thr Ala Pro Thr Thr Leu Lys Glu Pro 705 710 715 720 Ala Pro Thr Thr Pro Lys Lys Pro Ala Pro Lys Glu Leu Ala Pro Thr 725 730 735 Thr Thr Lys Glu Pro Thr Ser Thr Thr Ser Asp Lys Pro Ala Pro Thr 740 745 750 Thr Pro Lys Gly Thr Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr 755 760 765 Thr Pro Lys Glu Pro Ala Pro Thr Thr Pro Lys Gly Thr Ala Pro Thr 770 775 780 Thr Leu Lys Glu Pro Ala Pro Thr Thr Pro Lys Lys Pro Ala Pro Lys 785 790 795 800 Glu Leu Ala Pro Thr Thr Thr Lys Gly Pro Thr Ser Thr Thr Ser Asp 805 810 815 Lys Pro Ala Pro Thr Thr Pro Lys Glu Thr Ala Pro Thr Thr Pro Lys 820 825 830 Glu Pro Ala Pro Thr Thr Pro Lys Lys Pro Ala Pro Thr Thr Pro Glu 835 840 845 Thr Pro Pro Pro Thr Thr Ser Glu Val Ser Thr Pro Thr Thr Thr Lys 850 855 860 Glu Pro Thr Thr Ile His Lys Ser Pro Asp Glu Ser Thr Pro Glu Leu 865 870 875 880 Ser Ala Glu Pro Thr Pro Lys Ala Leu Glu Asn Ser Pro Lys Glu Pro 885 890 895 Gly Val Pro Thr Thr Lys Thr Pro Ala Ala Thr Lys Pro Glu Met Thr 900 905 910 Thr Thr Ala Lys Asp Lys Thr Thr Glu Arg Asp Leu Arg Thr Thr Pro 915 920 925 Glu Thr Thr Thr Ala Ala Pro Lys Met Thr Lys Glu Thr Ala Thr Thr 930 935 940 Thr Glu Lys Thr Thr Glu Ser Lys Ile Thr Ala Thr Thr Thr Gln Val 945 950 955 960 Thr Ser Thr Thr Thr Gln Asp Thr Thr Pro Phe Lys Ile Thr Thr Leu 965 970 975 Lys Thr Thr Thr Leu Ala Pro Lys Val Thr Thr Thr Lys Lys Thr Ile 980 985 990 Thr Thr Thr Glu Ile Met Asn Lys Pro Glu Glu Thr Ala Lys Pro Lys 995 1000 1005 Asp Arg Ala Thr Asn Ser Lys Ala Thr Thr Pro Lys Pro Gln Lys Pro 1010 1015 1020 Thr Lys Ala Pro Lys Lys Pro Thr Ser Thr Lys Lys Pro Lys Thr Met 1025 1030 1035 1040 Pro Arg Val Arg Lys Pro Lys Thr Thr Pro Thr Pro Arg Lys Met Thr 1045 1050 1055 Ser Thr Met Pro Glu Leu Asn Pro Thr Ser Arg Ile Ala Glu Ala Met 1060 1065 1070 Leu Gln Thr Thr Thr Arg Pro Asn Gln Thr Pro Asn Ser Lys Leu Val 1075 1080 1085 Glu Val Asn Pro Lys Ser Glu Asp Ala Gly Gly Ala Glu Gly Glu Thr 1090 1095 1100 Pro His Met Leu Leu Arg Pro His Val Phe Met Pro Glu Val Thr Pro 1105 1110 1115 1120 Asp Met Asp Tyr Leu Pro Arg Val Pro Asn Gln Gly Ile Ile Ile Asn 1125 1130 1135 Pro Met Leu Ser Asp Glu Thr Asn Ile Cys Asn Gly Lys Pro Val Asp 1140 1145 1150 Gly Leu Thr Thr Leu Arg Asn Gly Thr Leu Val Ala Phe Arg Gly His 1155 1160 1165 Tyr Phe Trp Met Leu Ser Pro Phe Ser Pro Pro Ser Pro Ala Arg Arg 1170 1175 1180 Ile Thr Glu Val Trp Gly Ile Pro Ser Pro Ile Asp Thr Val Phe Thr 1185 1190 1195 1200 Arg Cys Asn Cys Glu Gly Lys Thr Phe Phe Phe Lys Asp Ser Gln Tyr 1205 1210 1215 Trp Arg Phe Thr Asn Asp Ile Lys Asp Ala Gly Tyr Pro Lys Pro Ile 1220 1225 1230 Phe Lys Gly Phe Gly Gly Leu Thr Gly Gln Ile Val Ala Ala Leu Ser 1235 1240 1245 Thr Ala Lys Tyr Lys Asn Trp Pro Glu Ser Val Tyr Phe Phe Lys Arg 1250 1255 1260 Gly Gly Ser Ile Gln Gln Tyr Ile Tyr Lys Gln Glu Pro Val Gln Lys 1265 1270 1275 1280 Cys Pro Gly Arg Arg Pro Ala Leu Asn Tyr Pro Val Tyr Gly Glu Thr 1285 1290 1295 Thr Gln Val Arg Arg Arg Arg Phe Glu Arg Ala Ile Gly Pro Ser Gln 1300 1305 1310 Thr His Thr Ile Arg Ile Gln Tyr Ser Pro Ala Arg Leu Ala Tyr Gln 1315 1320 1325 Asp Lys Gly Val Leu His Asn Glu Val Lys Val Ser Ile Leu Trp Arg 1330 1335 1340 Gly Leu Pro Asn Val Val Thr Ser Ala Ile Ser Leu Pro Asn Ile Arg 1345 1350 1355 1360 Lys Pro Asp Gly Tyr Asp Tyr Tyr Ala Phe Ser Lys Asp Gln Tyr Tyr 1365 1370 1375 Asn Ile Asp Val Pro Ser Arg Thr Ala Arg Ala Ile Thr Thr Arg Ser 1380 1385 1390 Gly Gln Thr Leu Ser Lys Val Trp Tyr Asn Cys Pro 1395 1400 <210> 106 <211> 1427 <212> PRT <213> Artificial Sequence <220> <223> ATS13_Human <400> 106 Met His Gln Arg His Pro Arg Ala Arg Cys Pro Pro Leu Cys Val Ala 1 5 10 15 Gly Ile Leu Ala Cys Gly Phe Leu Leu Gly Cys Trp Gly Pro Ser His 20 25 30 Phe Gln Gln Ser Cys Leu Gln Ala Leu Glu Pro Gln Ala Val Ser Ser 35 40 45 Tyr Leu Ser Pro Gly Ala Pro Leu Lys Gly Arg Pro Pro Ser Pro Gly 50 55 60 Phe Gln Arg Gln Arg Gln Arg Gln Arg Arg Ala Ala Gly Gly Ile Leu 65 70 75 80 His Leu Glu Leu Leu Val Ala Val Gly Pro Asp Val Phe Gln Ala His 85 90 95 Gln Glu Asp Thr Glu Arg Tyr Val Leu Thr Asn Leu Asn Ile Gly Ala 100 105 110 Glu Leu Leu Arg Asp Pro Ser Leu Gly Ala Gln Phe Arg Val His Leu 115 120 125 Val Lys Met Val Ile Leu Thr Glu Pro Glu Gly Ala Pro Asn Ile Thr 130 135 140 Ala Asn Leu Thr Ser Ser Leu Leu Ser Val Cys Gly Trp Ser Gln Thr 145 150 155 160 Ile Asn Pro Glu Asp Asp Thr Asp Pro Gly His Ala Asp Leu Val Leu 165 170 175 Tyr Ile Thr Arg Phe Asp Leu Glu Leu Pro Asp Gly Asn Arg Gln Val 180 185 190 Arg Gly Val Thr Gln Leu Gly Gly Ala Cys Ser Pro Thr Trp Ser Cys 195 200 205 Leu Ile Thr Glu Asp Thr Gly Phe Asp Leu Gly Val Thr Ile Ala His 210 215 220 Glu Ile Gly His Ser Phe Gly Leu Glu His Asp Gly Ala Pro Gly Ser 225 230 235 240 Gly Cys Gly Pro Ser Gly His Val Met Ala Ser Asp Gly Ala Ala Pro 245 250 255 Arg Ala Gly Leu Ala Trp Ser Pro Cys Ser Arg Arg Gln Leu Leu Ser 260 265...

Claims

1. A fusion polypeptide, wherein the fusion polypeptide is represented by the following formula: N'-(Z)nYC' In the formula, N' is the N-terminus of the fusion polypeptide, and C' is the C-terminus of the fusion polypeptide, and Y is GDF15 consisting of the amino acid sequence of SEQ ID NO: 3, and Z is a polypeptide region capable of O-glycosylation, and n is the number of polypeptide regions capable of O-glycosylation that bind to the N-terminus of GDF15 and is an integer from 1 to 3, The polypeptide region capable of O-glycosylation is an IgD hinge region consisting of the amino acid sequence of SEQ ID NO:

1.

2. The fusion polypeptide according to claim 1, wherein the area under the blood concentration-time curve of GDF15 bound to the polypeptide region capable of O-glycosylation in the fusion polypeptide increases by at least 2 times until the last measurable blood sampling point after in vivo administration, compared with GDF15 not bound to the polypeptide region capable of O-glycosylation.

3. A nucleic acid molecule encoding the fusion polypeptide according to claim 1 or 2. A recombinant vector comprising the nucleic acid molecule according to claim 3 .

5. A method for preparing the fusion polypeptide according to claim 1 or 2, wherein the fusion polypeptide comprises GDF15 and a polypeptide region capable of O-glycosylation, the method comprising culturing a recombinant cell comprising the recombinant vector according to claim 4.

6. A method for preparing a fusion polypeptide comprising GDF15 having enhanced in vivo stability, The method comprises linking a total of 1 to 3 polypeptide regions capable of O-glycosylation to the N-terminus of GDF15, wherein the 1 to 3 polypeptide regions capable of O-glycosylation are each an IgD hinge region consisting of the amino acid sequence of SEQ ID NO: 1, and The GDF15 consists of the amino acid sequence of SEQ ID NO:

3.

7. A fusion polypeptide dimer, comprising two fusion polypeptides according to claim 1 or 2. The fusion polypeptide dimer according to claim 7 , wherein the GDF15 of each fusion polypeptide binds to each other to form a dimer.

9. The fusion polypeptide dimer according to claim 7, wherein the dimer is a homodimer. 10 . A pharmaceutical composition for preventing or treating a disease associated with GDF15 deficiency or dysfunction, the pharmaceutical composition comprising the fusion polypeptide according to claim 1 or 2, or the fusion polypeptide dimer according to any one of claims 7 to 9.

11. Use of the fusion polypeptide according to claim 1 or 2, the fusion polypeptide dimer according to any one of claims 7 to 9, or the pharmaceutical composition according to claim 10 in the preparation of a medicament for preventing or treating diabetes or hyperlipidemia.

12. Use of the fusion polypeptide according to claim 1 or 2, the fusion polypeptide dimer according to any one of claims 7 to 9, or the pharmaceutical composition according to claim 10 in the preparation of a medicament for preventing or treating obesity.

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