CA2319117A1 - Compounds for therapy and diagnosis of lung cancer and methods for their use - Google Patents

Abstract

Compounds and methods for treating lung cancer are provided. The inventive compounds include polypeptides containing at least a portion of a lung tumor protein. Vaccines and pharmaceutical compositions for immunotherapy of lung cancer comprising such polypeptides, or polynucleotides encoding such polypeptides, are also provided, together with polynucleotides for preparing the inventive polypeptides.

Description

COMPOUNDS FOR THERAPY AND DIAGNOSIS
OF LUNG CANCER AND METHODS FOR THEIR USE
s TECHNICAL FIELD
The present invention relates generally to compositions and methods for the treatment of lung cancer. The invention is more specifically related to nucleotide sequences that are preferentially expressed in lung tumor tissue, together with poiypeptides encoded by such nucleotide sequences. The inventive nucleotide sequences and polypeptides may be used 1 o in vaccines and pharmaceutical compositions for the treatment of lung cancer.
BACKGROUND OF THE INVENTION
Lung cancer is the primary cause of cancer death among both men and women in the U.S., with an estimated 172,000 new cases being reported in 1994. The five-year i 5 survival rate among all lung cancer patients, regardless of the stage of disease at diagnosis, is only 13%. This contrasts with a five-year survival rate of 46% among cases detected while the disease is still localized. However, only 16% of lung cancers are discovered before the disease has spread.
Early detection is difficult since clinical symptoms are often not seen until the 20 disease has reached an advanced stage. Currently, diagnosis is aided by the use of chest x-rays, analysis of the type of cells contained in sputum and fiberoptic examination of the bronchial passages. Treatment regimens are determined by the type and stage of the cancer, and include surgery, radiation therapy and/or chemotherapy. In spite of considerable research into therapies for the disease, lung cancer remains difficult to treat.
25 Accordingly, there remains a need in the art for improved vaccines, treatment methods and diagnostic techniques for lung cancer.
SUMMARY OF THE INVENTION
Briefly stated, the present invention provides compounds and methods for the 3o therapy of lung cancer. In a first aspect, isolated polynucleotides encoding lung tumor polypeptides are provided, such polynucleotides comprising a nucleotide sequence selected from the group consisting of: (a) sequences provided in SEQ ID NO: 1-11, 19, 22-25, 27-31, 51, 53. 55, 63, 70, 72, 79, 80, 86, 87, 89, 90, 102-107, 109, 139, 143-149, 151-154 and 156-158; (b) sequences complementary to a sequence provided in SEQ ID NO: 1-11, 19, 22-25, 27-31, 51, 53, 55, 63, 70, 72, 79, 80, 86, 87, 89, 90, 102-107, 109, 139, 143-149. 151-154 and 156-158; and (b) variants of the sequences of (a) or (b).
In a second aspect, isolated polypeptides are provided that comprise at least an immunogenic portion of a lung tumor protein or a variant thereof. In specific embodiments, such polypeptides comprise an amino acid sequence encoded by a DNA sequence comprising a nucleotide sequence selected from the-group consisting of (a) sequences recited in SEQ ID
1o NO: 1-11, 19, 22-25, 27-31. 51, 53, 55, 63, 70, 72, 79, 80, 86, 87, 89. 90, 102-107, 109, 139, 143-149. 151-154 and 156-158; (b) sequences complementary to a sequence provided in SEQ
ID NO: 1-11, 19, 22-25, 27-31, 51, 53, 55, 63, 70, 72, 79, 80, 86, 87, 89, 90, 102-107, 109, 139, 143-149. 151-154 and 156-158; and (c) variants of the sequences of (a) and (b).
In related aspects, expression vectors comprising the inventive polynucleotides, together with host cells transformed or transfected with such expression vectors are provided. In preferred embodiments, the host cells are selected from the group consisting of E. coli, yeast and mammalian cells.
In another aspect. fusion proteins comprising a first and a second inventive polypeptide or, alternatively, an inventive polypeptide and a known lung tumor antigen, are 2o provided. ._ The present invention further provides pharmaceutical compositions comprising one or more of the above polypeptides, fusion proteins or polynucleotides and a physiologically acceptable carrier, together with vaccines comprising one or more such polypeptides. fusion proteins or polynucleotides in combination with an immune response enhancer.
In related aspects, the present invention provides methods for inhibiting the development of lung cancer in a patient, comprising administering to a patient an effective amount of at least one of the above pharmaceutical compositions and/or vaccines.
In yet a further aspect of the present invention, methods are provided for 3o detecting lung cancer in a patient, comprising: (a) contacting a biological sample obtained from a patient with a binding agent that is capable of binding to a polypeptide disclosed herein; and (b) detecting in the sample a protein or polypeptide that binds to the binding agent. In preferred embodiments, the binding agent is an antibody, most preferably a monoclonal antibody.
In related aspects, methods are provided for monitoring the progression of lung cancer in a patient, comprising: (a) contacting a biological sample obtained from a patient with a binding agent that is capable of binding to one of the polypeptides disclosed herein; (b) determining in the sample an amount of a protein or polypeptide that binds to the binding agent; (c) repeating steps (a) and (b); and comparing the amounts of polypeptide detected in steps (b) and (c).
Within related aspects, the present invention provides antibodies, preferably monoclonal antibodies, that bind to the inventive polypeptides, as well as diagnostic kits comprising such antibodies, and methods of using such antibodies to inhibit the development of lung cancer.
The present invention further provides methods for detecting lung cancer comprising: (a) obtaining a biological sample from a patient; (b) contacting the sample with a first and a second oligonucleotide primer in a polymerase chain reaction, at least one of the oligonucleotide primers being specific for a polynucleotide that encodes one of the polypeptides disclosed herein; and (c) detecting in the sample a DNA sequence that amplifies in the presence of the first and second oligonucleotide primers. In a preferred embodiment, at least one of the oligonucleotide primers comprises at least about 10 contiguous nucleotides of a polynucleotide comprising a sequence selected from the group consisting of SEQ ID NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, I16-120 and 126-181.
In a further aspect, the present invention provides a method for detecting lung cancer in a patient comprising: (a) obtaining a biological sample from the patient; (b) contacting the sample with an oligonucleotide probe specific for a polynucleotide that encodes one of the poiypeptides disclosed herein; and (c) detecting in the sample a DNA
sequence that hybridizes to the oligonucleotide probe. Preferably, the oligonucleotide probe comprises at least about 15 contiguous nucleotides of a polynucleotide comprising a sequence selected from the group consisting of SEQ ID NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-I20 and 126-181.In related aspects, diagnostic kits comprising the above oligonucleotide probes or primers are provided.

In yet a further aspect, methods for the treatment of lung cancer in a patient are provided, the methods comprising obtaining PBMC from the patient, incubating the PBMC with a polypeptide of the present invention (or a polynucleotide that encodes such a polypeptide) to provide incubated T cells and administering the incubated T
cells to the patient. In present invention additionally provides methods for the treatment of lung cancer that comprise incubating antigen presenting cells with a polypeptide of the present invention (or a polynucleotide that encodes such a polypeptide) to provide incubated antigen presenting cells and administering the incubated antigen presenting cells to the patient. In certain embodiments, the-antigen presenting cells are selected from the group to consisting of dendritic cells and macrophages. Compositions for the treatment of lung cancer comprising T cells or antigen presenting cells that have been incubated with a polypeptide or polynucleotide of the present invention are also provided. These and other aspects of the present invention will become apparent upon reference to the following detailed description.
All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.
SEQUENCE IDENTIFIERS
SEQ ID NO: 1 is the determined cDNA sequence for L363CI.cons SEQ ID NO: 2 is the determined cDNA sequence for L263C2.cons 2o SEQ ID NO: 3 is the determined cDNA sequence for L263C2c SEQ ID NO: 4 is the determined cDNA sequence for L263Cl.cons SEQ ID NO: 5 is the determined cDNA sequence for L263C1b SEQ ID NO: 6 is the determined cDNA sequence for L164C2.cons SEQ ID NO: 7 is the determined cDNA sequence for L 164C l .cons SEQ ID NO: 8 is the determined cDNA sequence for L366C 1 a SEQ ID NO: 9 is the determined cDNA sequence for L260CI.cons SEQ ID NO: 10 is the determined cDNA sequence for L163CIc SEQ ID NO: 11 is the determined cDNA sequence for L 163C 1 b SEQ ID NO: 12 is the determined cDNA sequence for L255Cl.cons 3o SEQ ID NO: 13 is the determined cDNA sequence for L255C I b SEQ ID NO: 14 is the determined cDNA sequence for L355CI.cons SEQ ID NO: 15 is the determined cDNA sequence for L366Cl.cons SEQ ID NO: 16 is the determined cDNA sequence for L 163C 1 a SEQ ID NO: 17 is the determined cDNA sequence for LT86-I

5 SEQ ID NO: 18 is the determined cDNA sequence for LT86-2 SEQ ID NO: 19 is the determined cDNA sequence for LT86-3 SEQ ID NO: 20 is the determined cDNA sequence for LT86-4 SEQ ID NO: 21 is the determined cDNA sequence for LT86-5 SEQ ID NO: 22 is the determined cDNA sequence for LT86-6 SEQ ID NO: 23 is the determined cDNA sequence for LT86-7 SEQ ID NO: 24 is the determined cDNA sequence for LT86-8 SEQ ID NO: 25 is the determined cDNA sequence for LT86-9 SEQ ID NO: 26 is the determined cDNA sequence for LT86-10 SEQ ID NO: 27 is the determined cDNA sequence for LT86-11 SEQ ID NO: 28 is the determined cDNA sequence for LT86-12 SEQ ID NO: 29 is the determined cDNA sequence for LT86-13 SEQ ID NO: 30 is the determined cDNA sequence for LT86-14 SEQ ID NO: 31 is the determined cDNA sequence for LT86-15 SEQ ID NO: 32 is the predicted amino acid sequence for LT86-1 2o SEQ ID NO: 33 is the predicted amino acid sequence for LT86-2 SEQ ID NO: 34 is the predicted amino acid sequence for LT86-3 SEQ ID NO: 35 is the predicted amino acid sequence for LT86-4 SEQ ID NO: 36 is the predicted amino acid sequence for LT86-5 SEQ ID NO: 37 is the predicted amino acid sequence for LT86-6 SEQ ID NO: 38 is the predicted amino acid sequence for LT86-7 SEQ ID NO: 39 is the predicted amino acid sequence for LT86-8 SEQ ID NO: 40 is the predicted amino acid sequence for LT86-9 SEQ ID NO: 41 is the predicted amino acid sequence for LT86-10 SEQ ID NO: 42 is the predicted amino acid sequence for LT86-11 3o SEQ ID NO: 43 is the predicted amino acid sequence for LT86-12 SEQ ID NO: 44 is the predicted amino acid sequence for LT86-13 SEQ ID NO: 45 is the predicted amino acid sequence for LT86-14 SEQ ID NO: 46 is the predicted amino acid sequence for LT86-15 SEQ ID NO: 47 is a (dT),ZAG primer SEQ ID NO: 48 is a primer SEQ ID NO: 49 is the determined 5' cDNA sequence for L86S-3 SEQ ID NO: 50 is the determined 5' cDNA sequence for L86S-12 SEQ ID NO: 51 is the determined 5' cDNA sequence for L86S-16 SEQ ID NO: 52 is the determined 5' sDNA sequence for L86S-25 to SEQ ID NO: 53 is the determined 5' cDNA sequence for L86S-36 SEQ ID NO: 54 is the determined 5' cDNA sequence for L86S-40 SEQ ID NO: 55 is the determined 5' cDNA sequence for L86S-46 SEQ ID NO: 56 is the predicted amino acid sequence for L86S-3 SEQ ID NO: 57 is the predicted amino acid sequence for L86S-12 SEQ ID NO: 58 is the predicted amino acid sequence for L86S-16 SEQ ID NO: 59 is the predicted amino acid sequence for L86S-25 SEQ ID NO: 60 is the predicted amino acid sequence for L86S-36 SEQ ID NO: 61 is the predicted amino acid sequence for L86S-40 SEQ ID NO: 62 is the predicted amino acid sequence for L86S-46 2o SEQ ID NO: 63 is the determined 5' cDNA sequence for L86S-30 SEQ ID NO: 64 is the determined S' cDNA sequence for L86S-41 SEQ ID NO: 65 is the predicted amino acid sequence from the 5' end of LT86-9 SEQ ID NO: 66 is the determined extended cDNA sequence for LT86-4 SEQ ID NO: 67 is the predicted extended amino acid sequence for LT86-4 2s SEQ ID NO: 68 is the determined 5' cDNA sequence for LT86-20 SEQ ID NO: 69 is the determined 3' cDNA sequence for LT86-21 SEQ ID NO: 70 is the determined 5' cDNA sequence for LT86-22 SEQ ID NO: 71 is the determined 5' cDNA sequence for LT86-26 SEQ ID NO: 72 is the determined 5' cDNA sequence for LT86-27 3o SEQ ID NO: 73 is the predicted amino acid sequence for LT86-20 SEQ ID NO: 74 is the predicted amino acid sequence for LT86-21 SEQ ID NO: 75 is the predicted amino acid sequence for LT86-22 SEQ ID NO: 76 is the predicted amino acid sequence for LT86-26 SEQ ID NO: 77 is the predicted amino acid sequence for LT86-27 SEQ ID NO: 78 is the determined extended cDNA sequence for L86S-12 SEQ ID NO: 79 is the determined extended cDNA sequence for L86S-36 SEQ ID NO: 80 is the determined extended cDNA sequence for L86S-46 SEQ ID NO: 81 is the predicted extended amino acid sequence for L86S-12 SEQ ID NO: 82 is the predicted extended amino acid sequence for L86S-36 to SEQ ID NO: 83 is the predicted extended amino acid sequence for L86S-46 SEQ ID NO: 84 is the determined 5'cDNA sequence for L86S-6 SEQ ID NO: 85 is the determined 5'cDNA sequence for L86S-11 SEQ ID NO: 86 is the determined 5'cDNA sequence for L86S-14 SEQ ID NO: 87 is the determined 5'cDNA sequence for L86S-29 SEQ ID NO: 88 is the determined 5'cDNA sequence for L86S-34 SEQ ID NO: 89 is the determined 5'cDNA sequence for L86S-39 SEQ ID NO: 90 is the determined 5'cDNA sequence for L86S-47 SEQ ID NO: 91 is the determined 5'cDNA sequence for L86S-49 SEQ ID NO: 92 is the determined 5'cDNA sequence for L86S-S 1 -SEQ ID NO: 93 is the predicted amino acid sequence for L86S-6 SEQ ID NO: 94 is the predicted amino acid sequence for L86S-11 SEQ ID NO: 95 is the predicted amino acid sequence for L86S-14 SEQ ID NO: 96 is the predicted amino acid sequence for L86S-29 SEQ ID NO: 97 is the predicted amino acid sequence for L86S-34 SEQ ID NO: 98 is the predicted amino acid sequence for L86S-39 SEQ ID NO: 99 is the predicted amino acid sequence for L86S-47 SEQ ID NO: 100 is the predicted amino acid sequence for L86S-49 SEQ ID NO: 101 is the predicted amino acid sequence for L86S-51 SEQ ID NO: 102 is the determined DNA sequence for SLT-T1 3o SEQ ID NO: 103 is the determined 5' cDNA sequence for SLT-T2 SEQ ID NO: 104 is the determinedcDNA sequence for 5' SLT-T3 SEQ ID NO: 105 is the determinedcDNA sequence for 5' SLT-TS

SEQ ID NO: 106 is the determinedcDNA sequence for 5' SLT-T7 SEQ ID NO: 107 is the determinedcDNA sequence for 5' SLT-T9 SEQ ID NO: 108 is the cDNA sequence for determined 5' SLT-T 10 SEQ ID NO: 109 is the determined 5' cDNA sequence for SLT-T11 SEQ ID NO: 110 is the determined 5' cDNA sequence for SLT-T12 SEQ ID NO: 111 is the predicted amino acid sequence for SLT-Tl SEQ ID NO: 112 is the predicted amino-acid sequence for SLT-T2 1o SEQ ID NO: 113 is the predicted amino acid sequence for SLT-T3 SEQ ID NO: 114 is the predicted amino acid sequence for SLT-T10 SEQ ID NO: 11 S is the predicted amino acid sequence for SLT-T I 2 SEQ ID NO: 116 is the determined 5' cDNA sequence for SALT-T3 SEQ ID NO: 117 is the determined 5' cDNA sequence for SALT-T4 ~ 5 SEQ ID NO: 118 is the determined 5' cDNA sequence for SALT-T7 SEQ ID NO: 119 is the determined 5' cDNA sequence for SALT-T8 SEQ ID NO: 120 is the determined 5' cDNA sequence for SALT-T9 SEQ ID NO: 121 is the predicted amino acid sequence for SALT-T3 SEQ ID NO: 122 is the predicted amino acid sequence for SALT-T4 2o SEQ ID NO: 123 is the predicted amino acid sequence for SALT-T7 SEQ ID NO: 124 is the predicted amino acid sequence for SALT-T8 SEQ ID NO: 125 is the predicted amino acid sequence for SALT-T9 SEQ ID NO: 126 is the determined cDNA sequence for PSLT-1 SEQ ID NO: 127 is the determined cDNA sequence for PSLT-2 25 SEQ ID NO: 128 is the determined cDNA sequence for PSLT-7 SEQ ID NO: 129 is the determined cDNA sequence for PSLT-13 SEQ ID NO: 130 is the determined cDNA sequence for PSLT-27 SEQ ID NO: 131 is the determined cDNA sequence for PSLT-28 SEQ ID NO: 132 is the determined cDNA sequence for PSLT-30 3o SEQ ID NO: 133 is the determined cDNA sequence for PSLT-40 SEQ ID NO: 134 is the determined cDNA sequence for PSLT-69 SEQ ID NO: 135 is the determined cDNA sequence for PSLT-71 SEQ ID NO: 136 is the determined cDNA sequence for PSLT-73 SEQ ID NO: 137 is the determined cDNA sequence for PSLT-79 s SEQ ID NO: 138 is the determined cDNA sequence for PSLT-03 SEQ ID NO: 139 is the determined cDNA sequence for PSLT-09 SEQ ID NO: 140 is the determined cDNA sequence for PSLT-011 SEQ ID NO: 141 is the determined cDNA sequence for PSLT-041 SEQ ID NO: 142 is the determined cDNA sequence for PSLT-62 SEQ ID NO: 143 is the determined cDNA sequence for PSLT-6 SEQ ID Nu: i44 is the determined cDNA sequence for PSLT-37 SEQ ID NO: 145 is the determined cDNA sequence for PSLT-74 SEQ ID NO: 146 is the determined cDNA sequence for PSLT-010 SEQ ID NO: 147 is the determined cDNA sequence for PSLT-012 ~5 SEQ ID NO: 148 is the determined cDNA sequence for PSLT-037 SEQ ID NO: 149 is the determined 5' cDNA sequence for SAL-3 SEQ ID NO: 150 is the determined 5' cDNA sequence for SAL-24 SEQ ID NO: 151 is the determined 5' cDNA sequence for SAL-25 SEQ ID NO: 152 is the determined 5' cDNA sequence for SAL-33 2o SEQ ID NO: 153 is the determined 5' cDNA sequence for SAL-50 SEQ ID NO: 154 is the determined 5' cDNA sequence for SAL-57 SEQ ID NO: 155 is the determined 5' cDNA sequence for SAL-66 SEQ ID NO: 156 is the determined 5' cDNA sequence for SAL-82 SEQ ID NO: 157 is the determined 5' cDNA sequence for SAL-99 25 SEQ ID NO: 158 is the determined 5' cDNA sequence for SAL-104 SEQ ID NO: 159 is the determined 5' cDNA sequence for SAL-109 SEQ ID NO: 160 is the determined 5' cDNA sequence for SAL-5 SEQ ID NO: 161 is the determined 5' cDNA sequence for SAL-8 SEQ ID NO: 162 is the determined 5' cDNA sequence for SAL-12 3o SEQ ID NO: 163 is the determined 5' cDNA sequence for SAL-14 WO 99/38973 PCT/US99/O1b42 i0 SEQ ID NO: 164 is the determinedcDNA sequence for 5' SAL-16 SEQ ID NO: 165 is the determinedcDNA sequence for 5' SAL-23 SEQ ID NO: 166 is the determinedcDNA sequence for 5' SAL-26 SEQ ID NO: 167 is the determinedcDNA sequence for 5' SAL-29 SEQ ID NO: 168 is the cDNA sequence for determined 5' SAL-32 SEQ ID NO: 169 is the determinedcDNA sequence for 5' SAL-39 SEQ ID NO: 170 is the determinedcDNA sequence for 5' SAL-42 SEQ ID NO: 171 is the determinedcDNA sequence for 5' SAL-43 SEQ ID NO: 172 is the determinedsDNA sequence for 5' SAL-44 to SEQ ID NO: 173 is the cDNA sequence for determined 5' SAL-48 SEQ ID NO: 174 is the determinedcDNA sequence for 5' SAL-68 SEQ ID NO: 175 is the determinedcDNA sequence for 5' SAL-72 SEQ ID NO: 176 is the determinedcDNA sequence for 5' SAL-77 SEQ ID NO: 177 is the determinedcDNA sequence for 5' SAL-86 i s SEQ ID NO: 178 is the cDNA sequence for determined 5' SAL-88 SEQ ID NO: 179 is the determined 5' cDNA sequence for SAL-93 SEQ ID NO: 180 is the determined 5' cDNA sequence for SAL-100 SEQ ID NO: I 81 is the determined 5' cDNA sequence for SAL-105 SEQ ID NO: 182 is the predicted amino acid sequence for SAL-3 2o SEQ ID NO: 183 is the predicted amino acid sequence for SAL-24 SEQ ID NO: 184 is a first predicted amino acid sequence for SAL-25 SEQ ID NO: 185 is a second predicted amino acid sequence for SAL-25 SEQ ID NO: 186 is the predicted amino acid sequence for SAL-33 SEQ ID NO: 187 is a first predicted amino acid sequence for SAL-50 25 SEQ ID NO: 188 is the predicted amino acid sequence for SAL-57 SEQ ID NO: 189 is a first predicted amino acid sequence for SAL-66 SEQ ID NO: 190 is a second predicted amino acid sequence for SAL-66 SEQ ID NO: 191 is the predicted amino acid sequence for SAL-82 SEQ ID NO: 192 is the predicted amino acid sequence for SAL-99 3o SEQ ID NO: 193 is the predicted amino acid sequence for SAL-104 SEQ ID NO: 194 is the predicted amino acid sequence for SAL-5 SEQ ID NO: 195 is the predicted amino acid sequence for SAL-8 SEQ ID NO: 196 is the predicted amino acid sequence for SAL-12 SEQ ID NO: 197 is the predicted amino acid sequence for SAL-14 SEQ ID NO: 198 is the predicted amino acid sequence for SAL-16 SEQ ID NO: 199 is the predicted amino acid sequence for SAL-23 SEQ ID NO: 200 is the predicted amino acid sequence for SAL-26 SEQ ID NO: 201 is the predicted amino acid sequence for SAL-29 SEQ ID NO: 202 is the predicted amino-acid sequence for SAL-32 1o SEQ ID NO: 203 is the predicted amino acid sequence for SAL-39 SEQ ID NO: 204 is the predicted amino acid sequence for SAL-42 SEQ ID NO: 205 is the predicted amino acid sequence for SAL-43 SEQ ID NO: 206 is the predicted amino acid sequence for SAL-44 SEQ ID NO: 207 is the predicted amino acid sequence for SAL-48 SEQ ID NO: 208 is the predicted amino acid sequence for SAL-68 SEQ ID NO: 209 is the predicted amino acid sequence for SAL-72 SEQ ID NO: 210 is the predicted amino acid sequence for SAL-77 SEQ ID NO: 211 is the predicted amino acid sequence for SAL-86 SEQ ID NO: 212 is the predicted amino acid sequence for SAL-88 2o SEQ ID NO: 213 is the predicted amino acid sequence for SAL-93 SEQ ID NO: 214 is the predicted amino acid sequence for SAL-100 SEQ ID NO: 215 is the predicted amino acid sequence for SAL-105 SEQ ID NO: 216 is a second predicted amino acid sequence for SAL-50 DETAILED DESCRIPTION OF THE INVENTION
As noted above, the present invention is generally directed to compositions and methods for the therapy of lung cancer. The compositions described herein include polypeptides, fusion proteins and polynucleotides. Also included within the present invention are molecules (such as an antibody or fragment thereof) that bind to the inventive 3o polypeptides. Such molecules are referred to herein as "binding agents."

In one embodiment, the inventive polypeptides comprise at least a portion of a protein that is expressed at a greater level in human lung tumor tissue than in normal lung tissue. Preferably, the level of RNA encoding the polypeptide is at least 2-fold higher in tumor tissue. Such polypeptides include, but are not limited to, polypeptides (and immunogenic portions thereof) encoded by the nucleotide sequences provided in SEQ ID
NO: 1-16 and variants thereof.
In a second embodiment, the inventive polypeptides comprise at least a portion of a immunogenic lung tumor protein, including but not limited to polypeptides wherein the lung tumor protein includes an amino acid sequence encoded by a polynucleotide including a sequence selected from the group consisting of (a) nucleotide sequences recited in SEQ ID NO: 17-31, 49-55, 63,64, 66, 68-72, 78-80 and 84-92, (b) the complements of said nucleotide sequences, and (c) variants of such sequences.
In a third embodiment, the inventive polypeptides comprise at least a portion of a lung tumor protein, including polypeptides wherein the lung tumor protein includes an amino acid sequence encoded by a polynucleotide including a sequence selected from the group consisting of (a) nucleotide sequences recited in SEQ ID NO: 102-110, 116-120 and 126-181, (b) the complements of said nucleotide sequences, and (c) variants of such sequences.
As used herein, the term "polypeptide" encompasses amino acid chains of any length, including full length proteins, wherein the amino acid residues are linked by covalent peptide bonds. Thus, a polypeptide comprising a portion of one of the above lung tumor proteins may consist entirely of the portion, or the portion may be present within a larger polypeptide that contains additional sequences. The additional sequences may be derived from the native protein or may be heterologous, and such sequences may (but need not) be immunoreactive and/or antigenic. As detailed below, such polypeptides may be isolated from lung tumor tissue or prepared by synthetic or recombinant means.
As used herein, an "immunogenic portion" of a lung tumor protein is a portion that is capable of eliciting an immune response in a patient inflicted with lung cancer and as such binds to antibodies present within sera from a lung cancer patient. Such immunogenic 3o portions generally comprise at least about 5 amino acid residues, more preferably at least about 10, and most preferably at least about 20 amino acid residues.
Immunogenic portions WO 99/38973 PCT/US99/O1b42 of the proteins described herein may be identified in antibody binding assays.
Such assays may generally be performed using any of a variety of means known to those of ordinary skill in the art, as described, for example, in Harlow and Lane, Antibodies: A
Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1988. For example, a polypeptide may be immobilized on a solid support (as described below) and contacted with patient sera to allow binding of antibodies within the sera to the immobilized polypeptide.
Unbound sera may then be removed and bound antibodies detected using, for example, ''-SI-labeled Protein A. Alternatively, a polypeptide may be used to generate monoclonal and polyclonal antibodies for use in detection of the-polypeptide in blood or other fluids of lung cancer to patients. Methods for preparing and identifying immunogenic portions of antigens of known sequence are well known in the art and include those summarized in Paul, Fundamental Immunology, 3'd ed., Raven Press, 1993, pp. 243-247.
The term "polynucleotide(s)," as used herein, means a single or double-stranded polymer of deoxyribonucleotide or ribonucleotide bases and includes DNA and corresponding RNA molecules, including HnRNA and mRNA molecules, both sense and anti-sense strands, and comprehends cDNA, genomic DNA and recombinant DNA, as well as wholly or partially synthesized polynucleotides. An HnRNA molecule contains introns and corresponds to a DNA molecule in a generally one-to-one manner. An mRNA
molecule corresponds to an HnRNA and DNA molecule from which the introns have been excised. A
polynucleotide may consist of an entire gene, or any portion thereof. Operable anti-sense polynucleotides may comprise a fragment of the corresponding polynucleotide, and the definition of "polynucleotide" therefore includes all such operable anti-sense fragments.
The compositions and methods of the present invention also encompass variants of the above polypeptides and polynucleotides.
A polypeptide "variant," as used herein, is a polypeptide that differs from the recited polypeptide only in conservative substitutions and/or modifications, such that the antigenic properties of the polypeptide are retained. In a preferred embodiment, variant polypeptides differ from an identified sequence by substitution, deletion or addition of five amino acids or fewer. Such variants may generally be identified by modifying one of the 3o above polypeptide sequences, and evaluating the antigenic properties , of the modified polypeptide using, for example, the representative procedures described herein. Polypeptide variants preferably exhibit at least about 70%, more preferably at least about 90% and most preferably at least about 95% identity (determined as described below) to the identified polypeptides.
As used herein, a "conservative substitution" is one in which an amino acid is substituted for another amino acid that has similar properties, such that one skilled in the art of peptide chemistry would expect the secondary structure and hydropathic nature of the polypeptide to be substantially unchanged. In general, the following groups of amino acids represent conservative changes: ( 1 ) ala, pro, gly, glu, asp, gln, asn, ser, thr; (2) cys, ser, tyr, thr; (3) vah ile, leu, met, ala, phe; (4) lys, arg, his; and (5) phe, tyr, trp, his.
to Variants may also, or alternatively, contain other modifications, including the deletion or addition of amino acids that have minimal influence on the antigenic properties, secondary structure and hydropathic nature of the polypeptide. For example, a polypeptide may be conjugated to a signal (or leader) sequence at the N-terminal end of the protein which co-translationally or post-translationally directs transfer of the protein.
The polypeptide may t5 also be conjugated to a linker or other sequence for ease of synthesis, purification or identification of the polypeptide (e.g., poly-His), or to enhance binding of the polypeptide to a solid support. For example, a polypeptide may be conjugated to an immunoglobulin Fc region.
A nucleotide "variant" is a sequence that differs from the recited nucleotide 2o sequence in having one or more nucleotide deletions, substitutions or additions. Such modifications may be readily introduced using standard mutagenesis techniques, such as oligonucleotide-directed site-specific mutagenesis as taught, for example, by Adelman et al.
(DNA, 2:183, 1983). Nucleotide variants may be naturally occurring allelic variants, or non-. naturally occurring variants. Variant nucleotide sequences preferably exhibit at least about 25 70%, more preferably at least about 80% and most preferably at least about 90% identity (determined as described below) to the recited sequence.
The lung tumor antigens provided by the present invention include variants that are encoded by DNA sequences which are substantially homologous to one or more of the DNA sequences specifically recited herein. "Substantial homology," as used herein, 3o refers to DNA sequences that are capable of hybridizing under moderately stringent conditions. Suitable moderately stringent conditions include prewashing in a solution of 5X

SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50°C-65°C, SX SSC, overnight or, in the event of cross-species homology, at 45°C with O.SX SSC; followed by washing twice at 65°C for 20 minutes with each of 2X, 0.5X and 0.2X SSC containing 0.1% SDS. Such hybridizing DNA sequences are also within the scope of this invention, as are nucleotide 5 sequences that, due to code degeneracy, encode an immunogenic polypeptide that is encoded by a hybridizing DNA sequence.
Two nucleotide or polypeptide sequences are said to be "identical" if the sequence of nucleotides or amino acid residues in the two sequences is the same when aligned for maximum correspondence as described below. Comparisons between two sequences are typically performed by comparing the sequences over a comparison window to identify and compare local regions of sequence similarity. A "comparison window" as used herein, refers to a segment of at least about 20 contiguous positions, usually 30 to about 75, 40 to about 50, in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned.
~ 5 Optimal alignment of sequences for comparison may be conducted using the Megalign program in the Lasergene suite of bioinformatics software (DNASTAR, Inc., Madison, WI), using default parameters. This program embodies several alignment schemes described in the following references: Dayhoff, M.O. ( 1978) A model of evolutionary change in proteins - Matrices for detecting distant relationships. In Dayhoff; M.O.
(ed.) Atlas of 2o Protein Sequence and Structure. National Biomedical Resarch Foundaiton, Washington DC
Vol. 5, Suppl. 3, pp. 345-358; Hein J. (1990) Unified Approach to Alignment and Phylogenes pp. 626-645 Methods in Enzymology vol. 183, Academic Press, Inc., San Diego, CA;
Higgins, D.G. and Sharp, P.M. (1989) Fast and sensitive multiple sequence alignments on a microcomputer CABIOS 5:151-153; Myers, E.W. and Muller W. (1988) Optimal alignments in linear space CABIOS 4:11-17; Robinson, E.D. (1971) Comb. Theor 11:105;
Santou, N.
Nes, M. (1987) The neighbor joining method. A new method for reconstructing phylogenetic trees Mol. Biol. Evol. 4:406-425; Sneath, P.H.A. and Sokal, R.R. (1973) Numerical Taxonomy - the Principles and Practice of Numerical Taxonomy, Freeman Press, San Francisco, CA; Wilbur, W.J. and Lipman, D.J. (1983) Rapid similarity searches of nucleic 3o acid and protein data banks Proc. Natl. Acad., Sci. USA 80:726-?30.

Preferably, the "percentage of sequence identity" is determined by comparing two optimally aligned sequences over a window of comparison of at least 20 positions, wherein the portion of the polynucleotide sequence in the comparison window may comprise additions or deletions (i.e. gaps) of 20 percent or less, usually 5 to 15 percent, or 10 to 12 percent, as compared to the reference sequences (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid bases or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the reference sequence (i.e.
t o the window size) and multiplying the results by 100 to yield the percentage of sequence identity.
The lung tumor polypeptides of the present invention, and polynucleotides encoding such polypeptides, may be isolated from lung tumor tissue using any of a variety of methods well known in the art. For example, cDNA molecules encoding polypeptides t 5 preferentially expressed in lung tumor tissue may be cloned on the basis of the lung tumor-specific expression of the corresponding mRNAs, using differential display PCR. This technique compares the amplified products from RNA templates prepared from normal lung and lung tumor tissue. cDNA may be prepared by reverse transcription of RNA
using a (dT),zAG primer. Following amplification of the cDNA using a random primer, a band 2o corresponding to an amplified product specific to the tumor RNA may be cut out from a silver stained gel and subcloned into a suitable vector. Examples of cDNA
sequences that may be isolated using this procedure include those provided in SEQ ID NO: 1-16.
cDNA molecules encoding immunogenic lung tumor polypeptides may be prepared by screening a cDNA expression library prepared from a lung tumor sample with 25 sera from the same patient as the tumor sample, as described in detail in Example 2 below.
Examples of cDNA sequences that may be isolated using this procedure include those provided in SEQ ID NO: 17-3 ).. Additional cDNA molecules encoding lung tumor polypeptides may be obtained by screening such a cDNA expression library with mouse anti-lung tumor serum as described below in Example 3. Examples of cDNA sequences that may 3o thus be isolated are provided in SEQ ID NO: 49-55, 63, 64 and 126-148. cDNA
sequences encoding lung tumor antigens may also be isolated by screening of lung tumor cDNA

libraries prepared from SCID mice with mouse anti-tumor sera, as described below in Example 4. Examples of cDNA sequences that may be isolated using this technique are provided in SEQ ID NO: 149-181.
A gene encoding a polypeptide described herein (or a portion thereof) may, alternatively, be amplified from human genomic DNA, or from lung tumor cDNA, via polymerase chain reaction. For this approach, sequence-specific primers may be designed based on the nucleotide sequences provided herein and may be purchased or synthesized. An amplified portion of a specific nucleotide sequence may then be used to isolate the full length gene from a human genomic DNA library or from a lung tumor cDNA library, using well t o known techniques, such as those described in Sambrook et al., Molecular Cloning: A
Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY ( I
989).
Once a DNA sequence encoding a polypeptide is obtained, the polypeptide may be produced recombinantly by inserting the DNA sequence into an expression vector and expressing the polypeptide in an appropriate host. Any of a variety of expression vectors t 5 known to those of ordinary skill in the art may be employed to express recombinant polypeptides of this invention. Expression may be achieved in any appropriate host cell that has been transformed or transfected with an expression vector containing a polynucleotide that encodes the recombinant polypeptide. Suitable host cells include prokaryotes, yeast and higher eukaryotic cells. Preferably, the host cells employed are E. coli, yeast or a mammalian 2o cell line, such as COS or CHO cells. The DNA sequences expressed in this manner may encode naturally occurnng polypeptides, portions of naturally occurring polypeptides, or other variants thereof. Supernatants from suitable host/vector systems which secrete the recombinant polypeptide may be first concentrated using a commercially available filter. The concentrate may then be applied to a suitable purification matrix, such as an affinity matrix or 25 ion exchange resin. Finally, one or more reverse phase HPLC steps can be employed to further purify the recombinant polypeptide.
Such techniques may also be used to prepare polypeptides comprising portions or variants of the native polypeptides. Portions and other variants having fewer than about 100 amino acids, and generally fewer than about 50 amino acids, may be generated using 3o techniques well known to those of ordinary skill in the art. For example, such polypeptides may be synthesized using any of the commercially available solid-phase techniques, such as the Mernfield solid-phase synthesis method, where amino acids are sequentially added to a growing amino acid chain (see, for example, Merrifield, J. Am. Chem. Soc.
85:2149-2146, 1963). Equipment for automated synthesis of polypeptides is commercially available from suppliers such as Perkin Elmer/Applied BioSystems Division (Foster City, CA), and may be s operated according to the manufacturer's instructions.
In general, regardless of the method of preparation, the polypeptides disclosed herein are prepared in an isolated, substantially pure form (i.e., the polypeptides are homogenous as determined by amino acid composition and primary sequence analysis).
Preferably, the polypeptides are at least-about 90% pure, more preferably at least about 95%
to pure and most preferably at least about 99% pure. In certain preferred embodiments, described in more detail below, the substantially pure polypeptides are incorporated into pharmaceutical compositions or vaccines for use in one or more of the methods disclosed herein.
In a related aspect, the present invention provides fusion proteins comprising a 15 first and a second inventive polypeptide or, alternatively, a polypeptide of the present invention and a known lung tumor antigen, together with variants of such fusion proteins.
The fusion proteins of the present invention may (but need not) include a linker peptide between the first and second polypeptides.
A DNA sequence encoding a fusion protein of the present invention is 2o constructed using known recombinant DNA techniques to assemble separate DNA
sequences encoding the first and second polypeptides into an appropriate expression vector. The 3' end of a DNA sequence encoding the first polypeptide is ligated, with or without a peptide linker, to the 5' end of a DNA sequence encoding the second polypeptide so that the reading frames of the sequences are in phase to permit mRNA translation of the two DNA
sequences into a 25 single fusion protein that retains the biological activity of both the first and the second polypeptides.
A peptide linker sequence may be employed to separate the first and the second polypeptides by a distance sufficient to ensure that each polypeptide folds into its secondary and tertiary structures. Such a peptide linker sequence is incorporated into the 30 fusion protein using standard techniques well known in the art. Suitable peptide linker sequences may be chosen based on the following factors: ( 1 ) their ability to adopt a flexible extended conformation; (2) their inability to adopt a secondary structure that could interact with functional epitopes on the first and second polypeptides; and (3) the lack of hydrophobic or charged residues that might react with the polypeptide functional epitopes.
Preferred peptide linker sequences contain Gly, Asn and Ser residues. Other near neutral amino acids, such as Thr and Ala may also be used in the linker sequence. Amino acid sequences which may be usefully employed as linkers include those disclosed in Maratea et al., Gene 40:39-46, 1985; Murphy et al., Proc. Natl. Acad. Sci. USA 83:8258-8262, 1986; U.S.
Patent No. 4,935,233 and U.S. Patent No. 4,751,180. The linker sequence may be from 1 to about SO amino acids in length. Peptide sequences are not required when the first and second polypeptides have non-essential N-terminal amino acid regions that can be used to separate the functional domains and prevent steric interference.
The ligated DNA sequences are operably linked to suitable transcriptional or translational regulatory elements. The regulatory elements responsible for expression of DNA are located only 5' to the DNA sequence encoding the first polypeptides.
Similarly, stop codons require to end translation and transcription termination signals are only present 3' to the DNA sequence encoding the second polypeptide.
Fusion proteins are also provided that comprise a polypeptide of the present invention together with an unrelated immunogenic protein. Preferably the immunogenic protein is capable of eliciting a recall response. Examples of such proteins include tetanus, 2o tuberculosis and hepatitis proteins (see, for example, Stoute et al. New Engl. J. Med., 336:86-91 (1997)).
Polypeptides that comprise an immunogenic portion of a lung tumor protein may generally be used for therapy of lung cancer, wherein the polypeptide stimulates the . patient's own immune response to lung tumor cells. The present invention thus provides methods for using one or more of the compounds described herein (which may be polypeptides, polynucleotides or fusion proteins) for immunotherapy of lung cancer in a patient. As used herein, a "patient" refers to any warm-blooded animal, preferably a human.
A patient may be afflicted with disease, or may be free of detectable disease.
Accordingly, the compounds disclosed herein may be used to treat tong cancer or to inhibit the 3o development of lung cancer. In a preferred embodiment, the compounds are administered either prior to or following surgical removal of primary tumors and/or treatment by administration of radiotherapy and conventional chemotherapeutic drugs.
In these aspects, the inventive polypeptide is generally present within a pharmaceutical composition or a vaccine. Pharmaceutical compositions may comprise one or 5 more polypeptides, each of which may contain one or more of the above sequences (or variants thereof), and a physiologically acceptable carrier. The vaccines may comprise one or more such polypeptides and an immune response enhancer, such as an adjuvant, biodegradable microsphere (e.g., polylactic galactide) or a liposome (into which the polypeptide is incorporated). Pharmaceutical compositions and vaccines may also contain other epitopes of lung tumor antigens, either incorporated into a fusion protein as described above (i.e., a single polypeptide that contains multiple epitopes) or present within a separate polypeptide.
Alternatively, a pharmaceutical composition or vaccine may contain DNA
encoding one or muse of the above polypeptides and/or fusion proteins, such that the 15 polypeptide is generated in situ. In such pharmaceutical compositions and vaccines, the DNA
may be present within any of a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacteria and viral expression systems.
Appropriate nucleic acid expression systems contain the necessary DNA
sequences for expression in the patient (such as a suitable promoter). Bacterial delivery systems involve the 2o administration of a bacterium (such as Bacillus-Calmette-Guerrin) that expresses an epitope of a lung cell antigen on its cell surface. In a preferred embodiment, the DNA
may be introduced using a viral expression system (e.g., vaccinia or other pox virus, retrovirus, or adenovirus), which may involve the use of a non-pathogenic (defective), replication competent virus. Suitable systems are disclosed, for example, in Fisher-Hoch et al., PNAS
86:317-321, 1989; Flexner et al., Ann. N. Y. Acad Sci. 569:86-103, 1989:
Flexner et al., vaccine 8:17-21, 1990; U.S. Patent Nos.4,603,112, 4,769,330, and 5.017,487;
WO 89/01973; U.S. Patent No. 4,777,127; GB 2,200,651; EP 0,345,242; WO
91/02805;
Berkner, Biotechniques 6:616-627, 1988; Rosenfeld et al., Science 252:431-434, 1991; Kolls et al., PNAS 91:215-219, 1994; Kass-Eisler et al., PNAS 90:11498-11502, 1993;
Guzman et 3o al., Circulation 88:2838-2848, 1993; and Guzman et al., Cir. Res. 73:1202-1207, 1993.
Techniques for incorporating DNA into such expression systems are well known to those of ordinary skill in the art. The DNA may also be "naked," as described, for example, in published PCT application WO 90/11092, and Ulmer et al., Science 259:1745-1749, 1993, reviewed by Cohen, Science 259:1691-1692. 1993. The uptake of naked DNA may be increased by coating the DNA onto biodegradable beads, which are efficiently transported s into the cells.
Routes and frequency of administration, as well as dosage, will vary from individual to individual and may parallel those currently being used in immunotherapy of other diseases. In general, the pharmaceutical compositions and vaccines may be administered by injection (e.g., intracutaneous, intramuscular, intravenous or subcutaneous), to intranasally (e.g., by aspiration) or orally. Between 1 and 10 doses may be administered over a 3-24 week period. Preferably, 4 doses are administered, at an interval of 3 months, and booster administrations may be given periodically thereafter. Alternate protocols may be appropriate for individual patients. A suitable dose is an amount of polypeptide or DNA that is effective to raise an immune response (cellular and/or humoral) against lung tumor cells in 15 a treated patient. A suitable immune response is at least 10-50% above the basal {i.e., untreated) level. In general, the amount of polypeptide present in a dose (or produced in situ by the DNA in a dose) ranges from about I pg to about 100 mg per kg of host, typically from about 10 pg to about I mg, and preferably from about 100 pg to about 1 p,g.
Suitable dose sizes will vary with the size of the patient, but will typically range from about 0.01 mL to 2o about 5 mL.
While any suitable carrier known to those of ordinary skill in the art may be employed in the pharmaceutical compositions of this invention, the type of carrier will vary depending on the mode of administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline, alcohol, a lipid, a wax 25 and/or a buffer. For oral administration, any of the above earners or a solid carrier, such as mannitol, lactose, starch. magnesium stearate, sodium saccharine, talcum, cellulose, glucose, sucrose, and/or magnesium carbonate, may be employed. Biodegradable microspheres (e.g., polylactic glycolide) may also be employed as carriers for the pharmaceutical compositions of this invention. Suitable biodegradable microspheres are disclosed, for example, in U.S.
3o Patent Nos. 4,897,268 and 5,075,109.

Any of a variety of immune response enhancers may be employed in the vaccines of this invention. For example, an adjuvant may be included. Most adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a nonspecific stimulator of immune response, such as lipid A, Bordella pertussis or Mycobacterium tuberculosis. Such adjuvants are commercially available as, for example, Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, MI), and Merck Adjuvant 65 (Merck and Company, Inc., lRahway, NJ).
Within certain embodiments, polynucleotides of the present invention may be to formulated so as to permit entry into a cell of a mammal, preferably a human, and expression therein. Such formulations are particularly useful for therapeutic purposes.
Those of skill in the art will appreciate that there are many ways to achieve expression of a polynucleotide in a target cells, and any suitable method may be employed. For example, a polynucleotide may be incorporated into a viral vector such as, but not limited to, adenovirus, adeno-associated t5 virus, retrovirus, or vaccinia or other pox virus (e.g. avian pox virus).
Techniques for incorporating DNA into such vectors are well known to those of skill in the art. A retroviral vector may additionally transfer or incorporate a targeting moiety, such as a gene that encodes for a ligand for a receptor on a specific target cell, to render the vector target specific.
Targeting may also be accomplished using an antibody, by methods know to those of 20 ordinary skill in the art.
Polypeptides disclosed herein may also be employed in adoptive immunotherapy for the treatment of cancer. Adoptive immunotherapy may be broadly classified into either active or passive immunotherapy. In active immunotherapy, treatment relies on the in vivo stimulation of the endogenous host immune system to react against 25 tumors with the administration of immune response-modifying agents (for example, tumor vaccines, bacterial adjuvants, and/or cytokines).
In passive immunotherapy, treatment involves the delivery of biologic reagents with established tumor-immune reactivity (such as effector cells or antibodies) that can directly or indirectly mediate antitumor effects and does not necessarily depend on an 3o intact host immune system. Examples of effector cells include T lymphocytes (for example, CD8+ cytotoxic T-lymphocyte, CD4+ T-helper. tumor-infiltrating lymphocytes), killer cells (Natural Killer cells, lymphokine-activated killer cells), B cells, or antigen presenting cells (such as dendritic cells and macrophages) expressing the disclosed antigens.
The polypeptides disclosed herein may also be used to generate antibodies or anti-idiotypic antibodies (as in U.S. Patent No. 4,918,164), for passive immunotherapy.
s The predominant method of procuring adequate numbers of T-cells for adoptive immunotherapy is to grow immune T-cells in vitro. Culture conditions for expanding single antigen-specific T-cells to several billion in number with retention of antigen recognition in vivo are well known in the art. These in vitro culture conditions typically utilize intermittent stimulation-with antigen, often in the presence of cytokines, such 1o as IL-2, and non-dividing feeder cells. As noted above, the immunoreactive polypeptides described herein may be used to rapidly expand antigen-specific T cell cultures in order to generate sufficient number of cells for immunotherapy. In particular, antigen-presenting cells, such as dendritic, macrophage or B-cells, may be pulsed with immunoreactive polypeptides or transfected with a polynucleotide sequence(s), using standard techniques well 15 known in the art. For cultured T-cells to be effective in therapy, the cultured T-cells must be able to grow and distribute widely and to survive long term in vivo. Studies have demonstrated that cultured T-cells can be induced to grow in vivo and to survive long term in substantial numbers by repeated stimulation with antigen supplemented with IL-2 (see, for example, Cheever et al. Ibic~.
2o The polypeptides disclosed herein may also be employed to generate andlor isolate tumor-reactive T-cells, which can then be administered to the patient.
In one technique, antigen-specific T-cell lines may be generated by in vivo immunization with short peptides corresponding to immunogenic portions of the disclosed polypeptides.
The resulting . antigen specific CD8+ CTL clones may be isolated from the patient, expanded using standard 25 tissue culture techniques, and returned to the patient.
Alternatively, peptides con:esponding to immunogenic portions of the polypeptides may be employed to generate tumor reactive T cell subsets by selective in vitro stimulation and expansion of autologous T cells to provide antigen-specific T
cells which may be subsequently transferred to the patient as described, for example, by Chang et al.
30 (Crit. Rev. Oncol. Hematol., 22(3), 213, 1996).

In another embodiment, syngeneic or autologous dendritic cells may be pulsed with peptides corresponding to at least an immunogenic portion of a polypeptide disclosed herein. The resulting antigen-specific dendritic cells may either be transferred into a patient, or employed to stimulate T cells to provide antigen-specific T cells which may, in turn, be s administered to a patient. The use of peptide-pulsed dendritic cells to generate antigen-specific T cells and the subsequent use of such antige-specific T cells to eradicate tumors in a marine model has been demonstrated by Cheever et al. ("Therapy With Cultured T
Cells:
Principles Revisited, " Immunological Reviews, 157:177, 1997 Additionally vectors expressing-the disclosed polynucleotides may be introduced into stem cells taken from the patient and clonally propagated in vitro for autologous transplant back into the same patient.
In one embodiment, cells of the immune system, such as T cells, may be isolated from the peripheral blood of a patient, using a commercially available cell separation system, such as CellPro Incorporated's (Bothell, WA) CEPRATE'~"'' system (see U.S. Patent 15 No. 5,240,856; U.S. Patent No. 5,215,926; WO 89/06280; WO 91/16116 and WO
92/07243).
The separated cells are stimulated with one or more of the immunoreactive polypeptides contained within a delivery vehicle, such as a microsphere. to provide antigen-specific T
cells. The population of tumor antigen-specific T cells is then expanded using standard techniques and the cells are administered back to the patient.Polypeptides and fusion proteins 20 of the present invention may also be used to generate binding agents, such as antibodies or fragments thereof, that are capable of detecting metastatic human lung tumors.
Binding agents of the present invention may generally be prepared using methods known to those of ordinary skill in the art, including the representative procedures described herein. Binding agents are capable of differentiating between patients with and without lung cancer, using the 25 representative assays described herein. In other words, antibodies or other binding agents raised against a lung tumor protein, or a suitable portion thereof, will generate a signal indicating the presence of primary or metastatic lung cancer in at least about 20% of patients afflicted with the disease, and will generate a negative signal indicating the absence of the disease in at least about 90% of individuals without primary or metastatic lung cancer.
3o Suitable portions of such lung tumor proteins are portions that are able to generate a binding agent that indicates the presence of primary or metastatic lung cancer in substantially all (i.e., at least about 80%, and preferably at least about 90%) of the patients for which lung cancer would be indicated using the full length protein, and that indicate the absence of lung cancer in substantially all of those samples that would be negative when tested with full length protein. The representative assays described below, such as the two-antibody sandwich 5 assay, may generally be employed for evaluating the ability of a binding agent to detect metastatic human lung tumors.
The ability of a polypeptide prepared as described herein to generate antibodies capable of detecting primary or metastatic human lung tumors may generally be evaluated by raising one or more antibodies against the polypeptide (using, for example, a to representative method described herein) and determining the ability of such antibodies to detect such tumors in patients. This determination may be made by assaying biological samples from patients with and without primary or metastatic lung cancer for the presence of a polypeptide that binds to the generated antibodies. Such test assays may be performed, for example, using a representative procedure described below. Polypeptides that generate 15 antibodies capable of detecting at least 20% of primary or metastatic lung tumors by such procedures are considered to be useful in assays for detecting primary or metastatic human lung tumors. Polypeptide specific antibodies may be used alone or in combination to improve sensitivity.
Polypeptides capable of detecting primary or metastatic human lung tumors 2o may be used as markers for diagnosing lung cancer or for monitoring disease progression in patients. In one embodiment, lung cancer in a patient may be diagnosed by evaluating a biological sample obtained from the patient for the level of one or more of the above polypeptides, relative to a predetermined cut-off value. As used herein, suitable "biological samples" include blood, sera, urine and/or lung secretions.
25 The level of one or more of the above polypeptides may be evaluated using any binding agent specific for the polypeptide(s). A "binding agent," in the context of this invention, is any agent (such as a compound or a cell) that binds to a polypeptide as described above. As used herein, "binding" refers to a noncovalent association between two separate molecules (each of which may be free (i. e., in solution) or present on the surface of a cell or a 3o solid support), such that a "complex" is formed. Such a complex may be free or immobilized (either covalently or noncovalently) on a support material. The ability to bind may generally be evaluated by determining a binding constant for the formation of the complex. The binding constant is the value obtained when the concentration of the complex is divided by the product of the component concentrations. In general, two compounds are said to "bind"
in the context of the present invention when the binding constant for complex formation exceeds about 103 L/mol. The binding constant may be determined using methods well known to those of ordinary skill in the art.
Any agent that satisfies the above requirements may be a binding agent. For example, a binding agent may be a ribosome with or without a peptide component, an RNA
molecule or a peptide. In a preferred-embodiment, the binding partner is an antibody, or a fragment thereof. Such antibodies may be polyclonal, or monoclonal. In addition, the antibodies may be single chain, chimeric, CDR-grafted or humanized. Antibodies may be prepared by the methods described herein and by other methods well known to those of skill in the art.
There are a variety of assay formats known to those of ordinary skill in the art for using a binding partner to detect polypeptide markers in a sample. See, e.g., Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. In a preferred embodiment, the assay involves the use of binding partner immobilized on a solid support to bind to and remove the polypeptide from the remainder of the sample. The bound polypeptide may then be detected using a second binding partner that contains a reporter 2o group. Suitable second binding partners include antibodies that bind to the binding partner/polypeptide complex. Alternatively, a competitive assay may be utilized, in which a polypeptide is labeled with a reporter group and allowed to bind to the immobilized binding partner after incubation of the binding partner with the sample. The extent to which components of the sample inhibit the binding of the labeled polypeptide to the binding partner is indicative of the reactivity of the sample with the immobilized binding partner.
The solid support may be any material known to those of ordinary skill in the art to which the antigen may be attached. For example, the solid support may be a test well in a microtiter plate or a nitrocellulose or other suitable membrane.
Alternatively, the support may be a bead or disc, such as glass, fiberglass, latex or a plastic material such as polystyrene or polyvinylchloride. The support may also be a magnetic particle or a fiber optic sensor, such as those disclosed, for example, in U.S. Patent No. 5,359,681. The binding agent may be immobilized on the solid support using a variety of techniques known to those of skill in the art, which are amply described in the patent and scientific literature. In the context of the present invention, the term "immobilization" refers to both noncovalent association, such as adsorption, and covalent attachment (which may be a direct linkage between the antigen and functional groups on the support or may be a linkage by way of a cross-linking agent).
Immobilization by adsorption to a well in a microtiter plate or to a membrane is preferred. In such cases, adsorption may be achieved by contacting the binding agent, in a suitable buffer, with the solid support for a suitable amount of time. The contact time varies w;rt, temperature, but is typically between about 1 hour and about 1 day. In general, contacting a well of a plastic microtiter plate (such as polystyrene or polyvinylchloride) with an amount of binding agent ringing from about 10 ng to about 10 fig, and preferably about 100 ng to about I pg, is sufficient to immobilize an adequate amount of binding agent.
Covalent attachment of binding agent to a solid support may generally be achieved by first reacting the support with a bifunctional reagent that will react with both the support and a functional group, such as a hydroxyl or amino group, on the binding agent. For example, the binding agent may be covalently attached to supports having an appropriate polymer coating using benzoquinone or by condensation of an aldehyde group on the support with an amine and an active hydrogen on the binding partner (see, e.g., Pierce Immunotechnology Catalog and Handbook, 1991, at A12-A13).
2o In certain embodiments, the as .say is a two-antibody sandwich assay. This assay may be performed by first contacting an antibody that has been immobilized on a solid support, commonly the well of a microtiter plate, with the sample, such that polypeptides within the sample are allowed to bind to the immobilized antibody. Unbound sample is then removed from the immobilized polypeptide-antibody complexes and a second antibody (containing a reporter group) capable of binding to a different site on the polypeptide is added. The amount of second antibody that remains bound to the solid support is then determined using a method appropriate for the specific reporter group.
More specifically, once the antibody is immobilized on the support as described above, the remaining protein binding sites on the support are typically blocked.
3o Any suitable blocking agent known to those of ordinary skill in the art, such as bovine serum albumin or Tween 20TM (Sigma Chemical Co., St. Louis, MO). The immobilized antibody is then incubated with the sample, and polypeptide is allowed to bind to the antibody. The sample may be diluted with a suitable diluent, such as phosphate-buffered saline (PBS) prior to incubation. In general, an appropriate contact time (i.e., incubation time) is that period of time that is sufficient to detect the presence of polypeptide within a sample obtained from an individual with lung cancer. Preferably, the contact time is sufficient to achieve a level of binding that is at least about 95% of that achieved at equilibrium between bound and unbound polypeptide. Those of ordinary skill in the art will recognize that the time necessary to achieve equilibrium may be readily determined by assaying the level of binding that occurs over a period of time. At room temperature, an incubation time of about 30 minutes is generally sufficient.
Unbound sample may then be removed by washing the solid support with an appropriate buffer, such as PBS containing 0.1 % Tween 20T"'. The second antibody, which contains a reporter group, may then be added to the solid support. Preferred reporter groups include enzymes (such as horseradish peroxidase), substrates, cofactors, inhibitors, dyes, ~5 radionuclides, luminescent groups, fluorescent groups and biotin. The conjugation of antibody to reporter group may be achieved using standard methods known to those of ordinary skill in the art.
The second antibody is then incubated with the immobilized antibody-polypeptide complex for an amount of time sufficient to detect the bound polypeptide. An 20 appropriate amount of time may generally be determined by assaying the level of binding that occurs over a period of time. Unbound second antibody is then removed and bound second antibody is detected using the reporter group. The method employed for detecting the reporter group depends upon the nature of the reporter group. For radioactive groups, scintillation counting or autoradiographic methods are generally appropriate.
Spectroscopic 25 methods may be used to detect dyes, luminescent groups and fluorescent groups. Biotin may be detected using avidin, coupled to a different reporter group (commonly a radioactive or fluorescent group or an enzyme). Enzyme reporter groups may generally be detected by the addition of substrate (generally for a specific period of time), followed by spectroscopic or other analysis of the reaction products.
3o To determine the presence or absence of lung cancer, the signal detected from the reporter group that remains bound to the solid support is generally compared to a signal that corresponds to a predetermined cut-off value. In one preferred embodiment, the cut-off value is the average mean signal obtained when the immobilized antibody is incubated with samples from patients without lung cancer. In general, a sample generating a signal that is three standard deviations above the predetermined cut-off value is considered positive for lung cancer. In an alternate preferred embodiment, the cut-off value is determined using a Receiver Operator Curve, according to the method of Sackett et al., Clinical Epidemiology: A
Basic Science for Clinical Medicine, Little Brown and Co., 1985, p. 106-7.
Briefly, in this embodiment, the cut-off value may be determined from a plot of pairs of true positive rates (i. e., sensitivity) and false positive rates ( 100%-specificity) that correspond to each possible cut-off value for the diagnostic test result. The cut-off value on the plot that is the closest to the upper left-hand corner (i. e., the value that encloses the largest area) is the most accurate cut-off value, and a sample generating a signal that is higher than the cut-off value determined by this method may be considered positive. Alternatively, the cut-off value may be shifted to the left along the plot, to minimize the false positive rate, or to the right, to minimize the false negative rate. In general, a sample generating a signal that is higher than the cut-off value determined by this method is considered positive for lung cancer.
In a related embodiment, the assay is performed in a flow-through or strip test format, wherein the antibody is immobilized on a membrane, such as nitrocellulose. In the flow-through test, polypeptides within the sample bind to the immobilized antibody as the 2o sample passes through the membrane. A second, labeled antibody then binds to the antibody-polypeptide complex as a solution containing the second antibody flows through the membrane. The detection of bound second antibody may then be performed as described above. In the strip test format, one end of the membrane to which antibody is bound is . immersed in a solution containing the sample. The sample migrates along the membrane through a region containing second antibody and to the area of immobilized antibody.
Concentration of second antibody at the area of immobilized antibody indicates the presence of lung cancer. Typically, the concentration of second antibody at that site generates a pattern, such as a line, that can be read visually. The absence of such a pattern indicates a negative result. In general, the amount of antibody immobilized on the membrane is selected 3o to generate a visually discernible pattern when the biological sample contains a level of polypeptide that would be sufficient to generate a positive signai in the two-antibody sandwich assay, in the format discussed above. Preferably, the amount of antibody immobilized on the membrane ranges from about 25 ng to about 1 pg, and more preferably from about 50 ng to about 500 ng. Such tests can typically be performed with a very small amount of biological sample.
5 Of course, numerous other assay protocols exist that are suitable for use with the antigens or antibodies of the present invention. The above descriptions are intended to be exemplary only.
In another embodiment, the above polypeptides may be used as markers for the progression of lung cancer. In this embodiment, assays as described above for the diagnosis of lung cancer may be performed over time, and the change in the level of reactive polypeptide(s) evaluated. For example, the assays may be performed every 24-72 hours for a period of 6 months to 1 year, and thereafter performed as needed. In general, lung cancer is progressing in those patients in whom the level of polypeptide detected by the binding agent increases over time. In contrast, lung cancer is not progressing when the level of reactive ~ 5 polypeptide either remains constant or decreases with time.
Antibodies for use in the above methods may be prepared by any of a variety of techniques known to those of ordinary skill in the art. See, e.g., Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. In one such technique, an immunogen comprising the antigenic polypeptide is initially injected into any 20 of a wide variety of mammals (e.g., mice, rats, rabbits, sheep and goats).
In this step, the polypeptides of this invention may serve as the immunogen without modification.
Alternatively, particularly for relatively short polypeptides, a superior immune response may be elicited if the polypeptide is joined to a carrier protein, such as bovine serum albumin or keyhole limpet hemocyanin. The immunogen is injected into the animal host, preferably 25 according to a predetermined schedule incorporating one or more booster immunizations, and the animals are bled periodically. Polyclonal antibodies specific for the polypeptide may then be purified from such antisera by, for example, affinity chromatography using the polypeptide coupled to a suitable solid support.
Monoclonal antibodies specific for the antigenic polypeptide of interest may 3o be prepared, for example, using the technique of Kohler and Milstein, Eur.
J. Immunol.
6:511-519, 1976, and improvements thereto. Briefly, these methods involve the preparation of immortal cell lines capable of producing antibodies having the desired specificity (i.e., reactivity with the polypeptide of interest). Such cell lines may be produced, for example, from spleen cells obtained from an animal immunized as described above. The spleen cells are then immortalized by, for example, fusion with a myeloma cell fusion partner, preferably one that is syngeneic with the immunized animal. A variety of fusion techniques may be employed. For example, the spleen cells and myeloma cells may be combined with a nonionic detergent for a few minutes and then plated at low density on a selective medium that supports the growth of hybrid cells, but not myeloma cells. A preferred selection technique uses HAT (hypoxanthine, aminopterin, thymidine) selection. After a sufficient to time, usually about 1 to 2 weeks, colonies of hybrids are observed. Single colonies are selected and tested for binding activity against the polypeptide. Hybridomas having high reactivity and specificity are preferred.
Monoclonal antibodies may be isolated from the supernatants of growing hybridoma colonies. In addition, various techniques may be employed to enhance the yield, is such as injection of the hybridoma cell line into the peritoneal cavity of a suitable vertebrate host, such as a mouse. Monoclonal antibodies may then be harvested from the ascites fluid or the blood. Contaminants may be removed from the antibodies by conventional techniques, such as chromatography, gel filtration, precipitation, and extraction. The polypeptides of this invention may be used in the purification process in, for example, an affinity chromatography 2o step.
Monoclonal antibodies of the present invention may also be used as therapeutic reagents, to diminish or eliminate lung tumors. The antibodies may be used on their own (for instance, to inhibit metastases) or coupled to one or more therapeutic agents.
. Suitable agents in this regard include radionuclides, differentiation inducers, drugs, toxins, 25 and derivatives thereof. Preferred radionuclides include ~°Y, 'Z'I, 'ZSI, "'I, 'S6Re, 'Bane, '-"At, and Z'ZBi. Preferred drugs include methotrexate, and pyrimidine and purine analogs.
Preferred differentiation inducers include phorbol esters and butyric acid.
Preferred toxins include ricin, abrin, diptheria toxin, cholera toxin, gelonin, Pseudomonas exotoxin, Shigella toxin, and pokeweed antiviral protein.
3o A therapeutic agent may be coupled (e.g., covalently bonded) to a suitable monoclonal antibody either directly or indirectly (e.g., via a linker group).
A direct reaction between an agent and an antibody is possible when each possesses a substituent capable of reacting with the other. For example, a nucleophilic group, such as an amino or sulihydryl group, on one may be capable of reacting with a carbonyl-containing group, such as an anhydride or an acid halide, or with an alkyl group containing a good leaving group (e.g., a halide) on the other.
Alternatively, it may be desirable to couple a therapeutic agent and an antibody via a linker group. A linker group can function as a spacer to distance an antibody from an agent in order to avoid interference with binding capabilities. A
linker group can also serve to increase the chemical reactivity of a substituent on an agent or an antibody, and thus increase the coupling efficiency. An increase in chemical reactivity may also facilitate the use of agents, or functional groups on agents, which otherwise would not be possible.
It will be evident to those skilled in the art that a variety of bifunctional or polyfunctional reagents, both homo- and hetero-functional (such as those described in the catalog of the Pierce Chemical Co., Rockford, IL), may be employed as the linker group.
Coupling may be effected, for example, through amino groups, carboxyl groups, sulfhydryl groups or oxidized carbohydrate residues. There are numerous references describing such methodology, e.g., U.S. Patent No. 4,671,958, to Rodwell et al.
Where a therapeutic agent is more potent when free from the antibody portion of the immunoconjugates of the present invention, it may be desirable to use a linker group 2o which is cleavable during or upon internalization into a cell. A number of different cleavable linker groups have been described. The mechanisms for the intracellular release of an agent from these linker groups include cleavage by reduction of a disulfide bond (e.g., U.S. Patent No.4,489,710, to Spider), by irradiation of a photolabile bond (e.g., U.S.
Patent No. 4,625,014, to Senter et al.), by hydrolysis of derivatized amino acid side chains (e.g., U.S.
Patent No. 4,638,045, to Kohn et al.), by serum complement-mediated hydrolysis (e.g., U.S.
Patent No. 4,671,958, to Rodwell et al.), and acid-catalyzed hydrolysis (e.g., U.S. Patent No. 4,569,789, to Blattler et al.).
It may be desirable to couple more than one agent to an antibody. In one embodiment, multiple molecules of an agent are coupled to one antibody molecule. In 3o another embodiment, more than one type of agent may be coupled to one antibody.
Regardless of the particular embodiment, immunoconjugates with more than one agent may be prepared in a variety of ways. For example, more than one agent may be coupled directly to an antibody molecule, or linkers which provide multiple sites for attachment can be used.
Alternatively, a carrier can be used.
A carrier may bear the agents in a variety of ways, including covalent bonding either directly or via a linker group. Suitable carriers include proteins such as albumins (e.g., U.S. Patent No. 4,507,234, to Kato et al.), peptides and polysaccharides such as aminodextran (e.g., U.S. Patent No. 4,699,784, to Shih et al.). A carrier may also bear an agent by noncovalent bonding or by encapsulation, such as within a liposome vesicle (e.g., U.S. Patent Nos. 4,429.008 and 4,873,088). Carriers specific for radionuclide agents include 1o radiohalogenated small molecules and chelating compounds. For example, U.S.
Patent No.
4,735,792 discloses representative radiohalogenated small molecules and their synthesis. A
radionuclide chelate may be formed from chelating compounds that include those containing nitrogen and sulfur atoms as the donor atoms for binding the metal, or metal oxide, radionuclide. For example, U.S. Patent No. 4,673,562, to Davison et al.
discloses ~ 5 representative chelating compounds and their synthesis.
A variety of routes of administration for the antibodies and immunoconjugates may be used. Typically, administration will be intravenous, intramuscular, subcutaneous or in the bed of a resected tumor. It will be evident that the precise dose of the antibody/immunoconjugate will vary depending upon the antibody used, the antigen density 20 on the tumor. and the rate of clearance of the antibody.
Diagnostic reagents of the present invention may also comprise DNA
sequences encoding one or more of the above polypeptides, or one or more portions thereof.
For example, at least two oligonucleotide primers may be employed in a polymerase chain reaction (PCR) based assay to amplify lung tumor-specific cDNA derived from a biological 25 sample, wherein at least one of the oligonucleotide primers is specific for a polynucleotide encoding a lung tumor protein of the present invention. The presence of the amplified cDNA
is then detected using techniques well known in the art, such as gel electrophoresis. Similarly, oligonucleotide probes specific for a polynucleotide encoding a lung tumor protein of the present invention may be used in a hybridization assay to detect the presence of an inventive 30 polypeptide in a biological sample.

As used herein, the term "oligonucleotide primer/probe specific for a polynucleotide" means an oligonucleotide sequence that has at least about 60%, preferably at least about 75% and more preferably at least about 90%, identity to the polynucleotide in question. Oligonucleotide primers and/or probes which may be usefully employed in the inventive diagnostic methods preferably have at least about 10-40 nucleotides.
In a preferred embodiment, the oligonucleotide primers comprise at least about 10 contiguous nucleotides of a polynucleotide having a partial sequence selected from SEQ ID NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181. Preferably, oligonucleotide probes for use in the inventive diagnostic--methods comprise at least about 15 contiguous to ohgonucleotides of a polynucleotide having a partial sequence provided in SEQ ID NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181.
Techniques for both PCR based assays and hybridization assays are well known in the art (see, for example, Mullis et al. Ibid; Ehrlich, Ibid). Primers or probes may thus be used to detect lung tumor-specific sequences in biological samples, including blood, semen, lung tissue andlor lung tumor tissue.

The following Examples are offered by way of illustration and not by way of limitation.
EXAMPLES
5 Example 1 PREPARATION OF LUNG TUMOR-SPECIFIC cDNA SEQUENCES USING
DIFFERENTIAL DISPLAY RT-PCR
This example illustrates the preparation of cDNA molecules encoding lung t o tumor-specific polypeptides using a differential display screen.
Tissue samples were prepared from breast tumor and normal tissue of a patient with lung cancer that was confirmed by pathology after removal of samples from the patient.
Normal RNA and tumor RNA was extracted from the samples and mRNA was isolated and converted into cDNA using a (dT),zAG (SEQ ID NO: 47) anchored 3' primer.
Differential 15 display PCR was then executed using a randomly chosen primer (SEQ ID NO:
48).
Amplification conditions were standard buffer containing 1.5 mM MgCI,, 20 pmol of primer, 500 pmol dNTP and 1 unit of Taq DNA polymerase (Perkin-Elmer, Branchburg, NJ).
Forty cycles of amplification were performed using 94 °C denaturation for 30 seconds. 42 °C
annealing for 1 minute and 72 °C extension for 30 seconds. Bands that were repeatedly 20 observed to be specific to the RNA fingerprint pattern of the tumor were cut out of a silver stained gel, subcloned into the pGEM-T vector (Promega, Madison, WI) and sequenced. The isolated 3' sequences are provided in SEQ ID NO: 1-16.
Comparison of these sequences to those in the public databases using the BLASTN program, revealed no significant homologies to the sequences provided in SEQ ID
25 NO: 1-11. To the best of the inventors' knowledge, none of the isolated DNA
sequences have previously been shown to be expressed at a greater level in human lung tumor tissue than in normal lung tissue.

Example 2 USE OF PATIENT SERA TO IDENTIFY DNA SEQUENCES ENCODING LUNG
TUMOR ANTIGENS
This example illustrates the isolation of cDNA sequences encoding lung tumor antigens by expression screening of lung tumor samples with autologous patient sera.
A human lung tumor directional cDNA expression library was constructed employing the Lambda ZAP Express expression system (Stratagene, La Jolla, CA).
Total RNA for the library was taken from a late SCID mouse passaged human squamous epithelial t o lung carcinoma and poly A+ RNA was isolated using the Message Maker kit (Gibco BRL, Gaithersburg, MD). The resulting library was screened using E. coli-absorbed autologous patient serum, as described in Sambrook et al., (Molecular Cloning: A
Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, 1989), with the secondary antibody being goat anti-human IgG-A-M (H + L) conjugated with alkaline phosphatase, developed with NBTBCIP (Gibco BRL). Positive plaques expressing immunoreactive antigens were purified. Phagemid from the plaques was rescued and the nucleotide sequences of the clones was determined.
Fifteen clones were isolated, referred to hereinafter as LT86-I - LT86-15.
The isolated cDNA sequences for LT86-1 - LT86-8 and LT86-10 - LT86-I S are provided in SEQ ID NO: 17-24 and 26-31, respectively, with the corresponding predicted amino acid sequences being provided in SEQ ID NO: 32-39 and 41-46, respectively. The determined cDNA sequence for LT86-9 is provided in SEQ ID NO: 25, with the corresponding predicted amino acid sequences from the 3' and 5' ends being provided in SEQ ID NO: 40 and 65, . respectively. These sequences were compared to those in the gene bank as described above.
Clones LT86-3, LT86-6 - LT86-9, LT86-11 - LT86-13 and LT86-15 (SEQ ID NO: 19, 25, 27-29 and 31, respectively) were found to show some homology to previously identified expressed sequence tags (ESTs), with clones LT86-6, LT86-8, LT86-11, LT86-12 and LT86 15 appearing to be similar or identical to each other. Clone LT86-3 was found to show some homology with a human transcription repressor. Clones LT86-6, 8, 9, I1, 12 and 15 were 3o found to show some homology to a yeast RNA Pol II transcription regulation mediator.
Clone LT86-13 was found to show some homology with a C. elegans leucine aminopeptidase. Clone LT86-9 appears to contain two inserts, with the 5' sequence showing homology to the previously identified antisense sequence of interferon alpha-induced P27, and the 3' sequence being similar to LT86-6. Clone LT86-14 (SEQ ID NO: 30) was found to show some homology to the trithorax gene and has an "RGD" cell attachment sequence and a beta-Lactamase A site which functions in hydrolysis of penicillin. Clones LT86-1, LT86-2, LT86-4, LT86-5 and LT86-10 (SEQ ID NOS: 17, 18, 20, 21 and 26, respectively) were found to show homology to previously identified genes. A subsequently determined extended cDNA sequence for LT86-4 is provided in SEQ ID NO: 66, with the corresponding predicted amino acid sequence being provided in-SEQ ID NO: 67.
to Subsequent studies led to the isolation of five additional clones, referred to as LT86-20, LT86-21, LT86-22, LT86-26 and LT86-27. The determined S' cDNA
sequences for LT86-20, LT86-22, LT86-26 and LT86-27 are provided in SEQ ID NO: 68 and 70-72, respectively, with the determined 3' cDNA sequences for LT86-21 being provided in SEQ ID
NO: 69. The corresponding predicted amino acid sequences for LT86-20, LT86-21, ~ 5 22, LT86-26 and LT86-27 are provided in SEQ ID NO: 73-77, respectively.
LT86-22 and LT86-27 were found to be highly similar to each other. Comparison of these sequences to those in the gene bank as described above, revealed no significant homologies to LT86-22 and LT86-27. LT86-20, LT86-2 Z and LT86-26 were found to show homology to previously identified genes.

Example 3 USE OF MOUSE ANTISERA TO IDENTIFY DNA SEQUENCES ENCODING LUNG
TUMOR ANTIGENS
This example illustrates the isolation of cDNA sequences encoding lung tumor antigens by screening of lung tumor cDNA libraries with mouse anti-tumor sera.
A directional cDNA lung tumor expression library was prepared as described above in Example 2. Sera was obtained from SCID mice containing late passaged human squamous cell and adenocarcinoma tumors. These sera were pooled and injected into normal mice to produce anti-lung tumor serum: Approximately 200,000 PFUs were screened from 1o the unamplified library using this antiserum. Using a goat anti-mouse IgG-A-M (H+L) alkaline phosphatase second antibody developed with NBT/BCIP (BRL Labs.), approximately 40 positive plaques were identified. Phage was purified and phagemid excised for 9 clones with inserts in a pBK-CMV vector for expression in prokaryotic or eukaryotic cells.
The determined cDNA sequences for 7 of the isolated clones (hereinafter referred to as L86S-3, L86S-12, L86S-16, L86S-25, L86S-36, L86S-40 and L86S-46) are provided in SEQ ID NO: 49-55, with the corresponding predicted amino acid sequences being provided in SEQ ID NO: 56-62, respectively. The S' cDNA sequences for the remaining 2 clones (hereinafter referred to as L86S-30 and L86S-41 ) are provided in SEQ ID
2o NO: 63 and 64. L86S-36 and L86S-46 were subsequently determined to represent the same gene. Comparison of these sequences with those in the public database as described above, revealed no significant homologies to clones L86S-30, L86S-36 and L86S-46 (SEQ
ID NO:
63, 53 and 55, respectively). L86S-16 (SEQ ID NO: 51) was found to show some homology . to an EST previously identified in fetal lung and germ cell tumor. The remaining clones were found to show at least some degree of homology to previously identified human genes.
Subsequently determined extended cDNA sequences for L86S-12, L86S-36 and L86S-46 are provided in SEQ ID NO: 78-80, respectively, with the corresponding predicted amino acid sequences being provided in SEQ ID NO: 81-83.
Subsequent studies led to the determination of 5' cDNA sequences for an 3o additional nine clones, referred to as L86S-6, L86S-11. L86S-14, L86S-29, L86S-34, L86S-39, L86S-47, L86S-49 and L86S-S 1 (SEQ ID NO: 84-92, respectively). The corresponding WO 99/38973 PCT/US99/Ot642 predicted amino acid sequences are provided in SEQ ID NO: 93-101, respectively. L86S-30, L86S-39 and L86S-47 were found to be similar to each other. Comparison of these sequences with those in the gene bank as described above, revealed no significant homologies to L86S-14. L86S-29 was found to show some homology to a previously identified EST.
L86S-6, L86S-11, L86S-34, L86S-39, L86S-47, L86S-49 and L86S-51 were found to show some homology to previously identified genes.
In further studies, a directional cDNA library was constructed using a Stratagene kit with a Lambda Zap Express vector. Total RNA for the library was isolated from two primary squamous lung tumors and poly A+ RNA was isolated using an oligo dT
t o column. Antiserum was developed in normal mice using a pool of sera from three SCID
mice implanted with human squamous lung carcinomas. Approximately 700,000 PFUs were screened from the unamplified library with E. coli absorbed mouse anti-SCID
tumor serum.
Positive plaques were identified as described above. Phage was purified and phagemid excised for 180 clones with inserts in a pBK-CMV vector for expression in prokaryotic or ~ 5 eukaryotic cells.
The determined cDNA sequences for 23 of the isolated clones are provided in SEQ ID NO: 126-148. Comparison of these sequences with those in the public database as described above revealed no significant homologies to the sequences of SEQ ID
NO: 139 and 143-I48. The sequences of SEQ ID NO: 126-138 and 140-142 were found to show 2o homology previously identified human polynucleotide sequences.

Example 4 USE OF MOUSE ANTISERA TO SCREEN LUNG TUMOR LIBRARIES PREPARED
FROM SCID MICE
5 This example illustrates the isolation of cDNA sequences encoding Lung tumor antigens by screening of lung tumor cDNA libraries prepared from SCID mice with mouse anti-tumor sera.
A directional cDNA lung tumor expression library was prepared using a Stratagene kit with a Lambda Zap Express vector. Total RNA for the library was taken from i o a late passaged lung adenocarcinoma grown in SCID mice. Poly A+ RNA was isolated using a Message Maker Kit (Gibco BRL). Sera was obtained from two SCID mice implanted with lung adenocarcinomas. These sera were pooled and injected into normal mice to produce anti-lung tumor serum. Approximately 700,000 PFUs were screened from the unamplified library with E. coli-absorbed mouse anti-SCID tumor serum. Positive plaques were identified 15 with a goat anti-mouse IgG-A-M (H+L) alkaline phosphatase second antibody developed with NBT/BCIP (Gibco BRL). Phage was purified and phagemid excised for 100 clones with insert in a pBK-CMV vector for expression in prokaryotic or eukaryotic cells.
The determined 5' cDNA sequences for 33 of the isolated clones are provided in SEQ ID NO: 149-181. The corresponding predicted amino acid sequences for SEQ ID
2o NO: 149, 150, 152-154, 156-158 and 160-I8I are provided in SEQ ID NO: 182, 183, 186, 188-193 and 194-215, respectively. The clone of SEQ ID NO: 151 (referred to as SAL-25) was found to contain two open reading frames (ORFs). The predicted amino acid sequences encoded by these ORFs are provided in SEQ ID NO: 184 and 185. The clone of SEQ
ID NO:
153 (referred to as SAL-50) was found to contain two open reading frames encoding the 25 predicted amino acid sequences of SEQ ID NO: 187 and 216. Similarly, the clone of SEQ ID
NO: 155 (referred to as SAL-66) was found to contain two open reading frames encoding the predicted amino acid sequences of SEQ ID NO: 189 and 190. Comparison of the isolated sequences with those in the public database revealed no significant homologies to the sequences of SEQ ID NO: 151, 153 and 154. The sequences of SEQ ID NO: 149, 152, 156, 30 157 and 158 were found to show some homology to previously isolated expressed sequence tags (ESTs). The sequences of SEQ ID NO: 150, 155 and 159-181 were found to show homology to sequences previously identified in humans.

WO 99/38973 PC1'/US99/01642 Example S
DETERMINATION OF TISSUE SPECIFICITY OF LUNG TUMOR POLYPEPTIDES
Using gene specific primers, mRNA expression levels for representative lung tumor polypeptides were examined in a variety of normal and tumor tissues using RT-PCR.
Briefly, total RNA was extracted from a variety of normal and tumor tissues using Trizol reagent. First strand synthesis was carried out using 2 pg of total RNA with Superscript II reverse transcriptase (BRL Life Technologies) at 42 °C
for one hour. The cDNA was then amplified by PCR with gene-specific primers. To ensure the semi-quantitative nature of the RT-PCR, /3-actin was used as an internal control for each of the to tissues examined. 1 p.l of 1:30 dilution of cDNA was employed to enable the linear range amplifcation of the (3-actin template and was sensitive enough'to reflect the differences in the initial copy numbers. Using these conditions, the (3-actin levels were determined for each reverse transcription reaction from each tissue. DNA contamination was minimized by DNase treatment and by assuring a negative PCR result when using first strand cDNA that was prepared without adding reverse transcriptase.
mRNA Expression levels were examined in five different types of tumor tissue (lung squamous tumor from 3 patients, lung adenocarcinoma, prostate tumor colon tumor and breast tumor), and different normal tissues, including lung from four patients, prostate, brain, kidney, liver, ovary, skeletal muscle, skin, small intestine, myocardium, retina and testes.
2o L86S-46 was found to be expressed at high levels in lung squamous tumor, colon tumor and prostate tumor, and was undetectable in the other tissues examined. L86S-5 was found to be expressed in the lung tumor samples and in 2 out of 4 normal lung samples, but not in the other normal or tumor tissues tested. L86S-16 was found to be expressed in all tissues except normal liver and normal stomach. Using real-time PCR, L86S-46 was found to be over-expressed in lung squamous tissue and normal tonsil, with expression being low or undetectable in all other tissues examined.

Example 6 ISOLATION OF DNA SEQUENCES ENCODING LUNG TUMOR ANTIGENS
DNA sequences encoding antigens potentially involved in squamous cell lung tumor formation were isolated as follows.
A lung tumor directional cDNA expression library was constructed employing the Lambda ZAP Express expression system (Stratagene, La Jolla, CA). Total RNA
for the library was taken from a pool of two human squamous epithelial lung carcinomas and poly A+ RNA was isolated using oligo-dT cellulose (Gibco BRL, Gaithersburg, MD).
Phagemid 1 o were rescued at random and the cDNA sequences of isolated clones were determined.
The determined cDNA sequence for the clone SLT-T1 is provided in SEQ ID
NO: 102, with the determined S' cDNA sequences for the clones SLT-T2, SLT-T3, SLT-T5, SLT-T7, SLT-T9, SLT-T10, SLT-T11 and SLT-T12 being provided in SEQ ID NO: 103-110, respectively. The corresponding predicted amino acid sequence for SLT-T1, SLT-T2, SLT-T3, SLT-T10 and SLT-T12 are provided in SEQ ID NO: 111-115, respectively.
Comparison of the sequences for SLT-T2, SLT-T3, SLT-T5, SLT-T7, SLT-T9 and SLT-with those in the public databases as described above, revealed no significant homologies.
The sequences for SLT-TIO and SLT-T12 were found to show some homology to sequences previously identified in humans.
2o The sequence of SLT-T1 was determined to show some homology to a PAC
clone of unknown protein function. The cDNA sequence of SLT-T1 (SEQ ID NO:
102) was found to contain a mutator (MUTT) domain. Such domains are known to function in removal of damaged guanine from DNA that can cause A to G transversions (see, for example, el-Deity, W.S., 1997 Curr. Opin. Oncol. 9:79-87: Okamoto, K. et al. 1996 Int. J.
Cancer 65:437-41; Wu, C. et al. 1995 Biochem. Biophys. Res. Commun. 21:1:1239-45;
Porter, D.W.
et al. 1996 Chem. Res. Toxicol. 9:1375-81 ). SLT-T1 may thus be of use in the treatment, by gene therapy, of lung cancers caused by, or associated with, a disruption in DNA repair.

In further studies, DNA sequences encoding antigens potentially involved in adenocarcinoma lung tumor formation were isolated as follows. A human lung tumor directional cDNA expression library was constructed employing the Lambda ZAP
Express expression system (Stratagene, La Jolla, CA). Total RNA for the library was taken from a late SCID mouse passaged human adenocarcinoma and poly A+ RNA rv~ isolated using the Message Maker kit (Gibco BRL, Gaithersburg, MD). Phagemid were rescued at random and the cDNA sequences of isolated clones were determined.
The determined 5' cDNA sequences for five isolated clones (referred to as SALT-T3, SALT-T4, SALT-T7, SALT-T8, and SALT-T9) are provided in SEQ ID NO:

120, with the corresponding predicted amino acid sequences being provided in SEQ ID NO:
121-125. SALT-T3 was found to show 98% identity to the previously identified human transducin-like enhancer protein TLE2. SALT-T4 appears to be the human homologue of the mouse H beta 58 gene. SALT-T7 was found to have 97% identity to human 3-mercaptopyruvate sulfurtransferase and SALT-T8 was found to show homology to human interferon-inducible protein 1-8U. SALT-T9 shows approximately 90% identity to human mucin MUC 5B.

Example 7 SYNTHESIS OF POLYPEPTIDES
Polypeptides may be synthesized on a Perkin Elmer/Applied Biosystems 5 Division 430A peptide synthesizer using FMOC chemistry with HPTU (O-Benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate) activation. A Gly-Cys-Gly sequence may be attached to the amino terminus of the peptide to provide a method of conjugation, binding to an immobilized surface, or labeling of the peptide. Cleavage of the peptides from the solid support may be carried out -using the following cleavage mixture:
trifluoroacetic to acid:ethanedithiolahioanisole:water:phenol (40:1:2:2:3). After cleaving for 2 hours, the peptides may be precipitated in cold methyl-t-butyl-ether. The peptide pellets may then be dissolved in water containing 0.1 % trifluoroacetic acid (TFA) and lyophilized prior to purification by C 18 reverse phase HPLC. A gradient of 0%-60% acetonitrile (containing 0.1 % TFA} in water (containing 0.1 % TFA) may be used to elute the peptides.
Following 1s lyophilization of the pure fractions, the peptides may be characterized using electrospray or other types of mass spectrometry and by amino acid analysis.
From the foregoing, it will be appreciated that, although specific embodiments of the invention have been described herein for the purposes of illustration, various 2o modifications may be made without deviating from the spirit and scope of the invention.

SEQUENCE LISTING
<110> Corixa Corporation <120> COMPOUNDS FOR THERAPY AND DIAGNOSIS OF LUNG CANCER AND METHODS FOR
THEIR USE
<130> 210121.447PC
<140> PCT
<141> 1999-O1-28 <160> 216 <170> PatentIn Ver. 2.0 <210> 1 <211> 339 <212> DNA
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<213> Homo Sapiens <400> 2 gtactcagac cacgactgca ttttctccac tgctgacggg tctaatacca gctgcttccc 60 tttcttggag gcagagctng tgaccttgag aaagtgacct gtgaccatca tgtgggtagt 120 gagctgctgc aaggtgtcat gggagctccc acactccatg cactttwaga tctgggactt 180 gcaggcctca ractgccagg tgtagctcgc tccattttgg tagccatagc gsttgttgga 240 ggacaactgc aagttggcgt tcttctgaga agaaaaagaa tctgcaaaag atcctgtggt 300 tgaatcgggg gaacacggcc gattgacatc aaaaacgcgt ttcttagccc gggtgaccat 360 tttcgaggaa atggttgggg actggctcct tcaaaggcac tttttggtta tgttttgttt 420 yaatcatgtk gacgctccaa tcttggragg gaatcgaang rantcnccnc caaaacatrc 480 ~stttcagraa ccttttgarc atcctctttt ttccgtrtcc cggmaargcc cytttccckg 540 ggctttgaaa wyagcctsgt tgggttctta aattaccart ccacnwgttg gaattccccg 600 ggccccctgc ccggktccaa ccaattttgg graaaacccc cncansccgt tkggantgcn 660 acaacntggn ntttttcntt tcgtgntccc ctngaacc 6g8 <210> 3 <211> 697 <212> DNA
<213> Homo Sapiens <400> 3 gtactcagac ccccaacctc gaacagccag aagacaggtt gtctcctggg ccttggacac 60 agccngccag gccattgaag ganaagcaaa gacgaagcga accatctctc tccattgtgg 120 gggccaagta gctgcantan ccttcagtcc cagttgcatt gggttaaaga gctcatacat 180 actatgtgtn aggggtacag aagcttttcc tcatagggca tgagctctcc nagagttgac 240 cttttgcctn aacttggggt ttctgtggtt cataaagttn ggatatgtat tttttttcaa 300 atggaanaaa atccgtattt ggcaaaaaga ctccaggggg atgatactgt ccttgccact 360 tacagtccaa angatnttcc ccaaagaata gacatttttt cctctcatca cttctggatg 420 caaaatcttt tatttttttc ctttctcgca ccnccccaga ccccttnnag gttnaaccgc 480 ttcccatctc ccccattcca cacgatnttg aattngcann ncgttgntgg tcgggtcccn 540 nccgaaaggg tntttttatt cggggtnctg anttnnnaac cnctnagttg aatccgcggg 600 gcggccnngn gggttnnacc atgntgggga naactncccn ccgcgnttgg aatgccanag 660 ccttgaaant tttcttttgg tcgccccccn gagattc 697 <210> 4 <211> 712 <212> DNA
<213> Homo Sapiens <400> 4 gtactcagac aaccaatagg tgtgttyctc anatctgaaa cacaaaaaga ttctagctna 60 taatgttsaa tggttgaggg tttaagtgat cttggtatgt tngatttagc agcgatnggc 120 cgggtgcggt ggctcacgca tgtatcccag cactttggga ggccgaggca ggaggatcac 180 ctgaggtcag gagtttgaga ccagcctggc cgacatggtn aaaccccgtc tctactanga 240 atacanaaat tagcccgggc atagtggcgc gtgcctrtga cctcsgctac tttggggatt 300 ctcctgagga agaattgctt gaactcaggg aagtggargt ttgcagtgag cttaaatcaa 360 gccactggca ctcccagcct gggktaacag agccamgact ctkgccgaaa aaaaaraama 420 cgacggagaa nmagrtctgt tattccatgg gaaattkgaa tttccttcyt tkaaatatct 480 taaaatnggt cctcctwaaa aaagttcggc tggggcccgk tggctcacat tttkttaycc 540 cycccccttt tggggarggc caarggccgg kttgawtnnc ccttgagggg ccanaactcc 600 agnaaccrgn cccgggccar smgwkgkstr armccctttc cyyccmaraa aawwcsmaaa 660 wwttycccsc cygsykggct ggkasckgtt myyyyygmtm csyagcttgc tt 712 <210> 5 <211> 679 <212> DNA
<213> Homo sapiens <400> 5 gtactcagac cacctcacat gcagggtnag aaacatggag tgtgcggcag catcctcctc 60 acatcccttt gtgagcacgg ctgctccgga atactgacca tctgggctag cacgacctaa 120 cagagggttc tgcaggatgt gctattttaa agcagctggg tgcaacttgt gaaaacggga 180 atctngaagc agaacatgtn atcagcgatg gctgggattg gtggacagga ttgacaggag 240 tatttgaggc tctaccaggc ctgtctacag gacagcttca tcgaagggac attttttaac 300 ctgttatttt anatnccaca tatntttttt aatgctnaag catacaggtt gaatttctgg 360 atcgtaacta ctagtgactt ctgaggttta cagttngaat atgttctcnn aggtttatca 420 agttntgtta ttgatgatng gtaatctaca cctctggaag ctgtngaatg tgaaaaagat 480 ncntncanct gaccagtttg nagggcactc tcttctggna agnaatccgn ccaaaaaaat 540 tgtttcnagg gggcntgggg ggtttaaaaa aatgtttctn ttnccntaaa aatgtttacc 600 cnnctattga aaaaatgggg gtcgnggggg gcttnaaatc cccnanttnt gaatnttnta 660 tccggaanct tggtttccc <210> 6 <2I1> 369 <212> DNA
<213> Homo Sapiens <400> 6 tcagtccagt catgggtcct ataagagaag tcactctgtg agtttccatg gaggaagaaa 60 aagcttcatt tctttaccct gcagcaacag cggagggagg gagagcctat cttctttgca 120 aattcattaa ctttgtggtt gaagggagca gcgtcngaaa ctgctttagc acagtgggag 180 gaaaacaaac agattcatct ccggaaacca aaggaaaggg tragtgggtt tttattagcc 240 agctgtatcc tagatggtca atttccagtg gatgaataca ccttacgtac gtttctcttg 300 cttcctacct nggcctgatc agctnggcac ttraatcatt ccgtnggggt wgctgtnaca 360 ctggactga 369 <210> 7 <211> 264 <212> DNA
<213> Homo Sapiens <400> 7 tgctggatra gggatggggc acgggaccac agatmgactt taactgcccc cacgttntcm 60 aggaaaggat tacaggcgtg agccactgcg cccggcctct tctccacttt cataggttcc 120 agtctctggt tcttctttct cagtttgttg tttttgcttc ttaaatmatg gagatnagaa 180 tgaacactac actcggaatc aggaagccct gcctggcgcc tctgtcacct gtctaggggc 240 ttcttctcac tgagtcatcc agca 264 <210> 8 <211> 280 <212> DNA
<213> Homo Sapiens <400> 8 acctcaactg cccanaacan aactgttgta caagatttga ggatttaaca atatttcaca 60 tgaaatattt cagacctacg ngagggctta aagacnaatt aaatgagcac cngtgtgccc 120 accgccccna ttaagaatta gagcaagcag tgaggtgaag ccttgtcctt gcttttaaca 180 tagaaagtga tccaaattca ccaaacttga cttnnggttt tgcagtgtgg cctcctgatt 240 ctagacnctg gcgaaacatt tgatgggcaa aaaaaaaaaa 2g0 <210> 9 <211> 449 <212> DNA
<213> Homo Sapiens <400> 9 tcgtcaactc caggatggct ttgaaaatna atggacacag atctctcctg ttttgatrat 60 ntgcagtgct natgactggc tttgcagttn attttgattc aggcaacaga tgttcctttt 120 ggttccctgt ctcccatggg cgtcatttca tgttgtcctc tgccttcccc cagatattct 180 aagttcagga cacaagcttc tggcccatgc agagcagagg ccatgagggg tcacagcatg 240 ggtacgggag gaaacactgg gctnacccag atnctggact tgagtcttgc ctctgctgct 300 tgctgcacag cttctgtcat ggtgctaaac ctgtgacctg cctcacaggc ttagagcatg 360 cccgtagaag tactctnaac taaratgctt tccacaaatg agatggtttc atgaaaactt 420 caaatagagg gcctgggcaa aaaaaaaaa 449 <210> 10 <211> 538 <212> DNA
<213> Homo Sapiens <400> 10 tttttttttt ttcccaaagg cctcaraaca ctagtcttct aattccaagc agaaagttac 60 atccgccggg atacatgcca cttggtttga taaatcaaaa tacagcatcc ttcagatccc 120 tttgctgagc aatacaatta tttgtatatg ttactttttt ttctgtttgg ctnaaagatt 180 tgatatgagc tgaggaaaat gaagccntta ctgctatnag atctnatccc tttccaccac 240 ctttcaggga tnttggcact gcayatattc agaattcccc nnagtcgctn gtgataaaaa 300 tgtcttcaga gatggcagaa tatgtttcct ttggtacatg ttcattaaaa atatacacgt 360 gctcactact gtggatatgt atgtnttgac cgatnacaca ggctgattta gggaagagat 420 aaaagcacac ttngaattta ttagcctttc accnagacta anattctgaa attaagaatg 480 tattccttgg tcaacaattt tcctcttctc ttagccctct tacattgtan tggactga 538 <210> 11 <211> 543 <212> DNA
<2I3> Homo sapiens <400> 11 tttttttttt ttgcccacag ctgccatctt tgtgtgataa ggccaacctt ctatgggaat 60 caaccctcgc catcccagca aatcccctct ctcccttctc atgggagtgc cttgtattca 120 tcaggcatct gggacttgat gtgggtntgg gatttgaaat cagagcacct nggtctctst 180 caccattctn tcacttatta gctctnacct tgggtnaata cctgccttag tgtcntaggt 240 acaatatgaa tattgtctat ttctcaggga ttgcaatgac nagtnnatna gtgcatgaga 300 gggtaaaacc acagggtact ccgctcctcc naagaatgga gaattttttc tagaagccca 360 natntgcttg gaaggttggc caccnagagc cnnaatcttc ttttatttnc cactgaangc 420 ctaagaggna attctgaact catccccnna tgacctctcc cgaatmagaa tatctctggc 480 acttaccata ttttcttgcc ctcttccact tacnaaactc ctttattcct taacnggacg 540 aaa 543 <210> 12 <211> 329 <212> DNA
<213> Homo sapiens <400> 12 cgatgacttg ggcagtgagt gggcctcctg ccaggtggca gggcacagct tagaccaaac 60 ccttggcctc ccccctctgc agstacctct gaccaagaag gaaactagca agcctatgct 120 ggcaagacca taggtggggt gctgggaatc ctcggggccg gctggcaccc actcctggtg 180 ctcaagggag agacccactt gttcagatgc atrggcctca ggcggttcaa ggcrgtctta 240 gagccacaga gtcaaataaa aatcaatttt gagagaccac agcacctgct gctttgatcg 300 tgatgttcaa ggcaagttgc aagtcatcg 329 <210> 13 <211> 314 <212> DNA
<213> Homo sapiens <400> 13 cgatgacttg cacccgggag ctgtgacagt ggcctggaag cagatggcag ccccgtcaag 60 gcgggagtgg agaccaccaa accctccaaa cagagcaaca actagtacgc ggccagcagc 120 tacctgagcc tgacgcccga gcagtggaag tcccacagaa gctacagctg ccaggtcacg 180 catgaaggga gcaccgtgga gaagacagtg gcccctacag aatgttcata ggttcccnac 240 tctnacccca cccacgggag cctgganctg cangatcccg ggggaagggt ctctctcccc 300 atcccaagtc atcg 314 <210> 14 <211> 691 <212> DNA

<213> Homo sapiens <400> 14 cgattacttg cacaatgcan attagaaccc aaatgaaggg tacaacccag atcttctggc 60 ttccagttca gtgctgctgg gtttttctta ctaaaccaaa acaatkaaga gcatagaagg 120 gaagagaaga ataaagtcta ttttggtctt tggtagcchg ggtaangaga atgctstcac 180 tctacnagaa aacccnaagt gaacccggct aatcaggacc gtgcttggga agggagcagg 240 ggcattacct ttcaacacca gaggttcttt gccttctctc tgcagggact cgargactat 300 gtgaagtggc tgggarggca tcactcggct tggttcattg gtrttctcat cataaactat 360 natttctttg gaaaaagatc ctcttgaaag artccttgcc ttccctacag gaaatcaagt 420 ctaggacagt gatcttgccc ctgcttgcas tctccgccgg ctgatcttat csgscccagt 480 tkatgtgsam cgctccttgg atrtkactct tgttttwctc cvaggaaggg gcytgcmagt 540 ccnwtnaatg amssgggccc ttaactccgg scrggtnamy ncttgsctsc rattttgggt 600 ycytcttcyt ttgsccmggt tcktcnaaac cacttngttr aattccccgg sccgcctkgc 660 nggtycaacc wttttgggaa mamcyccccc c <210> 15 <211> 355 <212> DNA
<213> Homo Sapiens <400> 15 acctgaactg tgtgttgaag agtgatgtcc tgctgcctgg agctcaagtc actactgatg 60 accgtgccta tgtccgacag ctagttncct ccatggatgt gactgagacc aatgtcttct 120 tcyaccctcg gctcttacct ttgacnaagt ctcccgttga gagtactacc gaaccaccag 180 cagttcgagc ctctnaagag cgtctaagcg atggggatat atatttactg gagaatgggc 240 tcaacctctt cctctgggtg ggagcaagcg tccagcaggg tgttgtccag agccttttca 300 gcgtctcctc cttcagtcag atcaccagtg gtntgagtgt tctgccagtt caggt 355 <210> I6 <211> 522 <212> DNA
<213> Homo Sapiens <400> 16 tcagtccagt gaggtggaag acttcgaggc tcgtgggagc cgcttctcca agtctgctga 60 tgagagacag cgcatgctgg tgcagcgtan ggacgaactc ctccagcaag ctcgcagacg 120 tttcttgaac aaaagttctg aagatgatgc ggcctcagag agcttcctcc cctcggaagg 180 tgcgtcctct gaccccgtga ccctncgtcg aangatgctg gctgccgccg cggaacggan 240 gcttcagaag cagcagacct cctngcgctc ccttgccttc ctcagctgcc tcctgcgccc 300 tgtgcccggc tgactggagg aggcctgtcc aattctgccc gccccatgga aaagcgggct 360 tgactgcatt gccgctgtat naaagcatgt ggtcttacag tgttnggacn gctnatnaat 420 ttnatcctnc tntgtaatac ttcctatgtg acatttctct tccccttgga aacactgcan 480 attttaactg tgagtttgat ctcttctngt gttactggac tg 522 <210> 17 <211> 317 <212> DNA
<213> Homo Sapiens <400> 17 gtgtcgcgaa ttcgcggtgg tgctaagaaa aggaagaaga agtcttacac cactcccaag 60 aaggataagc accagagaaa gaaggttcag ccggccgtcc tgaaatatta taaggtggat 120 gagaatggca aaattagttg ccttcgtcga gagtgcccct ctgatgaatg tggtgctggg 180 gtgtttatgg caagtcactt tgacagacat tattgtggca aatgttgtct gacccactgt 240 ttcaactaac cagaagacaa gtaactgtat gagttaatta aagacatgaa ctaaaaaaaa 300 aaaaaaaaaa actcgag 317 <210> 18 <211> 392 <212> DNA
<213> Homo Sapiens <400> 18 tggagatttc taatgaggtg aggaagttcc gtacattgac agaattgatc ctcgatgctc 60 aggaacatgt taaaaatcct tacaaaggca aaaaactcaa gaaacaccca gacttcccca 120 agaagcccct gaccccttat ttccgcttct tcatggagaa gcgggccaag tatgcgaaac 180 tccaccctca gatgagcaac ctggacctga ccaagattct gtccaagaaa tacaaggagc 240 ttccggagaa gaagaagatg aaatatgttc cggacttcca gagaagagaa acaggagttc 300 gagcgaaacc tggcccgatt cagggaggat cacccccacc ttatccagaa tgccaagaat 360 cggacatccc agagaagccc caagaccccc cg 392 <210> 19 <211> 2624 <212> DNA
<213> Homo Sapiens <400> 19 gaaacagtga gaaggagatt cctgtgctca atgagctgcc agtccccatg gtggcccgct 60 acattcgcat aaaccctcag tcctggtttg ataacgggag catctgcatg aggatggaga 120 tcttgggctg cccactgccg gatcctaata actattatca ccgacgtaat gagatgacca 180 ccacggatga cctggatttt aagcaccaca actattagga aatgcgccag ttgatgaagg 240 ttgtcaatga aatgtgcccc aatattacca ggatttacaa cattggcaaa agccaccagg 300 gcctgaaatt gtatgcggta gagatctctg accatcctgg ggaacatgaa gttggtgagc 360 ccgagttcca ctacatcgca ggggcccacg gcaatgaggt tctgggacga gaactgctgc 420 tgctgctgct gcacttcctc tgccaggaat actcggcgca gaacgcacgc atcgtccgct 480 tggtggagga gactcgaatc cacattctac cctccctcaa tcctgatggc tatgagaagg 540 cctatgaagg aggttccgag ttgggaggct ggtccctggg acgttggacc catgatggca 600 tcgatatcaa caacaacttt ccggatttaa actcgctgct ctgggaggca gaggaccagc 660 agaatgcccc aaggaaggtc cccaaccact acattgccat ccctgagtgg tttctgtctg 720 agaatgccac agtggccaca gagaccagag ccgtcatcgc ctggatggag aagatcccgt 780 ttgtgctggg aggcaaccta caggggggtg agctggtcgt ggcatacccc tatgacatgg 840 tgcggtccct gtggaagacc caggagcaca ccccaacacc tgatgatcat gtgttccgct 900 ggctggcgta ttcctacgcc tccactcacc gcctcatgac agatgccagg aggcgagtgt 960 gccacacgga agattttcag aaggaggagg gcaccgtcaa tggggcttcc tggcacacag 1020 tggctggaag tctaaacgat ttcagctacc tccatacaaa ctgctttgag ctgtccatct 1080 acgtgggctg tgataaatac ccacacgaga gcgagctgcc ggaggaatgg gagaataacc 1140 gggagtctct gattgtgttc atggagcagg ttcatcgagg catcaaaggc atagtgagag 1200 atttacaagg gaaagggatt tcaaatgctg tcatctctgt ggaaggtgtt aaccatgaca 1260 tccggacagc cagcgatggg gattactggc gtctactgaa ccctggcgaa tatgtggtca 1320 cagccaaggc ggaaggcttt atcacttcca ccaagaactg catggttggc tatgatatgg 1380 gagctactcg gtgtgacttc accctcacaa agaccaacct ggctaggata agagaaatta 1440 tggagacatt tgggaagcag cctgtcagcc taccctccag gcgcctgaag ctgcggggac 1500 ggaaaaggcg gcagcgtggg tgaccctgtc ggacacttga gacatacccc agaccgtgca 1560 aataaaaatc cactccagta gtaactctgt agcaggcttt ccctgttgtt ttgactgtaa 1620 ttcaagagac actcaggagc atacctgcat ggcttggctg accccaaagg ggagggctgg 1680 tggctcaggg tgttttgttt tttgtttttt gttttttcct ttgttctcat ttatccaaat 1740 accttgaaca gagcagcaga gaaaggccgg tggcagtgag ggaattaatt cagtgagtca 1800 gtctgagatt ctaaaaaggg tgcttgacca ctggccagga agggaaatca ggccttcccc 1860 catttgcgtg acattcaagc ttcccagtgc atttgcaagt ggcacagttg acattgcagc 1920 acccagggaa tcctttgccc cagatgttat catttgagat gctcttatgc agcctaagaa 1980 aatccatcct ctctggcccc aggggacaag ccaagctgct atgtacacac tcggtgttct 2040 attgacaata gaggcattta ttaccaagtg tgcatcgctg agtcctaaat cagctctgtt 2100 cctttttcca acaaagcttg tcttcctaag agcagacaga agtggagagc acccaagaat 2160 gagtgctggg cagcagaccc tgggggaggg ggcttgctat cccagaaagc ccctaaaccc 2220 tttgctgctc cattagccct ggggtgagga gagccagaca tgttaggagg ccagagcagt 2280 cagtcagggc atcttggaaa agaccttgaa ggaagcaaac cctgggttcc ttttgctcca 2340 gaatgtgaga gctccaagtt ggccccaatc aggaggggag taatgatgaa catacagacg 2400 gccacatctt gccaatcaag catcatctga tgaaaaagaa agcaatctta ggattacctg 2460 ggacacgtca gtctgggaga ggtggttgaa tcattgtgta agggaatagt gtatctaatc 2520 tgtgttgatc ctgctgcctt gttgacctgg agagaatgaa acaaacaaac acataaacaa 2580 ataaagcaaa tggtaagatt aaaaaaaaaa aaaaaaaact cgag 2624 <210> 20 <211> 488 <212> DNA
<213> Homo Sapiens <400> 20 ctttcaaccc gcgctcgccg gctccagccc cgcgcgcccc caccccttgc cctcccggcg 60 gctccgcagg gtgaggtggc tttgaccccg ggttgcccgg ccagcacgac cgaggaggtg 120 gctggacagc tggaggatga acggagaagc cgactgcccc acagacctgg aaatggccgc 180 ccccagaggc caagaccgtt ggtcccagga agacatgctg actttgctgg aatgcatgaa 240 gaacaacctt ccatccaatg acagctccca gttcaaaacc acccaaacac acatggaccg 300 ggaaaaagtt gcattgaaag acttttctgg agacatgtgc aagctcaaat gggtcgagat 360 ctctaatgag gtgaggaagt tccgtacatt gacagaattg atcctcgata ctcaggaaca 420 tgtttaaaat ccttacaaag gcaaaaaatc aagaaacacc ccgacttccc cgagaaagcc 480 cctaaccc 488 <210> 21 <211> 391 <212> DNA
<213> Homo Sapiens <400> 21 atggaattgt ggttttctct ttgggatcaa tggtctcaga aattccagag aagaaagctg 60 tggcgattgc tgatgctttg ggcaaaatcc ctcagacagt cctgtggcgg tacactggaa 120 cccgaccatc gaatcttgcg aacaacacga tacttgttca gtggctaccc caaaacgatc 180 tgcttggtca cccaatgacc cgtgccttta tcacccatgc tagttcccat ggtgttaatg 240 aaagcatatg caatggcgtt cccatggtga tgataccctt atttggtgat cagatggaca 300 atgcaaagcg cagggagact aagggagctg gagtgaccct gaatgttctg gagatgactt 360 ctgaagatct agaagatgct ctgaagagca g 391 <210> 22 <211> 1320 <212> DNA
<213> Homo Sapiens <400> 22 aatctgctgg gaatttcttg ggttgacagc tcttggatcc ctattttgaa cagtggtagt 60 gtcctggatt acttttcaga aagaagtaat cctttttatg acagaacatg taataatgaa 120 gtggtcaaaa tgcagaggct aacattagaa cacttgaatc agatggttgg aatcgagtac 180 atccttttgc atgctcaaga gcccattctt ttcatcattc ggaagcaaca gcggcagtcc 240 cctgcccaag ttatcccact agctgattac tatatcattg ctggagtgat ctatcaggca 300 ccagacttgg gatcagttat aaactctaga gtgcttactg cagtgcatgg tattcagtca 360 gcttttgatg aagctatgtc atactgtcga tatcatcctt ccaaagggta ttggtggcac 420 ttcaaagatc atgaagagca agataaagtc agacctaaag ccaaaaggaa agaagaacca 480 agctctattt ttcagagaca acgtgtggat gctttacttt tagacctcag acaaaaattt 540 ccacccaaat ttgtgcagct aaagcctgga gaaaagcctg ttccagtgga tcaaacaaag 600 aaagaggcag aacctatacc agaaactgta aaacctgagg agaaggagac cacaaagaat 660 gtacaacaga cagtgagtgc taaaggcccc cctgaaaaac ggatgagact tcagtgagta 720 ctggacaaaa gagaagcctg gaagactcct catgctagtt atcatacctc agtactgtgg 780 ctcttgagct ttgaagtact ttattgtaac cttcttattt gtatggaatg cgcttatttt 840 ttgaaaggat attaggccgg atgtggtggc tcacgcctgt aatcccagca ctttgggagg 900 ccatggcggg tggatcactt gaggtcagaa gttcaagacc agcctgacca atatggtgaa 960 accccgtctc tactaaaaat acaaaaatta gccgggcgtg gtggcgggcg cccatagtcc 1020 cagctactcg ggaggctgag acaggagact tgcttgaacc cgggaggtgg aggttgccct 1080 gagctgatca tcctgctgtt gcactccagc ttgggcgaaa gagcgagact ttgtctctat 1140 aaagaaggaa agatattatt cccatcatga tttcttgtga atatttgtaa tatgtttttt 1200 gtaacctttc ctttcccgga cttgagcaac ctacacactc acatgtttaa tggtagatat 1260 gttttaaagc aagataaagg tattggtttt aaaaaaaaaa aaaaaaaaaa aaaactcgag 1320 <210> 23 -<211> 633 <212> DNA
<213> Homo Sapiens <400> 23 ctaagggcag tgaaggtgaa aaccctctca cggtcccagg gagggagaag gaaggcatgc 60 tgatgggggt taagccgggg gaggacgcat cggggcctgc tgaagacctt gtgagaagat 120 ctgagaaaga tactgcagct gttgtctcca gacagggcag ctccctgaac ctctttgaag 180 atgtgcagat cacagaacca gaagctgagc cagagtccaa gtctgaaccg agacctccaa 240 tttcctctcc gagggctccc cagaccagag ctgtcaagcc ccgacttcat cctgtgaagc 300 caatgaatgc cacggccacc aaggttgcta actgcagctt gggaactgcc accatcatcg 360 gtgagaactt gaacaatgag gtcatgatga agaaatacag cccctcggac cctgcatttg 420 catatgcgca gctgacccac gatgagctga ttcagctggt cctcaaacag aaggaaacga 480 taagcaagaa ggagttccag gtccgcgagc tggaagacta cattgacaac ctgctcgtca 540 gggtcatgga agaaaccccc aatatcctcc gcatcccgac tcaggttggc aaaaaagcag 600 gaaagatgta aattagcaga aaaaaaactc gag 633 <210> 24 <211> 1328 <212> DNA
<213> Homo sapiens <400> 24 gtaaacgctc tcggaattat ggcggcggtg gatatccgag acaatctgct gggaatttct 60 tgggttgaca gctcttggat ccctattttg aacagtggta gtgtcctgga ttacttttca 120 ~gaaagaagta atccttttta tgacagaaca tgtaataatg aagtggtcaa aatgcagagg 180 ctaacattag aacacttgaa tcagatggtt ggaatcgagt acatcctttt gcatgctcaa 240 gagcccattc ttttcatcat tcggaagcaa cagcggcagt cccctgccca agttatccca 300 ctagctgatt actatatcat tgctggagtg atctatcagg caccagactt gggatcagtt 360 ataaactcta gagtgcttac tgcagtgcat ggtattcagt cagcttttga tgaagctatg 420 tcatactgtc gatatcatcc ttccaaaggg tattggtggc acttcaaaga tcatgaagag 480 caagataaag tcagacctaa agccaaaagg aaagaagaac caagctctat ttttcagaga 540 caacgtgtgg atgctttact tttagacctc agacaaaaaa tttccaccca aatttgtgca 600 gtggatcaaa caaagaaaga ggcagaacct ataccagaaa ctgtaaGacc tgaggagaag 660 gagaccacaa agaatgtaca acagacagtg agtgctaaag gcccccctga aaaacggatg 720 agacttcagt gagtactgga caaaagagaa gcctggaaga ctcctcatgc tagttatcat 780 acctcagtac tgtggctctt gagctttgaa gtactttatt gtaaccttct tatttgtatg 840 gaatgcgctt atttttttga aaggatatta ggccggatgt ggtggctcac gcctgtaatc 900 ccagcacttt gggaggccat ggcgggtgga tcacttgagg tcagaagttc aagaccagcc 960 tgaccaatat ggtgaaaccc cgtctctact aaaaatacaa aaattagccg ggcgtggtgg 1020 cgggcgccca tagtcccagc tactcgggag gctgagacag gagacttgct tgaacccggg 1080 aggtggaggt tgccctgagc tgattatcat gctgttgcac tccagcttgg gcgacagagc 1140 gagactttgt ctcaaaaaag aagaaaagat attattccca tcatgatttc ttgtgaatat 1200 ttgtgatatg tcttctgtaa cctttcctct cccggacttg agcaacctac acactcacat 1260 gtttactggt agatatgttt aaaagcaaaa taaaggtatt tgtataaaaa aaaaaaaaaa 1320 aaactcga 1328 <210> 25 <211> 1758 <212> DNA
<213> Homo Sapiens <400> 25 gttttttttt tttttttttt aaagagttgc aacaattcat ctttatttct tattttcctc 60 tggagatgca gaatttggta tatttcaccc caagtatatt tgggatagtt ggctcctcgc 120 tgggtcagga tggctgggtg ccttctcccc tggcatggtt ctcttctctg cagggcgagg 180 ggcagggagc tagtaaaacc tcgcaatgac agccgcaatg gcagacccaa tggagcccag 240 gatgaacttg gtcaatccgg agagtccagt tgctcccagt gactgcagag tagccacaag 300 gctgcccgag gcaactccac ccccattggc aatggccgcc gcggacatca tcttggctgc 360 tatggaggac gaggcgattc ccgccgcagt gaagcccatg gcactgagtg gcggcggtgg 420 atatccgaga caatctgctg ggaatttctt gggttgacag ctcttggatc cctattttga 480 acagtggtag tgtcctggat tacttttcag aaagaagtaa tcctttttat gacagaacat 540 gtaataatga agtggtcaaa atgcagaggc taacattaga acacttgaat cagatggttg 600 gaatcgagta catccttttg catgctcaag agcccattct tttcatcatt cggaagcaac 660 agcggcagtc ccctgcccaa gttatcccac tagctgatta ctatatcatt gctggagtga 720 tctatcaggc accagacttg ggatcagtta taaactctag agtgcttact gcagtgcatg 780 gtattcagtc agcttttgat gaagctatgt catactgtcg atatcatcct tccaaagggt 840 attggtggca cttcaaagat catgaagagc aagataaagt cagacctaaa gccaaaagga 900 aagaagaacc aagctctatt tttcagagac aacgtgtgga tgctttactt ttagacctca 960 gacaaaaatt tccacccaaa tttgtgcagc taaagcctgg agaaaagcct gttccagtgg 1020 atcaaacaaa gaaagaggca gaacctatac cagaaactgt aaaacctgag gagaaggaga 1080 ccacaaagaa tgtacaacag acagtgagtg ctaaaggccc ccctgaaaaa cggatgagac 1140 ttcagtgagt actggacaaa agagaagcct gaaagactcc tcatgctagt tatcatacct 1200 cagtactgtg gctcttgagc tttgaagtac tttattgtaa ccttcttatt tgtatggaat 1260 gcgcttattt tttgaaagga tattaggccg gatgtggtgg ctcacgcctg taatcccagc 1320 actttgggag gccatggcgg gtggatcact tgaggtcaga agttcaagac cagcctgacc 1380 aatatggtga aaccccgtct ctactaaaaa tacaaaaatt agccgggcgt ggtggcgggc 1440 gcccatagtc ccagctactc gggaggctga gacaggagac ttgcttgaac ccgggaggtg 1500 gaggttgccc tgagctgatt atcatgctgt tgcactccag cttgggcgac agagcgagac 1560 tttgtctcaa aaaagaagaa aagatattat tcccatcatg atttcttgtg aatatttgtt 1620 atatgtcttc tgttaccttt cctctcccgg aattgagcaa cctacacact cacatgttta 1680 ctggtagata tgtttaaaag caaataaagg tattggtata tattgcttca aaaaaaaaaa 1740 aaaaaaaaaa aactcgag 1758 <210> 26 <211> 493 <212> DNA
<213> Homo Sapiens <400> 26 gaggcgagcg gcagggcctg gtggcgagag cgcggctgtc actgcgcccg agcatcccag 60 agctttccga gcggacgagc cggccgtgcc gggcatcccc agcctcgcta ccctcgcagc 120 acacgtcgag ccccgcacag gcaagggtcc ggaacttagc ccaaagcacg tttcccctgg 180 cagcgcagga gacgcccggc cgcgcgccgg cgcacgcccc cctctcctcc tttgttccgg 240 gggtcggcgg ccgctctcct gccagcgtcg ggatctcggc cccgggaggc gggccgtcgg 300 gcgcagccgc gaagattccg ttggaactga cgcagagccg agtgcagaag atctgggtgc 360 ccgtggacca caggccctcg ttgcccagat cctgtgggcc aaagctgacc aactcccccg 420 ccgtcttcgt catggtgggc ctcccccgcc cggggcaaga cctacttctc cacgaaagct 480 tactcgctgc ctc 493 <210> 27 <211> 1331 <212> DNA
<213> Homo Sapiens <400> 27 ggtggatatc cgagacaatc tgctgggaat ttcttgggtt gacagctctt ggatccctat 60 tttgaacagt ggtagtgtcc tggattactt ttcagaaaga agtaatcctt tttatgacag 120 aacatgtaat aatgaagtgg tcaaaatgca gaggctaaca ttagaacact tgaatcagat 180 ggttggaatc gagtacatcc ttttgcatgc tcaagagccc attcttttca tcattcggaa 240 gcaacagcgg cagtcccctg cccaagttat cccactagct gattactata tcattgctgg 300 agtgatctat caggcaccag acttgggatc agttataaac tctagagtgc ttactgcagt 360 gcatggtatt cagtcagctt ttgatgaagc tatgtcatac tgtcgatatc atccttccaa 420 agggtattgg tggcacttca aagatcatga agagcaagat aaagtcagac ctaaagccaa 480 aaggaaagaa gaaccaagct ctatttttca gagacaacgt gtggatgctt tacttttaga 540 cctcagacaa aaatttccac ccaaatttgt gcagctaaag cctggagaaa agcctgttcc 600 agtggatcaa acaaagaaag aggcagaacc tataccagaa actgtaaaac ctgaggagaa 660 ggagaccaca aagaatgtac aacagacagt gagtgctaaa ggcccccctg aaaaacggat 720 gagacttcag tgagtactgg acaaaagaga agcctggaag actcctcatg ctagttatca 780 tacctcagta ctgtggctct tgagctttga agtactttat tgtaaccttc ttatttgtat 840 ggaatgcgct tattttttga aaggatatta ggccggatgt ggtggctcac gcctgtaatc 900 ccagcacttt gggaggccat ggcgggtgga tcacttgagg tcagaagttc aagaccagcc 960 tgaccaatat ggtgaaaccc cgtctctact aaaaatacaa aaattagccg ggcgtggtgg 1020 cgggcgccca tagtcccagc tactcgggag gctgagacag gagacttgct tgaacccggg 1080 aggtggaggt tgccctgagc tgattatcat gctgttgcac tccagcttgg gcgacagagc 1140 gagactttgt ctcaaaaaaa gaagaaaaga tattattccc atcatgattt cttgtgaata 1200 tttgttatat gtcttctgta acctttcctc tcccggactt gagcaaccta cacactcaca 1260 tgtttactgg tagatatgtt taaaagcaaa ataaaggtat tggtataaaa aaaaaaaaaa 1320 aaaaactcga g 1331 <210> 28 c211> 1333 <212> DNA
c213> Homo Sapiens <~400> 28 cggcggtgga tatccgagac aatctgctgg gaatttcttg ggttgacagc tcttggatcc 60 ctattttgaa cagtggtagt gtcctggatt acttttcaga aagaagtaat cctttttatg 120 acagaacatg taataatgaa gtggtcaaaa tgcagaggct aacattagaa cacttgaatc 180 agatggttgg aatcgagtac atccttttgc atgctcaaga gcccattctt ttcatcattc 240 ggaagcaaca gcggcagtcc cctgcccaag ttatcccact agctgattac tatatcattg 300 ctggagtgat ctatcaggca ccagacttgg gatcagttat aaactctaga gtgcttactg 360 cagtgcatgg tattcagtca gcttttgatg aagctatgtc atactgtcga tatcatcctt 420 ccaaagggta ttggtggcac ttcaaagatc atgaagagca agataaagtc agacctaaag 480 ccaaaaggaa agaagaacca agctctattt ttcagagaca acgtgtggat gctttacttt 540 tagacctcag acaaaaattt ccacccaaat ttgtgcagct aaagcctgga gaaaagcctg 600 ttccagtgga tcaaacaaag aaagaggcag aacctatacc agaaactgta aaacctgagg 660 il agaaggagac cacaaagaat gtacaacaga cagtgagtgc taaaggcccc cctgaaaaac 720 ggatgagact tcagtgagta ctggacaaaa gagaagcctg gaagactcct catgctagtt 780 atcatacctc agtactgtgg ctcttgagct ttgaagtact ttattgtaac cttcttattt 840 gtatggaatg cgcttatttt ttgaaaggat attaggccgg atgtggtggc tcacgcctgt 900 aatcccagca ctttgggagg ccatggcggg tggatcactt gaggtcagaa gttcaagacc 960 agcctgacca atatggtgaa accccgtctc tactaaaaat acaaaaatta gccgggcgtg 1020 gtggcgggcg cccatagtcc cagctactcg ggaggctgag acaggagact tgcttgaacc 1080 cgggaggtgg aggttgccct gagctgatta tcatgctgtt gcactccagc ttgggcgaca 1140 gagcgagact ttgtctcaaa aaagaagaaa agatattatt cccatcatga tttcttgtga 1200 atatttgtga tatgtcttct gtaacctttc ctctcccgga cttgagcaac ctacacactc 1260 acatgtttac tggtagatat gtttaaaagc aaaataaagg tatttgtata aaaaaaaaaa 1320 aaaaaaactc gag 1333 <210> 29 <211> 813 <212> DNA
<213> Homo Sapiens <400> 29 ctgagctgca cttcagcgaa ttcacctcgg ctgtggctga catgaagaac tccgtggcgg 60 accgagacaa cagccccagc tcctgtgctg gcctcttcat tgcttcacac atcgggtttg 120 actggcccgg ggtctgggtc cacctggaca tcgctgctcc agtgcatgct ggcgagcgag 180 ccacaggctt tggggtggct ctcctactgg ctctttttgg ccgtgcctcc gaggacccgc 240 tgctgaacct ggtatccccg ctggactgtg aggtggatgc ccaggaaggc gacaacatgg 300 ggcgtgactc caagagacgg aggctcgtgt gagggctact tcccagctgg tgacacaggg 360 ttccttacct cattttgcac tgactgattt taagcaattg aaagattaac taactcttaa 420 gatgagtttg gcttctcctt ctgtgcccag tggtgacagg agtgagccat tcttctctta 480 gaagcagctt aggggcttgg tggggtctgg agaaaattgt cacagacccc ataggtctcc 540 atctgtaagc tctgtccctt gtcctccacc ctggtcttta gagccacctc aggtcaccct 600 ctgtagtgag tgtacttcct gacccaggcc cttgctcaag ctggggctcc ctggggtgtc 660 taaccagccc tgggtagatg tgactggctg ttagggaccc cattctgtga agcaggagac 720 cctcacagct cccaccaacc cccagttcac ttgaagttga attaaatatg gccacaacat 780 aaaaaaaaaa aaaaaaaaaa aaaaaaactc gag 813 <210> 30 <211> 1316 <212> DNA
<213> Homo Sapiens <400> 30 caggcgccca gtcatggccc aagagacagc accaccgtgt ggcccagtct caaggggtga 60 cagtccaatc atagaaaaga tggaaaaaag gacatgtgcc ctgtgccctg aaggccacga 120 gtggagtcaa atatactttt caccatcagg aaatatagtt gctcatgaaa actgtttgct 180 gtattcatca ggactggtgg agtgtgagac tcttgatcta cgtaatacaa ttagaaactt 240 tgatgtcaaa tctgtaaaga aagagatctg gagaggaaga agattgaaat gctcattctg 300 taacaaagga ggcgccaccg tggggtgtga tttatggttc tgtaagaaga gttaccacta 360 tgtctgtgcc aaaaaggacc aagcaattct tcaagttgat ggaaaccatg gaacttacaa 420 attattttgc ccagaacatt ctccagaaca agaagaggcc actgaaagtg ctgatgaccc 480 aagcatgaag aagaagagag gaaaaaacaa acgcc~ctca tcaggccctc ctgcacagcc 540 aaaaacgatg aaatgtagta acgccaaaag acatatgaca gaagagcctc atggtcacac 600 agatgcagct gtcaaatctc cttttcttaa gaaacgccag gaagcaggac ttcttactga 660 actatttgaa cacatactag aaaatatgga ttcagttcat ggaagacttg tggatgagac 720 tgcctcagag tcggactatg aagggatcga gaccttactg tttgactgtg gattatttaa 780 agacacacta agaaaattcc aagaagtaat caagagtaaa gcttgtgaat gggaagaaag 840 gcaaaggcag atgaagcagc agcttgaggc acttgcagac ttacaacaaa gcttgcgctc 900 atttcaagaa aatggggacc tggactgctc aagttctaca tcaggatcct tgctacctcc 960 tgaggaccac cagtaaaagc tgttcctcag gaaaactgga tggggcctcc atgttctcca 1020 aggatcgagg aagtcttcct gcctaccctg cccaccccag tcaagggcag caacaccaga 1080 gctttgctca gccttaaatg gaatcttaga gctttctctt gcttctgcta ctcctacaga 1140 tggcctcatc atggtctcca ctcagtatta ataactccat cagcatagag caaactcaac 1200 actgtgcatt gcacactgtt accatgggtt tatgctcact atcatatcac attgccaata 1260 tttagcacac ttaataaatg cttgtcaaaa cccaaaaaaa aaaaaaaaaa ctcgag 1316 <210> 31 <211> 1355 <212> DNA
<213> Homo Sapiens <400> 31 cggcggtgga tatccgagac aatctgctgg gaatttcttg ggttgacagc tcttggatcc 60 ctattttgaa cagtggtagt gtcctggatt acttttcaga aagaagtaat cctttttatg 120 acagaacatg taataatgaa gtggtcaaaa tgcagaggct aacattagaa cacttgaatc 180 agatggttgg aatcgagtac atccttttgc atgctcaaga gcccattctt ttcatcattc 240 ggaagcaaca gcggcagtcc cctgcccaag ttatcccact agctgattac tatatcattg 300 ctggagtgat ctatcaggca ccagacttgg gatcagttat aaactctaga gtgcttactg 360 cagtgcatgg tattcagtca gcttttgatg aagctatgtc atactgtcga tatcatcctt 420 ccaaagggta ttggtggcac ttcaaagatc atgaagagca agataaagtc agacctaaag 480 ccaaaaggaa agaagaacca agctctattt ttcagagaca acgtgtggat gctttacttt 540 tagacctcag acaaaaattt ccacccaaat ttgtgcagct aaagcctgga gaaaagcctg 600 ttccagtgga tcaaacaaag aaagaggcag aacctatacc agaaactgta aaacctgagg 660 agaaggagac cacaaagaat gtacaacaga cagtgagtgc taaaggcccc cctgaaaaac 720 ggatgagact tcagtgagta ctggacaaaa gagaagcctg gaagactcct catgctagtt 780 atcatacctc agtactgtgg ctcttgagct ttgaagtact ttattgtaac cttcttattt 840 gtatggaatg cgcttatttt ttgaaaggat attaggccgg atgtggtggc tcacgcctgt 900 aatcccagca ctttgggagg ccatggcggg tggatcactt gaggtcagaa gttcaagacc 960 agcctgacca atatggtgaa accccgtctc tactaaaaat acaaaaatta gccgggcgtg 1020 gtggcgggcg cccatagtcc cagctactcg ggaggctgag acaggagact tgcttgaacc 1080 cgggaggtgg aggttgccct gagctgatta tcatgctgtt gcactccagc ttgggcgaca 1140 gaacgagact ttgtctcaaa aaaagaagaa aagatattat tcccatcatg atttcttgtg 1200 aatatttgtt atatgtcttc tggtaacctt tcctctcccg gacttgaagc aacctcacac 1260 actcacatgt ttactggtag atatgtttta aaagcaaaat aaaggtattt gtttttccaa 1320 aaaaaaaaaa aaaaaaaaaa aaaaaaaaac tcgag 1355 <210> 32 <211> 80 <212> PRT
<213> Homo Sapiens <400> 32 Val Ser Arg Ile Arg Gly Gly Ala Lys Lys Arg Lys Lys Lys Ser Tyr Thr Thr Pro Lys Lys Asp Lys His Gln Arg Lys Lys Val Gln Pro Ala Val Leu Lys Tyr Tyr Lys Val Asp Glu Asn Gly Lys Ile Ser Cys Leu Arg Arg Glu Cys Pro Ser Asp Glu Cps Gly Ala Gly Val Phe Met Ala Ser His Phe Asp Arg His Tyr Cys Gly Lys Cys Cys Leu Thr His Cys <210> 33 <211> 130 <212> PRT
<213> Homo sapiens <400> 33 Glu Ile Ser Asn Glu Val Arg Lys Phe Arg Thr Leu Thr Glu Leu Ile Leu Asp Ala Gln Glu His Val Lys Asn.-Pro Tyr Lys Gly Lys Lys Leu Lys Lys His Pro Asp Phe Pro Lys Lys Pro Leu Thr Pro Tyr Phe Arg Phe Phe Met Glu Lys Arg Ala Lys Tyr Ala Lys Leu His Pro Gln Met Ser Asn Leu Asp Leu Thr Lys Ile L2u Ser Lys Lys Tyr Lys Glu Leu Pro Glu Lys Lys Lys Met Lys Tyr Val Pro Asp Phe Gln Arg Arg Glu Thr Gly Val Arg Ala Lys Pro Gly Pro Ile Gln Gly Gly Ser Pro Pro Pro Tyr Pro Glu Cys Gln Glu Ser Asp Ile Pro Glu Lys Pro Gln Asp Pro Pro <210> 34 <211> 506 <21~2> PRT
<213> Homo sapiens <400> 34 Asn Ser Glu Lys Glu Ile Pro Val Leu Asn Glu Leu Pro Val Pro Met Val Ala Arg Tyr Ile Arg Ile Asn Pro Gln Ser Trp Phe Asp Asn GIy Ser Ile Cys Met Arg Met Glu Ile Leu Gly Cys Pro Leu Pro Asp Pro Asn Asn Tyr Tyr His Arg Arg Asn Glu Met Thr Thr Thr Asp Asp Leu Asp Phe Lys His His Asn Tyr Lys Glu Met Arg Gln Leu Met Lys Val Val Asn Glu Met Cys Pro Asn Ile Thr Arg Ile Tyr Asn Ile Gly Lys Ser His Gln Gly Leu Lys Leu Tyr Ala Val Glu Ile Ser Asp His Pro Gly Glu His Glu Val Gly Glu Pro Glu Phe His Tyr Ile Ala Gly Ala His Gly Asn Glu Val Leu Gly Arg Glu-Leu Leu Leu Leu Leu Leu His Phe Leu Cys Gln Glu Tyr Ser Ala Gln Asn Ala Arg Ile Val Arg Leu Val Glu Glu Thr Arg Ile His Ile Leu Pro Ser Leu Asn Pro Asp Gly Tyr Glu Lys Ala Tyr Glu Gly Gly Ser Glu Leu Gly Gly Trp Ser Leu Gly Arg Trp Thr His Asp Gly Ile Asp Ile Asn Asn Asn Phe Pro Asp Leu Asn Ser Leu Leu Trp Glu Ala Glu Asp Gln Gln Asn Ala Pro Arg Lys Val Pro Asn His Tyr Ile Ala Ile Pro Glu Trp Phe Leu Ser Glu Asn Ala Thr Val Ala Thr Glu Thr Arg Ala Val Ile Ala Trp Met Glu Lys Ile Pro Phe Val Leu Gly Gly Asn Leu Gln Gly Gly Glu Leu Val VaI Ala Tyr Pro Tyr Asp Met Val Arg Ser Leu Trp Lys Thr Gln Glu His Thr Pro Thr Pro Asp Asp His Val Phe Arg Trp Leu Ala Tyr Ser Tyr Ala Ser Thr His Arg Leu Met Thr Asp Ala Arg Arg Arg Val Cars His Thr Glu Asp Phe Gln Lys Glu Glu Gly Thr Val Asn Gly Ala Ser Trp His Thr Val Ala Gly Ser Leu Asn Asp Phe Ser Tyr Leu His Thr Asn Cys Phe Glu Leu Ser Ile Tyr Val Gly Cys Asp Lys Tyr Pro His Glu Ser Glu Leu Pro Glu Glu Trp Glu Asn Asn Arg Glu Ser Leu Ile Val Phe Met Giu Gln Val His Arg Gly Ile Lys Gly Ile Val Arg Asp Leu Gln Gly Lys Gly Ile Ser Asn Ala Val Ile Ser Val Glu Gly Val Asn His Asp Ile Arg Thr Ala Ser Asp Gly Asp Tyr Trp Arg Leu Leu 420 425...- 430 Asn Pro Gly Glu Tyr Val Val Thr Ala Lys Ala Glu Gly Phe Ile Thr Ser Thr Lys Asn Cys Met Val Gly Tyr Asp Met Gly Ala Thr Arg Cys Asp Phe Thr Leu Thr Lys Thr Asn Leu Ala Arg Ile Arg Glu Ile Met Glu Thr Phe Gly Lys Gln Pro Val Ser Leu Pro Ser Arg Arg Leu Lys Leu Arg Gly Arg Lys Arg Arg Gln Arg Gly <210> 35 <211> 96 <212> PRT
<213> Homo Sapiens <400> 35 Met Asn Gly Glu Ala Asp Cys Pro Thr Asp Leu Glu Met Ala Ala Pro Arg Gly Gln Asp Arg Trp Ser Gln Glu Asp Met Leu Thr Leu Leu Glu Cys Met Lys Asn Asn Leu Pro Ser Asn Asp Ser Ser Gln Phe Lys Thr Thr Gln Thr His Met Asp Arg Glu Lys Val Ala Leu Lys Asp Phe Ser Gly Asp Met Cys Lys Leu Lys Trp Val Glu Ile Ser Asn Glu Val Arg 65 70 75 gp WO 99/38973 PC'T/US99/01642 Lys Phe Arg Thr Leu Thr Glu Leu Ile Leu Asp Thr Gln Glu His Val <210> 36 <211> i29 <212> PRT
<213> Homo Sapiens <400> 36 Gly Ile Val Val Phe Ser Leu Gly Ser Met Val Ser Glu Ile Pro Glu Lys Lys Ala Val Ala Ile Ala Asp Ala Leu Gly Lys Ile Pro Gln Thr Val Leu Trp Arg Tyr Thr Gly Thr Arg.Pro Ser Asn Leu Ala Asn Asn 3~ 40 45 Thr Ile Leu Val Gln Trp Leu Pro Gln Asn Asp Leu Leu Gly His Pro Met Thr Arg Ala Phe Ile Thr His Ala Ser Ser His Gly Val Asn Glu Ser Ile Cys Asn Gly Val Pro Met Val Met Ile Pro Leu Phe Gly Asp Gln Met Asp Asn Ala Lys Arg Arg Glu Thr Lys Gly Ala Gly Val Thr Leu Asn Val Leu Glu Met Thr Ser Glu Asp Leu Glu Asp Ala Leu Lys Ser <210> 37 <211> 238 <212> PRT
<213> Homo Sapiens <400> 37 Asn Leu Leu Gly Ile Ser Trp Val Asp Ser Ser Trp Ile Pro Ile Leu Asn Ser Gly Ser Val Leu Asp Tyr Phe Ser Glu Arg Ser Asn Pro Phe err Asp Arg Thr Cys Asn Asn Glu Val Val Lys Met Gln Arg Leu Thr Leu Glu His Leu Asn Gln Met Val Gly Ile Glu Tyr Ile Leu Leu His Ala Gln Glu Pro Ile Leu Phe Ile Ile Arg Lys Gln Gln Arg Gln Ser 65 70 75 g0 Pro Ala Gln Val Ile Pro Leu Ala Asp Tyr Tyr Ile Ile Ala Gly Val Ile Tyr Gln Ala Pro Asp Leu Gly Ser Val Ile Asn Ser Arg Val Leu Thr Ala Val His Gly Ile Gln Ser Ala Phe Asp Glu Ala Met Ser Tyr Cys Arg Tyr His Pro Ser Lys Gly Tyr Trp Trp His Phe Lys Asp His Glu Glu Gln Asp Lys Val Arg Pro Lys Ala Lys Arg Lys Glu Glu Pro Ser Ser Ile Phe Gln Arg Gln Arg Val Asp Ala Leu Leu Leu Asp Leu Arg Gln Lys Phe Pro Pro Lys Phe Val Gln Leu Lys Pro Gly Glu Lys Pro Val Pro Val Asp Gln Thr Lys Lys Glu Ala Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr Thr Lys Asn Val Gln Gln Thr Val Ser Ala Lys Gly Pro Pro Glu Lys Arg Met Arg Leu Gln <210> 38 <211> 202 <212> PRT
<213> Homo Sapiens <400> 38 Lys Gly Ser Glu Gly Glu Asn Pro Leu Thr Val Pro Gly Arg Glu Lys Glu Gly Met Leu Met Gly Val Lys Pro Gly Glu Asp Ala Ser Gly Pro Ala Glu Asp Leu Val Arg Arg Ser Glu Lys Asp Thr Ala Ala Val Val Ser Arg Gln Gly Ser Ser Leu Asn Leu Phe Glu Asp Val Gln Ile Thr Giu Pro Glu Ala Glu Pro Glu Ser Lys Ser Glu Pro Arg Pro Pro Ile 65 70 75 g0 Ser Ser Pro Arg Ala Pro Gln Thr Arg Ala Val Lys Pro Arg Leu His 85 90 g5 Pro Val Lys Pro Met Asn Ala Thr Ala Thr Lys Val Ala Asn Cys Ser Leu Gly Thr Ala Thr Ile Ile Gly Glu Asn Leu Asn Asn Glu Val Met Met Lys Lys Tyr Ser Pro Ser Asp Pro Ala Phe Ala Tyr Ala Gln Leu Thr His Asp Glu Leu Ile Gln Leu Val Leu Lys Gln Lys Glu Thr Ile Ser Lys Lys Glu Phe Gln Val Arg Glu Leu Glu Asp Tyr Ile Asp Asn Leu Leu Val Arg Val Met Glu Glu Thr Pro Asn Ile Leu Arg Ile Pro Thr Gln Val Giy Lys Lys Ala Gly Lys Met <210> 39 c211> 243 <212> PRT
c213> Homo sapiens <400> 39 Val Asn Ala Leu Gly Ile Met Ala Ala Val Asp Ile Arg Asp Asn Leu Leu Gly Ile Ser Trp Val Asp Ser Ser Trp Ile Pro Ile Leu Asn Ser Gly Ser Val Leu Asp Tyr Phe Ser Glu Arg Ser Asn Pro Phe Tyr Asp Arg Thr Cys Asn Asn Glu Val Val Lys Met Gln Arg Leu Thr Leu Glu His Leu Asn Gln Met Val Gly Ile Glu Tyr Ile Leu Leu His Ala Gln Glu Pro Ile Leu Phe Ile Ile Arg Lys Gln Gln Arg Gln Ser Pro Ala Gln Val Ile Pro Leu Ala Asp Tyr Tyr Ile Ile Ala Gly Val Ile Tyr Gln Ala Pro Asp Leu Gly Ser Val Ile Asn Ser Arg Val Leu Thr Ala Val His Gly Ile Gln Ser Ala Phe Asp Glu Ala Met Ser Tyr Cys Arg Tyr His Pro Ser Lys Gly Tyr Trp Trp His Phe Lys Asp His Glu Glu Gln Asp Lys Val Arg Pro Lys Ala Lys Arg Lys Glu Glu Pro Sex Sex Ile Phe Gln Arg Gln Arg Val Asp Ala Leu Leu Leu Asp Leu Arg Gln Lys Ile Ser Thr Gln Ile Cys Ala Val Asp Gln Thr Lys Lys Glu Ala Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr Thr Lys Asn Val Gln Gln Thr Val Ser Ala Lys Gly Pro Pro Glu Lys Arg Met Arg Leu Gln <210> 40 <211> 245 <212> PRT
<213> Homo Sapiens <400> 40 Ala Ala Val Asp Ile Arg Asp Asn Leu Leu Gly Ile Ser Trp Val Asp Ser Ser Trp Ile Pro Ile Leu Asn Ser Gly Ser Val Leu Asp Tyr Phe Ser Glu Arg Ser Asn Pro Phe Tyr Asp Arg Thr Cys Asn Asn Glu Val Val Lys Met Gln Arg Leu Thr Leu Glu His Leu Asn Gln Met Val Gly I~le Glu Tyr Ile Leu Leu His Ala Gln Glu Pro Ile Leu Phe Ile Ile Arg Lys Gln Gln Arg Gln Ser Pro Ala Gln Val Ile Pro Leu Ala Asp Tyr Tyr Ile Ile Ala Gly Val Ile Tyr Gln Ala Pro Asp Leu Gly Ser Val Ile Asn Ser Arg Val Leu Thr Ala Val His Gly Ile Gln Ser Ala Phe Asp Glu Ala Met Ser Tyr Cys Arg Tyr His Pro Ser Lys Gly Tyr Trp Trp His Phe Lys Asp His Glu Glu Gln Asp Lys Val Arg Pro Lys Ala Lys Arg Lys Glu Glu Pro Ser Ser Ile Phe Gln Arg Gln Arg Val Asp Ala Leu Leu Leu Asp Leu Arg Gln Lys Phe Pro Pro Lys Phe Val Gln Leu Lys Pro Gly Glu Lys Pro Val Pro Val Asp Gln Thr Lys Lys Glu Ala Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr Thr Lys Asn Val Gln Gln Thr Val 5er Ala Lys Gly Pro Pro Glu Lys Arg Met Arg Leu Gln <210> 41 <211> 163 <212> PRT
<213> Homo sapiens <400> 41 Gly Glu Arg Gln Gly Leu Val Ala Arg Ala Arg Leu Ser Leu Arg Pro Ser Ile Pro Glu Leu Ser Glu Arg Thr Ser Arg Pro Cys Arg Ala Ser Pro Ala Ser Leu Pro Ser Gln His Thr Ser Ser Pro Ala Gln Ala Arg Val Arg Asn Leu Ala Gln Ser Thr Phe Pro Leu Ala Ala Gln Glu Thr Pro Gly Arg Ala Pro Ala His Ala Pro Leu Ser Ser Phe Val Pro Gly ,65 70 ~ 75 80 Val Gly Gly Arg Ser Pro Ala Ser Val Gly Ile Ser Ala Pro Gly Gly Gly Pro Ser Gly Ala Ala Ala Lys Ile Pro Leu Glu Leu Thr Gln Ser Arg Val Gln Lys Ile Trp Val Pro Val Asp His Arg Pro Ser Leu Pro Arg Ser Cys Gly Pro Lys Leu Thr Asn Ser Pro Ala Val Phe Val Met Val Gly Leu Pro Arg Pro Gly Gln Asp Leu Leu Leu His Glu Ser Leu Leu Ala Ala <210> 42 <211> 243 <212> PRT
<213> Homo Sapiens <400> 42 Val Asp Ile Arg Asp Asn Leu Leu Gly Ile Ser Trp Val Asp Ser Ser Trp Ile Pro Ile Leu Asn Ser Gly Ser Val Leu Asp Tyr Phe Ser Glu Arg Ser Asn Pro Phe Tyr Asp Arg Thr Cys Asn Asn Glu Val Val Lys Met Gln Arg Leu Thr Leu Glu His Leu Asn Gln Met Val Gly Ile Glu Tyr Ile Leu Leu His Ala Gln Glu Pro Ile Leu Phe Ile Ile Arg Lys Gln Gln Arg Gln Ser Pro Ala Gln Val Ile Pro Leu Ala Asp Tyr Tyr Ile Ile Ala Gly Val Ile Tyr Gln Ala Pro Asp Leu Gly Ser Val Ile Asn Ser Arg Val Leu Thr Ala Val His Gly Ile Gln Ser Ala Phe Asp Glu Ala Met Ser Tyr Cys Arg Tyr His Pro Ser Lys Gly Tyr Trp Trp His Phe Lys Asp His Glu Glu GIn Asp Lys Val Arg Pro Lys Ala Lys Arg Lys Glu Glu Pro Ser Ser Ile Phe Gln Arg Gln Arg Val Asp Ala Leu Leu Leu Asp Leu Arg Gln Lys Phe Pro Pro Lys Phe Val Gln Leu Lys Pro Gly Glu Lys Pro Val Pro Val Asp Gln Thr Lys Lys Glu Ala Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr Thr Lys Asn Val Gln Gln Thr Val Ser Ala Lys Gly Pro Pro Glu Lys Arg Met Arg Leu Gln <210> 43 <211> 244 <212> PRT
<213> Homo sapiens <400> 43 Ala Val Asp Ile Arg Asp Asn Leu Leu Gly Ile Ser Trp Val Asp Ser Ser Trp Ile Pro Ile Leu Asn Ser Gly Ser Val Leu Asp Tyr Phe Ser 20 25..__ 30 Glu Arg Ser Asn Pro Phe Tyr Asp Arg Thr Cys Asn Asn Glu Val Val Lys Met Gln Arg Leu Thr Leu Glu His Leu Asn Gln Met Val Gly Ile Glu Tyr Ile Leu Leu His Ala Gln Glu Pro Ile Leu Phe Ile Ile Arg 65 70 75 g0 Lys Gln Gln Arg Gln Ser Pro Ala Gln Val Ile Pro Leu Ala Asp Tyr Tyr Ile Ile Ala Gly Val Ile Tyr Gln Ala Pro Asp Leu Gly Ser Val Ile Asn Ser Arg Val Leu Thr Ala Val His Gly Ile Gln Ser Ala Phe Asp Glu Ala Met Ser Tyr Cys Arg Tyr His Pro Ser Lys Gly Tyr Trp Trp His Phe Lys Asp His Glu Glu Gln Asp Lys Val Arg Pro Lys Ala Lys Arg Lys Glu Glu Pro Ser Ser ile Phe Gln Arg Gln Arg Val Asp Ala Leu Leu Leu Asp Leu Arg Gln Lys Phe Pro Pro Lys Phe Val Gln Leu Lys Pro Gly Glu Lys Pro Val Pro Val Asp Gln Thr Lys Lys Glu Ala Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr Thr Lys Asn Val Gln Gln Thr Val Ser Ala Lys Gly Pro Pro Glu Lys Arg Met Arg Leu Gln <210> 44 <211> 109 <212> PRT
<213> Homo Sapiens <400> 44 Glu Leu His Phe Ser Glu Phe Thr Ser Ala Val Ala Asp Met Lys Asn Ser Val Ala Asp Arg Asp Asn Ser Pro Ser Ser Cys Ala Gly Leu Phe Ile Ala Ser His Ile Gly Phe Asp Trp Pro Gly Val Trp Val His Leu Asp Ile Ala Ala Pro Val His Ala Gly Glu Arg Ala Thr Gly Phe Gly Val Ala Leu Leu Leu Ala Leu Phe Gly Arg Ala Ser Glu Asp Pro Leu 65' 70 75 80 Leu Asn Leu Val Ser Pro Leu Asp Cys Glu Val Asp Ala Gln Glu Gly Asp Asn Met Gly Arg Asp Ser Lys Arg Arg Arg Leu Val <210> 45 <211> 324 <212> PRT
<213> Homo Sapiens <400> 45 Arg Arg Pro Val Met Ala Gln Glu Thr Ala Pro Pro Cys Gly Pro Val Ser Arg Gly Asp Ser Pro Ile Ile Glu Lys Met Glu Lys Arg Thr Cys Ala Leu Cys Pro Glu Gly His Glu Trp Ser Gln Ile Tyr Phe Ser Pro Ser Gly Asn Ile Val Ala His Glu Asn Cys Leu Leu Tyr Ser Ser Gly Leu Val Glu Cys Glu Thr Leu Asp Leu Arg Asn Thr Ile Arg Asn Phe Asp Val Lys Ser VaI Lys Lys Glu Ile Trp Arg Gly Arg Arg Leu Lys Cys Ser Phe Cys Asn Lys Gly Gly Ala Thr Val Gly Cys Asp Leu Trp Phe Cys Lys Lys Ser Tyr His Tyr Val Cys Ala Lys Lys Asp Gln Ala Ile Leu Gln Val Asp Gly Asn His Gly Thr Tyr Lys Leu Phe Cys Pro Glu His Ser Pro Glu Gln Glu Glu Ala Thr Glu Ser Ala Asp Asp Pro Ser Met Lys Lys Lys Arg Gly Lys Asn Lys Arg Leu Ser Ser Gly Pro Pro Ala Gln Pro Lys Thr Met Lys Cys Ser Asn Ala Lys Arg His Met Thr Glu Glu Pro His Gly His Thr Asp Ala Ala Val Lys Ser Pro Phe Leu Lys Lys Cys Gln Glu Ala Gly Leu Leu Thr Glu Leu Phe Glu His Ile Leu Glu Asn Met Asp Ser Val His Gly Arg Leu Val Asp Glu Thr Ala Ser Glu Ser Asp Tyr Glu Gly Ile Glu Thr Leu Leu Phe Asp Cys Gly Leu Phe Lys Asp Thr Leu Arg Lys Phe Gln Glu Val Ile Lys Ser Lys Ala Cys Glu Trp Glu Glu Arg Gln Arg Gln Met Lys Gln Gln Leu Glu Ala Leu Ala Asp Leu Gln Gln Ser Leu Cys Ser Phe Gln Glu Asn Gly Asp Leu Asp Cys Ser Ser Ser Thr Ser GIy Ser Leu Leu Pro Pro Glu Asp His Gln <210> 46 <211> 244 <212> PRT
<213> Homo Sapiens <400> 46 Ala Val Asp Ile Arg Asp Asn Leu Leu Gly Ile Ser Trp Val Asp Ser Ser Trp Ile Pro Ile Leu Asn Ser Gly Ser Val Leu Asp Tyr Phe Ser Glu Arg Ser Asn Pro Phe Tyr Asp Arg Thr Cys Asn Asn Glu Val Val Lys Met Gln Arg Leu Thr Leu Glu His Leu Asn Gln Met Val Gly Ile Glu Tyr Ile Leu Leu His Ala Gln Glu Pro Ile Leu Phe Ile Ile Arg Lys Gln Gln Arg Gln Ser Pro Ala Gln Val Ile Pro Leu Ala Asp Tyr Tyr Ile Ile Ala Gly Val Ile Tyr Gln..Ala Pro Asp Leu Gly Ser Val leo los llo Ile Asn Ser Arg Val Leu Thr Ala Val His Gly Ile Gln Ser Ala Phe Asp Glu Ala Met Ser Tyr Cys Arg Tyr His Pro Ser Lys Gly Tyr Trp Trp His Phe Lys Asp His Glu Glu Gln Asp Lys Val Arg Pro Lys Ala Lys Arg Lys Glu Glu Pro Ser Ser Ile Phe Gln Arg Gln Arg Val Asp Ala Leu Leu Leu Asp Leu Arg Gln Lys Phe Pro Pro Lys Phe Val Gln Leu Lys Pro Gly Glu Lys Pro Val Pro Val Asp Gln Thr Lys Lys Glu Ala Glu Pro Ile Pro Glu Thr Val Lys Pro Glu Glu Lys Glu Thr Thr Lys Asn Val Gln Gln Thr Val Ser Ala Lys Gly Pro Pro Glu Lys Arg Met Arg Leu Gln <210> 47 <211> 14 <212> DNA
<213> Homo sapiens <400> 47 tttttttttt ttag 14 <210> 48 <211> 10 <212> DNA
<213> Homo Sapiens <400> 48 cttcaacctc 10 <210> 49 <211> 496 <212> DNA
<213> Homo Sapiens <400> 49 gcaccatgta ccgagcactt cggctcctcg cgcgctcgcg tcccctcgtg cgggctccag 60 ccgcagcctt agcttcggct cccggcttgg gtggcgcggc cgtgccctcg ttttggcctc 120 cgaacgcggc tcgaatggca agccaaaatt ccttccggat agaatatgat acctttggtg 180 aactaaaggt gccaaatgat aagtattatg gcgcccagac cgtgagatct acgatgaact 240 ttaagattgg aggtgtgaca gaacgcatgc caaccccagt tattaaagct tttggcatct 300 tgaagcgagc ggccgctgaa gtaaaccagg attatggtct tgatccaaag attgctaatg 360 caataatgaa ggcagcagat gaggtagctg aaggtaaatt aaatgatcat tttcctctcg 420 tggtatggca gactggatca ggaactcaga caaatatgaa tgtaaatgaa gtcattagcc 480 aatagagcaa ttgaaa 496 <210> 50 <211> 499 <212> DNA
<213> Homo sapiens <400> 50 agaaaaagtc tatgtttgca gaaatacaga tccaagacaa agacaggatg ggcactgctg 60 gaaaagttat taaatgcaaa gcagctgtgc tttgggagca gaagcaaccc ttctccattg 120 aggaaataga agttgcccca ccaaagacta aagaagttcg cattaagatt ttggccacag 180 gaatctgtcg cacagatgac catgtgataa aaggaacaat ggtgtccaag tttccagtga 240 ttgtgggaca tgaggcaact gggattgtag agagcattgg agaaggagtg actacagtga 300 aaccaggtga caaagtcatc cctctctttc tgccacaatg tagagaatgc aatgcttgtc 360 gcaacccaga tggcaacctt tgcattagga gcgatattac tggtcgtgga gtactggctg 420 atggcaccac cagatttaca tgcaagggcg aaccagtcca ccacttcatg aacaccagta 480 catttaccga gtacacagt 499 <2i0> 51 <211> 887 <212> DNA
<213> Homo Sapiens <400> 51 gagtctgagc agaaaggaaa agcagccttg gcagccacgt tagaggaata caaagccaca 60 gtggccagtg accagataga gatgaatcgc ctgaaggctc agctggagaa tgaaaagcag 120 aaagtggcag agctgtattc tatccataac tctggagaca aatctgatat tcaggacctc 180 ctggagagtg tcaggctgga caaagaaaaa gcagagactt tggctagtag cttgcaggaa 240 gatctggctc atacccgaaa tgatgccaat cgattacagg atgccattgc taaggtagag 300 gatgaatacc gagccttcca agaagaagct aagaaacaaa ttgaagattt gaatatgacg 360 ttagaaaaat taagatcaga cctggatgaa aaagaaacag aaaggagtga catgaaagaa 420 accatctttg aacttgaaga tgaagtagaa caacatcgtg ctgtgaaact tcatgacaac 480 ctcattattt ctgatctaga gaatacagtt aaaaaactcc aggaccaaaa gcacgacatg 540 gaaagagaaa taaagacact ccacagaaga cttcgggaag aatctgcgga atggcggcag 600 tttcaggctg atctccagac tgcagtagtc attgcaaatg acattaaatc tgaagcccaa 660 gaggagattg gtgatctaaa gcgccggtta catgaggctc aagaaaaaaa tgagaaactc 720 acaaaagaat tggaggaaat aaagtcacgc aagcaagagg aggagcgagg cgggtataca 780 attacatgaa tgccgttgag agagatttgg cagccttaag gcagggaatg ggactgagta 840 gaaggtcctc gacttcctca gagccaactc ctacagtaaa aaccctc 887 <210> 52 <211> 491 <212> DNA
<213> Homo sapiens <400> 52 ggcacgagct tttccaaaaa tcatgctgct cctttctcta aagttcttac attttataga 60 aaggaacctt tcactcttga ggcctactac agctctcctc aggatttgcc ctatccagat 120 cctgctatag ctcagttttc agttcagaaa gtcactcctc agtctgatgg ctccagttca 180 aaagtgaaag tcaaagttcg agtaaatgtc catggcattt tcagtgtgtc cagtgcatct 240 ttagtggagg ttcacaagtc tgaggaaaat gaggagccaa tggaaacaga tcagaatgca 300 aaggaggaag agaagatgca agtggaccag gaggaa,~cac atgttgaaga gcaacagcag 360 cagacaccag gcagaaaata aggcagagtc tgaagaaatg gagacctctc aagctggatc 420 caaggataaa aagatggacc aaccacccca agccaagaag gcaaaagtga agaccagtac 480 tgtggacctg g <210> 53 <211> 787 <212> DNA
<213> Homo Sapiens <400> 53 aagcagttga gtaggcagaa aaaagaacct cttcattaag gattaaaatg tataggccag 60 cacgtgtaac ttcgacttca agatttctga atccatatgt agtatgtttc attgtcgtcg 120 caggggtagt gatcctggca gtcaccatag ctctacttgt ttacttttta gcttttgatc 180 aaaaatctta cttttatagg agcagttttc aactcctaaa tgttgaatat aatagtcagt 240 taaattcacc agctacacag gaatacagga ctttgagtgg aagaattgaa tctctgatta 300 ctaaaacatt caaagaatca aatttaagaa atcagttcat cagagctcat gttgccaaac 360 tgaggcaaga tggtagtggt gtgagagcgg atgttgtcat gaaatttcaa ttcactagaa 420 ataacaatgg agcatcaatg aaaagcagaa ttgagtctgt tttacgacaa atgctgaata 480 actctggaaa cctggaaata aacccttcaa ctgagataac atcacttact gaccaggctg 540 cagcaaattg gcttattaat gaatgtgggg ccggtccaga cctaataaca ttgtctgagc 600 agagaatcct tggaggcact gaggctgagg agggaagctg gccgtggcaa gtcagtctgc 660 ggctcaataa tgcccaccac tgtggaggca gcctgatcaa taacatgtgg atcctgacag 720 cagctcactg cttcagaagc aactctaatc ctcgtgactg gattgccacg tctggtattt 780 ccacaac 787 <210> 54 <211> 386 <212> DNA
<213> Homo sapiens <400> 54 ggcattttca gtgtgtccag tgcatcttta gtggaggttc acaagtctga ggaaaatgag 60 gagccaatgg aaacagatca gaatgcaaag gaggaagaga agatgcaagt ggaccaggag 120 gaaccacatg ttgaagagca acagcagcag acaccagcag aaaataaggc agagtctgaa 180 gaaatggaga cctctcaagc tggatccaag gataaaaaga tggaccaacc accccaagcc 240 aagaaggcaa aagtgaagac cagtactgtg gacctgccaa tcgagaatca gctattatgg 300 cagatagaca gagagatgct caacttgtac attgaaaatg agggtaagat gatcatgcag 360 gataaactgg agaaggagcg gaatga <210> 55 <211> 1462 <212> DNA
<213> Homo sapiens <400> 55 aagcagttga gtaggcagaa aaaagaacct cttcattaag gattaaaatg tataggccag 60 cacgtgtaac ttcgacttca agatttctga atccatatgt agtatgtttc attgtcgtcg 120 caggggtagt gatcctggca gtcaccatag ctctacttgt ttacttttta gcttttgatc 180 aaaaatctta cttttatagg agcagttttc aactcctaaa tgttgaatat aatagtcagt 240 taaattcacc agctacacag gaatacagga ctttgagtgg aagaattgaa tctctgatta 300 ctaaaacatt caaagaatca aatttaagaa atcagttcat cagagctcat gttgccaaac 360 tgaggcaaga tggtagtggt gtgagagcgg atgttgtcat gaaatttcaa ttcactagaa 420 ataacaatgg agcatcaatg aaaagcagaa ttgagtctgt tttacgacaa atgctgaata 480 actctggaaa cctggaaata aacccttcaa ctgagataac atcacttact gaccaggctg 540 cagcaaattg gcttattaat gaatgtgggg ccggtccaga cctaataaca ttgtctgagc 600 agagaatcct tggaggcact gaggctgagg agggaagctg gccgtggcaa gtcagtctgc 660 ggctcaataa tgcccaccac tgtggaggca gcctgatcaa taacatgtgg atcctgacag 720 cagctcactg cttcagaagc aactctaatc ctcgtgactg gattgccacg tctggtattt 780 ccacaacatt tcctaaacta agaatgagag taagaaatat tttaattcat aacaattata 840 aatctgcaac tcatgaaaat gacattgcac ttgtgagact tgagaacagt gtcaccttta 900 ccaaagatat ccatagtgtg tgtctcccag ctgctaccca gaatattcca cctggctcta 960 ctgcttatgt aacaggatgg ggcgctcaag aatatgctgg ccacacagtt ccagagctaa 1020 ggcaaggaca ggtcagaata ataagtaatg atgtatgtaa tgcaccacat agttataatg 1080 gagccatctt gtctggaatg ctgtgtgctg gagtacctca aggtggagtg gacgcatgtc 1140 agggtgactc tggtggccca ctagtacaag aagactcacg gcggctttgg tttattgtgg 1200 ggatagtaag ctggggagat cagtgtggcc tgccggataa gccaggagtg tatactcgag 1260 tgacagcata cattgactgg attaggcaac aaactgggat ctagtgcaac aagtgcatcc 1320 ctgttgcaaa gtctgtatgc aggtgtgcct gtcttaaatt ccaaagcttt acatttcaac 1380 tgaaaaagaa actagaaatg tcctaattta acatcttgtt acataaatat ggtttaacaa 1440 aaaaaaaaaa aaaaaactcg ag 1462 <210> 56 <211> 159 <212> PRT
<213> Homo sapiens <400> 56 Thr Met Tyr Arg Ala Leu Arg Leu Leu Ala Arg Ser Arg Pro Leu Val Arg Ala Pro Ala Ala Ala Leu Ala Ser Ala Pro Gly Leu Gly Gly Ala Ala Val Pro Ser Phe Trp Pro Pro Asn Ala Ala Arg Met Ala Ser Gln Asn Ser Phe Arg Ile Glu Tyr Asp Thr Phe Gly Glu Leu Lys Val Pro Asn Asp Lys Tyr Tyr Gly Ala Gln Thr Val Arg Ser Thr Met Asn Phe Lys Ile Gly Gly Val Thr Glu Arg Met Pro Thr Pro Val Ile Lys Ala Phe Gly Ile Leu Lys Arg Ala Ala Ala Glu Val Asn Gln Asp Tyr Gly Leu Asp Pro Lys Ile Ala Asn Ala Ile Met Lys Ala Ala Asp Glu Val Ala Glu Gly Lys Leu Asn Asp His Phe Pro Leu Val Val Trp Gln Thr Gly Ser Gly Thr Gln Thr Asn Met Asn Val Asn Glu Val Ile Ser <210> 57 <211> 165 <212> PRT
<213> Homo sapiens <400> 57 Lys Lys Ser Met Phe Ala Glu Ile Gln Ile Gln Asp Lys Asp Arg Met 1 5 10 i5 Gly Thr Ala Gly Lys Val Ile Lys Cys Lys Ala Ala Val Leu Trp Glu Gln Lys Gln Pro Phe Ser Ile Glu Glu Ile Glu Val Ala Pro Pro Lys Thr Lys Glu Val Arg Ile Lys Ile Leu Ala Thr Gly Ile Cys Arg Thr Asp Asp His Val Ile Lys Gly Thr Met Val Ser Lys Phe Pro Val Ile Val Gly His Glu Ala Thr Gly Ile Val Glu Ser Ile Gly Glu Gly Val Thr Thr Val Lys Pro Gly Asp Lys Val Ile Pro Leu Phe Leu Pro Gln Cys Arg Glu Cys Asn Ala Cys Arg Asn Pro Asp Gly Asn Leu Cys Ile Arg Ser Asp Ile Thr Gly Arg Gly Val Leu Ala Asp Gly Thr Thr Arg Phe Thr Cys Lys Gly Glu Pro Val His His Phe Met Asn Thr Ser Thr Phe Thr Glu Tyr Thr <210> 58 <211> 259 <212> PRT
<213> Homo sapiens <400> 58 Glu Ser Glu Gln Lys Gly Lys Ala Ala Leu Ala Ala Thr Leu Glu Glu Tyr Lys Ala Thr Val Ala Ser Asp Gln Ile Glu Met Asn Arg Leu Lys Ala Gln Leu Glu Asn Glu Lys Gln Lys Val Ala Glu Leu Tyr Ser Ile His Asn Ser Gly Asp Lys Ser Asp Ile_Isln Asp Leu Leu Glu Ser Val Arg Leu Asp Lys Glu Lys Ala Glu Thr Leu Ala Ser Ser Leu Gln Glu Asp Leu Ala His Thr Arg Asn Asp Ala Asn Arg Leu Gln Asp Ala Ile Ala Lys Val Glu Asp Glu Tyr Arg Ala Phe Gln Glu Glu Ala Lys Lys Gln Ile Glu Asp Leu Asn Met Thr Leu Glu Lys Leu Arg Ser Asp Leu Asp Glu Lys Glu Thr Giu Arg Ser Asp Met Lys Glu Thr Ile Phe Glu Leu Glu Asp Glu Val Glu Gln His Arg Ala Val Lys Leu His Asp Asn Leu Ile Ile Ser Asp Leu Glu Asn Thr Val Lys Lys Leu Gln Asp Gln Lys His Asp Met Glu Arg Glu Ile Lys Thr Leu His Arg Arg Leu Arg Glu Glu Ser Ala Glu Trp Arg Gln Phe Gln Ala Asp Leu Gln Thr Ala Val Val Ile Ala Asn Asp Ile Lys Ser Glu Ala Gln Glu Glu Ile Gly Asp Leu Lys Arg Arg Leu His Glu Ala Gln Glu Lys Asn Glu Lys Leu Thr Lys Glu Leu Glu Glu Ile Lys Ser Arg Lys Gln Glu Glu Glu Arg Gly Gly Tyr <210> 59 <211> 125 <212> PRT
<213> Homo sapiens <400> 59 Gly Thr Ser Phe Ser Lys Asn His Ala Ala Pro Phe Ser Lys Val Leu Thr Phe Tyr Arg Lys Glu Pro Phe Thr Leu Glu Ala Tyr Tyr Ser Ser Pro Gln Asp Leu Pro Tyr Pro Asp Pro Ala Ile Ala Gln Phe Ser Val Gln Lys Val Thr Pro Gln Ser Asp Gly Ser Ser Ser Lys Val Lys Val Lys Val Arg Val Asn Val His Gly Ile Phe Ser Val Ser Ser Ala Ser Leu Val Glu Val His Lys Ser Glu Glu Asn Glu Glu Pro Met Glu Thr 85 90 g5 Asp Gln Asn Ala Lys Glu Glu Glu Lys Met Gln Val Asp Gln Glu Glu Pro His Val Glu Glu Gln Gln Gln Gln Thr Pro Gly Arg lI5 120 125 <210> 60 <211> 246 <212> PRT
<213> Homo sapiens <400> 60 Met Tyr Arg Pro Ala Arg Val Thr Ser Thr Ser Arg Phe Leu Asn Pro ~'yr Val Val Cars Phe Ile Val Val Ala Gly Val Val Ile Leu Ala Val Thr Ile Ala Leu Leu Val Tyr Phe Leu Ala Phe Asp Gln Lys Ser Tyr Phe Tyr Arg Ser Ser Phe Gln Leu Leu Asn Val Glu Tyr Asn Sar Gln Leu Asn Ser Pro Ala Thr Gln Glu Tyr Arg Thr Leu Ser Gly Arg Ile 65 70 75 g0 Glu Ser Leu Ile Thr Lys Thr Phe Lys Glu Ser Asn Leu Arg Asn Gln Phe Ile Arg Ala His Val Ala Lys Leu Arg Gln Asp Gly Ser Gly Val Arg Ala Asp Val Val Met Lys Phe Gln Phe Thr Arg Asn Asn Asn Gly Ala Ser Met Lys Ser Arg Ile Glu Ser Val Leu Arg Gln Met Leu Asn Asn Ser Gly Asn Leu Glu Ile Asn Pro Ser Thr Glu Ile Thr Ser Leu Thr Asp Gln Ala Ala Ala Asn Trp Leu Ile Asn Glu Cys Gly Ala Gly Pro Asp Leu Ile Thr Leu Ser Glu Gln Arg Ile Leu Gly Gly Thr Glu Ala Glu Glu Gly Ser Trp Pro Trp Gln Val Ser Leu Arg Leu Asn Asn Ala His His Cars Gly Gly Ser Leu Ile Asn Asn Met Trp Ile Leu Thr Ala Ala His Cys Phe Arg Ser Asn Ser Asn Pro Arg Asp Trp Ile Ala Thr Ser Gly Ile Ser Thr <210> 61 <211> 128 <212> PRT
<213> Homo sapiens <400> 61 Gly Ile Phe Ser Val Ser Ser Ala Ser Leu Val Glu Val His Lys Ser Glu Glu Asn Glu Glu Pro Met Glu Thr Asp Gln Asn Ala Lys GIu Glu Glu Lys Met Gln Val Asp Gln Glu Glu Pro His Val Glu Glu Gln Gln Gln Gln Thr Pro Ala Glu Asn Lys Ala Glu Ser Glu Glu Met Glu Thr Ser Gln Ala Gly Ser Lys Asp Lys Lys Met Asp Gln Pro Pro Gln Ala Lys Lys Ala Lys Val Lys Thr Ser Thr Val Asp Leu Pro Ile Glu Asn WO 99/38973 PC'TNS99/01642 Gln Leu Leu Trp Gln Ile Asp Arg Glu Met Leu Asn Leu Tyr Ile Glu Asn Glu Gly Lys Met Ile Met Gln Asp Lys Leu Glu Lys Glu Arg Asn <210> 62 <211> 418 <212> PRT
<213> Homo sapiens <400> 62 Met Tyr Arg Pro Ala Arg Val Thr Ser Thr Ser Arg Phe Leu Asn Pro Tyr Val Val Cars Phe Ile Val Val Ala Gly Val Val Ile Leu Ala Val Thr Ile Ala Leu Leu Val Tyr Phe Leu Ala Phe Asp Gln Lys Ser Tyr Phe Tyr Arg Ser Ser Phe Gln Leu Leu Asn Val Glu Tyr Asn Ser Gln Leu Asn Ser Pro Ala Thr Gln Glu Tyr Arg Thr Leu Ser Gly Arg Ile Glu Ser Leu Ile Thr Lys Thr Phe Lys Glu Ser Asn Leu Arg Asn Gln Phe Ile Arg Ala His Val Ala Lys Leu Arg Gln Asp Gly Ser Gly Val Arg Ala Asp Val Val Met Lys Phe Gln Phe Thr Arg Asn Asn Asn Gly Ala Ser Met Lys Ser Arg Ile Glu Ser Val Leu Arg Gln Met Leu Asn Asn Ser Gly Asn Leu Glu Ile Asn Pro Ser Thr Glu Ile Thr Ser Leu Thr Asp Gln Ala Ala Ala Asn Trp Leu Ile Asn Glu Cars Gly Ala Gly Pro Asp Leu Ile Thr Leu Ser Glu Gln Arg Ile Leu Gly Gly Thr Glu Ala Glu Glu Gly Ser Trp Pro Trp Gln Val Ser Leu Arg Leu Asn Asn Ala His His Cars Gly Gly Ser Leu Ile Asn Asn Met Trp Ile Leu Thr Ala Ala His Cys Phe Arg Ser Asn Ser Asn Pro Arg Asp Trp Ile Ala Thr Ser Gly Ile Ser Thr Thr Phe Pro Lys Leu Arg Met Arg Val Arg Asn Ile Leu Ile His Asn Asn Tyr Lys Ser Ala Thr His Glu Asn Asp Ile Ala Leu VaI Arg Leu Glu Asn Ser Val Thr Phe Thr Lys Asp Ile His Ser Val Gars Leu Pro Ala Ala Thr Gln Asn Ile Pro Pro Gly Ser Thr Ala Tyr Val Thr Gly Trp Gly Ala._Gln Glu Tyr Ala Gly His Thr Val Pro Glu Leu Arg Gln Gly Gln Val Arg Ile Ile Ser Asn Asp Val Cars Asn Ala Pro His Ser Tyr Asn Gly Ala Ile Leu Ser Gly Met Leu Cys Ala Gly Val Pro Gln Gly Gly Val Asp Ala Cys Gln Gly Asp Ser Gly Gly Pro Leu Val Gln Glu Asp Ser Arg Arg Leu Trp Phe Ile Val Gly Ile Val Ser Trp Gly Asp Gln Cars Gly Leu Pro Asp Lys Pro Gly Val Tyr Thr Arg Val Thr Ala Tyr Ile Asp Trp Ile Arg Gln Gln Thr Gly Ile <210> 63 <211> 776 <212> DNA
<213> Homo Sapiens <400> 63 cacagatggt gatagaggaa tccatcttgc agtcagataa agccctcact gatagagaga 60 aggcagtagc agtggatcgg gccaagaagg aggcagctga gaaggaacag gaacttttaa 120 aacagaaatt acaggagcag ccagcaacag atggaggctc aagataagag tcgcaaggaa 180 aactagccaa ctgaaggaga agctgcagat ggagagagaa cacctactga gagagcagat 240 tatgatgttg gagcacacgc agaaggtcca aaatgattgg cttcatgaag gatttaagaa 300 gaagtatgag gagatgaatg cagagataag tcaatttaaa cgtatgattg atactacaaa 360 aaatgatgat actccctgga ttgcacgaac cttggacaac cttgccgatg agctaactgc 420 aatattgtct gctcctgcta aattaattgg tcatggtgtc aaaggtgtga gctcactctt 480 taaaaagcat aagctcccct tttaaggata ttatagattg tacatatatg ctttggacta 540 tttttgatct gtatgttttt cattttcatt cagcaagttt tttttttttt tcagagtctt 600 actctgttgc ccaggctgga gtacagtggt gcaatctcag ctcactgcaa cctctgcctc 660 ctgggttcaa gagattcacc tgcctcagcc ccctagtagc tgggattata ggtgtacacc 720 accacaccca gctaattttt gtatttttag tagagatggg gtttcactat gttggc 776 <210> 64 <211> 160 <212> DNA
<213> Homo Sapiens <400> 64 gcagcgctct cggttgcagt acccactgga aggacttagg cgctcgcgtg gacaccgcaa 60 gcccctcagt agcctcggcc caagaggcct gctttccact cgctagcccc gccgggggtc 120 cgtgtcctgt ctcggtggcc ggacccgggc ccgagcccga 160 <210> 65 __ <211> 72 <212> PRT
<213> Homo Sapiens <400> 65 Leu Ser Ala Met Gly Phe Thr Ala Ala Gly Ile Ala Ser Ser Ser Ile Ala Ala Lys Met Met Ser Ala Ala Ala Ile Ala Asn Gly Gly Gly Val Ala Ser Gly Ser Leu Val Ala Thr Leu Gln Ser Leu Gly Ala Thr Gly Leu Ser Gly Leu Thr Lys Phe Ile Leu Gly Ser Ile Gly Ser Ala Ile Ala Ala Val Ile Ala Arg Phe Tyr <210> 66 <211> 2581 <212> DNA
<213> Homo Sapiens <400> 66 ctttcaaccc gcgctcgccg gctccagccc cgcgcgcccc caccccttgc cctcccggcg 60 gctccgcagg gtgaggtggc tttgaccccg ggttgcccgg ccagcacgac cgaggaggtg 120 gctggacagc tggaggatga acggagaagc cgactgcccc acagacctgg aaatggccgc 180 ccccaaaggc caagaccgtt ggtcccagga agacatgctg actttgctgg aatgcatgaa 240 gaacaacctt ccatccaatg acagctccaa gttcaaaacc accgaatcac acatggactg 300 ggaaaaagta gcatttaaag acttttctgg agacatgtgc aagctcaaat gggtggagat 360 ttctaatgag gtgaggaagt tccgtacatt gacagaattg atcctcgatg ctcaggaaca 420 tgttaaaaat ccttacaaag gcaaaaaact caagaaacac ccagacttcc caaagaagcc 480 cctgacccct tatttccgct tcttcatgga gaagcgggcc aagtatgcga aactccaccc 540 tgagatgagc aacctggacc taaccaagat tctgtccaag aaatacaagg agcttccgga 600 gaagaagaag atgaaatata ttcaggactt ccagagagag aaacaggagt tcgagcgaaa 660 cctggcccga ttcagggagg atcaccccga cctaatccag aatgccaaga aatcggacat 720 cccagagaag cccaaaaccc cccagcagct gtggtacacc cacgagaaga aggtgtatct 780 caaagtgcgg ccagatgcca ctacgaagga ggtgaaggac tccctgggga agcagtggtc 840 tcagctctcg gacaaaaaga ggctgaaatg gattcataag gccctggagc agcggaagga 900 gtacgaggag atcatgagag actatatcca gaagcaccca gagctgaaca tcagtgagga 960 gggtatcacc aagtccaccc tcaccaaggc cgaacgccag ctcaaggaca agtttgacgg 1020 gcgacccacc aagccacctc cgaacagcta ctcgctgtac tgcgcagagc tcatggccaa 1080 catgaaggac gtgcccagca cagagcgcat ggtgctgtgc agccagcagt ggaagctgct 1140 gtcccagaag gagaaggacg cctatcacaa gaagtgtgat cagaaaaaga aagattacga 1200 ggtggagctg ctccgtttcc tcgagagcct gcctgaggag gagcagcagc gggtcttggg 1260 ggaagagaag atgctgaaca tcaacaagaa gcaggccacc agccccgcct ccaagaagcc 1320 agcccaggaa gggggcaagg gcggctccga gaagcccaag cggcccgtgt cggccatgtt 1380 catcttctcg gaggagaaac ggcggcagct gcaggaggag cggcctgagc tctccgagag 1440 cgagctgacc cgcctgctgg cccgaatgtg gaacgacctg tctgagaaga agaaggccaa 1500 gtacaaggcc cgagaggcgg cgctcaaggc tcagtcggag aggaagcccg gcggggagcg 1560 cgaggaacgg ggcaagctgc ccgagtcccc caaaagagct gaggagatct ggcaacagag 1620 cgttatcggc gactacctgg cccgcttcaa gaatgaccgg gtgaaggcct tgaaagccat 1680 ggaaatgacc tggaataaca tggaaaagaa ggagaaactg atgtggatta agaaggcagc 1740 cgaagaccaa aagcgatatg agagagagct gagtgagatg cgggcacctc cagctgctac 1800 aaattcttcc aagaagatga aattccaggg agaacccaag aagcctccca tgaacggtta 1860 ccagaagttc tcccaggagc tgctgtccaa tggggagctg aaccacctgc cgctgaagga 1920 gcgcatggtg gagatcggca gtcgctggca gcgcatctcc cagagccaga aggagcacta 1980 caaaaagctg gccgaggagc agcaaaagca gtacaaggtg cacctggacc tctgggttaa 2040 gagcctgtct ccccaggacc gtgcagcata taaagagtac atctccaata aacgtaagag 2100 catgaccaag ctgcgaggcc caaaccccaa atccagccgg actactctgc agtccaagtc 2160 ggagtccgag gaggatgatg aagaggatga ggatgacgag gacgaggatg aagaagagga 2220 agatgatgag aatggggact cctctgaaga tggcggcgac tcctctgagt ccagcagcga 2280 ggacgagagc gaggatgggg atgagaatga agaggatgac gaggacgaag acgacgacga 2340 ggatgacgat gaggatgaag ataatgagtc cgagggcagc agctccagct cctcctcctt 2400 aggggactcc tcagactttg actccaactg aggcttagcc ccaccccagg ggagccaggg 2460 agagcccagg agctcccctc cccaactgac cacctttgtt tcttccccat gttctgtccc 2520 ttgcccccct ggcctccccc actttctttc tttctttaaa aaaaaaaaaa aaaaactcga 2580 g 2581 <210> 67 <211> 764 <212 > PRT
<213> Homo sapiens <400> 67 Met Asn Gly Glu Ala Asp Gars Pro Thr Asp Leu Glu Met Ala Ala Pro Lys Gly Gln Asp Arg Trp Ssr Gln Glu Asp Met Leu Thr Leu Leu Glu Cps Met Lys Asn Asn Leu Pro Ser Asn Asp Ser Ser Lys Phe Lys Thr Thr Glu Ser His Met Asp Trp Glu Lys Val Ala Phe Lys Asp Phe Ser Gly Asp Met Cys Lys Leu Lys Trp Val Glu Ile Ser Asn Glu Val Arg 65 70 75 g0 Lys Phe Arg Thr Leu Thr Glu Leu Ile Leu Asp Ala Gln Glu His Val Lys Asn Pro Tyr Lys Gly Lys Lys Leu Lys Lys His Pro Asp Phe Pro Lys Lys Pro Leu Thr Pro Tyr Phe Arg Phe Phe Met Glu Lys Arg Ala Lys Tyr Ala Lys Leu His Pro Glu Met Ser Asn Leu Asp Leu Thr Lys Ile Leu Ser Lys Lys Tyr Lys Glu Leu Pro Glu Lys Lys Lys Met Lys Tyr Ile Gln Asp Phe Gln Arg Glu Lys Gln Glu Phe Glu Arg Asn Leu Ala Arg Phe Arg Glu Asp His Pro Asp Leu Ile Gln Asn Ala Lys Lys Ser Asp Ile Pro Glu Lys Pro Lys Thr Pro Gln Gln Leu Trp Tyr Thr His Glu Lys Lys Val Tyr Leu Lys Val Arg Pro Asp Ala Thr Thr Lys Glu Val Lys Asp Ser Leu Gly Lys Gln Trp Ser Gln Leu Ser Asp Lys Lys Arg Leu Lys Trp Ile His Lys Ala Leu Glu Gln Arg Lys Glu Tyr Glu Glu Ile Met Arg Asp Tyr Ile Gln Lys His Pro Glu Leu Asn Ile Ser Glu Glu Gly Ile Thr Lys Ser Thr Leu Thr Lys Ala Glu Arg Gln Leu Lys Asp Lys Phe Asp Gly Arg Pro Thr Lys Pro Pro Pro Asn Ser Tyr Ser Leu Tyr Cys Ala Glu Leu Met Ala Asn Met Lys Asp Val Pro Ser Thr Glu Arg Met Val Leu Cys 5er Gln Gln Trp Lys Leu Leu Ser Gln Lys Glu Lys Asp Ala Tyr His Lys Lys Cys Asp Gln Lys Lys Lys Asp Tyr Glu Val Glu Leu Leu Arg Phe Leu Glu Ser Leu Pro Glu Glu Glu Gln Gln Arg Val Leu Gly Glu Glu Lys Met Leu Asn Ile Asn Lys Lys Gln Ala Thr Ser Pro Ala Ser Lys Lys Pro Ala Gln Glu Gly Gly Lys Gly Gly Ser Glu Lys Pro Lys Arg Pro Val Ser Ala Met Phe Ile Phe Ser Glu Glu Lys Arg Arg Gln Leu Gln Glu Glu Arg Pro Glu Leu Ser Glu Ser Glu Leu Thr Arg Leu Leu Ala Arg Met Trp Asn Asp Leu Ser Glu Lys Lys Lys Ala Lys Tyr Lys Ala Arg Glu Ala Ala Leu Lys Ala Gln Ser Glu Arg Lys Pro Gly Gly Glu Arg Glu Glu Arg Gly Lys 465 . 470 475 480 Leu Pro Glu Ser Pro Lys Arg Ala Glu Glu Ile Trp Gln Gln Ser Val Ile Gly Asp Tyr Leu Ala Arg Phe Lys Asn Asp Arg Val Lys Ala Leu Lys Ala Met Glu Met Thr Trp Asn Asn Met Glu Lys Lys Glu Lys Leu Met Trp Ile Lys Lys Ala Ala Glu Asp Gln Lys Arg Tyr Glu Arg Glu Leu Ser Glu Met Arg Ala Pro Pro Ala Ala Thr Asn Ser Ser Lys Lys Met Lys Phe Gln Gly Glu Pro Lys Lys Pro Pro Met Asn Gly Tyr Gln Lys Phe Ser Gln Glu Leu Leu Ser Asn Gly Glu Leu Asn His Leu Pro Leu Lys Glu Arg Met Val Glu Ile Gly Ser Arg Trp Gln Arg Ile Ser Gln Ser Gln Lys Glu His Tyr Lys Lys Leu Ala Glu Glu Gln Gln Lys Gln Tyr Lys Val His Leu Asp Leu Trp Val Lys Ser Leu Ser Pro Gln Asp Arg Ala Ala Tyr Lys Glu Tyr Ile Ser Asn Lys Arg Lys Ser Met Thr Lys Leu Arg Gly Pro Asn Pro Lys Ser Ser Arg Thr Thr Leu Gln Ser Lys Ser Glu Ser Glu Glu Asp Asp Glu Glu Asp Glu Asp Asp Glu Asp Glu Asp Glu Glu Glu Glu Asp Asp Glu Asn Gly Asp Ser Ser Glu Asp Gly Gly Asp Ser Ser Glu Ser Ser Ser Glu Asp Glu Ser Glu Asp Gly Asp Glu Asn Glu Glu Asp Asp Glu Asp Glu Asp Asp Asp Glu Asp Asp Asp Glu Asp Glu Asp Asn Glu Ser Glu Gly Ser Ser Ser Ser Ser Ser Ser Leu Gly Asp Ser Ser Asp Phe Asp Ser Asn <210> 68 <211> 434 <212> DNA
<213> Homo sapiens <400> 68 ctaagatgct ggatgctgaa gacatcgtcg gaactgcccg gccagatgag aaagccatta 60 tgacttatgt gtctagcttc tatcatgcct tctctggagc ccagaaggca gaaacagcag 120 ccaatcgcat ctgcaaagtg ttggcggtca atcaagagaa cgagcagctt atggaagact 180 atgagaagct ggccagtgat ctgttggagt ggatccgccg caccatccca tggctggaga 240 atcgggtgcc tgagaacacc atgcatgcca tgcagcagaa gctggaggac ttccgagact 300 atagacgcct gcacaagccg cccaaggtgc aggagaagtg ccagctggag atcaacttta 360 acacgctgca gaccaaactg cggctcagca accggcctgc cttcatgccc tccgagggca 420 ggatggtctc ggat 434 <210> 69 <211> 244 <212> DNA
<213> Homo Sapiens <400> 69 aggcagcatg ctcgttgaga gtcatcacca ctccctaatc tcaagtacgc agggacacaa 60 acactgcgga aggccgcagg gtcctctgcc taggaaaacc agagaccttt gttcacttgt 120 ttatgtgctg accttccctc cactactgtc ctgtgaccct gccaaatccc cctttgtgag 180 aaacacccaa gaatgatcaa taaaaaataa attaatttag gaaaaaaaaa aaaaaaaact 240 cgag 244 <210> 70 <211> 437 <212> DNA
<213> Homo Sapiens <400> 70 ctgggacggg agcgtccagc gggactcgaa ccccagatgt gaaggcgttt ctggaaagtc 60 cttggtccct ggatccagcg tcggccagcc cagagcccgt gccgcacatc cttgcgtcct 120 ccaggcagtg ggaccccgcg agctgcacgt ccctgggcac ggacaagtgt gaggcactgt 180 tggggctgtg ccaggtgcgg ggtgggctgc cccctttctc agaaccttcc agcctggtgc 240 cgtggccccc aggccggagt cttcctaagg ctgtgaggcc acccctgtcc tggcctccgt 300 tctcgcagca gcagaccttg cccgtgatga gcggggaggc ccttggctgg ctgggccagg 360 ctggttccct ggccatgggg gctgcacctc tgggggagcc agccaaggag gaccccatgc 420 tggcgcagga agccggg 437 <210> 71 <211> 271 <212> DNA
<213> Homo Sapiens <400> 71 gcgcagagtt ctgtcgtcca ccatcgagtg aggaagagag cattggttcc cctgagatag 60 aagagatggc tctcttcagt gcccagtctc catacattaa cccgatcatc ccctttactg 120 gaccaatcca aggagggctg caggagggac ttcaggtgac cctccagggg actaccgaga 180 gttttgcaca aaagtttgtg gtgaactttt cagaacagct tcaatggaga tgacttggcc 240 ttccacttca accccggtta tgaggaagga g_ 271 <210> 72 <211> 290 <212> DNA
<213> Homo Sapiens <400> 72 ccgagcccta cccggaggtc tccagaatcc ccaccgtcag gggatgcaac ggctccctgt 60 ctggtgccct ctcctgctgc gaggactcgg cccagggctc gggcccgccc aaggccccta 120 cggtggccga gggtcccagc tcctgccttc ggcggaacgt gatcagcgag agggagcgca 180 ggaagcggat gtcgttgagc tgtgagcgtc tgcgggccct gctgccccag ttcgatggcc 240 ggcgggagga catggcctcg gtcctggaga tgtctgttgc aattcctgcg 290 <210> 73 <211> 144 <212> PRT
<213> Homo Sapiens <400> 73 Lys Met Leu Asp Ala Glu Asp Ile Val Gly Thr Ala Arg Pro Asp Glu Lys Ala Ile Met Thr Tyr Val Ser Ser Phe Tyr His Ala Phe Ser Gly Ala Gln Lys Ala Glu Thr Aia Ala Asn Arg Ile Cys Lys Val Leu Ala Val Asn Gln Glu Asn Glu Gln Leu Met Glu Asp Tyr Glu Lys Leu Ala Ser Asp Leu Leu Glu Trp Iie Arg Arg Thr Ile Pro Trp Leu Glu Asn Arg Val Pro Glu Asn Thr Met His Ala Met Gln Gln Lys Leu Glu Asp Phe Arg Asp Tyr Arg Arg Leu His Lys Pro Pro Lys Val Gln Glu Lys Cys Gln Leu Glu Ile Asn Phe Asn Thr Leu Gln Thr Lys Leu Arg Leu Ser Asn Arg Pro Ala Phe Met Pro Ser Glu Gly Arg Met Val Ser Asp <210> 74 <211> 64 <212> PRT
<213> Homo Sapiens <400> 74 Gly Ser Met Leu Val Glu Ser His His His Sex Leu Ile Ser Ser Thr Gln Gly His Lys His Cys Gly Arg Pro Gln Gly Pro Leu Pro Arg Lys Thr Arg Asp Leu Cys Ser Leu Val Tyr Val Leu Thr Phe Pro Pro Leu Leu Ser Cys Asp Pro Ala Lys Ser Pro Phe Val Arg Asn Thr Gln Glu <210> 75 <211> 145 <212> PRT
<213> Homo sapiens <400> 75 Gly Thr Gly Ala Ser Ser Gly Thr Arg Thr Pro Asp Val Lys Ala Phe Leu Glu Ser Pro Trp Ser Leu Asp Pro Ala Ser Ala Ser Pro Glu Pro Val Pro His Ile Leu Ala Ser 5er Arg Gln Trp Asp Pro Ala Ser Cys Thr Ser Leu Gly Thr Asp Lys Cys Glu Ala Leu Leu Gly Leu Cys Gln Val Arg Gly Gly Leu Pro Pro Phe Ser Glu Pro Sex Ser Leu Val Pro Trp Pro Pro Gly Arg Ser Leu Pro Lys Ala Val Arg Pro Pro Leu Ser Trp Pro Pro Phe Ser Gln Gln Gln Thr Leu Pro Val Met Ser Gly Glu Ala Leu Gly Trp Leu Gly Gln Ala Gly Ser Leu Ala Met Gly Ala Ala Pro Leu Gly Glu Pro Ala Lys Glu Asp Pro Met Leu Ala Gln Glu Ala Gly <210> 76 <211> 69 <212> PRT
<213> Homo sapiens <400> 76 Ala Glu Phe Cars Arg Pro Pro Ser Ser._Glu Glu Glu Ser Ile Gly Ser Pro Glu Ile Glu Glu Met Ala Leu Phe Ser Ala Gln Ser Pro Tyr Ile Asn Pro Ile Ile Pro Phe Thr Gly Pro Ile Gln Gly Gly Leu Gln Glu Gly Leu Gln Val Thr Leu Gln Gly Thr Thr Glu Ser Phe Ala Gln Lys Phe Val Val Asn Phe <2I0> 77 <211> 96 <212> PRT
<213> Homo Sapiens <400> 77 Glu Pro Tyr Pro Glu Val Ser Arg Ile Pro Thr Val Arg Gly Cys Asn Gly Ser Leu Ser Gly Ala Leu Ser Cars Cys Glu Asp Ser Ala Gln Gly Ser Gly Pro Pro Lys Ala Pro Thr Val Ala Glu Gly Pro Ser Ser Cys Leu Arg Arg Asn Val Ile Ser Glu Arg Glu Arg Arg Lys Arg Met Ser Leu Ser Cys Glu Arg Leu Arg Ala Leu Leu Pro Gln Phe Asp Gly Arg 65 70 75 $0 Arg Glu Asp Met Ala Ser Val Leu Glu Met Ser Val Ala Ile Pro Ala <210> 78 <211> 2076 <212> DNA
<213> Homo sapiens <400> 78 agaaaaagtc tatgtttgca gaaatacaga tccaagacaa agacaggatg ggcactgctg 60 gaaaagttat taaatgcaaa gcagctgtgc tttgggagca gaagcaaccc ttctccattg 120 aggaaataga agttgcccca ccaaagacta aagaagttcg cattaagatt ttggccacag 180 gaatctgtcg cacagatgac catgtgataa aaggaacaat ggtgtccaag tttccagtga 240 ttgtgggaca tgaggcaact gggattgtag agagcattgg agaaggagtg actacagtga 300 aaccaggtga caaagtcatc cctctctttc tgccacaatg tagagaatgc aatgcttgtc 360 gcaacccaga tggcaacctt tgcattagga gcgatattac tggtcgtgga gtactggctg 420 atggcaccac cagatttaca tgcaagggca aaccagtcca ccacttcatg aacaccagta 480 catttaccga gtacacagtg gtggatgaat cttrtgttgc taagattgat gatgcagctc 540 ctcctgagaa agtctgttta attggctgtg ggttttccac tggatatggc gctgctgtta 600 aaactggcaa ggtcaaacct ggttccactt gcgtcgtctt tggcctgaga ggagttggcc 660 tgtcagtcat catgggctgt aagtcagctg gtgcatctag gatca~tggg attgacctca 720 acaaagacaa atttgagaag gccatggctg taggtgccac tgagtgtatc agtcccaagg 780 actctaccaa acccatcagt gaggtgctgt cagaaatgac aggcaacaac gtgggataca 840 cctttgaagt tattgggcat cttgaaacca tgattgatgc cctggcatcc tgccacatga 900 actatgggac cagcgtggtt gtaggagttc ctccatcagc caagatgctc acctatgacc 960 cgatgttgct cttcactgga cgcacatgga agggatgtgt ctttggaggt ttgaaaagca 1020 gagatgatgt cccaaaacta gtgactgagt tcctggcaaa gaaatttgac ctggaccagt 1080 tgataactca tgtcttacca tttaaaaaaa tcagtgaagg atttgagctg ctcaattcag 1140 gacaaagcat tcgaacggtc ctgacgtttt gagatccaaa gtggcaggag gtctgtgttg 1200 tcatggtgaa ctggagtttc tcttgtgaga gttccctcat ctgaaatcat gtatctgtct 1260 cacaaataca agcataagta gaagatttgt tgaagacata gaacccttat aaagaattat 1320 taacctttat aaacatttaa agtcttgtga gcacctggga attagtataa taacaatgtt 1380 aatatttttg atttacattt tgtaaggcta taattgtatc ttttaagaaa acatacactt 1440 ggatttctat gttgaaatgg agatttttaa gagttttaac cagctgctgc agatatatat 1500 ctcaaaacag atatagcgta taaagatata gtaaatgcat ctcctagagt aatattcact 1560 taacacattg aaactattat tttttagat= tgaatataaa tgtatttttt aaacacttgt 1620 tatgagttaa cttggattac attttgaaat cagttcattc catgatgcat attactggat 1680 tagattaaga aagacagaaa agattaaggg acgggcacat ttttcaacga ttaagaatca 1740 tcattacata acttggtgaa actgaaaaag tatatcatat gggtacacaa ggctatttgc 1800 cagcatatat taatatttta gaaaatattc cttttgtaat actgaatata aacatagagc 1860 tagaatcata ttatcatact tatcataatg ttcaatttga tacagtagaa ttgcaagtcc 1920 ttaagtccct attcactgtg cttagtagtg actccattta ataaaaagtg tttttagttt 1980 ttaacaacta cactgatgta tttatatata tttataacat gttaaaaatt tttaaggaaa 2040 ttaaaaatta tataaaaaaa aaaaaaaaaa ctcgag 2076 <210> 79 <211> 2790 <212> DNA
<213> Homo sapiens <400> 79 aagcagttga gtaggcagaa aaaagaacct cttcattaag gattaaaatg tataggccag 60 cacgtgtaac ttcgacttca agatttctga atccatatgt agtatgtttc attgtcgtcg 120 caggggtagt gatcctggca gtcaccatag ctctacttgt ttacttttta gcttttgatc 180 aaaaatctta cttttatagg agcagttttc aactcctaaa tgttgaatat aatagtcagt 240 taaattcacc agctacacag gaatacagga ctttgagtgg aagaattgaa tctctgatta 300 ctaaaacatt caaagaatca aatttaagaa atcagttcat cagagctcat gttgccaaac 360 tgaggcaaga tggtagtggt gtgagagcgg atgttgtcat gaaatttcaa ttcactagaa 420 ataacaatgg agcatcaatg aaaagcagaa ttgagtctgt tttacgacaa atgctgaata 480 actctggaaa cctggaaata aacccttcaa ctgagataac atcacttact gaccaggctg 540 cagcaaattg gcttattaat gaatgtgggg ccggtccaga cctaataaca ttgtctgagc 600 agagaatcct tggaggcact gaggctgagg agggaagctg gccgtggcaa gtcagtctgc 660 ggctcaataa tgcccaccac tgtggaggca gcctgatcaa taacatgtgg atcctgacag 720 cagctcactg cttcagaagc aactctaatc ctcgtgactg gattgccacg tctggtattt 780 ccacaacatt tcctaaacta agaatgagag taagaaatat tttaattcat aacaattata 840 aatctgcaac tcatgaaaat gacattgcac ttgtgagact tgagaacagt gtcaccttta 900 ccaaagatat ccatagtgtg tgtctcccag ctgctaccca gaatattcca cctggctcta 960 ctgcttatgt aacaggatgg ggcgctcaag aatatgctgg ccacacagtt ccagagctaa 1020 ggcaaggaca ggtcagaata ataagtaatg atgtatgtaa tgcaccacat agttataatg 1080 gagccatctt gtctggaatg ctgtgtgctg gagtacctca aggtggagtg gacgcatgtc 1140 agggtgactc tggtggccca ctagtacaag aagactcacg gcggctttgg tttattgtgg 1200 ggatagtaag ctggggagat cagtgtggcc tgccggataa gccaggagtg tatactcgag 1260 tgacagccta ccttgactgg attaggcaac aaactgggat ctagtgcaac aagtgcatcc 1320 ctgttgcaaa gtctgtatgc aggtgtgcct gtcttaaatt ccaaagcttt acatttcaac 1380 tgaaaaagaa actagaaatg tcctaattta acatcttgtt acataaatat ggtttaacaa 1440 acactgttta acctttcttt attattaaag gttttctatt ttctccagag aactatatga 1500 atgttgcata gtactgtggc tgtgtaacag aagaaacaca ctaaactaat tacaaagtta 1560 acaatttcat tacagttgtg ctaaatgccc gtagtgagaa gaacaggaac cttgagcatg 1620 tatagtagag gaacctgcac aggtctgatg ggtcagaggg gtcttctctg ggtttcactg 1680 aggatgagaa gtaagcaaac tgtggaaaca tgcaaaggaa aaagtgatag aataatattc 1740 aagacaaaaa gaacagtatg aggcaagaga aatagtatgt atttaaaatt tttggttact 1800 caatatctta tacttagtat gagtcctaaa attaaaaatg tgaaactgtt gtactatacg 1860 tataacctaa ccttaattat tctgtaagaa catgcttcca taggaaatag tggataattt 1920 tcagctattt aaggcaaaag ctaaaatagt tcactcctca actgagaccc aaagaattat 1980 agatattttt catgatgacc catgaaaaat atcactcatc tacataaagg agagactata 2040 Cctattttat agagaagcta agaaatatac ctacacaaac ttgtcaggtg ctttacaact 2100 acatagtact ttttaacaac aaaataataa ttttaagaat gaaaaattta atcatcggga 2160 agaacgtccc actacagact tcctatcact ggcagttata tttttgagcg taaaagggtc 2220 gtcaaacgct aaatctaagt aatgaattga aagtttaaag agggggaaga gttggtttgc 2280 aaaggaaaag tttaaatagc ttaatatcaa tagaatgatc ctgaagacag aaaaaacttt 2340 gtcactcttc ctctctcatt ttctttctct ctctctcccc ttctcataca catgcctccc 2400 cgaccaaaga atataatgta aattaaatcc actaaaatgt aatggcatga aaatctctgt 2460 agtctgaatc actaatattc ctgagttttt atgagctcct agtacagcta aagtttgcct 2520 atgcatgatc atctatgcgt cagagcttcc tccttctaca agctaactcc ctgcatctgg 2580 gcatcaggac tgctccatac atttgctgaa aacttcttgt atttcctgat gtaaaattgt 2640 gcaaacacct acaataaagc catctacttt tagggaaagg gagttgaaaa tgcaaccaac 2700 tcttggcgaa ctgtacaaac aaatctttgc tatactttat ttcaaataaa ttctttttga 2760 aatgaaaaaa aaaaaaaaaa aaaactcgag 2790 <210> 80 <211> 1460 <212> DNA
<213> Homo sapiens <400> 80 ctcaaagcag ttgagtaggc agaaaaaaga acctcttcat taaggattaa aatgtatagg 60 ccagcacgtg taacttcgac ttcaagattt ctgaatccat atgtagtatg tttcattgtc 120 gtcgcagggg tagtgatcct ggcagtcacc atagctctac ttgtttactt tttagctttt 180 gatcaaaaat cttactttta taggagcagt tttcaactcc taaatgttga atataatagt 240 cagttaaatt caccagctac acaggaatac aggactttga gtggaagaat tgaatctctg 300 atctgtaagc tctgtccctt gtcctccacc ctggtcttta gagccacctc attactaaaa cattcaaaga atcaaattta agaaatcagt tcatcagagc tcatgttgcc 360 aaactgaggc aagatggtag tggtgtgaga gcggatgttg tcatgaaatt tcaattcact 420 agaaataaca atggagcatc aatgaaaagc agaattgagt ctgttttacg acaaatgctg 480 aataactctg gaaacctgga aataaaccct tcaactgaga taacatcact tactgaccag 540 gctgcagcaa attggcttat taatgaatgt ggggccggtc cagacctaat aacattgtct 600 gagcagagaa tccttggagg cactgaggct gaggagggaa gctggccgtg gcaagtcagt 660 ctgcggctca ataatgccca ccactgtgga ggcagcctga tcaataacat gtggatcctg 720 acagcagctc actgcttcag aagcaactct aatcctcgtg actggattgc cacgtctggt 780 atttccacaa catttcctaa actaagaatg agagtaagaa atattttaat tcataacaat 840 tataaatctg caactcatga aaatgacatt gcacttgtga gacttgagaa cagtgtcacc 900 tttaccaaag atatccatag tgtgtgtctc ccagctgcta cccagaatat tccacctggc 960 tctactgctt atgtaacagg atggggcgct caagaatatg ctggccacac agttccagag 1020 ctaaggcaag gacaggtcag aataataagt aatgatgtat gtaatgcacc acatagttat 1080 aatggagcca tcttgtctgg aatgctgtgt gctggagtac ctcaaggtgg agtggacgca 1140 tgtcagggtg actctggtgg cccactagta caagaagact cacggcggct ttggtttatt 1200 gtggggatag taagctgggg agatcagtgt ggcctgccgg ataagccagg agtgtatact 1260 cgagtgacag cctaccttga ctggattagg caacaaactg ggatctagtg caacaagtgc 1320 atccctgttg caaagtctgt atgcaggtgt gcctgtctta aattccaaag ctttacattt 1380 caactgaaaa agaaactaga aatgtcctaa tttaacatct tgttacataa atatggttta 1440 acaaaaaaaa aaaaaaaaaa 1460 <210> 81 <211> 386 <212> PRT
<213> Homo sapiens <400> 81 Met Phe Ala Glu Ile GIn Ile Gln Asp Lys Asp Arg Met Gly Thr Ala Gly Lys Val Ile Lys Cys Lys Ala Ala Val Leu Trp Glu Gln Lys Gln Pro Phe Ser Ile Glu Glu Ile Glu Val Ala Pro Pro Lys Thr Lys Glu Val Arg Ile Lys Ile Leu Ala Thr Gly Ile Cys Arg Thr Asp Asp His Val Ile Lys Gly Thr Met Val Ser Lys Phe Pro Val Ile Val Gly His Glu Ala Thr Gly Ile Val Glu Ser Ile Gly Glu Gly Val Thr Thr Val Lys Pro Gly Asp Lys Val Ile Pro Leu Phe Leu Pro Gln Cys Arg Glu Cys Asn Ala Cys Arg Asn Pro Asp Gly Asn Leu Cys Ile Arg Ser Asp lI5 120 125 Ile Thr Gly Arg Gly Val Leu Ala Asp Gly Thr Thr Arg Phe Thr Cys Lys Gly Lys Pro Val His His Phe Met Asn Thr Ser Thr Phe Thr Glu Tyr Thr Val Val Asp Glu Ser Ser Val Ala Lys Ile Asp Asp Ala Ala Pro Pro Glu Lys Val Cys Leu Ile Gly Cys Gly Phe Ser Thr Gly Tyr Gly Ala Ala Val Lys Thr Gly Lys Val Lys Pro Gly Ser Thr Cys Val Val Phe Gly Leu Arg Gly Val Gly Leu Ser Val Ile Met Gly Cys Lys Ser Ala Gly Ala Ser Arg Ile Ile Gly Ile Asp Leu Asn Lys Asp Lys Phe Glu Lys Ala Met Ala Val Gly Ala_Thr Glu Cys Ile Ser Pro Lys Asp Ser Thr Lys Pro Ile Ser Glu Val Leu Ser Glu Met Thr Gly Asn Asn Val Gly Tyr Thr Phe Glu Val Ile Gly His Leu Glu Thr Met Ile Asp Ala Leu Ala Ser Cys His Met Asn Tyr Gly Thr Ser Val Val Val Gly Val Pro Pro Ser Ala Lys Met Leu Thr Tyr Asp Pro Met Leu Leu Phe Thr Gly Arg Thr Trp Lys Gly Cys Val Phe Gly Gly Leu Lys Ser Arg Asp Asp Val Pro Lys Leu Va1 Thr Glu Phe Leu Ala Lys Lys Phe Asp Leu Asp Gln Leu Ile Thr His Val Leu Pro Phe Lys Lys Ile Ser Glu Gly Phe Glu Leu Leu Asn Ser Gly Gln Ser Ile Arg Thr Val Leu Thr Phe <210> 82 <211> 418 <212> PRT
<213> Homo sapiens <400> 82 Met Tyr Arg Pro Ala Arg Val Thr Ser Thr Ser Arg Phe Leu Asn Pro Tyr Val Val Cys Phe Ile Val Val Ala Gly Val Val Ile Leu Ala Val Thr Ile Ala Leu Leu Val Tyr Phe Leu Ala Phe Asp Gln Lys Ser Tyr Phe Tyr Arg Ser Ser Phe Gln Leu Leu Asn Val Glu Tyr Asn Ser Gln Leu Asn Ser Pro Ala Thr Gln Glu Tyr Arg Thr Leu Ser Gly Arg Ile Glu Ser Leu Ile Thr Lys Thr Phe Lys Glu Ser Asn Leu Arg Asn Gln Phe Ile Arg Ala His Val Ala Lys Leu.__Arg Gln Asp Gly Ser Gly Val Arg Ala Asp Val Val Met Lys Phe Gln Phe Thr Arg Asn Asn Asn Gly Ala Ser Met Lys Ser Arg Ile Glu Ser Val Leu Arg Gln Met Leu Asn Asn Ser Gly Asn Leu Glu Ile Asn Pro Ser Thr Glu Ile Thr Ser Leu 145 150 155 ?60 Thr Asp Gln Ala Ala Ala Asn Trp Leu Ile Asn Glu Cys Gly Ala Gly Pro Asp Leu Ile Thr Leu Ser Glu Gln Arg Ile Leu Gly Gly Thr GIu Ala Glu Glu Gly Ser Trp Pro Trp Gln Val Ser Leu Arg Leu Asn Asn Ala His His Cys Gly Gly Ser Leu Ile Asn Asn Met Trp Ile Leu Thr Ala Ala His Cys Phe Arg Ser Asn Ser Asn Pro Arg Asp Trp Ile Ala Thr Ser Gly Ile Ser Thr Thr Phe Pro Lys Leu Arg Met Arg Val Arg Asn Ile Leu Ile His Asn Asn Tyr Lys Ser Ala Thr His Glu Asn Asp Ile Ala Leu Val Arg Leu Glu Asn Ser Val Thr Phe Thr Lys Asp Ile His Ser Val Cys Leu Pro Ala Ala Thr Gln Asn Ile Pro Pro Gly Ser Thr Ala Tyr Val Thr Gly Trp Gly Ala Gln Glu Tyr Ala Gly His Thr Vai Pro Glu Leu Arg Gln Gly Gln Val Arg Ile Ile Ser Asn Asp Val Cys Asn Ala Pro His Ser Tyr Asn Gly Ala Ile Leu Ser Gly Met Leu Cys Ala Gly Val Pro Gln Gly Gly Val Asp Ala Cys Gln Gly Asp Ser Gly Gly Pro Leu Val Gln Glu Asp Ser Arg Arg Leu Trp Phe Ile Val Gly Ile Val Ser Trp Gly Asp Gln Cys Gly Leu Pro Asp Lys Pro Gly 385 390 __ 395 400 Val Tyr Thr Arg VaI Thr Ala Tyr Leu Asp Trp Ile Arg Gln Gln Thr Gly Ile <210> 83 <211> 418 <212> PRT
<213> Homo sapiens <400> 83 Met Tyr Arg Pro Ala Arg Val Thr Ser Thr Ser Arg Phe Leu Asn Pro Tyr Val Val Cys Phe Ile Val Val Ala Gly Val Val Ile Leu Ala Val Thr Ile Ala Leu Leu Val Tyr Phe Leu Ala Phe Asp Gln Lys Ser Tyr Phe Tyr Arg Ser Ser Phe Gln Leu Leu Asn Val Glu Tyr Asn Ser Gln Leu Asn Ser Pro Ala Thr Gln Glu Tyr Arg Thr Leu Ser Gly Arg Ile Glu Ser Leu Ile Thr Lys Thr Phe Lys Glu Ser Asn Leu Arg Asn Gln Phe Ile Arg Ala His Val Ala Lys Leu Arg Gln Asp Gly Ser Gly Val Arg Ala Asp Val Val Met Lys Phe Gln Phe Thr Arg Asn Asn Asn Gly Ala Ser Met Lys Ser Arg Ile Glu Ser Val Leu Arg Gln Met Leu Asn Asn Ser Gly Asn Leu Glu Ile Asn Pro Ser Thr Glu Ile Thr Ser Leu Thr Asp Gln Ala Ala Ala Asn Trp Leu Ile Asn Glu Cars Gly Ala Gly Pro Asp Leu Ile Thr Leu Ser Glu Gln Arg Ile Leu Gly Gly Thr Glu Ala Glu Glu Gly Ser Trp Pro Trp Gln Val Ser Leu Arg Leu Asn Asn Ala His His C'ys Gly Gly Ser Leu I1e Asn Asn Met Trp Ile Leu Thr Ala Ala His Cys Phe Arg Ser Asn Ser Asn Pro Arg Asp Trp Ile Ala Thr Ser Gly Ile Ser Thr Thr Phe Pro Lys Leu Arg Met Arg Val Arg Asn Ile Leu Ile His Asn Asn Tyr Lys Ser Ala Thr His Glu Asn Asp Ile Ala Leu Val Arg Leu Glu Asn Ser Val Thr Phe Thr Lys Asp Ile His Ser Val Cys Leu Pro Ala Ala Thr Gln Asn Ile Pro Pro Gly Ser Thr Ala Tyr Val Thr Gly Trp GIy Ala Gln Glu Tyr Ala Gly His Thr VaI Pro Glu Leu Arg Gln Gly Gln Val Arg Ile Ile Ser Asn Asp Val Cys Asn Ala Pro His Ser Tyr Asn Gly Ala Ile Leu Ser Gly Met Leu ~C~s Ala Gly Val Pro Gln Gly Gly Val Asp Ala Cys Gln Gly Asp Ser Gly Gly Pro Leu Val Gln Glu Asp Ser Arg Arg Leu Trp Phe Ile Val Gly Ile Val Ser Trp Gly Asp Gln Cars Gly Leu Pro Asp Lys Pro Gly Val Tyr Thr Arg Val Thr Ala Tyr Leu Asp Trp Ile Arg Gln Gln Thr Gly Ile <210> 84 <211> 489 <212> DNA
<213> Homo Sapiens <400> 84 aaaagggtaa gcttgatgat taccaggaac gaatgaacaa aggggaaagg cttaatcaag 60 atcagctgga tgccgtttct aagtaccagg aagtcacaaa taatttggag tttgcaaaag 120 aattacagag gagtttcatg gcactaagtc aagatattca gaaaacaata aagaagacag 180 cacgtcggga gcagcttatg agagaagaag ctgaacagaa acgtttaaaa actgtacttg 240 agctacagta tgttttggac aaattgggag atgatgaagt gcggactgac ctgaaacaag 300 gtttgaatgg agtgccaata ttgtccgaag aggagttgtc attgttggat gaattctata 360 agctagtaga ccctgaacgg gacatgagct tgaggttgaa tgaacagtat gaacatgcct 420 ccattcacct gtgggacctg ctggaaggga aggaaaaacc tgtatgtgga accacctata 480 aagttctaa .__ 489 <210> 85 <211> 304 <212> DNA
<213> Homo Sapiens <400> 85 gggacctgga ggaggccacg ctgcagcatg aagccacagc agccaccctg aggaagaagc 60 acgcggacag cgtggccgag ctcggggagc agatcgacaa cctgcagcgg gtgaagcaga 120 agctggagaa ggagaagagc gagatgaaga tggagatcga tgacctcgct tgtaacatgg 180 aggtcatctc caaatctaag ggaaaccttg agaagatgtg ccgcacactg gaggaccaag 240 tgagtgagct gaagacccag gaggaggaac agcagcggct gatcaatgaa ctgactgcgc 300 agag <210> 86 <2I1> 296 <212> DNA
<213> Homo Sapiens <400> 86 gaaaatcctt cctttgaatg ggaatctcca agcagttgaa ttgggcgaaa aaagaacctc 60 ttccttaagg attaaaatgt ttagggcaac acgtgttact tccacttcca gatttctgaa 120 tccatatgtt gtatgtttcc ttgtcctccc aggggttgtg atcctggcag tccccatagc 180 tctacttgtt tactttttag cttttgatca aaaatcttac ttttattgga gcaattttcc 240 actcccaaat gttgaatata atagtccgtt taattccccc gcttcaccgg gaattc 296 <210> 87 <211> 904 <212> DNA
<213> Homo sapiens <400> 87 gtgtccagga aacgattcat gaacataaca agcttgctgc aaattcagat catctcatgc 60 agattcaaaa atgtgagttg gtcttgatcc acacctaccc agttggtgaa gacagccttg 120 tatctgatcg ttctaaaaaa gagttgtccc cggttttaac cagtgaagtt catagtgttc 180 gtgcaggacg gcatcttgct accaaattga atattttagt acagcaacat tttgacttgg 240 cttcaactac tattacaaat attccaatga aggaagaaca gcatgctaac acatctgcca 300 attatgatgt ggagctactt catcacaaag atgcacatgt agatttcctg aaaagtggtg 360 $1 attcgcatct aggtggcggc agtcgagaag gctcgtttaa agaaacaata acattaaagt 420 ggtgtacacc aaggacaaat aacattgaat tacactattg tactggagct tatcggattt 480 cacctgtaga tgtaaatagt agaccttcct cctgccttac taattttctt ctaaatggtc 540 gttctgtttt attggaacaa ccacgaaagt caggttctaa agtcattagt catatgctta 600 gtagccatgg aggagagatt tttttgcacg tccttagcag ttctcgatcc attctagaag 660 atccaccttc aattagtgaa ggatgtggag gaagagttac agactaccgg attacagatt 720 ttggtgaatt tatgagggga aaacagatta actccttttc tacaccccag atataaaatc 780 gatggaagtc ttgaggtccc tttggaaccg agccaaaaga tcagttaaaa aaacataccc 840 gttactggcc tatgatttca aaaacccacc atttttaaca tgcaagcggt agttccgtta 900 acca <210> 88 <211> 387 <212> DNA
<213> Homo Sapiens <400> 88 cgtctctccc ccagtttgcc gttcacccgg agcgctcggg acttgccgat agtggtgacg 60 gcggcaacat gtctgtggct ttcgcggccc cgaggcagcg aggcaagggg gagatcactc 120 ccgctgcgat tcagaagatg ttggatgaca ataaccatct tattcagtgt ataatggact 180 ctcagaataa aggaaagacc tcagagtgtt ctcagtatca gcagatgttg cacacaaact 240 tggtatacct tgctacaata gcagattcta atcaaaatat gcagtctctt ttaccagcac 300 cacccacaca gaatatgcct atgggtcctg gagggatgaa tcagagcggg cctcccccac 360 ctccacgctc tcacaacatg ccttcaa 387 <210> 89 <211> 481 <212> DNA
<213> Homo sapiens <400> 89 tgttcttgga cctgcggtgc tatagagcag gctcttctag gttggcagtt gccatggaat 60 ctggacccaa aatgttggcc cccgtttgcc tggtggaaaa taacaatgag cagctattgg 120 tgaaccagca agctatacag attcttgaaa agatttctca gccagtggtg gtggtggcca 180 ttgtaggact gtaccgtaca gggaaatcct acttgatgaa ccatctggca ggacagaatc 240 atggcttccc tctgggctcc acggtgcagt ctgaaaccaa gggcatctgg atgtggtgcg 300 tgccccaccc atccaagcca aaccacaccc tggtccttct ggacaccgaa ggtctgggcg 360 atgtggaaaa gggtgaccct aagaatgact cctggatctt tgccctggct gtgctcctgt 420 gcagcacctt tgtctacaac agcatgagca ccatcaacca ccaggccctg gagcagctgc 480 a 481 <210> 90 <211> 491 <212> DNA
<213> Homo Sapiens <400> 90 tgaaaactgt tcttggacct gcggtgctat agagcaggtt ggcagttgcc atggaatctg 60 gacccaaaat gttggccccc gtttgcctgg tggaaaataa caatgagcag ctattggtga 120 accagcaagc tatacagatt cttgaaaaga tttctcagcc agtggtggtg gtggccattg 180 taggactgta ccgtacaggg aaatcctact tgatgaacca tctggcagga cagaatcatg 240 gcttccctct gggctccacg gtgcagtctg aaaccaaggg catctggatg tggtgcgtgc 300 cccacccatc caagccaaac cacaccctgg tccttctgga caccgaaggt ctgggcgatg 360 tggaaaaggg tgaccctaag aatgactcct ggatctttgc cctggctgtg ctcctgtgca 420 gcacctttgt ctacaacagc atgagcacca tcaaccacca agccctggag cagctgcatt 480 atgtgacgga c 491 <210> 91 <211> 488 <212> DNA
<2i3> Homo sapiens <400> 91 ttcgacagtc agccgcatct tcttttgcgt cgccagccga gccacatcgc tcagacacca 60 tggggaaggt gaaggtcgga gtcaacggat ttggtcgtat tgggcgcctg gtcaccaggg 120 ctgcttttaa ctctggtaaa gtggatattg ttgccatcaa tgaccccttc attgacctca 180 actacatggt ttacatgttc caatatgatt ccacccatgg caaattccat ggcaccgtcg 240 aggctgagaa cgggaagctt gtcatcaatg gaaatcccat caccatcttc caggagcgag 300 atccctccaa aatcaagtgg ggcgatgctg gcgctgagta cgtcgtggag tccactggcg 360 tcttcaccac catggagaag gctggggctc atttgcaggg gggagccaaa agggtcatca 420 tctctgcccc tctgctgatg ccccatgttc gtcatgggtg tgaaccatga gaagtatgac 480 acagcctc 488 <210> 92 <211> 384 <212> DNA
<213> Homo sapiens <400> 92 gacagtcagc cgcatcttct tttgcgtcgc cagccgagcc acatcgctca gacaccatgg 60 ggaaggtgaa ggtcggagtc aacggatttg gtcgtattgg gcgcctggtc accagggctg 120 cttttaactc tggtaaagtg gatattgttg ccatcaatga ccccttcatt gacctcaact 180 acatggttta catgttccaa tatgattcca cccatggcaa attccatggc accgtcgagg 240 ctgagaacgg gaagcttgtc atcaatggaa atcccatcac catcttccag gagcgagatc 300 cctccaaaat caagtggggc gatactggcg ctgagtacgt cgtggagtcc actggcgtct 360 tcaccaccat ggagaaggct gggg 384 <210> 93 <211> 162 <212> PRT
<213> Homo Sapiens <400> 93 Lys Gly Lys Leu Asp Asp Tyr Gln Glu Arg Met Asn Lys Gly Glu Arg Leu Asn Gln Asp Gln Leu Asp Ala Val Ser Lys Tyr Gln Glu Val Thr Asn Asn Leu Glu Phe Ala Lys Glu Leu Gln Arg Ser Phe Met Ala Leu Ser Gln Asp Ile Gln Lys Thr Ile Lys Lys Thr Ala Arg Arg Glu Gln Leu Met Arg Glu Glu Ala Glu Gln Lys Arg Leu Lys Thr Val Leu Glu 65 70 75 g0 Leu Gln Tyr VaI Leu Asp Lys Leu Gly Asp Asp Glu Val Arg Thr Asp Leu Lys Gln Gly Leu Asn Gly Val Pro Ile Leu Ser Glu Glu Glu Leu loo los llo SerLeu Leu Glu TyrLys LeuVal Pro Arg Met Asp Phe Asp Glu Asp SerLeu Arg Asn GlnTyr GluHis Ser His Trp Leu Glu Ala Ile Leu AspLeu Leu Gly GluLys ProVal Gly Thr Lys Glu Lys Cys Thr Tyr ValLeu <210> 94 <211> 100 <212> PRT
<213> Homo Sapiens <400> 94 Asp Leu Glu Glu Ala Thr Leu Gln His Glu Ala Thr Ala Ala Thr Leu Arg Lys Lys His Ala Asp Ser Val Ala Glu Leu Gly Glu Gln Ile Asp Asn Leu Gln Arg Val Lys Gln Lys Leu Glu Lys Glu Lys Ser Glu Met Lys Met Glu Ile Asp Asp Leu Ala Cars Asn Met Glu Val Ile Ser Lys Ser Lys Gly Asn Leu Glu Lys Met Cys Arg Thr Leu Glu Asp Gln Val Ser Glu Leu Lys Thr Gln Glu Glu Glu Gln Gln Arg Leu Ile Asn Glu Leu Thr Ala Gln <210> 95 <211> 99 <212> PRT
<213> Homo Sapiens <400> 95 Lys Ile Leu Pro Leu Asn Gly Asn Leu Gln Ala Val Glu Leu Gly Glu Lys Arg Thr Ser Ser Leu Arg Ile Lys Met Phe Arg Ala Thr Arg Val WO 99!38973 PCT/US99/01642 Thr Ser Thr Ser Arg Phe Leu Asn Pro Tyr Val Val Cys Phe Leu Val Leu Pro Gly Val Val Ile Leu Ala Val Pro Ile Ala Leu Leu Val Tyr Phe Leu Ala Phe Asp Gln Lys Ser Tyr Phe Tyr Trp Ser Asn Phe Pro Leu Pro Asn Val Glu Tyr Asn Ser Pro Phe Asn Ser Pro Ala Ser Pro Gly Ile Pro <210> 96 <211> 257 <212> PRT
<213> Homo sapiens <400> 96 Val Gln Glu Thr Ile His Glu His Asn Lys Leu Ala Ala Asn Ser Asp His Leu Met Gln Ile Gln Lys Cys Glu Leu Val Leu Ile His Thr Tyr Pro Val Gly Glu Asp Ser Leu Val Ser Asp Arg Ser Lys Lys Glu Leu Ser Pro Val Leu Thr Ser Glu Val His Ser Val Arg Ala Gly Arg His Leu Ala Thr Lys Leu Asn Ile Leu Val Gln Gln His Phe Asp Leu Ala Ser Thr Thr Ile Thr Asn Ile Pro Met Lys Glu Glu Gln His Ala Asn Thr Ser Ala Asn Tyr Asp Val Glu Leu Leu His His Lys Asp Ala His Val Asp Phe Leu Lys Ser Gly Asp Ser His Leu Gly Gly Gly Ser Arg Glu Gly Ser Phe Lys Glu Thr Ile Thr Leu Lys Trp Cys Thr Pro Arg Thr Asn Asn Ile Glu Leu His Tyr Cys Thr Gly Ala Tyr Arg IIe Ser Pro Val Asp Val Asn Ser Arg Pro Ser Ser Cys Leu Thr Asn Phe Leu Leu Asn Gly Arg Ser Val Leu Leu Glu Gln Pro Arg Lys Ser Gly Ser Lys Val Ile Ser His Met Leu Ser Ser His Gly Gly Glu Ile Phe Leu His Val Leu Ser Ser Ser Arg Ser Ile Leu Glu Asp Pro Pro Sex Ile Ser Glu Gly Cys Gly Gly Arg Val Thr Asp Tyr Arg Ile Thr Asp Phe Gly Glu Phe Met Arg Gly Lys Gln Ile Asn Ser Phe Ser Thr Pro Gln Ile <210> 97 <211> 128 <212> PRT
<213> Homo sapiens <400> 97 Ser Leu Pro Gln Phe Ala Val His Pro Glu Arg Ser Gly Leu Ala Asp Ser Gly Asp Gly Gly Asn Met Ser Val Ala Phe Ala Ala Pro Arg Gln Arg Gly Lys Gly Glu Ile Thr Pro Ala Ala Ile Gln Lys Met Leu Asp Asp Asn Asn His Leu Ile Gln Cps Ile Met Asp Ser Gln Asn Lys Gly Lys Thr Ser Glu Cars Ser Gln Tyr Gln Gln Met Leu His Thr Asn Leu Val Tyr Leu Ala Thr Ile Ala Asp Ser Asn Gln Asn Met Gln Ser Leu Leu Pro Ala Pro Pro Thr Gln Asn Met Pro Met Gly Pro Gly Gly Met Asn Gln Ser Gly Pro Pro Pro Pro Pro Arg Ser His Asn Met Pro Ser <210> 98 <211> 159 <212> PRT
<213> Homo sapiens <400> 98 Phe Leu Asp Leu Arg Cys Tyr Arg Ala Gly Ser Ser Arg Leu Ala Val Ala Met Glu Ser Gly Pro Lys Met Leu Ala Pro Val Cys Leu Val Glu Asn Asn Asn Glu Gln Leu Leu Val Asn Gln Gln Ala Ile Gln Ile Leu Glu Lys Ile Ser Gln Pro Val Val Val Val Ala Ile Val Gly Leu Tyr Arg Thr Gly Lys Ser Tyr Leu Met Asn His Leu Ala Gly Gln Asn His ss 70 7s so Gly Phe Pro Leu Gly Ser Thr Val Glr~-Ser Glu Thr Lys Gly Ile Trp Met Trp Cys Val Pro His Pro Ser Lys Pro Asn His Thr Leu Val Leu Leu Asp Thr Glu Gly Leu Gly Asp Val Glu Lys Gly Asp Pro Lys Asn Asp Ser Trp Ile Phe Ala Leu Ala Val Leu Leu Cys Ser Thr Phe Val Tyr Asn Ser Met Ser Thr Ile Asn His Gln Ala Leu Glu Gln Leu <210> 99 <211> 147 <212> PRT
<213> Homo Sapiens <400> 99 Met Glu Ser Gly Pro Lys Met Leu Ala Pro Val Cys Leu Val Glu Asn Asn Asn Glu Gln Leu Leu Val Asn Gln Gln Ala Ile Gln Ile Leu Glu ' 20 25 30 Lys Ile Ser Gln Pro Val Val Val Val Ala Ile Val Gly Leu Tyr Arg Thr Gly Lys Ser Tyr Leu Met Asn His Leu Ala Gly Gln Asn His Gly Phe Pro Leu Gly Ser Thr Val Gln Ser Glu Thr Lys Gly Ile Trp Met Trp Cys Val Pro His Pro Ser Lys Pro Asn His Thr Leu Val Leu Leu AspThr Gly LeuGly ValGlu Gly Pro LysAsn Glu Asp Lys Asp Asp SerTrp Phe AlaLeu ValLeu Cys Thr PheVal Ile Ala Leu Ser Tyr AsnSer Ser ThrIle HisGln Leu Gln LeuHis Met Asn Ala Glu Tyr ValThr Asp <210> I00 <211> 124 <212> PRT
<213> Homo Sapiens <400> 100 Met Gly Lys Val Lys Val Gly Val Asn Gly Phe Gly Arg Ile Gly Arg Leu Val Thr Arg Ala Ala Phe Asn Ser Gly Lys Val Asp Ile Val Ala Ile Asn Asp Pro Phe Ile Asp Leu Asn Tyr Met Val Tyr Met Phe Gln Tyr Asp Ser Thr His Gly Lys Phe His Gly Thr Val Glu Ala Glu Asn Gly Lys Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe Gln Glu Arg Asp Pro Ser Lys Ile Lys Trp Gly Asp Ala Gly Ala Glu Tyr Val Val Glu Ser Thr Gly Val Phe Thr Thr Met Glu Lys Ala Gly Ala His Leu Gln Gly Gly Ala Lys Arg Val Ile Ile Ser Ala Pro <210> 101 <211> 127 <212> PRT
<213> Homo sapiens <400> 101 Gln Ser Ala Ala Ser Ser Phe Ala Ser Pro Ala Glu Pro His Arg Ser WO 99/38973 PCT/US99/fl1642 Asp Thr Met Gly Lys Val Lys Val Gly Val Asn Gly Phe Gly Arg Ile Gly Arg Leu Val Thr Arg Ala Ala Phe Asn Ser Gly Lys Val Asp Ile Val Ala Ile Asn Asp Pro Phe Ile Asp Leu Asn Tyr Met Val Tyr Met Phe Gln Tyr Asp Ser Thr His Gly Lys Phe His Gly Thr Val Glu Ala Glu Asn Gly Lys Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe Gln Glu Arg Asp Pro Ser Lys Ile Lys Trp GIy Asp Thr Gly Ala GIu Tyr Val Val Glu Ser Thr Gly Val Phe Thr Thr Met Glu Lys Ala Gly <210> 102 <211> 1225 <212> DNA
<213> Homo sapiens <400> 102 atggcggcgc ggtcgtcgtc gggggtggcg gcggcagagg gggcggcggc cctggcggca 60 gcggagacgg cagccgtgac ggtggcagcg gcggcgcggg acctgggcct gggggaatga 120 ggcggccgcg gcgggccagc ggcggagccg tgtagcggag aagctccccc tccctgcttc 180 ccttggccga gccgggggcg cgcgcgcacg cggccgtcca gagcgggctc cccacccctc 240 gactcctgcg acccgcaccg cacccccacc cgggcccgga ggatgatgaa gctcaagtcg 300 aaccagaccc gcacctacga cggcgacggc tacaagaagc gggccgcatg cctgtgtttc 360 cgcagcgaga gcgaggagga ggtgctactc gtgagcagta gtcgccatcc agacagatgg 420 attgtccctg gaggaggcat ggagcccgag gaggagccaa gtgtggcagc agttcgtgaa 480 gtctgtgagg aggctggagt aaaagggaca ttgggaagat tagttggaat ttttgagaac 540 caggagagga agcacaggac gtatgtctat gtgctcattg tcactgaagt gctggaagac 600 tgggaagatt cagttaacat tggaaggaag agggaatggt ttaaaataga agacgccata 660 aaagtgctgc agtatcacaa acccgtgcag gcatcatatt ttgaaacatt gaggcaaggc 720 tactcagcca acaatggcac cccagtcgtg gccaccacat actcggtttc tgctcagagc 780 tcgatgtcag gcatcagatg actgaagact tcctgtaaga gaaatggaaa ttggaaacta 840 gactgaagtg caaatcttcc ctctcaccct ggctctttcc acttctcaca ggcctcctct 900 ttcaaataag gcatggtggg cagcaaagaa agggtgtatt gataatgttg ctgtttggtg 960 ttaagtgatg gggctttttc ttctgttttt attgagggtg ggggttgggt gtgtaatttg 1020 taagtacttt tgtgcatgat ctgtccctcc ctcttcccac ccctgcagtc ctctgaagag 1080 aggccaacag ccttcccctg ccttggattc tgaagtgttc ctgtttgtct tatcctggcc 1140 ctggccagac gttttctttg atttttaatt tttttttttt attaaaagat accagtatga 1200 gaaaaaaaaa aaaaaaaaac tcgag 1225 <210> 103 <211> 741 <2I2> DNA
<213> Homo Sapiens Asp Pro Ser Lys Ile Lys Trp Gly Asp Ala G

<4oa> l03 agaaacctca atcggattca gcaaaggaat ggtgttatta tcactacata ccaaatgtta 60 atcaataact ggcagcaact ttcaagcttt aggggccaag agtttgtgtg ggactatgtc 120 atcctcgatg aagcacataa aataaaaacc tcatctacta agtcagcaat atgtgctcgt 180 gctattcctg caagtaatcg cctcctcctc acaggaaccc caatccagaa taatttacaa 240 gaactatggt ccctatttga ttttgcttgt caagggtccc tgctgggaac attaaaaact 300 tttaagatgg agtatgaaaa tcctattact agagcaagag agaaggatgc taccccagga 360 gaaaaagcct tgggatttaa aatatctgaa aacttaatgg caatcataaa accctatttt 420 ctcaggagga ctaaagaaga cgtacagaag aaaaagtcaa gcaacccaga ggccagactt 480 aatgaaaaga atccagatgt tgatgccatt tgtgaaatgc cttccctttc caggagaaat 540 gatttaatta tttggatacg acttgtgcct ttacaagaag aaatatacag gaaatttgtg 600 tctttagatc atatcaagga gttgctaatg gagacgcgct cacctttggc tgagctaggt 660 gtcttaaaga agctgtgtga tcatcctagg ctgctgtctg cacgggcttg ttgtttgcta 720 aatcttggga cattctctgc t 741 <210> 104 <211> 321 <212> DNA
<213> Homo Sapiens <400> 104 ttgctctgcg tcatcaaaga caccaaactg ctgtgctata aaagttccaa ggaccagcag 60 cctcagatgg aactgccact ccaaggctgt aacattacgt acatcccgaa agacagcaaa 120 aagaagaagc acgagctgaa gattactcag cagggcacgg acccgcttgt tctcgccgtc 180 cagagcaagg aacaggccga gcagtggctg aaggtgatca aagaagccta cagtggttgt 240 agtggccccg tggattcaga gtgtcctcct ccaccaagct ccccggtgca caaggcagaa 300 ctggagaaga aactgtcttc a 321 <210> 105 <211> 389 <212> DNA
<213> Homo Sapiens <400> 105 cagcactggc cacactataa aattcaggtt cagaaaaaca gggtaagtca cagacagcaa 60 cgcttccagc atttattttc tttgcaccca tgggcaattt gagaaaattt acctttagaa 120 cgaactctgt taaaggtaca gacagtacaa tactttttat tcagaaggtt tctgcataaa 180 ggtgatagtc ttttgactta atatattatt gtctcctgcc ttgtgtttct ggaatgaatg 240 aaggtcatta tttagaagat aatctgggtt gtatttgtgt cgtcagattg aattttcatt 300 gcacatgcta cttaatgtct ttaccaaata ataacaaagg gaaagaaaac caaatataga 360 tgtataataa ggaaaagctg gcctataga 389 <210> 106 <211> 446 <212> DNA
<213> Homo Sapiens <400> 106 gccacatttg ccctggtcat agtttaaaca ccaggtcctg tgtcacatct ttttggtgcc 60 acaagtatca ctccattgtt cagagagtaa tgtattagtt ctgcccaatt ca~tcttcac 120 ttttatttct tccatttcat tagcatttat atcagctcaa gaagttaagg ttagaaaatt 180 ttccacttca aattttcagt acagaaatgt gctgtgatgt ttgacaagac tatttcatag 240 taagtgagtt aatgtttatt ggcctctgct ctcctctgtg tcagacctag gaagcctgag 300 gattacttag ttgttctgtc tctgggtcca caggcagaat ttggcccatc caaagactgg 360 ccaagtgcca aaaaaaggcc tgattaggcc ctgaaattca gtgaaattct gcctgaagaa 420 acctcttatt gaatttgaaa accata 446 <210> 107 <21I> 467 <212> DNA
<213> Homo Sapiens <400> 107 ccgccgctgc cgtcgccttc ctgggattgg agtctcgagc tttcttcgtt cgttcgccgg 60 cgggttcgcg cccttctcgc gcctcggggc tgcgaggctg gggaaggggt tggagggggc 120 tgttgatcgc cgcgtttaag ttgcgctcgg ggcggccatg tcggccggcg aggtcgagcg 180 cctagtgtcg gagctgagcg gcgggaccgg aggggatgag gaggaagagt ggctctatgg 240 cgatgaagat gaagttgaaa ggccagaaga agaaaatgcc agtgctaatc ctccatctgg 300 aattgaagat gaaactgctg aaaatggtgt accaaaaccg aaagtgactg agaccgaaga 360 tgatagtgat agtgacagcg atgatgatga agatgatgtg catgtcacta taggagacat 420 taaaacggga gcaccacagt atgggagtta tggtacagca cctgtaa 467 <210> 108 ---<211> 491 <212> DNA
<213> Homo Sapiens <400> 108 gaaagataca acttccccaa cccaaacccg tttgtggagg acgacatgga taagaatgaa 60 atcgcctctg ttgcgtaccg ttaccgcagg tggaagcttg gagatgatat tgaccttatt 120 gtccgttgtg agcacgatgg cgtcatgact ggagccaacg gggaagtgtc cttcatcaac 180 atcaagacac tcaatgagtg ggattccagg cactgtaatg gcgttgactg gcgtcagaag 240 ctggactctc agcgaggggc tgtcattgcc acggagctga agaacaacag ctacaagttg 300 gcccggtgga cctgctgtgc tttgctggct ggatctgagt acctcaagct tggttatgtg 360 tctcggtacc acgtgaaaga ctcctcacgc cacgtcatcc taggcaccca gcagttcaag 420 cctaatgagt ttgccagcca gatcaacctg agcgtggaga atgcctgagg cattttacgc 480 tgcgtcattg a <210> 109 <211> 489 <212> DNA
<213> Homo Sapiens <400> 109 ctcagatagt actgaaccct ttatcaacta tgttttttca gtctgacaac caaggcggct 60 actaagtgac taaggggcag gtagtataca gtgtggataa gcaggacaaa ggggtgattc 120 acatcccagg caggacagag caggagatca tgagatttca tcactcagga tggcttgtga 180 tttattttat tttattcttt tttttttttg agatggagtc tcactcttgc ccaggctgga 240 gtgcagtggt gcgatcttgg ctcactgcaa cctctgcctc ctgggttcaa gcagttctcc 300 tgcctcagcc tcccaagtag ctgggattac aggcgtccgc caccatgccc agccaatttt 360 tgtactttta gtagagatgg ggtttcacca tgttggccag gctggtctcg aactcctgac 420 ctcaggtgat ccactcgcct cggcctccca aagtgctggg attataggca tgcgccacca 480 tgcccgggc 489 <210> 110 <211> 391 <212> DNA
<213> Homo sapiens <400> 110 gcggagtccg ctggctgacc cgagcgctgg tctccgccgg gaaccctggg gcatggagag 60 gtctgagtac ctcggccgcg gcgcacgctg catcgcggag ccaggctgcc gctgtcccag 120 tggagttcca ggagcaccac ctgagtgagg tgcagaatat ggcatctgag gagaagctgg 180 agcaggtgct gagttccatg aaggagaaca aagtggccat cattggaaag attcataccc 240 cgatggagta taagggggag ctagcctcct atgatatgcg gctgaggcgt aagttggact 300 tatttgccaa cgtaatccat gtgaagtcac ttcctgggta tatgactcgg cacaacaatc 360 tagacctggt gatcattcga gagcagacag a 391 <210> 111 <211> 172 <212> PRT
<213> Homo Sapiens <400> 111 Met Met Lys Leu Lys Ser Asn Gln Thr Arg Thr Tyr Asp Gly Asp Gly Tyr Lys Lys Arg Ala Ala Cys Leu Cys Phe Arg Ser Glu Ser Glu Glu Glu Val Leu Leu Val Ser Ser Ser Arg His Pro Asp Arg Trp IIe Val Pro Gly Gly Gly Met Glu Pro Glu Glu Glu Pro Ser Val Ala Ala Val Arg Glu Val Cys Glu Glu Ala Gly Val Lys Gly Thr Leu Gly Arg Leu Val Gly Ile Phe Glu Asn Gln Glu Arg Lys His Arg Thr Tyr Val Tyr Val Leu Ile Val Thr Glu Val Leu Glu Asp Trp Glu Asp Ser Val Asn Ile Gly Arg Lys Arg Glu Trp Phe Lys Ile Glu Asp Ala Ile Lys Val Leu Gln Tyr His Lys Pro Val Gln Ala Ser Tyr Phe Glu Thr Leu Arg Gln Gly Tyr Ser Ala Asn Asn Gly Thr Pro Val Val Ala Thr Thr Tyr Ser Val Ser Ala Gln Ser Ser Met Ser Gly Ile Arg <210> 112 <211> 247 <212> PRT
<213> Homo Sapiens <400> I12 Arg Asn Leu Asn Arg Ile Gln Gln Arg Asn Gly Val Ile Ile Thr Thr Tyr Gln Met Leu Ile Asn Asn Trp Gln Gln Leu Ser Ser Phe Arg Gly Gln Glu Phe Val Trp Asp Tyr Val Iie Leu Asp Glu Ala His Lys Ile Lys Thr Ser Ser Thr Lys Ser Ala Ile Cys Ala Arg Ala Ile Pro Ala Ser Asn Arg Leu Leu Leu Thr Gly Thr Pro Ile Gln Asn Asn Leu Gln Glu Leu Trp Ser Leu Phe Asp Phe Ala Cys Gln Gly Ser Leu Leu Gly Thr Leu Lys Thr Phe Lys Met Glu Tyr Glu Asn Pro Ile Thr Arg Ala Arg Glu Lys Asp Ala Thr Pro Gly Glu Lys Ala Leu Gly Phe Lys Ile Ser Glu Asn Leu Met Ala Ile Ile Lys Pro Tyr Phe Leu Arg Arg Thr Lys Glu Asp Val Gln Lys Lys Lys Ser Ser Asn Pro Glu Ala Arg Leu Asn Glu Lys Asn Pro Asp Val Asp Ala Ile Cys Glu Met Pro Ser Leu Ser Arg Arg Asn Asp Leu Ile Ile Trp Ile Arg Leu Val Pro Leu Gln Glu Glu Ile Tyr Arg Lys Phe Val Ser Leu Asp His Ile Lys Glu Leu Leu Met Glu Thr Arg Ser Pro Leu Ala Glu Leu Gly VaI Leu Lys Lys Leu Cys Asp His Pro Arg Leu Leu Ser Ala Arg Ala Cys Cys Leu Leu Asn Leu Gly Thr Phe Ser Ala <210> 113 <211> 107 <212> PRT
<213> Homo sapiens <400> 113 Leu Leu Cys Val Ile Lys Asp Thr Lys Leu Leu Cys Tyr Lys Ser Ser Lys Asp Gln Gln Pro Gln Met Glu Leu Pro Leu Gln Gly Cys Asn Ile Thr Tyr Ile Pro Lys Asp Ser Lys Lys Lys Lys His Glu Leu Lys Ile Thr Gln Gln Gly Thr Asp Pro Leu Val Leu Ala Val Gln Ser Lys Glu Gln Ala Glu Gln Trp Leu Lys Val Ile Lys Glu Ala Tyr Ser Gly Cys Ser Gly Pro Val Asp Ser Glu Cys Pro Pro Pro Pro Ser Ser Pro Val His Lys Ala Glu Leu Glu Lys Lys Leu Ser Ser 100 105' <210> 114 <211> 155 <212> PRT
<213> Homo sapiens <400> 114 Glu Arg Tyr Asn Phe Pro Asn Pro Asn Pro Phe Val Glu Asp Asp Met Asp Lys Asn Glu Ile Ala Ser Val Ala Tyr Arg Tyr Arg Arg Trp Lys Leu Gly Asp Asp Ile Asp Leu Ile Val Arg Cys Glu His Asp Gly Val Met Thr Gly Ala Asn Gly Glu Val Ser Phe Ile Asn Ile Lys Thr Leu Asn Glu Trp Asp Ser Arg His Cys Asn Gly Val Asp Trp Arg Gln Lys Leu Asp Ser Gln Arg Gly Ala Val Ile Ala Thr Glu Leu Lys Asn Asn 85 ~ 90 95 Ser Tyr Lys Leu Ala Arg Trp Thr Cys Cys Ala Leu Leu Ala Gly Ser Glu Tyr Leu Lys Leu Gly Tyr Val Ser Arg Tyr His Val Lys Asp Ser Ser Arg His Val Ile Leu Gly Thr Gln Gln Phe Lys Pro Asn Glu Phe Ala Ser Gln Ile Asn Leu Ser Val Glu Asn Ala <210> 115 <211> 129 <212> PRT
<213> Homo sapiens <400> 115 Gly Val Arg Trp Leu Thr Arg Ala Leu Val Ser Ala Gly Asn Pro Gly Ala Trp Arg Gly Leu Ser Thr Ser Ala Ala Ala His Ala Ala Ser Arg Ser Gln Ala Ala Ala Val Pro Val Glu Phe Gln Glu His His Leu Ser Glu Val Gln Asn Met Ala Ser Glu Glu Lys Leu Glu Gln Val Leu Ser Ser Met Lys Glu Asn Lys Val Ala Ile Ile Gly Lys Ile His Thr Pro Met Glu Tyr Lys Gly Glu Leu Ala Ser Tyr Asp Met Arg Leu Arg Arg Lys Leu Asp Leu Phe Ala Asn Val Ile His Val Lys Ser Leu Pro Gly Tyr Met Thr Arg His Asn Asn Leu Asp Leu Val Ile Ile Arg Glu Gln Thr <210> 116 <211> 550 <212> DNA
<213> Homo Sapiens <400> 116 gaattcggca ccagcctcag agccccccag cccggctacc accccctgcg gaaaggtacc 60 catctgcatt cctgcccgtc gggacctggt ggacagtcca gcctccttgg cctctagcct 120 tggctcaccg ctgcctagag ccaaggagct catcctgaac gaccttcccg ccagcactcc 180 tgcctccaaa tcctgtgact cctccccgcc ccaggacgct tccaccccca ggcccagctc 240 ggccagtcac ctctgccagc ttgctgccaa gccagcacct tccacggaca gcgtcgccct 300 gaggagcccc ctgactctgt ccagtccctt caccacgtcc ttcagcctgg gctcccacag 360 cactctcaac ggagacctct ccgtgcccag ctcctacgtc agcctccacc tgtcccccca 420 ggtcagcagc tctgtggtgt acggacgctc ccccgtgatg gcatttgagt ctcatcccca 480 tctccgaggg tcatccgtct cttcctccct acccagcatc cctgggggaa agccggccta 540 ctccttccac 550 <210> 117 <211> 154 b5 <212> DNA
<213> Homo sapiens <400> 117 ttctgaggga aagccgagtg gagtgggcga cccggcggcg gtgacaatga gttttcttgg 60 aggctttttt ggtcccattt gtgagattga tgttgccctt aatgatgggg aaaccaggaa 120 aatggcagaa atgaaaactg aggatggcaa agta 154 <210> 118 <211> 449 <212> DNA
<213> Homo sapiens <400> 118 gaattcggca ccagggcccg cagcccgagt gtcgccgcca tggcttcgcc gcagctctgc 60 cgcgcgctgg tgtcggcgca atgggtggcg gaggcgctgc gggccccgcg cgctgggcag 120 cctctgcagc tgctggacgc ctcctggtac ctgccgaagc tggggcgcga cgcgcgacgc 180 gagttcgagg agcgccacat cccgggcgcc gct-ttcttcg acatcgacca gtgcagcgac 240 cgcacctcgc cctacgacca catgctgccc ggggccgagc atttcgcgga gtacgcaggc 300 cgcctgggcg tgggcgcggc cacccacgtc gtgatctacg acgccagcga ccagggcctc 360 tactccgccc cgcgcgtctg gtggatgttc cgcgccttcg gccaccacgc cgtgtcactg 420 cttgatggcg gcctccgcca ctggctgcg 449 <210> 119 <211> 642 <212> DNA
<213> Homo sapiens <400> 119 gaattcggca cgagcagtaa cccgaccgcc gctggtcttc gctggacacc atgaatcaca 60 ctgtccaaac cttcttctct cctgtcaaca gtggccagcc ccccaactat gagatgctca 120 aggaggagca cgaggtggct gtgctggggg cgccccacaa ccctgctccc ccgacgtcca 180 ccgtgatcca catccgcagc gagacctccg tgcccgacca tgtcgtctgg tccctgttca 240 acaccctctt catgaacccc tgctgcctgg gcttcatagc attcgcctac tccgtgaagt 300 ctagggacag gaagatggtt ggcgacgtga ccggggccca ggcctatgcc tccaccgcca 360 agtgcctgaa catctgggcc ctgattctgg gcatcctcat gaccattctg ctcatcgtca 420 tcccagtgct gatcttccag gcctatggat agatcaggag gcatcactga ggccaggagc 480 tctgcccatg acctgtatcc cacgtactcc aacttccatt cctcgccctg cccccggagc 540 cgagtcctgt atcagccctt tatcctcaca cgcttttcta caatggcatt caataaagtg 600 cacgtgtttc tggtgaaaaa aaaaaaaaaa aaaaaactcg ag 642 <210> 120 <211> 603 <'212 > DNA
<213> Homo Sapiens <400> 120 gaattcggca cgagccacaa cagccactac gactgcatcc actggatcca cggccacccc 60 gtcctccacc ccgggaacag ctccccctcc caaagtgctg accagcccgg ccaccacacc 120 catgtccacc atgtccacaa tccacacctc ctctactcca gagaccaccc acacctccac 180 agtgctgacc accacagcca ccatgacaag ggccaccaat tccacggcca caccctcctc 240 cactctgggg acgacccgga tcctcactga gctgaccaca acagccacta caactgcagc 300 cactggatcc acggccaccc tgtcctccac cccagggacc acctggatcc tcacagagcc 360 gagcactata gccaccgtga tggtgcccac cggttccacg gccaccgcct cctccactct 420 gggaacagct cacaccccca aagtggtgac caccatggcc actatgccca cagccactgc 480 PC1'/US99/01642 ctccacggtt cccagctcgt ccaccgtggg gaccacccgc acccctgcag tgctccccag 540 cagcctgcca accttcagcg tgtccactgt gtcctcctca gtcctcacca ccctgagacc 600 cac 603 <210> 121 <211> 178 <212> PRT
<213> Homo sapiens <400> 121 Ser GIu Pro Pro Ser Pro Ala Thr Thr Pro Cys Gly Lys Val Pro Ile Cys Ile Pro Ala Arg Arg Asp Leu Val Asp Ser Pro Ala Ser Leu Ala Ser Ser Leu Gly Ser Pro Leu Pro Arg_ Ala Lys Glu Leu Ile Leu Asn Asp Leu Pro Ala Ser Thr Pro Ala Ser Lys Ser Cys Asp Ser Ser Pro Pro Gln Asp Ala Ser Thr Pro Arg Pro Ser Ser Ala Ser His Leu Cys Gln Leu Ala Ala Lys Pro Ala Pro Ser Thr Asp Ser Val Ala Leu Arg Ser Pro Leu Thr Leu Ser Ser Pro Phe Thr Thr Ser Phe Ser Leu Gly Ser His Ser Thr Leu Asn Gly Asp Leu Ser Val Pro Ser Ser Tyr Val Ser Leu His Leu Ser Pro Gln Val Ser Ser Ser Val Val Tyr Gly Arg Ser Pro Val Met Ala Phe Glu Ser His Pro His Leu Arg Gly Ser Ser Val Ser Ser Ser Leu Pro Ser Ile Pro Gly Gly Lys Pro Ala Tyr Ser Phe His <210> 122 <211> 36 <212> PRT
<213> Homo sapiens <400> 122 Met Ser Phe Leu Gly Gly Phe Phe Gly Pro Ile Cys Glu Ile Asp Val WO 99/38973 PC'T/US99/0164Z

Ala Leu Asn Asp Gly Glu Thr Arg Lys Met Ala Glu Met Lys Thr Glu Asp Gly Lys Val <210>

<211>

<212>
PRT

<213> sapiens Homo <400>

Met Ala Pro Gln CarsArg Leu Ser GlnTrpVal Ser Leu Ala Val Ala Ala Glu Leu Arg Pro Arg _Gly Pro GlnLeuLeu Ala Ala Ala_ Gln Leu Asp Ala Trp Tyr Pro Lys Gly Asp ArgArgGlu Ser Leu Leu Arg Ala Phe Glu Arg His Pro Gly Ala Phe IleAspGln Glu Ile Ala Phe Asp Cars Ser Asp Arg Thr Ser Pro Tyr Asp His Met Leu Pro Gly Ala Glu His Phe Ala Glu Tyr Ala Gly Arg Leu Gly Val Gly Ala Ala Thr His Val Val Ile Tyr Asp Ala Ser Asp Gln Gly Leu Tyr Ser Ala Pro Arg Val Trp Trp Met Phe Arg Ala Phe Gly His His Ala Val Ser Leu Leu Asp Gly GIy Leu Arg His Trp Leu <210> 124 <211> 133 <212> PRT
<213> Homo sapiens <400> 124 Met Asn His Thr Val Gln Thr Phe Phe Ser Pro Val Asn Ser Gly Gln Pro Pro Asn Tyr Glu Met Leu Lys Glu Glu His Glu Val Ala Val Leu Gly Ala Pro His Asn Pro Ala Pro Pro Thr Ser Thr Val Ile His Ile Arg Ser Glu Thr Ser VaI Pro Asp His Val Val Trp Ser Leu Phe Asn Thr Leu Phe Met Asn Pro Cys Cys Leu Gly Phe Ile Ala Phe Ala Tyr Ser Val Lys Ser Arg Asp Arg Lys Met Val Gly Asp Val Thr Gly Ala Gln Ala Tyr Ala Ser Thr Ala Lys Cys Leu Asn Ile Trp Ala Leu Ile Leu Gly Ile Leu Met Thr Ile Leu Leu Ile Val Ile Pro Val Leu Ile Phe Gln Ala Tyr Gly 130 w-<210> 125 <211> 195 <212> PRT
<213> Homo sapiens <400> 125 Thr Thr Ala Thr Thr Thr Ala Ser Thr Gly Ser Thr Ala Thr Pro Szr Ser Thr Pro Gly Thr Ala Pro Pro Pro Lys Val Leu Thr Ser Pro Ala Thr Thr Pro Met Ser Thr Met Ser Thr Ile His Thr Ser Ser Thr Pro Glu Thr Thr His Thr Ser Thr Val Leu Thr Thr Thr Ala Thr Met Thr Arg Ala Thr Asn Ser Thr Ala Thr Pro Ser Ser Thr Leu Gly Thr Thr Arg Ile Leu Thr Glu Leu Thr Thr Thr Ala Thr Thr Thr Ala Ala Thr Gly Ser Thr Ala Thr Leu Ser Ser Thr Pro Gly Thr Thr Trp Ile Leu Thr Glu Pro Ser Thr Ile Ala Thr Val Met Val Pro Thr Gly Ser Thr Ala Thr Ala Ser Ser Thr Leu Gly Thr Ala His Thr Pro Lys Val Val Thr Thr Met Ala Thr Met Pro Thr Ala Thr Ala Ser Thr Val Pro Ser Ser Ser Thr Val Gly Thr Thr Arg Thr Pro Ala Val Leu Pro Ser Ser Leu Pro Thr Phe Ser Val Ser Thr Val Ser Ser Ser Val Leu Thr Thr Leu Arg Pro <210> 126 <211> 509 <212> DNA
<213> homo sapien <400>

gaattcggcacgagccaagtaccccctgaggaatctgcagcctgcatctgagtacaccgt 60 atccctcgtggccataaagggcaaccaagagagccccaaagccactggagtctttaccac 120 actgcagcctgggagctctattccaccttacaacaccgaggtgactgagaccaccattgt 180 gatcacatggacgcctgctccaagaattggttttaagctgggtgtacgaccaagccaggg 240 aggagaggcaccacgagaagtgacttcagactcaggaagcatcgttgtgtccggcttgac 300 tccaggagtagaatacgtctacaccatccaagtcctgagagatggacaggaaagagatgc 360 gccaattgtaaacaaagtggtgacaccattgtctccaccaacaaacttgcatctggaggc 420 aaaccctgacactggagtgctcacagtctcctggagaggagcaccaccccagacattact 480 gggtatagaattaccacaacccctacaaa 509 <210> 127 <211> 500 <212> DNA
<213> homo sapien <400>

gaattcggcacgagccactgatgtccggggagtcagccaggagcttggggaagggaagcg 60 cgcccccggggccggtcccggagggctcgatccgcatctacagcatgaggttctgcccgt 120 ttgctgagaggacgcgtctagtcctgaaggccaagggaatcaggcatgaagtcatcaata 180 tcaacctgaaaaataagcctgagtggttctttaagaaaaatccctttggtctggtgccag 240 ttctggaaaacagtcagggtcagctgatctacgagtctgccatcacctgtgagtacctgg 300 atgaagcatacccagggaagaagctgttgccggatgacccctatgagaaagcttgccaga 360 agatgatcttagagttgttttctaaggtgccatccttggtaggaagctttattagaagcc 420 aaaataaagaagactatgctggcctaaaagaagaatttcgtaaagaatttaccaagctag 480 aggaggttctgactaataag 500 <210> 128 <211> 500 <212> DNA
<213> homo sapien <400>

agctttcctctgctgccgctcggtcacgcttgtgcccgaaggaggaaacagtgacagacc60 tggagactgcagttctctatccttcacacagctctttcaccatgcctggatcacttcctt120 tgaatgcagaagcttgctggccaaaagatgtgggaattgttgcccttgagatctattttc180 cttctcaatatgttgatcaagcagagttggaaaaatatgatggtgtagatgctggaaagt240 ataccattggcttgggccaggccaagatgggcttctgcacagatagagaagatattaact300 ctctttgcatgactgtggttcagaatcttatggagagaaataacctttcctatgattgca360 ttgggcggct ggaagttgga acagagacaa tcatcgacaa atcaaagtct gtgaagacta 420 atttgatgca gctgtttgaa gagtctggga atacagatat agaaggaatc gacacaacta 480 atgcatgcta tggaggcaca <210> 129 <211> 497 <212> DNA
<213> homo sapien <400>

gaattcggcacgagcagaggtctccagagccttctctctcctgtgcaaaatggcaactct60 taaggaaaaactcattgcaccagttgcggaagaagaggcaacagttccaaacaataagat120 cactgtagtgggtgttggacaagttggtatggcgtgtgctatcagcattctgggaaagtc180 tctggctgatgaacttgctcttgtggatgttttggaagataagcttaaaggagaaatgat240 ggatctgcagcatgggagcttatttcttcagacacctaaaattgtggcagataaagatta300 ttctgtgaccgccaattctaagattgtagtggtaactgcaggagtccgtcagcaagaagg360 ggagagtcggctcaatctggtgcagagaaatgttaatgtcttcaaattcattattcctca420 gatcgtcaagtacagtcctgattgcatcata_a_ttgtggtttccaacccagtggacattct480 tacgtatgttacctgga <210> 130 <211> 383 <212> DNA
<213> homo sapien <400> 130 gaattcggcacgagggccgcggctgccgactgggtcccctgccgctgtcgccaccatggc 60 tccgcaccgccccgcgcccgcgctgctttgcgcgctgtccctggcgctgtgcgcgctgtc 120 gctgcccgtccgcgcggccactgcgtcgcggggggcgtcccaggcgggggcgccccaggg 180 gcgggtgcccgaggcgcggcccaacagcatggtggtggaacaccccgagttcctcaaggc 240 agggaaggagcctggcctgcagatctggcgtgtggagaaagttcgatctggtggcccgtg 300 cccaccaacctttatggagacttcttcacgggcgacgcctacgtcatcctgaagacagtg 360 cagcttaagaacggaaaatcttg 383 <210> 131 <21I> 509 <212> DNA
<213> homo sapien <400>

gaattcggcacgagagtcagccgcatcttcttttgcgtcgccagccgagccacatcgctc 60 agacaccatggggaaggtgaaggtcggagtcaacggatttggtcgtattgggcgcctggt 120 caccagggctgcttttaactctggtaaagtggatattgttgccatcaatgaccccttcat 180 tgacctcaactacatggtttacatgttccaatatgattccacccatggcaaattccatgg 240 caccgtcaaggctgagaacgggaagcttgtcatcaatggaaatcccatcaccatcttcca 300 ggagcgagatccctccaaaatcaagtggggcgatgctggcgctgagtacgtcgtggagtc 360 cactggccgtcttcaccaccatggagaaggctggggctcatttgcaggggggagccaaaa 420 gggtcatcatctctgccccctctgctgacgcccccatgttcgtcatgggtgtgaaccatg 480 agaagtatgacaacagcctcaagatcatc 509 <210> 132 <211> 357 <212> DNA
<213> homo sapien <400>

gaattcggcacgagtaagaagaagcccctagaccacagctccacaccatggactggacct60 ggaggatcctcttcttggtggcagcagcaacaggtgcccactcccaggtgcaactggtgc120 aatctgggtctgagttgaagaagcctggggcctcagtgaaggtttcctgcaaggcttctg180 gacacatcttcagtatctatggtttgaattgggtgcgacaggcccctggtcaaggccttg240 agtggatgggatggatcaaagtcgacactgcgaacccaacgtatgcccagggcttcacag300 gacgatttgtcttctccctggacacctctgtcagcacggcatatctgcagatcagca 357 <210> 133 <211> 468 <212> DNA
<213> homo sapien <400>

gaattcggcacgaggcgccccgaaccgtcctcctgctgctctcggcggccctggccctga 60 ccgagacctgggccggctcccactccatgaggtatttcgacaccgccatgtcccggcccg 120 gccgcggggagccccgcttcatctcagtgggctacgtggacgacacgcagttcgtgaggt 180 tcgacagcgacgccgcgagtccgagagaggagccgcgggcgccgtggatagagcaggagg 240 ggccggagtattgggaccggaacacacagatcttcaagaccaacacacagactgaccgag 300 agagcctgcggaacctgcgcggctactacaaccagagcgaggccgggtctcacaccctcc 360 agagcatgtacggctgcgacgtggggccggacgggcgcctcctccgcgggcataaccagt 420 acgcctacgacggcaaggattacatcgccctgaacgaggacctgcgct 468 <210> 134 <211> 214 <212> DNA
<213> homo sapien <400> 134 gaattcggca cgagctgcgt cctgctgagc tctgttctct ccagcacctc ccaacccact 60 agtgcctggt tctcttgctc caccaggaac aagccaccat gtctcgccag tcaagtgtgt 120 ccttccggag cgggggcagt cgtagcttca gcaccgcctc tgccatcacc ccgtctgtct 180 cccgcaccag cttcacctcc gtgtcccggt ccgg 214 <210> 135 <211> 355 <212> DNA
<213> homo sapien <400> 135 gaattcggcacgaggtgaacaggacccgtcgccatgggccgtgtgatccgtggacagagg60 aagggcgccgggtctgtgttccgcgcgcacgtgaagcaccgtaaaggcgctgcgcgcctg120 cgcgccgtggatttcgctgagcggcacggctacatcaagggcatcgtcaaggacatcatc180 ~cacgacccgggccgcggcgcgcccctcgccaaggtggtcttccgggatccgtatcggttt240 aagaagcggacggagctgttcattgccgccgagggcattcacacgggccagtttgtgtat300 tgcggcaagaaggcccagctcaacattggcaatgtgctccctgtgggcaccatgc 355 <210> 136 <211> 242 <212> DNA
<213> homo sapien <400> 136 gaattcggca cgagccagct cctaaccgcg agtgatccgc cagcctccgc ctcccgaggt 60 gcccggattg cagacggagt ctccttcact cagtgctcaa tggtgcccag gctggagtgc 120 agtggtgtga tctcggctcg ctacaacatc cacctcccag cagcctgcct tggcctccca 180 aagtgccgag attgcagctc tctgcccggc cgccacccct gtctgggaag tgaggatgct 240 gt 242 <210> 137 <211> 424 <212> DNA
<213> homo sapien <400>

gaattcggcacgagcccagatcccgaggtccgacagcgcccggcccagatccccacgcct 60 gccaggagcaagccgagagccagccggccggcgcactccgactccgagcagtctctgtcc 120 ttcgacccgagccccgcgccctttccgggacccctgccccgcgggcagcgctgccaacct 180 gccggccatggagaccccgtcccagcggcgcgccacccgcagcggggcgcaggccagctc 240 cactccgctgtcgcccacccgcatcacccggctgcaggagaaggaggacctgcaggagct 300 caatgatcgcttggcggtctacatcgaccgtgtgcgctcgctggaaacggagaacgcagg 360 gctgcgccttcgcatcaccgagtctgaagaggtggtcagccgcgaggtgtccggcatcaa 420 ggcc --<210> 138 <211> 448 <212> DNA
<213> homo sapien <400>

gaattcggcacgagcctgtgttccaggagccgaatcagaaatgtcatcctcaggcacgcc 60 agacttacctgtcctactcaecgatttgaagattcaatatactaagatcttcataaacaa 120 tgaatggcatgattcagtgagtggcaagaaatttcctgtctttaatcctgcaactgagga 180 ggagctctgccaggtagaagaaggagataaggaggatgttgacaaggcagtgaaggccgc 240 aagacaggcttttcagattggatccccgtggcgtactatggatgcttccgagagggggcg 300 actattatacaagttggctgatttaatcgaaagagatcgtctgctgctggccgacaatgg 360 agtcaatgaatggtggaaaactctattccaatgcatatctgaatgatttagcaggctgca 420 tcaaaacattgcgctactgtgcaggttg 448 <210> 139 <211> 510 <212> DNA
<213> homo sapien <400> 139 gaattcggcacgaggttccgtgcagctcacggagaagcgaatggacaaagtcggcaagta 60 ccccaaggagctgcgcaagtgctgcgaggacggcatgcgggagaaccccatgaggttctc 120 gtgccagcgccggacccgtttcatctccctggcgaggcgtgcaagaaggtcttcctggac 180 tgctgcaactacatcacagagctgcggcggcagcacgcgcgggccagccacctggcctgc 240 caggagtaacctggatgaggacatcattgcagaagagaacatcgtttcccgaagtgagtt 300 cccagagagctggctgtggaacgttgaggacttgaaagagccaccgaaaaatggaatctc 360 tacgaagctcatgaatatatttttgaaagactccatcaccacgtgggagattctggctgt 420 gagcatgtcggacaagaaagggatctgtgtggcagaccccttcgaggtcacagtaatgca 480 ggacttcttcatcgacctgcggctacccta 510 <210> 140 <211> 360 <212> DNA
<213> homo sapien <400> 140 gaattcggcacgagcggtaactaccccggctgcgcacagctcggcgctccttcccgctcc 60 ctcacacaccggcctcagcccgcaccggcagtagaagatggtgaaagaaacaacttacta 120 cgatgttttgggggtcaaacccaatgctactcaggaagaattgaaaaaggcttataggaa 180 actggctttgaagtaccatcctgataagaacccaaatgaaggagagaagtttaaacagat 240 ttctcaagcttacgaagttctctctgatgcaaagaaaagggaattatatgacaaaggagg 300 agaacaggcaattaaagagggtggagcaggtggcggttttggctcccccatggacatctt 360 <210> 141 <211> 483 <212> DNA
<213> homo sapien <400> 141 gaattcggcacgagagcagaggctgatctttgctggaaaacagctggaagatgggctgca 60 ccctgtctgactacaacatccagaaagagtccaccctgcacctggtgctccgtctcagag 120 gtgggatgcaaatcttcgtgaagacactcactggcaagaccatcacccttgaggtggagc 180 ccagtgacaccatcgagaacgtcaaagcaaagatccaggacaaggaaggcattcctcctg 240 accagcagaggttgatctttgccggaaagcagctggaagatgggcgcaccctgtctgact 300 acaacatccagaaagagtctaccctgcacctggtgctccgtctcagaggtgggatgcaga 360 tcttcgtgaagaccctgactggtaagaccatcaccctcgaggtggagcccagtgacacca 420 tcgagaatgtcaaggcaaagatccaagataaggaaggcattcctcctgatcagcagaggt 480 tga 483 <210> 142 <211> 500 <212> DNA
<213> homo sapien <400> 142 gaattcggcacgaggcggcgacgaccgccgggagcgtgtgcagcggcggcggcggaagtg 60 gccggcgagcccggtccccgccggcaccatgcttcccttgtcactgctgaagacggctca 120 gaatcaccccatgttggtggagctgaaaaatggggagacgtacaatggacacctggtgag 180 ctgcgacaactggatgaacattaacctgcgagaagtcatctgcacgtccagggacgggga 240 caagttctggcggatgcccgagtgctacatccgcggcagcaccatcaagtacctgcgcat 300 ccccgacgagatcatcgacatggtcaaggaggaggtggtggccaagggccgcggccgcgg 360 aggcctgcagcagcagaagcagcagaaaggccgcggcatgggcggcgctggccgaggtgt 420 gtttggtggccggggccgaggtgggatcccgggcacaggcagaagccagccagagaagaa 480 gcctggcagacaggcgggca 500 <210> 143 <211> 400 <212> DNA
<213> homo sapien <400> 143 gaattcggcacgagctcggatgtcagcaggcgtcccaacccagcaggaactggctcaatt 60 ctcagaagaaagcgatcggccccgaggcaggaaggccggctccggtgcagggcgcgccgc 120 ctgcgggctgcttcgggccagggtcgacccgagggccagcgcaagcagcggcaacaggag 180 cgccaggaggacatgaggctctgcctgcagtcagcaacttggaatattcagacttcagac 240 cagcatcacagattataaccctccgtaaatcatctgcatcccagctcccatcaaaagcca 300 gcctgaaggacccatggacacgtgactccagtgttctcaacaacatcttagatcaagttg 360 gtttgcacaacatttgcatctacttgggacaaagcaagaa 400 <210> 144 PCTNS99/O1 b42 <211> 243 <212> DNA
<213> homo sapien <400> 144 gaattcggcacgagccagctcctaaccgcgagtgatccgccagcctccgcctcccgaggt 60 gcccggattgcagacggagtctccttcactcagtgctcaatggtgcccaggctggagtgc 120 agtggtgtgatctcggctcgctacaacatccacctcccagcagcctgccttggcctccca 180 aagtgccgagattgcagcctctgcccggccgtcaccccgtctgggaagtgaggagcgttt 240 ctg <210> 145 <211> 450 <212> DNA
<213> homo sapien <400> 145 gaattcggcacgaggacagcaggaccgtggaggccgcggcaggggtggcagtggtggcgg cggcggcggcggcggtggtggttacaaccgcagcagtggtggctatgaacccagaggtcg 120 tggaggtggccgtggaggcagaggtggcatgggcggaagtgaccgtggtggcttcaataa 180 atttggtggccctcgggaccaaggatcacgtcatgactccgaacaggataattcagacaa 240 caacaccatctttgtgcaaggcctgggtgagaatgttacaattgagtctgtggctgatta 300 cttcaagcagattggtattattaagacaaacaagaaaacgggacagcccatgattaattt 360 gtacacagacagggaaactggcaagctgaagggagaggcaacggtctcttttgatgaccc 420 accttcagctaaagcagcctattgactggt 450 <210> 146 <211> 451 <212> DNA
<213> homo sapien <400> 146 gaattcggcacgagccatcgagtccctgcctttcgacttgcagagaaatgtctcgctgat 60 gcgggagatcgacgcgaaataccaagagatcctgaaggagctagacgagtgctacgagcg 120 cttcagtcgcgagacagacggggcgcagaagcggcggatgctgcactgtgtgcagcgcgc 180 gctgatccgcaccaggagctgggcgacgagaagatccagatcgtgagccagatggtggag 240 ctggtggagaaccgcacgcggcaggtggacagccacgtggagctgttcgaggcgcagcag gagctgggcgacacagcgggcaacagcggcaaggctggcgcggacaggcccaaaggcgag gcggcagcgcaggctgacaagcccaacagcaagcgctcacggcggcagcgcaacaacgag 420 aaccgtgagaacgcgtccagcaaccacgacc 451 <210> 147 <211> 400 <212> DNA
<213> homo sapien <400> 147 gaattcggcacgagctcggatgtcagcaggcgtcccaacccagcaggaactggctcaatt 60 ctcagaagaaagcgatcggccccgaggcaggaaggccggctccggtgcagggcgcgccgc 120 ctgcgggctgcttcgggccagggtcgacccgagggccagcgcaagcagcggcaacaggag 180 cgccaggaggacatgaggctctgcctgcagtcagcaacttggaatattcagacttcagac 240 cagcatcacagattataaccctccgtaaatcatctgcatcccagctcccatcaaaagcca 300 gcctgaaggacccatggacacgtgactccagtgttctcaacaacatcttagatcaagttg 360 gtttgcacaacatttgcatctacttgggacaaagcaagaa 400 <210> 148 <211> 503 <212> DNA
<213> Homo sapien <400>

aaaagaattcggcacgagcggcgccgctcatccccctctcccagcagattcccactggaa 60 attcgttgtatgaatcttattacaagcaggtcgatccggcatacacagggagggtggggg 120 cgagtgaagctgcgctttttctaaagaagtctggcctctcggacattatccttgggaaga 180 tatgggacttggccgatccagaaggtaaagggttcttggacaaacagggtttctatgttg 240 cactgagactggtggcctgtgcacagagtggccatgaagttaccttgagcaatctgaatt 300 tgagcatgccaccgcctaaatttcacgacaccagcagccctctgatggtcacaccgccct 360 ctgcagaggcccactgggctgtgagggtggaagaaaaggccaaatttgatgggatttttg 420 aaagcctcttgcccatcaatggtttgctctctggagacaaagtcaagccagtcctcatga 480 actcaaagctgcctcttgatgtc 503 <210> 149 __ <211> 1061 <212> DNA
<213> homo sapien <400>

gaattcggcacgaggccttttccagcaaccccaaggtccaggtggaggccatcgaagggg60 gagccctgcagaagctgctggtcatcctggccacggagcagccgctcactgcaaagaaga120 aggtcctgtttgcactgtgctccctgctgcgccacttcccctatgcccagcggcagttcc180 tgaagctcggggggctgcaggtcctgaggaccctggtgcaggagaagggcacggaggtgc240 tcgccgtgcgcgtggtcacactgctctacgacctggtcacggagaagatgttcgccgagg300 aggaggctgagctgacccaggagatgtccccagagaagctgcagcagtatcgccaggtac360 acctcctgccaggcctgtgggaacagggctggtgcgagatcacggcccacctcctggcgc420 tgcccgagcatgatgcccgtgagaaggtgctgcagacactgggcgtcctcctgaccacct480 gccgggaccgctaccgtcaggacccccagctcggcaggacactggccagcctgcaggctg540 agtaccaggtgctggccagcctggagctgcaggatggtgaggacgagggctacttccagg600 agctgctgggctctgtcaacagcttgctgaaggagctgagatgaggccccacaccagtac660 tggactgggatgccgctagtgaggctgaggggtgccagcgtgggtgggcttctcaggcag720 gaggacatcttggcagtgctggcttggccattaaatggaaacctgaaggccatcctcttt780 ctgctgtgtgtctgtgtagactgggcacagccctgtggccggggggtcaggtgagtggtt840 gggtgatgggctctgctgacgtgcagggctcagcccagggcatccaggaacaggctccag900 ggcaggaacctgggcccaggagttgcaagtctctgcttcttaccaagcagcagctctgta960 ccttgggaagtcgcttaattgctctgagcttgtttcctcatctgtcaggagtgccattaa1020 aggagaaaaatcacgtaaaaaaaaaaaaaaaaaaactcgag 1061 <210> 150 <211> 781 <212> DNA
<213> homo sapien <400> 150 gaattcggcacgagaaatggcggcaggggtcgaagcggcagccgaagtggcggcgacaga 60 acccaaaatggaggaagagagcggcgcgccctgcgtgccgagcggcaacggagctccggg 120 cccgaagggtgaagaacgacctactcagaatgagaagaggaaggagaaaaacataaaaag 180 aggaggcaatcgctttgagccatattccaacccaactaaaagatacagagccttcattac 240 aaatataccttttgatgtgaaatggcagtcacttaaagacctggttaaagaaaaagttgg 300 tgaggtaacatacgtggagctcttaatggacgctgaaggaaagtcaaggggatgtgctgt 360 tgttgaattcaagatggaggagagcatgaaaaaagctgctgaagttctaaacaagcatag 420 tctgagtggaaggccactgaaagtcaaggaagatcctgatggtgaacatgcaaggagagc 480 aatgcaaaaggctggaagacttggaagcacagtatttgtagcaaatctggattataaagt 540 tggctggaagaaactgaaggaagtatttagtatggctggtgtggtggtccgagcagacat 600 tctggaagataaagatgggaaaagtcgtggaataggcattgtgacttttgaacagtccat 660 tgaagctgtgcaagcaatatctatgtttaatggccagttgctgtttgatagaccgatgca 720 cgtcaagatggatgagagggctttaccaaagggagacttttttcctcctgaacgccacag 780 c 781 <210> 151 <211> 3275 <212> DNA
<213> Homo sapien <400> 151 cttaagtggatcctgcatcaggagggagcagacaccggagaaagaaaaacaagttgtgct 60 gtttgaggaagcaagttggacctgcactccagcctgtggagatgaacctaggactgtgat 120 tctgctatccagtatgttggctgaccacaggctcaaactggaggattataaggatcgcct 180 gaaaagtggagagcatcttaatccagaccagttggaagctgtagagaaatatgaagaagt 240 gctacataatttggaatttgccaaggagcttcaaaaaaccttttctgggttgagcctaga 300 tctactaaaagcgcaaaagaaggcccagagaagggagcacatgctaaaacttgaggctga 360 gaagaaaaagcttcgaactatacttcaagttcagtatgtattgcagaacttgacacagga 420 gcacgtacaaaaagacttcaaagggggtttgaatggtgcagtgtatttgccttcaaaaga 480 acttgactacctcattaagttttcaaaactgacctgccctgaaagaaatgaaagtctgag 540 acaaacacttgaaggatctactgtctaaattgctgaactcaggctattttgaaagtatcc 600 cagttcccaaaaatgccaaggaaaaggaagtaccactggaggaagaaatgctaatacaat 660 cagagaaaaaaacacaattatcgaagactgaatctgtcaaagagtcagagtctctaatgg 720 aatttgcccagccagagatacaaccacaagagtttcttaacagacgctatatgacagaag 780 tagattattcaaacaaacaaggcgaagagcaaccttgggaagcagattatgctagaaaac 840 caaatctcccaaaacgttgggatatgcttactgaaccagatggtcaagagaagaaacagg 900 agtcctttaagtcctgggaggcttctggtaagcaccaggaggtatccaagcctgcagttt 960 ccttagaacagaggaaacaagacacctcaaaactcaggtctactctgccggaagagcaga 1020 agaagcaggagatctccaaatccaagccatctcctagccagtggaagcaagatacaccta 1080 aatccaaagcagggtatgttcaagaggaacaaaagaaacaggagacaccaaagctgtggc 1140 cagttcagctgcagaaagaacaagatccaaagaagcaaactccaaagtcttggacacctt 1200 ccatgcagagcgaacagaacaccaccaagtcatggaccactcccatgtgtgaagaacagg 1260 attcaaaacagccagagactccaaaatcctgggaaaacaatgttgagagtcaaaaacact 1320 ctttaacatcacagtcacagatttctccaaagtcctggggagtagctacagcaagcctca 1380 taccaaatgaccagctgctgcccaggaagttgaacacagaacccaaagatgtgcctaagc 1440 ctgtgcatcagcctgtaggttcttcctctacccttccgaaggatccagtattgaggaaag 1500 aaaaactgcaggatctgatgactcagattcaaggaacttgtaactttatgcaagagtctg 1560 ttcttgactttgacaaaccttcaagtgcaattccaacgtcacaaccgccttcagctactc 1620 caggtagccccgtagcatctaaagaacaaaatctgtccagtcaaagtgattttcttcaag 1680 agccgttacaggtatttaacgttaatgcacctctgcctccacgaaaagaacaagaaataa 1740 aagaatccccttattcacctggctacaatcaaagttttaccacagcaagtacacaaacac 1800 caccccagtgccaactgccatctatacatgtagaacaaactgtccattctcaagagactg 1860 cagcaaattatcatcctgatggaactattcaagtaagcaatggtagccttgccttttacc 1920 cagcacagacgaatgtgtttcccagacctactcagccatttgtcaatagccggggatctg 1980 ttagaggatgtactcgtggtgggagattaataaccaattcctatcggtcccctggtggtt 2040 ataaaggttttgatacttatagaggactcccttcaatttccaatggaaattatagccagc 2100 tgcagttccaagctagagagtattctggagcaccttattcccaaagggataatttccagc 2160 agtgttataagcgaggagggacatctggtggtccacgagcaaattcgagagcagggtgga 2220 gtgattcttctcaggtgagcagcccagaaagagacaacgaaacctttaacagtggtgact 2280 ctggacaaggagactcccgtagcatgacccctgtggatgtgccagtgacaaatccagcag 2340 ccaccatactgccagtacacgtctaccctctgcctcagcagatgcgagttgccttctcag 2400 cagccagaacctctaatctggcccctggaactttagaccaacctattgtgtttgatcttc 2460 ttctgaacaacttaggagaaacttttgatcttcagcttggtagatttaattgcccagtga 2520 atggcacttacgttttcatttttcacatgctaaagctggcagtgaatgtgccactgtatg 2580 tcaacctcatgaagaatgaagaggtcttggtatcagcctatgccaatgatggtgctccag 2640 accatgaaactgctagcaatcatgcaattcttcagctcttccagggagaccagatatggt 2700 tacgtctgcacaggggagcaatttatggaagtagctggaaatattctacgttttcaggct 2760 atcttctttatcaagattgaaagtcagtacagtattgacaataaaaggatggtgttctaa 2820 ttagtgggattgaaggaaaagtagtctttgccctcatgactgattggtttaggaaaatgt 2880 ttttgttcctagagggaggaggtccttacttttttgttttccttcctgaggtgaaaaatc 2940 aagctgaatgacaattagcactaatctggcactttataaattgtgatgtagcctcgctag 3000 tcaagctgtgaatgtatattgtttgcacttaatccttaactgtattaacgttcagcttac 3060 taaactgactgcctcaagtccaggcaagttacaatgccttgttgtgcctcaataaaaaag 3120 ttacatgcaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa 3180 aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa 3240 aaaaaaaaaaaaaaaaaaaaaaaaaaaaactcgag 3275 <210> 152 <211> 2179 <212> DNA
<213> homo sapien __ <400> 152 gaattcggcaccaggcactattaaatgtgaggcagcctccatctactacaacatttgtgc tgaatcaaataaatcatcttccacccttgggatctacaattgtaatgactaaaacaccac 120 ctgtaacaaccaacaggcaaaccatcactttaactaagtttatccagactactgcaagca 180 cacgcccgtcagtctcagcaccaacagtacgaaatgccatgacctctgcaccttcaaaag 240 accaagttcagcttaaagatctactgaaaaataatagtcttaatgaactgatgaaactaa 300 agccacctgctaatattgctcagccagtagcaacagcagctactgatgtaagcaatggta 360 cagtaaagaaagagtcttctaataaagaaggagctagaatgtggataaacgacatgaaga 420 tgaggagtttttccccaaccatgaaggttcctgttgtaaaagaagatgatgaaccagagg 480 aagaagatgaagaagaaatgggtcatgcagaaacctatgcagaatacatgccaataaaat 540 taaaaattggcctacgtcatccagatgctgtagtggaaaccagctctttatccagtgtta 600 ctcctcctgatgtttggtacaaaacatccatttctgaggaaaccattgataatggctggt 660 tatcagcattgcagcttgaggcaattacatatgcagcccagcaacatgaaactttcctac 720 ctaatggagatcgtgctggcttcttaataggtgatggtgccggtgtaggaaaaggaagga 780 cgatagcaggaatcatctatgaaaattatttgttgagtagaaaacgagcattgtggttta 840 gtgtttcaaatgacttaaagtatgatgctgaaagagatttaagggatattggagcaaaaa 900 acattttggttcattcgttaaataagtttaaatacggaaaaatttcttccaaacataatg 960 ggagtgtgaaaaagggtgttatttttgctacttactcttcacttattggtgaaagccagt 1020 ctggcggcaagtataaaactaggttaaaacaacttctgcattggtgcggtgatgacttcg 1080 atggagtgatagtgtttgatgagtgtcataaagccaaaaacttatgtcctgttggttctt 1140 caaagccaaccaagacaggcttagcagttttagagcttcagaacaaattgccaaaagcca 1200 gagttgtttatgctagtgcaactggtgcttctgaaccacgcaacatggcctatatgaacc 1260 gtcttggcatatggggtgagggtactccatttagagaattcagtgattttattcaagcag 1320 tagaacggagaggagttggtgccatggaaatagttgctatggatatgaagcttagaggaa 1380 tgtacattgctcgacaactgagctttactggagtgaccttcaaaattgaggaagttcttc 1440 tttctcagagctacgttaaaatgtataacaaagctgtcaagctgtgggtcattgccagag 1500 agcggtttcagcaagctgcagatctgattgatgctgagcaacgaatgaagaagtccatgt 1560 ggggtcagttctggtctgctcaccagaggttcttcaaatacttatgcatagcatccaaag 1620 ttaaaagggttgtgcaactagctcgagaggaaatcaagaatggaaaatgtgttgtaattg 1680 gtctgcagtctacaggagaagctagaacattagaagctttggaagagggcgggggagaat 1740 tgaatgattttgtttcaactgccaaaggtgtgttgcagtcactcattgaaaaacattttc 1800 ctgctccagacaggaaaaaactttatagtttactaggaatcgatttgacagctccaagta 1860 acaacagttcgccaagagatagtccttgtaaagaaaataaaataaagaagcggaaaggtg 1920 aagaaataactcgagaagccaaaaaagcacgaaaagtaggtggccttactggtagcagtt 1980 ctgacgacagtggaagtgaatctgatgcctctgataatgaagaaagtgactatgagagct 2040 ctaaaaacatgagttctggagatgatgacgatttcaacccatttttagatgagtctaatg 2100 aggatgatga aaatgatccc tggttaatta,aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2160 aaaaaaaaaa aaactcgag 2179 <210> 153 <211> 2109 <212> DNA
<213> Homo sapien <400> 153 cagagagccccaggcatcgaggagaaggcggcggagaatggggccctggggtcccccgag60 agagaagagaaagtgctggagaatggggagctgacacccccaaggagggaggagaaagcg120 ctggagaatggggagctgaggtccccagaggccggggagaaggtgctggtgaatgggggc180 ctgacacccccaaagagcgaggacaaggtgtcagagaatgggggcctgagattccccagg240 aacacggagaggccaccagagactgggccttggagagccccagggccctgggagaagacg300 cccgagagttggggtccagcccccacgatcggggagccagccccagagacctctctggag360 agagcccctgcacccagcgcagtggtctcctcccggaacggcggggagacagcccctggc420 ccccttggcccagcccccaagaacgggacgctggaacccgggaccgagaggagagccccc480 gagactgggggggcgccgagagccccaggggctgggaggctggacctcgggagtgggggc540 cgagccccagtgggcacggggacggcccccggcggcggccccggaagcggcgtggacgca600 aaggccggatgggtagacaacacgaggccgcagccaccgccgccaccgctgccaccgcca660 ccggaggcacagccgaggaggctggagccagcgcccccgagagccaggccggaggtggcc720 cccgagggagagcccggggccccagacagcagggccggcggagacacggcactcagcgga780 gacggggacccccccaagcccgagaggaagggccccgagatgccacgactattcttggac840 ttgggaccccctcaggggaacagcgagcagatcaaagccaggctctcccggctctcgctg900 gcgctgccgccgctcacgctcacgccattcccggggccgggcccgcggcggcccccgtgg960 gagggcgcggacgccggggcggctggcggggaggccggcggggcgggagcgccggggccg1020 gcggaggaggacggggaggacgaggacgaggacgaggaggaggacgaggaggcggcggcg1080 ccgggcgcggcggcggggccgcggggccccgggagggcgcgagcagccccggtgcccgtc1140 gtggtgagcagcgccgacgcggacgcggcccgcccgctgcgggggctgctcaagtctccg1200 cgcggggccgacgagccagaggacagcgagctggagaggaagcgcaagatggtctccttc1260 cacggggacgtgaccgtctacctcttcgaccaggagacgccaaccaacgagctgagcgtc1320 caggccccccccgagggggacacggacccgt~aacgcctccagcgcccccgacacctccc1380 caccccgccacccccggagatgggtttcccagcaacgacagcggctttggaggcagtttc1440 gagtgggcggaggatttccccctcctcccccctccaggccccccgctgtgcttctcccgc1500 ttctccgtctcgcctgcgctggagaccccggggccacccgcccgggcccccgacgcccgg1560 cccgcaggccccgtggagaattgattccccgaagacccgaccccgctgcaccctcagaag1620 aggggttgagaatggaatcctctgtggatgacggcgccactgccaccaccgcagacgccg1680 cctctggggaggcccccgaggctgggccctccccctcccactcccctaccatgtgccaaa1740 cgggaggccccgggcccccgcccccccagccccccagatggctcccctgacccccctgac1800 cccctcggagccaaatgaggcaggaatccccccgcccctccatagagagccgcctttctc1860 ggaactgaactgaactcttttgggcctggagcccctcgacacagcggaggtccctcctca1920 cccactcctggcccaagacaggggccgcaggcttcggggacccggaccccccatttcgcg1980 tctcccctttccctccccagcccggcccctggaggggcctctggttcaaaccttcgcgtg2040 gcattttcacattatttaaaaaagacaaaaacaactttttggaggaaaaaaaaaaaaaaa2100 aaactcgag 2109 <210> 154 <211> 1411 <212> DNA
<213> homo sapien <400> 154 gaattcggca ccaggggaga tgaggaagtt cgatgttcct agcatggagt ctacccttaa 60 ccagccagcc atgctagaga cgttatactc agatccacat taccgagccc atttccccaa 120 cccaagacct gatacaaata aggatgtata caaagtattg ccagaatcca agaaggcacc 180 gggcagtggtgcagtatttgagaggaacggaccacatgctagcagtagtggggtgctccc240 tttgggactccagcctgcgcctggactttccaagtcactatcctctcaggtgtggcaacc300 aagtcctgacccttggcatcctggagaacaatcctgtgaactcagtacttgtcgacagca360 gttggaattgatccgtttacagatggagcaaatgcagcttcagaacggagccatgtgtca420 ccatcctgctgctttcgctccattactgcccaccctagagccagcacagtggctcagcat480 cctgaacagtaacgagcatctcctgaaggagaaggagctcctcattgacaagcaaaggaa540 gcatatctctcagctggagcagaaagtgcgagagagtgaactgcaagtccacagtgccct600 tttgggccgccctgccccctttggggatgtctgcttattgaggctacaggagttgcagcg660 agagaacactttcttacgggcacagtttgcacagaagacagaagccctgagcaaggagaa720 gatggagcttgaaaagaaactctctgcatctgaagttgaaattcagctcattagggagtc780 tctaaaagtgacactacagaagcattcggaggaggggaagaaacaggaggaaagggtcaa840 aggtcgtgataaacatatcaataatttgaaaaagaaatgtcagaaggaatcagagcagaa900 ccgggagaagcagcagcgtattgaaaccttggagcgctatctagctgacctgcccaccct960 agaagaccatcagaaacagacggagcagcttaaggacgctgaattaaagaacacagaact1020 gcaagagagagtggctgagctggagactttgctggaggacacccaggcaacctgcagaga1080 gaaggaggttcagctggaaagtctgagacaaagagaagcagacctctcctctgctagaca1140 taggtaatgccctgtgt,acttgggggaaggagggagttcggttctggtgctctgttaact1200 cttgtgtgttcaacagtgttcatttcaagttcctttcttctaagagctttgtgttctttg1260 aattgaaagtcacttatggccgggtgtggtggcgcacacctttaatcccagcacttggga1320 gtcagaggcaggctaatttctgagtttcaggacagccagggctatacagagaaaccctgt1380 ctcaaacaaaaaaaaaaaaaaaaaactcgag 1411 <210> 155 <211> 678 <212> DNA
<213> homo sapien <400>

ctggagtgaagggagctagtggtaaagggagctggtggaggggtggcggcaggggtaagg 60 ggcaggggacaccctctagacggagagcgggctccgaggtcctggctggccctcggtgcg 120 cccgcccctgtgttggtcccacaatccctggcaatgagaggccagggtttattggacaga 180 gtcagttgtggggttcagagggtcagcaatcaatcaatcctccgaatccagagatttaga 240 cccagtcgtccgtattaggactggaggggggtcaataggttcagtgtttgagatgccaag 300 ggaacctgtcttttgatttggggttcaacatacagagttcaggtacctgcaggaatttgc 360 ccccctaggcacagggggtggtctttaccattttcgagaccagatcctggctgggagccc 420 cgaggcattcttcgtgctcaatgctgatgtctgctccgacttccccttgagtgctatgtt 480 ggaagcccaccgacgccagcgtcaccctttcttactccttggcactacggctaacaggac 540 gcaatccctcaactacggctgcatcgttgagaatccacagacacacgaggtattgcacta 600 tgtggagaaacccagcacatttatcagtgacatcatcaactgcggcacctacctcttttc 660 tcctgaagccttgaagcc 678 <210> 156 <211> 2668 <212> DNA
<213> Homo sapien <400>

gggaaggcggctgcgctgctgggcgggggcgggagctggagccggagctggagccggggc 60 cggggcccgggtcagcgcttgagccgggagaagagtttgagatcgtggaccgaagccagc 120 tgcccggcccaggcgacctgcggagcgcaacgaggccgcgggcggccgagggctggtcgg 180 cgcccatcctgaccctggcacgcagggccaccgggaacctgtcggcgagctgcgggagcg 240 cgctgcgcgcggccgcggggctgggcggcggggacagcggggacggcacggcgcgcgcag 300 cttctaagtgccagatgatggaggagcgtgccaacctgatgcacatgatgaaactcagca 360 tcaaggtgttgctccagtcggctctgagcctgggccgcagcctggatgcggaccatgccc 420 ccttgcagcagttctttgtagtgatggagcactgcctcaaacatgggctgaaagttaaga 480 agagcccctgcacccagcgcagtggtctcctcccggaacggcggggagacagcccctggc420 ccccttggcccagcccccaagaacgggacgctggaacccgggaccgagaggagagccccc480 gagactg PCfNS99/01642 agagttttattggccaaaataaatcattctttggtcctttggagctggtggagaaacttt540 gtccagaagcatcagatatagcgactagtgtcagaaatcttccagaattaaagacagctg600 tgggaagaggccgagcgtggctttatcttgcactcatgcaaaagaaactggcagattatc660 tgaaagtgcttatagacaataaacatctcttaagcgagttctatgagcctgaggctttaa720 tgatggaggaagaagggatggtgattgttggtctgctggtgggactcaatgttctcgatg780 ccaatctctgcttgaaaggagaagacttggattctcaggttggagtaatagatttttccc840 tctaccttaaggatgtgcaggatcttgatggtggcaaggagcatgaaagaattactgatg900 tccttgatcaaaaaaattatgtggaagaacttaaccggcacttgagctgcacagttgggg960 atcttcaaaccaagatagatggcttggaaaagactaactcaaagcttcaagaagagcttt1020 cagctgcaacagaccgaatttgctcacttcaagaagaacagcagcagttaagagaacaaa1080 atgaattaattcgagaaagaagtgaaaagagtgtagagataacaaaacaggataccaaag1140 ttgagctggagacttacaagcaaactcggcaaggtctggatgaaatgtacagtgatgtgt1200 ggaagcagctaaaagaggagaagaaagtccggttggaactggaaaaagaactggagttac1260 aaattggaatgaaaaccgaaatggaaattgcaatgaagttactggaaaaggacacccacg1320 agaagcaggacacactagttgccctccgccagcagctggaagaagtcaaagcgattaatt1380 tacagatgtttcacaaagctcagaatgcagagagcagtttgcagcagaagaatgaagcca1440 tcacatcctttgaaggaaaaaccaaccaagttatgtccagcatgaaacaaatggaagaaa1500 ggttgcagcactcggagcgggcgaggcagggggctgaggagcggagccacaagctgcagc1560 aggagctgggcgggaggatcggcgccctgcagctgcagctctcccagctgcacgagcaat1620 gctcaagcctggagaaagaattgaaatcagaaaaagagcaaagacaggctcttcagcgcg1680 aattacagcacgagaaagacacttcctc~ctactcaggatggagctgcaacaagtggaag1740 gactgaaaaaggagttgcgggagcttcaggacgagaaggcagagctgcagaagatctgcg1800 aggagcaggaacaagccctccaggaaatgggcctgcacctcagccagtccaagctgaaga1860 tggaagatataaaagaagtgaaccaggcactgaagggccacgcctggctgaaagatgacg1920 aagcgacacactgtaggcagtgtgagaaggagttctccatttcccggagaaagcaccact1980 gccggaactgtggccacatcttctgcaacacctgctccagcaacgagctggccctgccct2040 cctaccccaagccggtgcgagtgtgcgacagctgccacaccctgctcctgcagcgctgct2100 cctccacggcctcctgaacgtccgtcctcaggagcacagcctcacggacagtgccaaacc2160 ctgtgggtctccaggggcttgggaaatgtgttctttcccaagagtatcaaaggaaagaat2220 caaatttcttgcccggtcactggcactccagaagacagcgtgccggaaccggcagctctc2280 acctttctgtgacttgttcggaattaactcctctggatggaaacttccatcttacttggt2340 tacatcacggctctggttcagatacaac~tcatgattttgctactatcatttttcacttt2400 tcaaagaatttaacctattttacagcagttcagttctgctagtgagtagttttcctctcc2460 taccttccttctaaaaacctgattcatgcacagcgtttgacacacatggagtctgccagt2520 gtgccttctctgcttcagacaagagatctgccatttcatgcccttgtgactacctatcat2580 tggccctgcaataaaatcatttatttttcaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa2640 aaaaaaaaaaaaaaaaaaaaaactcgag 2668 <210> 157 <211> 2313 <212> DNA
<213> homo sapien <400> 157 gaattcggcaccaggccgggcgggcgcctcagccatggccctgcgcaaggaactgctcaa 60 gtccatctggtacgcctttaccgcgctggacgtggagaagagtggcaaagtctccaagtc 120 ccagctcaaggtgctgtcccacaacctgtacacggtcctgcacatcccccatgaccccgt 180 ggccctggaggaacacttccgagatgatgatgacggccctgtgtccagccagggatacat 240 gccctacctcaacaagtacatcctggacaaggtggaggagggggcttttgttaaagagca 300 ctttgatgagctgtgctggacgctgacggccaagaagaactatcgggcagatagcaacgg 360 gaacagtatgctctccaatcaggatgccttccgcctctggtgcctcttcaacttcctgtc 420 tgaggacaagtaccctctgatcatggtt~ctgatgaggtggaatacctgctgaaaaaggt 480 actcagcagcatgagcttggaggtgagcttgggtgagctggaggagcttctggcccagga 540 ggcccaggtggcccagaccaccggggggctcagcgtctggcagttcctggagctcttcaa 600 ttcgggccgctgcctgcggggcgtgggccgggacaccctcagcatggccatccacgaggt 660 ctaccaggagctcatccaagatgtcctgaagcagggctacctgtggaagcgagggcacct720 gagaaggaactgggccgaacgctggttccagctgcagcccagctgcctctgctactttgg780 gagtgaagagtgcaaagagaaaaggggcattatcccgctggatgcacactgctgcgtgga840 ggtgctgccagaccgcgacggaaagcgctgcatgttctgtgtgaagacagccacccgcac900 gtatgagatgagcgcctcagacacgcgccagcgccaggagtggacagctgccatccagat960 ggcgatccggctgcaggccgaggggaagacgtccctacacaaggacctgaagcagaaacg1020 gcgcgagcagcgggagcagcgggagcggcgccgggcggccaaggaagaggagctgctgcg1080 gctgcagcagctgcaggaggagaaggagcggaagctgcaggagctggagctgctgcagga1140 ggcgcagcggcaggccgagcggctgctgcaggaggaggaggaacggcgccgcagccagca1200 ccgcgagctgcagcaggcgctcgagggccaactgcgcgaggcggagcaggcccgggcctc1260 catgcaggctgagatggagctgaaggaggaggaggctgcccggcagcggcagcgcatcaa1320 ggagctggaggagatgcagcagcggttgcaggaggccctgcaactagaggtgaaagctcg1380 gcgagatgaagaatctgtgcgaatcgctcagaccagactgctggaagaggaggaagagaa1440 gctgaagcagttgatgcagctgaaggaggagcaggagcgctacatcgaacgggcgcagca1500 ggagaaggaagagctgcagcaggagatggcacagcagagccgctccctgcagcaggccca1560 gcagcagctggaggaggtgcggcagaaccggcagagggctgacgaggatgtggaggctgc1620 ccagagaaaactgcgccaggccagcaccaa_cgtgaaacactggaatgtccagatgaaccg1680 gctgatgcatccaattgagcctggagataagcgtccggtcacaagcagctccttctcagg1740 cttccagccccctctgcttgcccaccgtgactcctccctaaagcgcctgacccgctgggg1800 atcccagggcaacaggaccccctcgcccaacagcaatgagcagcagaagtccctcaatgg1860 tggggatgaggctcctgccccggcttccacccctcaggaagataaactggatccagcacc1920 agaaaattagcctctcttagccccttgttcttcccaatgtcatatccaccaggacctggc1980 cacagctggcctgtgggtgatcccagctcttactaggagagggagctgaggtcctggtgc2040 caggggcccaggccctccaaccataaacagtccaggatggaacctggttcacccttcata2100 ccagctccaagccccagaccatgggagctgtctgggatgttgatccttgagaacttggcc2160 ctgtgctttagacccaaggacccgattcctgggctaggaaagagagaacaagcaagccgg,2220 ggctacctgcccccaggtggccaccaagttgtggaagcacatttctaaataaaaactgct2280 cttagaatgaaaaaaaaaaaaaaaaaactcgag 2313 <210> 158 <211> 2114 <212> DNA
<213> homo sapien <400> 158 gaattcggcacgaggaagaactcgcctctgttgagtgtaagtagccaaacaataaccaag 60 gagaataacagaaatgtccatttggagcactcagagcagaatcctggttcatcagcaggt 120 gacacctcagcagcgcaccaggtggttttaggagaaaacttgatagccacagccctttgt 180 ctttctggcagtgggtctcagtctgatttgaaggatgtggccagcacagcaggagaggag 240 ggggacacaagccttcgggagagcctccatccagtcactcggtctcttaaggcagggtgc 300 catactaagcagcttgcctccaggaattgctctgaagagaaatccccacaaacctccatc 360 ctaaaggaaggtaacagggacacaagcttggatttccgacctgtagtgtctccagcaaat 420 ggggttgaaggagtccgagtggatcaggatgatgatcaagatagctcttccctgaagctt 480 tctcagaacattgctgtacagactgactttaagacagctgattcagaggtaaacacagat 540 caagatattgaaaagaatttggataaaatgatgacagagagaaccctgttgaaagagcgt 600 taccaggaggtcctggacaaacagaggcaagtggagaatcagctccaagtgcaattaaag 660 cagcttcagcaaaggagagaagaggaaatgaagaatcaccaggagatattaaaggctatt 720 caggatgtgacaataaagcgggaagaaacaaagaagaagatagagaaagagaagaaggag 780 tttttgcagaaggagcaggatctgaaagctgaaattgagaagctttgtgagaagggcaga 840 agagaggtgtgggaaatggaactggatagactcaagaatcaggatggcgaaataaatagg 900 aacattatggaagagactgaacgggcctggaaggcagagatcttatcactagagagccgg 960 aaagagttactggtactgaaactagaagaagcagaaaaagaggcagaattgcaccttact 1020 tacctcaagtcaactcccccaacactggagacagttcgttccaaacaggagtgggagacg 1080 agactgaatggagttcggataatgaaaaagaatgttcgtgaccaatttaatagtcatatc 1140 cagttagtgaggaacggagccaagctgagcagccttcctcaaatccctactcccacttta 1200 cctccacccccatcagagacagacttcatgcttcaggtgtttcaacccagtccctctctg1260 gctcctcggatgcccttctccattgggcaggtcacaatgcccatggttatgcccagtgca1320 gatccccgctccttgtctttcccaatcctgaaccctgccctttcccagcccagccagcct1380 tcctcaccccttcctggctcccatggcagaaatagccctggcttgggttcccttgtcagc1440 cctggtgccgaattcggcacgaggtaccactggtctgtgtgctagaggagggtgttgcca1500 tagaaccagtggccacagttgtggtggtggtggtcagcactgtgggggtgtgggtggtcc1560 ccgggacggaggagggggtcaccgtgaagccactggttgtgggtgtggtggttgtgctga1620 tccacactggaggcgtgcgtgccgtccctgggctgaaggagggggtgactgtgaagcccg1680 tggttgtggtagtcggcactttggtagtgtgagctgttcctggggtggaagagggggtgg1740 ccacagagccggtggccctggttgtggtggccgtggtggtaagcactgtggaggtgtggg1800 cagtctctggagtggaggagggtgtggctgtggacatggtggccgtgggtgtggtggtct1860 gtgataggcgggtccaggtggtgcccagggaggaggaggggatggctgtaaagctggtag1920 ctgtgggtgtggtggctgtgcttctcagtgctggaagggcggttgcagtccctggactgg1980 agaagggagtggctttggagctggtgactgtgggtgtcgtggccgtggtgctcacatgtg2040 gggtgccagcagttgcctgggtggaggaggcggtggccgtggatccggtgggcaccgtca2100 cgggagtacttcta 2114 <210> 159 .__ <211> 278 <212> DNA
<213> homo sapien <400> 159 gaattcggcacaggtaactttgcctggggtatttaaaaaaaaaaaaaaaa aaaaaaaaag60 tcaaatatctgagtactaatttcctgaaaagtatgttccgatagatgaac agatcattaa120 tgcagaatgagaatcactcctaaaataggtaatggtaaaaattaaattga caattacctc180 tctctatgcagaaggaaatatcacctatatgacatcatcatcatctattg atacttgctg240 gcagtgctaataatggttttaatgccaatttgtaagaa 278 <210> 160 <211> 848 <212> DNA
<213> homo sapien <400> 160 gaattcggcacgagccccagaggagctcggcctgcgctgcgccacgatgtccggggagtc 60 agccaggagcttggggaagggaagcgcgcccccggggccggtcccggagggctcgatccg 120 catctacagcatgaggttctgcccgtttgctgagaggacgcgtctagtcctgaaggccaa 180 gggaatcaggcatgaagtcatcaatatcaacctgaaaaataagcctgagtggttctttaa 240 gaaaaatccctttggtctggtgccagttctggaaaacagtcagggtcagctgatctacga 300 gtctgccatcacctgtgagtacctggatgaagcatacccagggaagaagctgttgccgga 360 tgacccctatgagaaagcttgccagaagatgatcttagagttgttttctaaggtgccatc 420 cttggtaggaagctttattagaagccaaaataaagaagactatgctggcctaaaagaaga 480 atttcgtaaagaatttaccaagctagaggaggttctgactaataagaagacgaccttctt 540 tggtggcaattctatctctatgattgattacctcatctggccctggtttgaacggctgga 600 agcaatgaagttaaatgagtgtgtagaccacactccaaaactgaaactgtggatggcagc 660 catgaaggaagatcccacagtctcagccctgcttactagtgagaaagactggcaaggttt 720 cctagagctctacttacagaacagccctgaggcctgtgactatgggctctgaagggggca 780 ggagtcagcaataaagctatgtctgatattttccttcactaaaaaaaaaaaaaaaaaaaa 840 aactcgag 848 <210> 161 <211> 432 <212> DNA
<213> homo sapien <400>

gaattcggcacgagggcagaccaagatcctggaggaggacctggaacagatcaagctgtc 60 cttgagagagcgaggccgggagctgaccactcagaggcagctgatgcaggaacgggcaga 120 ggaagggaagggcccaagtaaagcacagcgcgggagcctagagcacatgaagctgatcct 180 gcgtgataaggagaaggaggtggaatgtcagcaggagcatatccatgaactccaggagct 240 caaagaccagctggagcagcagctccagggcctgcacaggaaggtaggtgagaccagcct 300 cctcctgtcccagcgagagcaggaaatagtggtcctgcagcagcaactgcaggaagccag 360 ggaacaaggggagctgaaggagcagtcacttcagagtcaactggatgaggcccagagagc 420 cctagcccagag <210> i62 <211> 433 <212> DNA
<213> homo sapien <400>

gattcggcacgagccggagctgggttgctcctgctcccgtctccaagtccggtacctcc 60 t ttcaagctgggagagggctctagtccctggttctgaacactctggggttctcgggtgcag 120 gccgccatgagcaaacggaaggcgccgcaggagactctcaacgggggaatcaccgacatg 180 ctcacagaactcgcaaactttgagaagaacgtgagccaagctatccacaagtacaatgct 240 tacagaaaagcagcatctgttatagcaaaatacccacacaaaataaagagtggagctgaa 300 gctaagaaattgcctggagtaggaacaaaaattgctgaaaagattgatgagtttttagca 360 actggaaaattacgtaaactggaaaagattcggcaggatgatacgagttcatccatcaat 420 ttcctgactcgag <210> 163 <211> 432 <212> DNA
<213> homo sapien <400>

gaattcggcaccagatgaggccaacgaggtgacggacagcgcgtacatgggctccgagag60 cacctacagtgagtgtgagaccttcacggacgaggacaccagcaccctggtgcaccctga120 gctgcaacctgaaggggacgcagacagtgccggcggctcggccgtgccctctgagtgcct180 ggacgccatggaggagcccgaccatggtgccctgctgctgctcccaggcaggcctcaccc240 ccatggccagtctgtcatcacggtgatcgggggcgaggagcactttgaggactacggtga300 aggcagtgaggcggagctgtccccagagaccctatgcaacgggcagctgggctgcagtga360 ccccgctttcctcacgcccagtccgacaaagcggctctccagcaagaaggtggcaaggta420 cctgcaccagtc <210> 164 <211> 395 <212> DNA
<213> homo sapien <400>

gacacttgaatcatgggtgacgttaaaaattttctgtatgcctggtgtggcaaaaggaag60 atgaccccatcctatgaaattagagcagtggggaacaaaaacaggcagaaattcatgtgt120 gaggttcaggtggaaggttataattacactggcatgggaaattccaccaataaaaaagat180 gcacaaagcaatgctgccagagactttgttaactatttggttcgaataaatgaaataaag240 agtgaagaagttccagcttttggggtagcatctccgcccccacttactgatactcctgac300 actacagcaaatgctgaaggcatcttgttgacatcgaatatgactttgataataaatacc360 ggttcctgaaaaaaaaaaaaaaaaaaaaactcgag 395 <210> 165 <211> 503 <212> DNA
<213> homo sapien <400>

gaattcggcaccaggaacgctcggtgagaggcggaggagcggtaactaccccggttgcgc 60 acagctcggcgctccttcccgctccctcacacaccggcctcagcccgcaccggcagtaga 120 agatggtgaaagaaacaacttactacgatgttttgggggtcaaacccaatgctactcagg 180 aagaattgaaaaaggcttataggaaactggccttgaagtaccatcctgataagaacccaa 240 atgaaggagagaagtttaaacagatttctcaagcttacgaagttctctctgatgcaaaga 300 aaagggaattatatgacaaaggaggagaacaggcaattaaagagggtggagcaggtggcg 360 gttttggctcccccatggacatctttgatatgttttttggaggaggaggaaggatgcaga 420 gagaaaggagaggtaaaaatgttgtacatcagctctcagtaaccctagaagacttatata 480 atggtgcaacaagaaaactgget <210> 166 <211> 893 __ <212> DNA
<213> homo sapien <400>

gaattcggcacgagaggaacttctcttgacgagaagagagaccaaggaggccaagcaggg 60 gctgggccagaggtgccaacatggggaaactgaggctcggctcggaagggtgagagtgag 120 actacatctcaaaaaaaaaaaaaaaaaaaaaaaagaaagaaaagaaaagaaaaaagaaag 180 aacggaagtagttgtaggtagtggtatggtggtatgagtctgttttctgttacttataac 240 sacaacaacaacaaaaaacgctgaaactgggtaatttataaagaaaaggaaaaaaagcag 300 aaaaaaatcaggaagaagagaaaggaaaagaagacaaataaatgaaatttatgtattaca 360 gttctgaaggctgagacatcccaggtcaagggtccacacttggcgagggctttcttgctg 420 gtggagactctttgtggagtcctgggacagtgcagaaggatcacgcctccctaccgctcc 480 aagcccagccctcagccatggcatgccccctggatcaggccattggcctcctcgtggcca 540 tcttccacaagtactccggcagggagggtgacaagcacaccctgagcaagaaggagctga 600 aggagctgatccagaaggagctcaccattggctcgaagctgcaggatgctgaaattgcaa 660 ggctgatggaagacttggaccggaacaaggaccaggaggtgaacttccaggagtatgtca 720 ccttcctgggggccttggctttgatctacaatgaagccctcaagggctgaaaataaatag 780 ggaagatggagacaccctctgggggtcctctctgagtcaaatccagtggtgggtaattgt 840 acaataaattttttttggtcaaatttaaaaaaaaaaaaaaaaaaaaactcgag 893 <210> 167 <211> 549 <212> DNA
<213> homo sapien <400>

gaattcggcacgagcccagatcccgaggtccgacagcgcccggcccagatccccacgcct 60 gccaggagcaagccgagagccagccggccggcgcactccgactccgagcagtctctgtcc 120 ttcgacccgagccccgcgccctttccgggacccctgccccgcgggcagcgctgccaacct 180 gccggccatggagaccccgtcccagcggcgcgccacccgcagcggggcgcaggccagctc 240 cactccgctgtcgcccacccgcatcacccggctgcaggagaaggaggacctgcaggagct 300 caatgatcgcttggcggtctacatcgaccgtgtgcgctcgctggaaacggagaacgcagg 360 gctgcgccttcgcatcaccgagtctgaagaggtggtcagccgcgaggtgtccggcatcaa 420 ggccgcctacgaggccgagctcggggatgcccgcaagacccttgactcagtagccaagga 480 gcgcgcccgcctgcagctggagctgagcaaagtgcgtgaagagtttaaggagctgaaagc 540 gcgcaatac 549 <210> 168 <211> 547 <212> DNA
<213> homo sapien <400>

gaattcggcacgagatggcggcaggggtcgaagcggcggcggaggtggcggcgacggaga60 tcaaaatggaggaagagagcggcgcgcccggcgtgccgagcggcaacggggctccgggcc120 ctaagggtgaaggagaacgacctgctcagaatgagaagaggaaggagaaaaacataaaaa180 gaggaggcaatcgctttgagccatatgccaatccaactaaaagatacagagccttcatta240 caaacataccttttgatgtgaaatggcagtcacttaaagacctggttaaagaaaaagttg300 gtgaggtaacatacgtggagctcttaatggacgctgaaggaaagtcaaggggatgtgctg360 ttgttgaattcaagatggaagagagcatgaaaaaagctgcggaagtcctaaacaagcata420 gtctgagcggaagaccactgaaagtcaaagaagatcctgatggtgaacatgccaggagag480 caatgcaaaaggctggaagacttggaagcacagtatttgtagcaaatctggattataaag540 ttggctg <210> 169 __ <211> 547 <212> DNA
<213> homo sapien <400>

gaattcggcaccaggagtccgactgtgctcgctgctcagcgccgcacccggaagatgagg60 ctcgccgtgggagccctgctggtctgcgccgtcctggggctgtgtctggctgtccctgat120 aaaactgtgagatggtgtgcagtgtcggagcatgaggccactaagtgccagagtttccgc190 gaccatatgaaaagcgtcattccatccgatggtcccagtgttgcttgtgtgaagaaagcc240 tcctaccttgattgcatcagggccattgcggcaaacgaagcggatgctgtgacactggat300 gcaggtttggtgtatgatgcttacctggctcccaataacctgaagcctgtggtggcagag360 ttctatgggtcaaaagaggatccacagactttctattatgctgttgctgtggtgaagaag420 gatagtggcttccagatgaaccagcttcgaggcaagaagtcctgccacacgggtctaggc480 aggtccgctgggtggaacatccccataggcttactttactgtgacttacctgagccacgt540 aaacctc <210> 170 <211> 838 <212> DNA
<213> homo sapien <400>

gaattcggcaccagaggagctcggcctgcgctgcgccacgatgtccggggagtcagccag60 gagcttggggaagggaagcgcgcccccggggccggtcccggagggctcgatccgcatcta120 cagcatgaggttctgcccgtttgctgagaggacgcgtctagtcctgaaggccaagggaat180 caggcatgaagtcatcaatatcaacctgaaaaataagcctgagtggttctttaagaaaaa240 tccctttggtctggtgccagttctggaaaacagtcagggtcagctgatctacgagtctgc300 catcacctgtgagtacctggatgaagcatacccagggaagaagctgttgccggatgaccc360 ctatgagaaagcttgccagaagatgatcttagagttgttttctaaggtgccatccttggt420 aggaagctttattagaagccaaaataaagaagactatgatggcctaaaagaagaatttcg480 taaagaatttaccaagctagaggaggttctgactaataagaagacgaccttctttggtgg540 caattctatctctatgattgattacctcatctggccctggtttgaacggctggaagcaat600 gaagttaaatgagtgtgtagaccacactccaaaactgaaactgtggatggcagccatgaa660 ggaagatcccacagtctcagccctgcttactagtgagaaagactggcaaggtttcctaga720 gctctacttacagaacagccctgaggcctgtgactatgggctctgaagggggcaggagtc780 agcaataaagctatgtctgatattttccttcactaaaaaaaaaaaaaaaaaactcgag 838 <210> 171 <211> 547 <212> DNA
<213> homo sapien <400> 171 gaattcggcaccagcgggatttgggtcgcagttcttgtttgtggattgctgtgatcgtca cttgacaatgcagatcttcgtgaagactctgactggtaagaccatcaccctcgaggttga 120 gcccagtgacaccatcgagaatgtcaaggcaaagatccaagataaggaaggcatccctcc 180 tgaccagcagaggctgatctttgctggaaaacagctggaagatgggcgcaccctgtctga 240 ctacaacatccagaaagagtccaccctgcacctggtgctccgtctcagaggtgggatgca 300 aatcttcgtgaagacactcactggcaagaccatcacccttgaggtcgagcccagtgacac 360 catcgagaacgtcaaagcaaagatccaggacaaggaaggcattcctcctgaccagcagag 420 gttgatctttgccggaaagcagctggaagatgggcgcaccctgtctgactacaacatcca 480 gaaagagtctaccctgcacctggtgctccgtctcagaggtgggatgcagatcttcgtgaa 540 gaccctg <210> 172 __ <211> 608 <212> DNA
<213> homo sapien <400> 172 gaattcggcaccagagacttctccctctgaggcctgcgcacccctcctcatcagcctgtc 60 caccctcatctacaatggtgccctgccatgtcagtgcaaccctcaaggttcactgagttc 120 tgagtgcaaccctcatggtggtcagtgcctgtgcaagcctggagtggttgggcgccgctg 180 tgacctctgtgcccctggctactatggctttggccccacaggctgtcaaggcgcttgcct 240 gggctgccgtgatcacacagggggtgagcactgtgaaaggtgcattgctggtttccacgg 300 ggacccacggctgccatatgggggccagtgccggccctgtccctgtcctgaaggccctgg 360 gagccaacggcactttgctacttcttgccaccaggatgaatattcccagcagattgtgtg 420 ccactgccgggcaggctatacggggctgcgatgtgaagcttgtgcccctgggcactttgg 480 ggacccatcaaggccaggtggccggtgccaactgtgtgagtgcagtgggaacattgaccc 540 aatggatcctgatgcctgtgacccccacacggggcaatgcctgcgctgtttacaccacac 600 agagggtc <210> 173 <211> 543 <212> DNA
<213> homo sapien <400> 173 gaattcggcaccagagatcatccgccagcagggtctggcctcctacgactacgtgcgccg ccgcctcacggctgaggacctgttcgaggctcggatcatctctctcgagacctacaacct 120 gctccgggagggcaccaggagcctccgtgaggctctcgaggcggagtccgcctggtgcta 180 , acgggctccgtggctggtgtctacctgcccggttccaggcagacactgag 240 cctctatggc catctaccaggctctcaagaaagggctgctgagtgccgaggtggcccgcctgctgctgga 300 ggcacaggcagccacaggcttcctgctggacccggtgaagggggaacggctgactgtgga 360 tgaagctgtgcggaagggcctcgtggggcccgaactgcacgaccgcctgctctcggctga 420 gcgggcggtcaccggctaccgtgacccctacaccgagcagaccatctcgctcttccaggc 480 catgaagaaggaactgatccctactgaggaggccctgcggctgtggatgcccagctggcc 540 acc <210> 174 <211> 548 <212> DNA

<213> homo sapien <400>

gaattcggcacgagaaatggcggcaggggtcgaagcggcggcggaggtggcggcgacgga 60 gatcaaaatggaggaagagagcggcgcgcccggcgtgccgagcggcaacggggctccggg 120 ccctaagggtgaaggagaacgacctgctcagaatgagaagaggaaggagaaaaacataaa 180 aagaggaggcaatcgctttgagccatatgccaatccaactaaaagatacagagccttcat 240 tacaaacataccttttgatgtgaaatggcagtcacttaaagacctggttaaagaaaaagt 300 tggtgaggtaacatacgtggagctcttaatggacgctgaaggaaagtcaaggggatgtgc 360 tgttgttgaattcaagatggaagagagcatgaaaaaagctgcggaagtcctaaacaagca 420 tagtctgagcggaagaccactgaaagtcaaagaagatcctgatggtgaacatgccaggag 480 agcaatgcaaaaggtgatggctacgactggtgggatgggtatgggaccaggtggcccagg 540 aatgatta 548 <210> 175 <211> 604 <212 > DNA __ _ <213> homo sapien <400>

gaattcggcaccagaggacctccaggacatgttcatcgtccataccatcgaggagattga 60 gggcctgatctcagcccatgaccagttcaagtccaccctgccggacgccgatagggagcg 120 cgaggccatcctggccatccacaaggaggcccagaggatcgctgagagcaaccacatcaa 180 gctgtcgggcagcaacccctacaccaccgtcaccccgcaaatcatcaactccaagtggga 240 gaaggtgcagcagctggtgccaaaacgggaccatgccctcctggaggagcagagcaagca 300 gcagtccaacgagcacctgcgccgccagttcgccagccaggccaatgttgtggggccctg 360 gatccagaccaagatggaggagatcgggcgcatctccattgagatgaacgggaccctgga 420 ggaccagctgagccacctgaagcagtatgaacgcagcatcgtggactacaagcccaacct 480 ggacctgctggagcagcagcaccagcttatccaggaggccctcatcttcgacaacaagca 540 caccaactataccatggagcacatccgcgtgggctgggagcagctgctcaccaccattgc 600 ccgg 604 <210> 176 <211> 486 <212> DNA
<213> homo sapien <400>

gaattcggcaccagccaagctcactattgaatccacgccgttcaatgtcgcagaggggaa 60 ggaggttcttctactcgcccacaacctgccccagaatcgtattggttacagctggtacaa 120 aggcgaaagagtggatggcaacagtctaattgtaggatatgtaataggaactcaacaagc 180 taccccagggcccgcatacagtggtcgagagacaatataccccaatgcatccctgctgat 240 ccagaacgtcacccagaatgacacaggattctataccctacaagtcataaagtcagatct 300 tgtgaatgaagaagcaaccggacagttccatgtatacccggagctgcccaagccctccat 360 ctccagcaacaactccaaccccgtggaggacaaggatgctgtggccttcacctgtgaacc 420 tgaggttcagaacacaacctacctgtggtgggtaaatggtcagagcctcccggtcagtcc 480 caaggc 486 <210> 177 <211> 387 <212> DNA
<213> homo sapien <400> 177 gaattcggca ccagggacag cagaccagac agtcacagca gccttgacaa aacgttcctg 60 gaactcaagctcttctccacagaggaggacagagcagacagcagagaccatggagtctcc120 ctcggcccctccccacagatggtgcatcccctggcagaggctcctgctcacagcctcact180 tctaaccttctggaacccgcccaccactgccaagctcactattgaatccacgccgttcaa240 tgtcgcagaggggaaggaggtgcttctacttgtccacaatctgccccagcatctttttgg300 ctacagctggtacaaaggtgaaagagtggatggcaaccgtcaaattataggatatgtaat360 aggaactcaacaagctaccccagggcc 387 <210> 178 <211> 440 <212> DNA
<213> homo sapien <400> 178 ca cgaggagaagcagaaaaacaaggaatttagccagactttagaaaatgaga 60 ttc gg actgagtcagatatcaacaaaggatggtgaactaaaaatgcttcaggagg 120 gaa aaaatacctt aagtaaccaaaatgaacctgttaaatcagcaaatccaagaagaactctctagagttacca 180 aactaaaggagacagcagaagaagagaaagatgatttggaagagaggcttatgaatcaat 240 tagcagaacttaatggaagcattgggaattactgtcaggatgttacagatgcccaaataa 300 aaaatgagctattggaatctgaaatgaagaaccttaaaaagtgtgtgagtgaattggaag 360 aaaagca gcagttagtcaaggaaaaaactaaggtggaatcagaaatacgaaaggaat 420 aa g 440 atttggagaa aatacaaggt <210> 179 <211> 443 <212> DNA
<213> homo sapien <400> 179 gaattcggcaccagcggggggctacggcggcggctacggcggcgtcctgaccgcgtccga 60 cgggctgctggcgggcaacgagaagctaaccatgcagaacctcaacgaccgcctggcctc 120 ctacctggacaaggtgcgcgccctggaggcggccaacggcgagctagaggtgaagatccg 180 cgactggtaccagaagcaggggcctgggccctcccgcgactacagccactactacacgac 240 catccaggacctgcgggacaagattcttggtgccaccattgagaactccaggattgtcct 300 gcagatcgacaacgcccgtctggctgcagatgacttccgaaccaagtttgagacggaaca 360 ggctctgcgcatgagcgtggaggccgacatcaacggcctgcgcagggtgctggatgagct 420 gaccctggccaggaccgacctgg <210> 180 <211> 403 <212> DNA
<213> homo sapien <400> 180 ca cgaggttatgagagtcgacttcaatgttcctatgaagaacaaccagataa60 attc gg gaggattaaggctgctgtcccaagcatcaaattctgcttggacaatggag120 ga caaacaacca ccaagtcggtagtccttatgagccacctaggccggcctgatggtgtgcccatgcctgaca180 agtactccttagagccagttgctgtagaactcagatctctgctgggcaaggatgttctgt240 tcttgaaggactgtgtaggcccagaagtggagaaagcctgtgccaacccagctgctgggt300 ctgtcatcctgctggagaacctccgctttcatgtggaggaagaagggaagggaaaagatg360 cttctgggaacaaggttaaagccgagccagccaaaatagaagc 403 <210> 181 <2I1> 493 <212> DNA
<213> homo sapien <400> 181 gaattcggcaccagcagaggtctccagagccttctctctcctgtgcaaaatggcaactct60 taaggaaaaactcattgcaccagttgcggaagaagaggcaacagttccaaacaataagat120 cactgtagtgggtgttggacaagttggtatggcgtgtgctatcagcattctgggaaagtc180 tctggctgatgaacttgctcttgtggatgttttggaagataagcttaaaggagaaatgat240 ggatctgcagcatgggagcttatttcttcagacacctaaaattgtggcagataaagatta300 ttctgtgaccgccaattctaagattgtagtggtaactgcaggagtccgtcagcaagaagg360 ggagagtcggctcaatctggtgcagagaaatgttaatgtcttcaaattcattattcctca420 gatcgtcaagtacagtcctgattgcatcataattgtggtttccaacccagtggacattct480 tacgtatgttacc 493 <210> 182 <211> 209 <212> PRT
<213> homo sapien <400> 182 Ala Phe Ser Ser Asn Pro Lys Val Gln Val Glu Aia Ile Glu Gly Gly Ala Leu Gln Lys Leu Leu Val Ile Leu Ala Thr Glu Gln Pro Leu Thr Ala Lys Lys Lys Val Leu Phe Ala Leu Cys Ser Leu Leu Arg His Phe Pro Tyr Ala Gln Arg Gln Phe Leu Lys Leu Gly Gly Leu Gln Val Leu Arg Thr Leu Val Gln Glu Lys Gly Thr Glu Val Leu Ala Val Arg Val Val Thr Leu Leu Tyr Asp Leu Val Thr Glu Lys Met Phe Ala Glu Glu Glu Ala Glu Leu Thr Gln Glu Met Ser Pro Glu Lys Leu Gln Gln Tyr Arg Gln Val His Leu Leu Pro Gly Leu Trp Glu Gln Gly Trp Cys Glu Ile Thr Ala His Leu Leu Ala Leu Pro Glu His Asp Ala Arg Glu Lys Val Leu Gln Thr Leu Gly Val Leu Leu Thr Thr Cys Arg Asp Arg Tyr Arg Gln Asp Pro Gln Leu Gly Arg Thr Leu Ala Ser Leu Gln Ala Glu Tyr Gln Val Leu Ala Ser Leu Glu Leu Gln Asp Gly Glu Asp Glu Gly Tyr Phe Gln Glu Leu Leu Gly Ser Val Asn Ser Leu Leu Lys Glu Leu Arg <210> 183 <211> 255 <212> PRT
<213> homo sapien <400> 183 Met Ala Ala Gly Val Glu Ala Ala Ala Glu Val Ala Ala Thr Glu Pro WO 99/38973 . PCT/US99/01642 Lys Met Glu Glu Glu Ser Gly Ala Pro Cys Val Pro Ser Gly Asn Gly Ala Pro Gly Pro Lys Gly Glu Glu Arg Pro Thr Gln Asn Glu Lys Arg Lys Glu Lys Asn Ile Lys Arg Gly Gly Asn Arg Phe Glu Pro Tyr Ser Asn Pro Thr Lys Arg Tyr Arg Ala Phe Ile Thr Asn Ile Pro Phe Asp Val Lys Trp Gln Ser Leu Lys Asp Leu Val Lys Glu Lys Val Gly Glu Val Thr Tyr Val Glu Leu Leu Met Asp Ala Glu Gly Lys Ser Arg Gly Cys Ala Val Val Glu Phe Lys Met Glu Glu Ser Met Lys Lys Ala Ala Glu Val Leu Asn Lys His Ser Leu Ser Gly Arg pro Leu Lys Val Lys Glu Asp Pro Asp Gly Glu His Ala Arg Arg Ala Met Gln Lys Ala Gly Arg Leu Gly Ser Thr Val Phe Val Ala Asn Leu Asp Tyr Lys Val Gly Trp Lys Lys Leu Lys Glu Val Phe Ser Met Ala Gly Val Val Val Arg Ala Asp Ile Leu Glu Asp Lys Asp Gly Lys Ser Arg Gly Ile Gly Ile Val Thr Phe Glu Gln Ser Ile Glu Ala Val Gln Ala Ile Ser Met Phe Asn Gly Gln Leu Leu Phe Asp Arg pro Met His Val Lys Met Asp GIu Arg Ala Leu Pro Lys Gly Asp Phe Phe Pro Pro Glu Arg His Ser <210> 184 <211> 188 <212> PRT
<213> Homo sapien <400> 184 Leu Ser Gly Ser Cys Ile Arg Arg Glu Gln Thr Pro Glu Lys Glu Lys Gln Val Val Leu Phe Glu Glu Ala Ser Trp Thr Cys Thr Pro Ala Cars Gly Asp Glu Pro Arg Thr Val Ile Leu Leu Ser Ser Met Leu Ala Asp His Arg Leu Lys Leu Glu Asp Tyr Lys Asp Arg Leu Lys Ser Gly Glu His Leu Asn Pro Asp Gln Leu Glu Ala Val Glu Lys Tyr Glu Glu Val Leu His Asn Leu Glu Phe Ala Lys Glu Leu Gln Lys Thr Phe Ser Gly Leu Ser Leu Asp Leu Leu Lys Ala Gln Lys Lys Ala Gln Arg Arg Glu His Met Leu Lys Leu Glu Ala Glu Lys Lys Lys Leu Arg Thr Ile Leu Gln Val Gln Tyr Val Leu Gln Asn Leu Thr Gln Glu His Val Gln Lys Asp Phe Lys Gly Gly Leu Asn Gly Ala Val Tyr Leu Pro Ser Lys Glu Leu Asp Tyr Leu Ile Lys Phe Ser Lys Leu Thr Cys Pro Glu Arg Asn Glu Ser Leu Arg Gln Thr Leu Glu Gly Ser Thr Val 180 1,85 <210> 185 <211> 746 <212> PRT
<213> Homo sapien <400> 185 Asp Lys His Leu Lys Asp Leu Leu Ser Lys Leu Leu Asn Ser Gly Tyr Phe Glu Ser Ile Pro Val Pro Lys Asn Ala Lys Glu Lys Glu Val Pro Leu Glu Glu Glu Met Leu Ile Gln Ser Glu Lys Lys Thr Gln Leu Ser Lys Thr Glu Ser Val Lys Glu Ser Glu Ser Leu Met Glu Phe Ala Gln Pro Glu Ile Gln Pro Gln Glu Phe Leu Asn Arg Arg Tyr Met Thr Glu Val Asp Tyr Ser Asn Lys Gln Gly Glu Glu Gln Pro Trp Glu Ala Asp Tyr Ala Arg Lys Pro Asn Leu Pro Lys Arg Trp Asp Met Leu Thr Glu Pro Asp Gly Gln Glu Lys Lys Gln Glu Ser Phe Lys Ser Trp Glu Ala Ser Gly Lys His Gln Glu Val Ser Lys Pro Ala Val Ser Leu Glu Gln Arg Lys Gln Asp Thr Ser Lys Leu Arg Ser Thr Leu Pro Glu Glu Gln Lys Lys Gln Glu Ile Ser Lys Ser Lys Pro Ser Pro Ser Gln Trp Lys 165 17fl 175 Gln Asp Thr Pro Lys Ser Lys Ala Gly Tyr Val Gln Glu Glu Gln Lys Lys Gln Glu Thr Pro Lys Leu Trp Pro Val Gln Leu Gln Lys Glu Gln Asp Pro Lys Lys Gln Thr Pro Lys Ser Trp Thr Pro Ser Met Gln Ser Glu Gln Asn Thr Thr Lys Ser Trp Thr Thr Pro Met Cys Glu Glu Gln asp Ser Lys Gln Pro Glu Thr Pro Lys Ser Trp Glu Asn Asn Val Glu Ser Gln Lys His Ser Leu Thr Ser Gln Ser Gln Ile Ser Pro Lys Ser Trp Gly Val Ala Thr Ala Ser Leu Ile Pro Asn Asp Gln Leu Leu Pro Arg Lys Leu Asn Thr Glu Pro Lys Asp Val Pro Lys Pro Val His Gln Pro Val Gly Ser Ser Ser Thr Leu Pro Lys Asp Pro Val Leu Arg Lys Glu Lys Leu Gln Asp Leu Met Thr Gln Ile Gln Gly Thr Cys Asn Phe Met Gln Glu Ser Val Leu Asp Phe Asp Lys Pro Ser Ser Ala Ile Pro Thr Ser Gln Pro Pro Ser Ala Thr Pro Gly Ser Pro Val Ala Ser Lys Glu Gln Asn Leu Ser Ser Gln Ser Asp Phe Leu Gln Glu Pro Leu Gln Val Phe Asn Val Asn Ala Pro Leu Pro Pro Arg Lys Glu Gln Glu Ile Lys Glu Ser Pro Tyr Ser Pro Gly Tyr Asn Gln Ser Phe Thr Thr Ala Ser Thr Gln Thr Pro Pro Gln Cys Gln Leu Pro Ser Ile His Val Glu Gln Thr Val His Ser Gln Glu Thr Ala Ala Asn Tyr His Pro Asp Gly Thr Ile Gln Val Ser Asn Gly Ser Leu Ala Phe Tyr Pro Ala Gln Thr Asn Val Phe Pro Arg Pro Thr Gln Pro Phe Val Asn Ser Arg Gly Ser 465 470 .__ 475 480 Val Arg Gly Cys Thr Arg Gly Gly Arg Leu Ile Thr Asn Ser Tyr Arg Ser Pro Gly Gly Tyr Lys Gly Phe Asp Thr Tyr Arg Gly Leu Pro Ser Ile Ser Asn Gly Asn Tyr Ser Gln Leu Gln Phe Gln Ala Arg Glu Tyr Ser Gly Ala Pro Tyr Ser Gln Arg Asp Asn Phe Gln Gln Cys Tyr Lys Arg Gly Gly Thr Ser Gly Gly Pro Arg Ala Asn Ser Arg Ala Gly Trp Ser Asp Ser Ser Gln Val Ser Ser Pro Glu Arg Asp Asn Glu Thr Phe Asn Ser Gly Asp Ser Gly Gln Gly Asp Ser Arg Ser Met Thr Pro Val Asp Val Pro Val Thr Asn Pro Ala Ala Thr Ile Leu Pro Val His Val Tyr Pro Leu Pro Gln Gln Met Arg Val Ala Phe Ser Ala Ala Arg Thr Ser Asn Leu Ala Pro Gly Thr Leu Asp Gln Pro Ile Val Phe Asp Leu Leu Leu Asn Asn Leu Gly Glu Thr Phe Asp Leu Gln Leu Gly Arg Phe Asn Cys Pro Val Asn Gly Thr Tyr Val Phe Ile Phe His Met Leu Lys Leu Ala Val Asn Val Pro Leu Tyr Val Asn Leu Met Lys Asn Glu Glu Val Leu Val Ser Ala Tyr Ala Asn Asp Gly Ala Pro Asp His Glu Thr Ala Ser Asn His Ala Ile Leu Gln Leu Phe Gln Gly Asp Gln Ile Trp Leu Arg Leu His Arg Gly Ala Ile Tyr Gly Ser Ser Trp Lys Tyr Ser Thr Phe Ser Gly Tyr Leu Leu Tyr Gln Asp <210> 186 <211> 705 <212> PRT
<213> Homo sapien <400> 186 Ala Leu Leu Asn Val Arg Gln Pro Pro Ser Thr Thr Thr Phe Val Leu Asn Gln Ile Asn His Leu Pro Pro Leu Gly Ser Thr Ile Val Met Thr Lys Thr Pro Pro Val Thr Thr Asn Arg Gln Thr Ile Thr Leu Thr Lys Phe Ile Gln Thr Thr Ala Ser Thr Arg Pro Ser Val Ser Ala Pro Thr Val Arg Asn Ala Met Thr Ser Ala Pro Ser Lys Asp Gln Val Gln Leu Lys Asp Leu Leu Lys Asn Asn Ser Leu Asn Glu Leu Met Lys Leu Lys Pro Pro Ala Asn Ile Ala Gln Pro Val Ala Thr Ala Ala Thr Asp Val Ser Asn Gly Thr Val Lys Lys Glu Ser Ser Asn Lys Glu Gly Ala Arg Met Trp Ile Asn Asp Met Lys Met Arg Ser Phe Ser Pro Thr Met Lys Val Pro Val Val Lys Glu Asp Asp Glu Pro Glu Glu Glu .Asp Glu Glu Glu Met Gly His Ala Glu Thr Tyr Ala Glu Tyr Met Pro Ile Lys Leu Lys Ile Gly Leu Arg His Pro Asp Ala Val Val Glu Thr Ser Ser Leu Ser Ser Val Thr Pro Pro Asp Val Trp Tyr Lys Thr Ser Ile Ser Glu Glu Thr Ile Asp Asn Gly Trp Leu Ser Ala Leu Gln Leu Glu Ala Ile Thr Tyr Ala Ala Gln Gln His Glu Thr Phe Leu Pro Asn Gly Asp Arg Ala Gly Phe Leu Ile Gly Asp Gly Ala Gly Val Gly Lys Gly Arg Thr Ile Ala Gly Ile Ile Tyr Glu Asn Tyr Leu Leu Ser Arg Lys Arg Ala Leu Trp Phe Ser Val Ser Asn Asp Leu Lys Tyr Asp Ala Glu Arg Asp Leu Arg Asp Ile Gly Ala Lys Asn Ile Leu Val His Ser Leu Asn Lys Phe Lys Tyr Gly Lys Ile Ser Ser Lys His Asn Gly Ser Val Lys Lys Gly Val Ile Phe Ala Thr Tyr Ser Ser Leu Ile Gly Glu Ser Gln Ser Gly Gly Lys Tyr Lys Thr Arg Leu Lys Gln Leu Leu His Trp Cys Gly Asp Asp Phe Asp Gly Val Ile Val Phe Asp Glu Cys His Lys Ala Lys Asn Leu Cys Pro Val Gly Ser Ser Lys Pro Thr Lys Thr Gly Leu Ala Val Leu Glu Leu Gln Asn Lys Leu Pro Lys Ala Arg Val Val Tyr Ala Ser Ala Thr Gly Al.a Ser Glu Pro Arg Asn Met Ala Tyr Met Asn Arg WO 99/3$973 PCT/US99/01642 Leu Gly Ile Trp Gly Glu Gly Thr Pro Phe Arg Glu Phe Ser Asp Phe Ile Gln Ala Val Glu Arg Arg Gly Val Gly Ala Met Glu Ile Val Ala Met Asp Met Lys Leu Arg Gly Met Tyr Ile Ala Arg Gln Leu Ser Phe Thr Gly Val Thr Phe Lys Ile Glu Glu Val Leu Leu Ser Gln Ser Tyr Val Lys Met Tyr Asn Lys Ala Val Lys Leu Trp Val Ile Ala Arg Glu Arg Phe Gln Gln Ala Ala Asp Leu Ile Asp Ala Glu Gln Arg Met Lys Lys Ser Met Trp Gly Gln Phe Trp Ser Ala His Gln Arg Phe Phe Lys Tyr Leu Cps Ile Ala Ser Lys Val Lys Arg Val Val Gln Leu Ala Arg Glu Glu Ile Lys Asn Gly L~ys Cps Va_1_ Val Ile Gly Leu Gln Ser Thr Gly Glu Ala Arg Thr Leu Glu Ala Leu Glu Glu Gly Gly Gly Glu Leu Asn Asp Phe Val Ser Thr Ala Lys Gly Val Leu Gln Ser Leu Ile Glu Lys His Phe Pro Ala Pro Asp Arg Lys Lys Leu Tyr Ser Leu Leu Gly Ile Asp Leu Thr Ala Pro Ser Asn Asn Ser Ser Pro Arg Asp Ser Pro Cys Lys Glu Asn Lys Ile Lys Lys Arg Lys Gly Glu Glu Ile Thr Arg Glu Ala Lys Lys Ala Arg Lys Val Gly Gly Leu Thr Gly Ser Ser Ser Asp Asp Ser Gly Ser Glu Ser Asp Ala Ser Asp Asn Glu Glu Ser Asp Tyr Glu Ser Ser Lys Asn Met Ser Ser Gly Asp Asp Asp Asp Phe Asn Pro Phe Leu Asp Glu Ser Asn Glu Asp Asp Glu Asn Asp Pro Trp Leu Ile <210> 187 <211> 595 <212> PRT
<213> Homo sapien <400> I87 Glu Ser Pro Arg His Arg Gly Glu Gly Gly Gly Glu Trp Gly Pro Gly Val Pro Arg Glu Arg Arg Glu Ser Ala Gly Glu Trp Gly Ala Asp Thr Pro Lys Glu Gly Gly Glu Ser Ala Gly Glu Trp Gly Ala Glu Val Pro Arg Gly Arg Gly Glu Gly Ala Gly Glu Trp Gly Pro Asp Thr Pro Lys Glu Arg Gly Gln Gly Val Arg Glu Trp Gly Pro Glu Ile Pro Gln Glu His Gly Glu Ala Thr Arg Asp Trp Ala Leu Glu Ser Pro Arg Ala Leu Gly Glu Asp AIa Arg Glu Leu Gly Ser Ser Pro His Asp Arg Gly Ala Ser Pro Arg Asp Leu Ser Gly Glu Ser Pro Cys Thr Gln Arg Ser Gly Leu Leu Pro Glu Arg Arg Gly Asp Ser Pro Trp Pro Pro Trp Pro Ser Pro Gln GIu Arg Asp Ala Gly Thr Arg Asp Arg Glu Glu Ser Pro Arg Asp Trp Gly Gly Ala Glu Ser Pro Arg Gly Trp Glu Ala Gly Pro Arg Glu Trp Gly Pro Ser Pro Ser Gly His Gly Asp Gly Pro Arg Arg Arg Pro Arg Lys Arg Arg Gly Arg Lys Gly Arg Met Gly Arg Gln His Glu Ala Ala Ala Thr Ala Ala Thr Ala A1~_Thr Ala Thr Gly Gly Thr Ala Glu Glu Ala Gly Ala Ser Ala Pro Glu Ser Gln Ala Gly Gly Gly pro Arg Gly Arg Ala Arg Gly Pro Arg Gln Gln Gly Arg Arg ,~.g His Gly Thr Gln Arg Arg Arg Gly pro Pro Gln Ala Arg Glu Glu Gly pro pu.g Asp Ala Thr Thr Ile Leu Gly Leu Gly Thr Pro Ser Gly Glu Gln Arg Ala Asp Gln Ser Gln Ala Leu Pro Ala Leu Ala Gly Ala Ala Ala Ala His Ala His Ala Ile Pro Gly Ala GIy Pro Ala Ala Ala Pro Val Gly Gly Arg GIy Arg Arg Gly Gly Trp Arg Gly Gly Arg Arg Gly Gly Ser Ala Gly Ala Gly Gly Gly GIy Arg Gly Gly Arg GIy Arg Gly Arg Gly Gly Gly Arg Gly Gly Gly Gly Ala Gly Arg Gly Gly Gly Ala Ala Gly pro Arg Glu Gly Ala Ser Ser Pro Gly Ala Arg Arg Gly Glu Gln Arg Ax'g Arg Gly Arg Gly Pro Pro Ala Ala Gly Ala Ala Gln Val Ser Ala 'erg Gly ~'9 Arg AIa Arg Gly Gln Arg Ala Gly Glu Glu Ala GIn Asp Gly Leu Leu Pro Arg Gly Arg Asp Arg Leu Pro Leu Arg pro Gly Asp Ala Asn Gln Arg AIa Glu Arg Pro Gly Pro Pro Arg Gly Gly His Gly Pro Val Asn Ala Ser Ser Ala Pro Asp Thr Ser Pro Pro Arg His Pro ~'g Arg Trp Val Ser Gln Gln Arg Gln Arg Leu Trp Arg Gln Phe Arg Val Gly Gly Gly Phe Pro Pro Pro Pro Pro Ser Arg Pro Pro Ala Val Leu Leu Pro Leu Leu Arg Leu Ala Cars Ala Gly Asp Pro Gly Ala Thr Arg Pro Gly Pro Arg Arg Pro Ala Arg Arg Pro Arg Gly Glu Leu Ile Pro Arg Arg Pro Asp Pro Ala Ala Pro Ser Glu Glu Gly Leu Arg Met Glu Ser Ser Val Asp Asp Gly Ala Thr Ala Thr Thr Ala Asp Ala Ala Ser Gly Glu Ala Pro Glu Ala Gly Pro Ser Pro Ser His Ser Pro Thr Met Cys Gln Thr Gly Gly Pro Gly Pro Pro Pro Pro Gln Pro Pro Arg Trp Leu Pro 590 <210> 188 <211> 376 <212> PRT
<213> Homo sapien <400> 188 Glu Met Arg Lys Phe Asp Val Pro Ser Met Glu Ser Thr Leu Asn Gln Pro Ala Met Leu Glu Thr Leu Tyr Ser Asp Pro His Tyr Arg Ala His Phe Pro Asn Pro Arg Pro Asp Thr Asn Lys Asp Val Tyr Lys Val Leu Pro Glu Ser Lys Lys Ala Pro Gly Ser Gly Ala Val Phe Glu Arg Asn Gly Pro His Ala Ser Ser Ser Gly Val Leu Pro Leu Gly Leu Gln Pro Ala Pro Gly Leu Sex Lys Ser Leu Ser Ser Gln Val Trp Gln Pro Ser Pro Asp Pro Trp His Pro Gly G1u Gln Ser Cys Glu Leu Ser Thr Cys 100 105 lI0 Arg Gln Gln Leu Glu Leu Ile Arg Leu Gln Met Glu Gln Met Gln Leu Gln Asn Gly Ala Met Cys His His Pro Ala Ala Phe Ala Pro Leu Leu Pro Thr Leu Glu Pro Ala Gln Trp Leu Ser Ile Leu Asn Ser Asn Glu His Leu Leu Lys Glu Lys Glu Leu Leu Ile Asp Lys Gln Arg Lys His Ile Ser Gln Leu Glu Gln Lys Val Arg Glu Ser Glu Leu Gln Val His Ser Ala Leu Leu Gly Arg Pro Ala Pro Phe Gly Asp Val Cys Leu Leu Arg Leu Gln Glu Leu Gln Arg Glu Asn Thr Phe Leu Arg Ala Gln Phe Ala Gln Lys Thr Glu Ala Leu Sar Lys Glu Lys Met Glu Leu Glu Lys Lys Leu Ser Ala Ser Glu Val Glu IIe Gln Leu Ile Arg Glu Ser Leu Lys Val Thr Leu Gln Lys His Ser Glu Glu Gly Lys Lys Gln Glu Glu Arg Val Lys Gly Arg Asp Lys His Ile Asn Asn Leu Lys Lys Lys Cys Gln Lys Glu Ser Glu Gln Asn Arg Glu Lys Gln GIn Arg Ile Glu Thr Leu Glu Arg Tyr Leu Ala Asp Leu Pro Thr Leu Glu Asp His Gln Lys Gln Thr Glu Gln Leu Lys Asp Ala Glu Leu Lys Asn Thr Glu Leu Gln Glu Arg Val Ala Glu Leu Glu Thr Leu Leu Glu Asp Thr Gln Ala Thr Cps Arg Glu Lys Glu Val Gln Leu Glu Ser Leu Arg Gln Arg Glu Ala Asp Leu Ser Ser Ala Arg His Arg <210> 189 <211> 160 <212> PRT
<213> Homo sapien <400> 189 Met Leu Glu Ala His Arg Arg Gln Arg His Pro Phe Leu Leu Leu Gly Thr Thr Ala Asn Arg Thr Gln Ser Leu Asn Tyr Gly Cys Ile Val Glu Asn Pro Gln Thr His Glu Val Leu His Tyr Val Glu Lys Pro Ser Thr Phe Ile Ser Asp Ile Ile Asn Cys Gly Ile Tyr Leu Phe Ser Pro Glu Ala Leu Lys Pro Leu Arg Asp Val Phe Gln Arg Asn Gln Gln Asp Gly Gln Leu Glu Asp Ser Pro Gly Leu Trp Pro Gly Ala Gly Thr Ile Arg Leu Glu Gln Asp Val Phe Ser Ala Leu Ala Gly Gln Gly Gln Ile Tyr Val His Leu Thr Asp Gly Ile Trp Ser Gln Ile Lys Ser Ala Gly Ser Ala Leu Tyr Ala Ser Arg Leu Tyr Leu Ser Arg Tyr Gln Asp Thr His Pro Glu Arg Leu Ala Lys His Thr Pro Gly Gly Pro Trp Ile Arg Gly <2I0> 190 <211> 146 <212> PRT
<213> Homo sapien <400> 190 Met Asp Pro Arg Ala Ser Leu Leu Leu Leu Gly Asn Val Tyr Ile His Pro Thr Ala Lys Val Ala Pro Ser Ala Val Leu Gly Pro Asn Val Ser Ile Gly Lys Gly Val Thr Val Gly Glu Gly Val Arg Leu Arg Glu Ser Ile Val Leu His Gly Ala Thr Leu Gln Glu His Thr Cys Val Leu His Ser Ile Val Gly Trp Gly Ser Thr Val Gly Arg Trp Ala Arg Val Glu GlyThrPro SerAsp ProAsnPro AsnAspProArg A
Ala rg Met Asp SerGluSer LeuPhe LysAspGly LysLeuL

eu Pro Ile Ile 100 Ala Thr LeuGlyCys ArgVal ArgIlePro AlaGl V

u al Leu Leu Ser 115 Ile Asn IleValLeu ProHis LysGluLeu S

er ArgSerPhe Asn Ile 130 Thr Gln IleLeu <210> 191 <211> 704 <212> PRT
<213> Homo sapien <400> 191 .__ Glu Gly Gly Cys Ala Ala Gly Arg Gly Arg GIu Leu Glu Pro Glu Leu Giu Pro Gly Pro Gly Pro Gly Ser Ala Leu Glu Pro Gly Glu Glu Phe Glu Ile Val Asp Arg Ser Gln Leu Pro Gly Pro Gly Asp Leu Arg Ser Ala Thr Arg Pro Arg Ala Ala Glu Gly Trp Ser Ala Pro Ile Leu Thr 50 55 u0 Leu Ala Arg Arg Ala Thr Gly Asn Leu Ser Ala Ser Cys Gly Ser Ala Leu Arg Ala Ala Ala Gly Leu Gly Gly Gly Asp Ser Gly Asp Gly Thr Ala Arg Ala Ala Ser Lys Cys Gln Met Met Glu Glu Arg Ala Asn Leu Met His Met Met Lys Leu Ser Ile Lys Val Leu Leu Gln Ser Ala Leu Ser Leu Gly Arg Ser Leu Asp Ala Asp His Ala Pro Leu Gln Gln Phe Phe Val Val Met Glu His Cys Leu Lys His Gly Leu Lys Val Lys Lys Ser Phe Ile Gly Gln Asn Lys Ser Phe Phe Gly Pro Leu Glu Leu Val Glu Lys Leu Cys Pro Glu Ala Ser Asp Ile Ala Thr Ser Val Arg Asn 'Leu Pro Glu Leu Lys Thr Ala Val Gly Arg Gly Arg Ala Trp Leu Tyr Leu Ala Leu Met Gln Lys Lys Leu Ala Asp Tyr Leu Lys Val Leu Ile Asp Asn Lys His Leu Leu Ser Glu Phe Tyr Glu Pro Glu Ala Leu Met Met Glu Glu Glu Gly Met Val Ile Val Gly Leu Leu Val Gly Leu Asn Val Leu Asp Ala Asn Leu Cys Leu Lys Gly Glu Asp Leu Asp Ser Gln Val Gly Val Ile Asp Phe Ser Leu Tyr Leu Lys Asp Val Gln Asp Leu Asp Gly Gly Lys Glu His Glu Arg Ile Thr Asp Val Leu Asp Gln Lys Asn Tyr Val Glu Glu Leu Asn Arg His Leu Ser Cys Thr Val Gly Asp Leu Gln Thr Lys Ile Asp Gly Leu Glu Lys Thr Asn Ser Lys Leu Gln Glu Glu Leu Ser Ala Ala Thr Asp Arg Ile Cys Ser Leu Gln Glu Glu Gln Gln Gln Leu Arg Glu Gln Asn GIu Leu Ile Arg Glu Arg Ser Glu Lys Ser Val Glu Ile Thr Lys Gln Asp Thr Lys Val Glu Leu Glu Thr Tyr Lys Gln Thr Arg Gln Gly Leu Asp Glu Met Tyr Ser Asp Val Trp Lys Gln Leu Lys Glu Glu Lys Lys Val Arg Leu Glu Leu Glu Lys Glu Leu Glu Leu Gln Ile Gly Met Lys Thr Glu Met Glu Ile Ala Met Lys Leu Leu Glu Lys Asp Thr His Glu Lys Gln Asp Thr Leu Val Ala Leu Arg Gln Gln Leu Glu Glu Val Lys Ala Ile Asn Leu Gln Met Phe His Lys Ala Gln Asn Ala Glu Ser Ser Leu Gln Gln Lys Asn Glu Ala Ile Thr Ser Phe Glu Gly Lys Thr Asn Gln Val Met Ser Ser Met Lys Gln Met Glu Glu Arg Leu Gln His Ser Glu Arg Ala Arg Gln Gly Ala Glu Glu Arg Ser His Lys Leu Gln Gln Glu Leu Gly Gly Arg Ile Gly Ala Leu Gln Leu Gln Leu Ser Gln Leu His Glu Gln Cys Ser Ser Leu Glu Lys Glu Leu Lys Ser Glu Lys Glu Gln Arg Gln Ala Leu Gln Arg Glu Leu Gln His Glu Lys Asp Thr Ser Ser Leu Leu Arg Met Glu Leu Gln Gln Val Glu Gly Leu Lys Lys Glu Leu Arg Glu Leu Gln Asp Glu Lys Ala Glu Leu Gln Lys Ile Cys Glu Glu Gln Glu Gln Ala Leu Gln Glu Met Gly Leu His Leu Ser Gln Ser Lys Leu Lys Met Glu Asp Ile Lys Glu Val Asn Gln Ala Leu Lys Gly His Ala Trp Leu Lys Asp Asp Glu Ala Thr His Cys Arg Gln Cys Glu Lys Glu Phe Ser Ile Ser Arg Arg Lys His His Cys Arg Asn Cys Gly His Ile Phe Cys Asn Thr Cys Ser Ser Asn Glu Leu Ala Leu Pro Ser Tyr Pro Lys Pro Val Arg Val Cys Asp Ser Cys His Thr Leu Leu Leu Gln Arg Cys Ser Ser Thr Ala Ser <210> 192 <211> 331 <212> PRT

<213> Homo sapien <400> 192 Arg Ala Gly Ala Ser Ala Met Ala Leu Arg Lys Glu Leu Leu Lys Ser Ile Trp Tyr Ala Phe Thr Ala Leu Asp Val Glu Lys Ser Gly Lys Val Ser Lys Ser Gln Leu Lys Val Leu Ser His Asn Leu Tyr Thr Val Leu His Ile Pro His Asp Pro Val Ala Leu Glu Glu His Phe Arg Asp Asp Asp Asp Gly Pro Val Ser Ser Gln Gly Tyr Met Pro Tyr Leu Asn Lys Tyr Ile Leu Asp Lys Val Glu Glu Gly Ala Phe Val Lys Glu His Phe Asp Glu Leu Cys Trp Thr Leu Thr Ala Lys Lys Asn Tyr Arg Ala Asp Ser Asn Gly Asn Ser Met Leu Ser Asn Gln Asp Ala Phe Arg Leu Trp Cys Leu Phe Asn Phe Leu Ser Glu Asp Lys Tyr Pro Leu Ile Met Val Pro Asp Glu Val Glu Tyr Leu Leu Lys Lys Val Leu Ser Ser Met Ser Leu Glu Val Ser Leu Gly Glu Leu Glu Glu Leu Leu Ala Gln Glu Ala Gln Val Ala Gln Thr Thr Gly Gly Leu Ser Val Trp Gln Phe Leu Glu Leu Phe Asn Ser Gly Arg Cys Leu Arg Gly Val Gly Arg Asp Thr Leu Ser Met Ala Ile His Glu Val Tyr Gln Glu Leu Ile Gln Asp Val Leu Lys Gln Gly Tyr Leu Trp Lys Arg Gly His Leu Arg Arg Asn Trp Aia Glu Arg Trp Phe Gln Leu Gln Pro Ser Cys Leu Cys Tyr Phe Gly Ser Glu Glu Cys Lys Glu Lys Arg Gly Ile Ile Pro Leu Asp Ala His Cys Cys Val Glu Val Leu Pro Asp Arg Asp Gly Lys Arg Cys Met Phe Cys Val Lys Thr Ala Thr Arg Thr Tyr Glu Met Ser Ala Ser Asp Thr Arg Gln Arg Gln Glu Trp Thr Ala Ala Ile Gln Met Ala Ile Arg Leu Gln Ala Glu Gly Lys Thr Ser Leu His Lys Asp Leu <210> 193 <211> 475 <212> PRT
<213> Homo sapien <400> 193 Lys Asn Ser Pro Leu Leu Ser Val Ser Ser GIn Thr Ile Thr Lys Glu Asn Asn Arg Asn Val His Leu Glu His Ser Glu Gln Asn Pro Gly Ser WO 99/38973 PC'TNS99/01642 Ser Ala Gly Asp Thr Ser Ala Ala His Gln Val Val Leu Gly Glu Asn Leu Ile Ala Thr Ala Leu Cys Leu Ser Gly Ser Gly Ser Gln Ser Asp Leu Lys Asp Val Ala Ser Thr Ala Gly Glu Glu Gly Asp Thr Ser Leu Arg Glu Ser Leu His Pro Val Thr Arg Ser Leu Lys Ala Gly Cys His Thr Lys Gln Leu Ala Ser Arg Asn Cys Ser Glu Glu Lys Ser Pro Gln Thr Ser Ile Leu Lys Glu Gly Asn Arg Asp Thr Ser Leu Asp Phe Arg Pro Val Val Ser Pro Ala Asn Gly Val Glu Gly Val Arg Val Asp Gln Asp Asp Asp Gln Asp Ser Ser Ser Leu Lys Leu Ser Gln Asn Ile Ala Val Gln Thr Asp Phe Lys Thr Ala Asp Ser Glu Val Asn Thr Asp Gln Asp Ile Glu Lys Asn Leu Asp Lys Met Met Thr Glu Arg Thr Leu Leu Lys Glu Arg Tyr Gln Glu Val Leu Asp Lys Gln Arg Gin Val Glu Asn Gln Leu Gln Val Gln Leu Lys Gln Leu Gln Gln Arg Arg Glu Glu Glu Met Lys Asn His Gln Glu Ile Leu Lys Ala Ile Gln Asp Val Thr Ile Lys Arg Glu Glu Thr Lys Lys Lys Ile Glu Lys Glu Lys Lys Glu Phe Leu Gln Lys Glu Gln Asp Leu Lys Ala Glu Ile Glu Lys Leu Cys Glu Lys Gly Arg Arg Glu Val Trp Glu Met Glu Leu Asp Arg Leu Lys Asn Gln Asp Gly Glu Ile Asn Arg Asn Ile Met Glu Glu Thr Glu Arg Ala Trp Lys Ala Glu Ile Leu Ser Leu Glu Ser Arg Lys Glu Leu Leu Val Leu Lys Leu Glu Glu Ala Glu Lys Glu Ala Glu Leu His Leu Thr Tyr Leu Lys Ser Thr Pro Pro Thr Leu Glu Thr Val Arg Ser Lys Gln Glu Trp Glu Thr Arg Leu Asn Gly Val Arg Ile Met Lys Lys Asn Val Arg Asp Gln Phe Asn Ser His Ile Gln Leu Val Arg Asn Gly Ala Lys Leu Ser Ser Leu Pro Gln Ile Pro Thr Pro Thr Leu Pro Pro Pro Pro Ser Glu Thr Asp Phe Met Leu Gln Val Phe Gln Pro Ser Pro Ser Leu Ala Pro Arg Met Pro Phe Ser Ile Gly Gln Val Thr Met Pro Met Val Met Pro Ser Ala Asp Pro Arg Ser Leu Ser Phe Pro Ile Leu Asn Pro Ala Leu Ser Gln Pro Ser Gln Pro Ser Ser Pro Leu Pro Gly Ser His G7.y Arg Asn Ser Pro Gly Leu Gly Ser Leu Val Ser <210> 194 <211> 241 <212> PRT
<213> Homo sapien <400> 194 Met Ser Gly Glu Ser Ala Arg Ser Leu Gly Lys Gly Ser Ala Pro Pro Gly Pro Val Pro Glu Gly Ser Ile Arg Ile Tyr Ser Met Arg Phe Cys Pro Phe Ala Glu Arg Thr Arg Leu Val Leu Lys Ala Lys Gly Ile Arg His Glu Val Ile Asn Ile Asn Leu Lys Asn Lys Pro Glu Trp Phe Phe Lys Lys Asn Pro Phe Gly Leu Val P.ro Val Leu Glu Asn Ser Gln Gly Gln Leu Ile Tyr Glu Ser Ala Ile Thr Cys Glu Tyr Leu Asp Glu Ala Tyr Pro Gly Lys Lys Leu Leu Pro Asp Asp Pro Tyr Glu Lys Ala Cys Gln Lys Met Ile Leu Glu Leu Phe Ser Lys Val Pro Ser Leu Val Gly Ser Phe Ile Arg Ser Gln Asn Lys Glu Asp Tyr Ala Gly Leu Lys Glu Glu Phe Arg Lys Glu Phe Thr Lys Leu Glu Glu Val Leu Thr Asn Lys Lys Thr Thr Phe Phe Gly Gly Asn Ser Ile Ser Met Ile Asp Tyr Leu Ile Trp Pro Trp Phe Glu Arg Leu Glu Ala Met Lys Leu Asn Glu Cys Val Asp His Thr Pro Lys Leu Lys Leu Trp Met Ala Ala Met Lys Glu Asp Pro Thr Val Ser Ala Leu Leu Thr Ser Glu Lys Asp Trp Gln Gly Phe Leu Glu Leu Tyr Leu Gln Asn Ser Pro Glu Ala Cys Asp Tyr Gly Leu <210> 195 <211> 138 <212> PRT
<213> Homo sapien <400> 195 Gln Thr Lys Ile Leu Glu Glu Asp Leu Glu Gln Ile Lys Leu Ser Leu Arg Glu Arg Gly Arg Glu Leu Thr Thr Gln Arg Gln Leu Met Gln Glu Arg Ala Glu Glu Gly Lys Gly Pro Ser Lys Ala Gln Arg Gly Ser Leu Glu His Met Lys Leu Ile Leu Arg Asp Lys Glu Lys Glu Val Glu Cys Gln Gln Glu His ile His Glu Leu Gln Glu Leu Lys Asp Gln Leu Glu Gln Gln Leu Gln Gly Leu His Arg Lys Val Gly Glu Thr Ser Leu Leu Leu Ser Gln Arg Glu Gln Glu Ile Val Val Leu Gln Gln Gln Leu Gln Glu Ala Arg Glu Gln Gly Glu Leu Lys Glu Gln Ser Leu Gln Ser Gln Leu Asp Glu Ala Gln Arg Ala Leu Ala Gln <210> 196 <211> 102 <212> PRT
<213> Homo sapien <400> 196 Met Ser Lys Arg Lys Ala Pro Gln Glu Thr Leu Asn Gly Gly Ile Thr Asp Met Leu Thr Glu Leu Ala Asn Phe Glu Lys Asn Val Ser Gln Ala Ile His Lys Tyr Asn Ala Tyr Arg Lys Ala Ala Ser Val Ile Ala Lys Tyr Pro His Lys Ile Lys Ser Gly Ala Glu Ala Lys Lys Leu Pro Gly Val Gly Thr Lys Ile Ala Glu Lys Ile Asp Glu Phe Leu Ala Thr Gly Lys Leu Arg Lys Leu Glu Lys Ile Arg Gln Asp Asp Thr Ser Ser Ser Ile Asn Phe Leu Thr Arg <210> 197 <211> 138 <212> PRT
<213> Homo sapien <400> 197 Glu Ala Asn Glu Val Thr Asp Ser Ala Tyr Met Gly Ser Glu Ser Thr Tyr Ser Glu Cys Glu Thr Phe Thr Asp Glu Asp Thr Ser Thr Leu Val His Pro Glu Leu Gln Pro Glu Gly Asp Ala Asp Ser Ala Gly Gly Ser Ala Val Pro Ser Glu Cys Leu Asp Ala Met Glu Glu Pro Asp His Gly Ala Leu Leu Leu Leu Pro Gly Arg Pro His Pro His Gly Gln Ser Val Ile Thr Val Ile Gly Gly Glu Glu His Phe Glu Asp Tyr Gly Glu Gly Ser Glu Ala Glu Leu Ser Pro Glu Thr Leu Cys Asn Gly Gln Leu Gly Cys Ser Asp Pro Ala Phe Leu Thr Pro Ser Pro Thr Lys Arg Leu Ser Ser Lys Lys Val Ala Arg Tyr Leu His Gln <210> 198 <211> 100 <212> PRT
<213> Homo sapien <400> 198 Met Gly Asp Val Lys Asn Phe Leu Tyr Ala Trp Cys Gly Lys Arg Lys Met Thr Pro Ser Tyr Glu Ile Arg Ala Val Gly Asn Lys Asn Arg Gln Lys Phe Met Cys Glu Val Gln Val Glu Gly Tyr Asn Tyr Thr Gly Met Gly Asn Ser Thr Asn Lys Lys Asp Ala Gln Ser Asn Ala Ala Arg Asp Phe Val Asn Tyr Leu Val Arg Ile Asn G1u Ile Lys Ser Glu Glu Val Pro Ala Phe Gly Val Ala Ser Pro Pro Pro Leu Thr Asp Thr Pro Asp Thr Thr Ala Asn <210> 199 <211> 127 <212> PRT
<213> Homo sapien <400> 199 Met Val Lys Glu Thr Thr Tyr Tyr Asp Val Leu Gly Val Lys Pro Asn Ala Thr Gln Glu Glu Leu Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys Tyr His Pro Asp Lys Asn Pro Asn Glu Gly Glu Lys Phe Lys Gln Ile Ser Gln Ala Tyr Glu Val Leu Ser Asp Ala Lys Lys Arg Glu Leu Tyr Asp Lys Gly Gly Glu Gln Ala Ile Lys Glu Gly Gly Ala Gly Gly Gly Phe Gly Ser Pro Met Asp Ile Phe Asp Met Phe Phe Gly Gly Gly Gly Arg Met Gln Arg Glu Arg Arg Gly Lys Asn Val Val His Gln Leu Ser Val Thr Leu Glu Asp Leu Tyr Asn Gly Ala Thr Arg Lys Leu Ala <210> 200 <211> 90 <212> PRT
<213> Homo sapien <400> 200 Met Ala Cys Pro Leu Asp Gln Ala Ile Gly Leu Leu Val Ala Ile Phe PC'f/US99/01642 His Lys Tyr Ser Gly Arg Glu Gly Asp Lys His Thr Leu Ser Lys Lys Glu Leu Lys Glu Leu Ile Gln Lys Glu Leu Thr Ile Gly Ser Lys Leu Gln Asp Ala Glu Ile Ala Arg Leu Met Glu Asp Leu Asp Arg Asn Lys Asp Gln Glu Val Asn Phe Gln Glu Tyr Val Thr Phe Leu Gly Ala Leu Ala Leu Ile Tyr Asn Glu Ala Leu Lys Gly <210> 201 <211> 120 <212> PRT
<213> Homo sapien <400> 201 Met Glu Thr Pro Ser Gln Arg Arg Ala-Thr Arg Ser Gly Ala Gln Ala Ser Ser Thr Pro Leu Ser Pro Thr Arg Ile Thr Arg Leu Gln Glu Lys Glu Asp Leu Gln Glu Leu Asn Asp Arg Leu Ala Val Tyr Ile Asp Arg Val Arg Ser Leu Glu Thr Glu Asn Ala Gly Leu Arg Leu Arg Ile Thr Glu Ser Glu Glu Val Val Ser Arg Glu Val Ser Gly Ile Lys Ala Ala Tyr Glu Ala Glu Leu Gly Asp Ala Arg Lys Thr Leu Asp Ser Val Ala Lys Glu Arg Ala Arg Leu Gln Leu Glu Leu Ser Lys Val Arg Glu Glu Phe Lys Glu Leu Lys Ala Arg Asn <210> 202 <211> 177 <212> PRT
<213> Homo sapien <400> 202 Met Ala Ala Gly Val Glu Ala Ala Ala Glu Val Ala Ala Thr Glu Ile Lys Met Glu Glu Glu Ser Gly Ala Pro Gly Val Pro Ser Gly Asn Gly Ala Pro Gly Pro Lys Gly Glu Gly Glu Arg Pro Ala Gln Asn Glu Lys Arg Lys Glu Lys Asn Ile Lys Arg Gly Gly Asn Arg Phe Glu Pro Tyr Ala Asn Pro Thr Lys Arg Tyr Arg Ala Phe Ile Thr Asn Ile Pro Phe Asp Val Lys Trp Gln Ser Leu Lys Asp Leu Val Lys Glu Lys Val Gly Glu Val Thr Tyr Val Glu Leu Leu Met Asp Ala Glu Gly Lys Ser Arg Gly Cys Ala Val Val Glu Phe Lys Met Glu Glu Ser Met Lys Lys Ala Ala Glu Val Leu Asn Lys His Ser Leu Ser Gly Arg Pro Leu Lys Val Lys Glu Asp Pro Asp Gly Glu His Ala Arg Arg Ala Met Gln Lys Ala Gly Arg Leu Gly Ser Thr Val Phe Val Ala Asn Leu Asp Tyr Lys Val Gly <210> 203 <211> 164 <2I2> PRT
<213> Homo sapien <400> 203 Met Arg Leu Ala Val Gly Ala Leu Leu Val Cys Ala Val Leu Gly Leu Cys Leu Ala Val Pro Asp Lys Thr Val Arg Trp Cys Ala Val Ser Glu His Glu Ala Thr Lys Cys Gln Ser Phe Arg Asp His Met Lys Ser Val Ile Pro 5er Asp Gly Pro Ser Val Ala Cys Val Lys Lys Ala Ser Tyr Leu Asp Cys Ile Arg Ala Ile Ala Ala Asn Glu Ala Asp Ala Val Thr Leu Asp Ala Gly Leu Val Tyr Asp Ala Tyr Leu Ala Pro Asn Asn Leu Lys Pro Val Val Ala Glu Phe Tyr Gly Ser Lys Glu Asp Pro Gln Thr Phe Tyr Tyr Ala Val Ala Val Val Lys Lys Asp Ser Gly Phe Gln Met Asn Gln Leu Arg Gly Lys Lys Ser Cys His Thr Gly Leu Gly Arg Ser Ala Gly Trp Asn Ile Pro Ile Gly Leu Leu Tyr Cys Asp Leu Pro Glu Pro Arg Lys Pro <210> 204 <211> 241 <212> PRT
<213> Homo sapien <400> 204 Met Ser Gly Glu Ser Ala Arg Ser Leu Gly Lys Gly Ser Ala Pro Pro Gly Pro Val Pro Glu Gly Ser Ile Arg Ile Tyr Ser Met Arg Phe Cys Pro Phe Ala Glu Arg Thr Arg Leu Val Leu Lys Ala Lys Gly Ile Arg His Glu Val Ile Asn Ile Asn Leu Lys Asn Lys Pro Glu Trp Phe Phe Lys Lys Asn Pro Phe Gly Leu Val Pro Val Leu Glu Asn Ser Gln GIy Gln Leu Ile Tyr Glu Ser Ala Ile Thr Cys Glu Tyr Leu Asp Glu Ala Tyr Pro Gly Lys Lys Leu Leu Pro Asp Asp Pro Tyr Glu Lys Ala Cys Gln Lys Met Ile Leu Glu Leu Phe Ser Lys Val Pro Ser Leu Val Gly Ser Phe Ile Arg Ser Gln Asn Lys Glu Asp Tyr Asp Gly Leu Lys Glu Glu Phe Arg Lys Glu Phe Thr Lys Leu Glu Glu Val Leu Thr Asn Lys Lys Thr Thr Phe Phe Gly Gly Asn Ser Ile Ser Met Ile Asp Tyr Leu Ile Trp Pro Trp Phe Glu Arg Leu Glu Ala Met Lys Leu Asn Glu Cys Val Asp His Thr Pro Lys Leu Lys Leu Trp Met Ala Ala Met Lys Glu Asp Pro Thr Val Ser Ala Leu Leu Thr Ser Glu Lys Asp Trp Gln Gly 210 215 __ 220 Phe Leu Glu Leu Tyr Leu Gln Asn Ser Pro Glu Ala Cys Asp Tyr Gly Leu <210> 205 <211> 160 <212> PRT
<213> Homo sapien <400> 205 Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe Val Lys Thr Leu <210> 206 <211> I97 <212> PRT
<213> Homo sapien <400> 206 Thr Ser Pro Ser Glu Ala Cys Ala Pro Leu Leu Ile Ser Leu Ser Thr Leu Ile Tyr Asn Gly Ala Leu Pro Cys Gln Cys Asn Pro Gln Gly Ser Leu Ser Ser Glu Cys Asn Pro His Gly Gly Gln Cys Leu Cys Lys Pro Gly Val Val Gly Arg Arg Cys Asp Leu Cys Ala Pro Gly Tyr Tyr Gly Phe Gly Pro Thr Gly Cys Gln Gly Ala Cys Leu Gly Cys Arg Asp His Thr Gly Gly Glu His Cys Glu Arg Cys Ile Ala Gly Phe His Gly Asp Pro Arg Leu Pro Tyr Gly Gly Gln Cys Arg Pro Cys Pro Cys Pro Glu Gly Pro Gly Ser Gln Arg His Phe Ala Thr Ser Cys His Gln Asp Glu Tyr Ser Gln Gln Ile Val Cys His Cy_s_ Arg Ala Gly Tyr Thr Gly Leu Arg Cys Glu Ala Cys Ala Pro Gly His Phe Gly Asp Pro Ser Arg Pro Gly Gly Arg Cys Gln Leu Cys Glu Cys Ser Gly Asn Ile Asp Pro Met Asp Pro Asp Ala Cys Asp Pro His Thr Gly Gln Cys Leu Arg Cys Leu His His Thr Glu GIy <210> 207 <211> 175 <212> PRT
<213> Homo sapien <400> 207 Ile Ile Arg Gln Gln Gly Leu Ala Ser Tyr Asp Tyr Val Arg Arg Arg Leu Thr Ala Glu Asp Leu Phe Glu Ala Arg Ile Ile Ser Leu Glu Thr Tyr Asn Leu Leu Arg Glu Gly Thr Arg Ser Leu Arg Glu Ala Leu Glu Ala Glu Ser Ala Trp Cys Tyr Leu Tyr Gly Thr Gly Ser Val Ala Gly Val Tyr Leu Pro Gly Ser Arg Gln Thr Leu Ser Ile Tyr Gln Ala Leu Lys Lys Gly Leu Leu Ser Ala Glu Val Ala Arg Leu Leu Leu Glu Ala Gln Ala Ala Thr Gly Phe Leu Leu Asp Pro Val Lys Gly Glu Arg Leu Thr Val Asp Glu Ala Val Arg Lys Gly Leu Val Gly Pro Glu Leu His Asp Arg Leu Leu Ser Ala Glu Arg Ala Val Thr Gly Tyr Arg Asp Pro Tyr Thr Glu Gln Thr Ile Ser Leu Phe Gln Ala Met Lys Lys Glu Leu Ile Pro Thr Glu Glu Ala Leu Arg Leu Trp Met Pro Ser Trp Pro <210> 208 <211> 177 <212> PRT
<213> Homo sapien <400> 208 Met Ala Ala Gly Val Glu Ala Ala Ala Glu Val Ala Ala Thr Glu Ile Lys Met Glu Glu Glu Ser Gly Ala Pro Gly Val Pro Ser Gly Asn Gly Ala Pro Gly Pro Lys Gly Glu Gly Glu Arg Pro Ala Gln Asn Glu Lys Arg Lys Glu Lys Asn Ile Lys Arg Gly Gly Asn Arg Phe Glu Pro Tyr Ala Asn Pro Thr Lys Arg Tyr Arg Ala Phe Ile Thr Asn Ile Pro Phe Asp Val Lys Trp Gln Ser Leu Lys Asp Leu Val Lys Glu Lys Val Gly Glu Val Thr Tyr Val Glu Leu Leu Met Asp Ala Glu Gly Lys Ser Arg Gly Cys Ala Val Val Glu Phe Lys Met Glu Glu Ser Met Lys Lys Ala Ala Glu Val Leu Asn Lys His Ser Leu SEr Gly Arg Pro Leu Lys Val Lys Glu Asp Pro Asp Gly Glu His Ala Arg Arg Ala Met Gln Lys Val Met Ala Thr Thr Gly Gly Met Gly Met Gly Pro Gly Gly Pro Gly Met Ile <210> 209 <211> 196 <212> PRT
<213> Homo sapien <400> 209 Asp Leu Gln Asp Met Phe Ile Val His Thr Ile Glu Glu Ile Glu Gly Leu Ile Ser Ala His Asp Gln Phe Lys Ser Thr Leu Pro Asp Ala Asp ~Arg Glu Arg Glu Ala Ile Leu Ala Ile His Lys Glu Ala Gln Arg Ile Ala Glu Ser Asn His Ile Lys Leu Ser Gly Ser Asn Pro Tyr Thr Thr Val Thr Pro Gln Ile Ile Asn Ser Lys Trp Glu Lys Val Gln Gln Leu Val Pro Lys Arg Asp His Ala Leu Leu Glu Glu Gln Ser Lys Gln Gln Ser Asn Glu His Leu Arg Arg Gln Phe Ala Ser Gln Ala Asn Val Val Gly Pro Trp Ile Gln Thr Lys Met Glu Glu Ile Gly Arg Ile Ser Ile Glu Met Asn Gly Thr Leu Glu Asp Gln Leu Ser His Leu Lys Gln Tyr Glu Arg Ser Ile Val Asp Tyr Lys Pro Asn Leu Asp Leu Leu GIu Gln Gln His Gln Leu Ile Gln Glu Ala Leu Ile Phe Asp Asn Lys His Thr Asn Tyr Thr Met Glu His Ile Arg Val Gly Trp Glu Gln Leu Leu Thr Thr Ile Ala Arg <210> 210 <211> 156 <212> PRT
<213> Homo sapien <400> 210 Lys Leu Thr Ile Glu Ser Thr Pro Phe Asn Val Ala Glu Gly Lys Glu Val Leu Leu Leu Ala His Asn Leu Pro Gln Asn Arg Ile Gly Tyr Ser Trp Tyr Lys Gly Glu Arg Val Asp Gly Asn Ser Leu Ile Val Gly Tyr Val Ile Gly Thr Gln Gln Ala Thr Pro Gly Pro Ala Tyr Ser Gly Arg Glu Thr Ile Tyr Pro Asn Ala Ser Leu Leu Ile Gln Asn Val Thr Gln Asn Asp Thr Gly Phe Tyr Thr Leu Gln Val Ile Lys Ser Asp Leu Val Asn Glu Glu Ala Thr Gly Gln Phe His Val Tyr Pro Glu Leu Pro Lys Pro Ser Ile Ser Ser Asn Asn Ser Asn Pro Val Glu Asp Lys Asp Ala Val Ala Phe Thr Cys Glu Pro Glu Val Gln Asn Thr Thr Tyr Leu Trp Trp Val Asn Gly Gln Ser Leu Pro Val Ser Pro Lys <210> 211 <211> 92 <212> PRT
<213> Homo sapien <400> 211 Met Glu Ser Pro Ser Ala Pro Pro His Arg Trp Cys Ile Pro Trp Gln Arg Leu Leu Leu Thr Ala Ser Leu Leu Thr Phe Trp Asn Pro Pro Thr Thr Ala Lys Leu Thr Ile Glu Ser Thr Pro Phe Asn Val Ala Glu Gly Lys Glu Val Leu Leu Leu Val His Asn Leu Pro Gln His Leu Phe Gly Tyr Ser Trp Tyr Lys Gly Glu Arg Val Asp Gly Asn Arg Gln Ile Ile Gly Tyr Val Ile Gly Thr Gln Gln Ala Thr Pro Gly <210> 212 <211> 142 <212> PRT
<2i3> Homo sapien <400> 212 Glu Lys Gln Lys Asn Lys Glu Phe Ser Gln Thr Leu Glu Asn Glu Lys Asn Thr Leu Leu Ser Gln Ile Ser Thr Lys Asp Gly Glu Leu Lys Met Leu Gln Glu Glu Val Thr Lys Met Asn Leu Leu Asn Gln Gln Ile Gln Glu Glu Leu Ser Arg Val Thr Lys Leu Lys Glu Thr Ala Glu Glu Glu Lys Asp Asp Leu Glu Glu Arg Leu Met Asn Gln Leu Ala Glu Leu Asn Gly Ser Ile Gly Asn Tyr Cys Gln Asp Val Thr Asp Ala Gln Ile Lys Asn Glu Leu Leu Glu Ser Glu Met Lys Asn Leu Lys Lys Cys Val Ser Glu Leu Glu Glu Glu Lys Gln Gln Leu Val Lys Glu Lys Thr Lys Val Glu Ser Glu Ile Arg Lys Glu Tyr Leu Glu Lys Ile Gln Gly <210> 213 <211> 142 <212> PRT
<213> Homo sapien <400> 213 Gly Gly Tyr Gly Gly Gly Tyr Gly Gly Val Leu Thr Ala Ser Asp Gly Leu Leu Ala Gly Asn Glu Lys Leu Thr Met Gln Asn Leu Asn Asp Arg Leu Ala Ser Tyr Leu Asp Lys Val Arg Ala Leu Glu Ala Ala Asn Gly Glu Leu Glu Val Lys Ile Arg Asp Trp Tyr Gln Lys Gln Gly Pro Gly Pro Ser Arg Asp Tyr Ser His Tyr Tyr Thr Thr Ile Gln Asp Leu Arg Asp Lys Ile Leu Gly Ala Thr Ile Glu Asn Ser Arg Ile Val Leu Gln Ile Asp Asn Ala Arg Leu Ala Ala Asp Asp Phe Arg Thr Lys Phe Glu Thr Glu Gln Ala Leu Arg Met Ser Val Glu Ala Asp Ile Asn Gly Leu Arg Arg Val Leu Asp Glu Leu Thr Leu Ala Arg Thr Asp Leu <210> 214 <211> 129 <212> PRT

<213> Homo sapien <400> 214 Val Met Arg Val Asp Phe Asn Val Pro Met Lys Asn Asn Gln Ile Thr Asn Asn Gln Arg Ile Lys Ala Ala Val Pro Ser Ile Lys Phe Cys Leu Asp Asn Gly Ala Lys Ser Val Val Leu Met Ser His Leu Gly Arg Pro Asp Gly Val Pro Met Pro Asp Lys Tyr Ser Leu Glu Pro Val Ala Val Glu Leu Arg Ser Leu Leu Gly Lys Asp Val Leu Phe Leu Lys Asp Cys Val Gly Pro Glu Val Glu Lys Ala Cars Ala Asn Pro Ala Ala Gly Ser Val Ile Leu Leu Glu Asn Leu Arg Phe His Val Glu Glu Glu Gly Lys Gly Lys Asp Ala Ser Gly Asn Lys Val_Lys Ala Glu Pro Ala Lys Ile Glu <210> 215 <211> 148 <212> PRT
<213> Homo sapien <400> 215 Met Ala Thr Leu Lys Glu Lys Leu Iie Ala Pro Val Ala Glu Glu Glu Ala Thr Val Pro Asn Asn Lys Ile Thr Val Val Gly Val Gly Gln Val Gly Met Ala Cys Ala Ile Ser Ile Leu Gly Lys Ser Leu Ala Asp Glu Leu Ala Leu Val Asp Val Leu Glu Asp Lys Leu Lys Gly Glu Met Met Asp Leu Gln His Gly Ser Leu Phe Leu Gln Thr Pro Lys IIe Val Ala Asp Lys Asp Tyr Ser Val Thr Ala Asn Ser Lys Ile Val Val Val Thr Ala Gly Val Arg Gln Gln Glu Gly Glu Ser Arg Leu Asn Leu Val Gln Arg Asn Val Asn Val Phe Lys Phe Ile Ile Pro Gln Ile Val Lys Tyr Ser Pro Asp Cys Ile Ile Ile Val Val Ser Asn Pro Val Asp Ile Leu Thr Tyr Val Thr <210> 216 <211> 527 <212> PRT
<213> Homo sapien <400> 216 Gln Arg Ala Pro Gly Ile Glu Glu Lys Ala Ala Glu Asn Gly Ala Leu Gly Ser Pro Glu Arg Glu Glu Lys Val Leu Glu Asn Gly Glu Leu Thr Pro Pro Arg Arg Glu Glu Lys Ala Leu Glu Asn Gly Glu Leu Arg Ser Pro Glu Ala Gly Glu Lys Val Leu Val Asn Gly Gly Leu Thr Pro Pro 50 . 55 60 Lys Ser Glu Asp Lys Val Ser Glu Asn Gly Gly Leu Arg Phe Pro Arg Asn Thr Glu Arg Pro Pro Glu Thr Gly Pro Trp Arg Ala Pro Gly Pro Trp Glu Lys Thr Pro Glu Ser Trp GIy Pro Ala Pro Thr Ile Gly Glu Pro Ala Pro Glu Thr Ser Leu Glu Arg Ala Pro Ala Pro Ser Ala Val Val Ser Ser Arg Asn Gly Gly Glu Thr Ala Pro Gly Pro Leu Gly Pro 130 135 _ 140 Ala Pro Lys Asn Gly Thr Leu Glu Pro Gly Thr Glu Arg Arg Ala Pro Glu Thr Gly Gly Ala Pro Arg Ala Pro Gly Ala Gly Arg Leu Asp Leu Gly Ser Gly Gly Arg Ala Pro Val Gly Thr Gly Thr Ala Pro Gly Gly Gly Pro Gly Ser Gly Val Asp Ala Lys Ala Gly Trp Val Asp Asn Thr Arg Pro Gln Pro Pro Pro Pro Pro Leu Pro Pro Pro Pro Glu Ala Gln Pro Arg Arg Leu Glu Pro Ala Pro Pro Arg Ala Arg Pro Glu Val Ala Pro Glu Gly Glu Pro Gly Ala Pro Asp Ser Arg Ala Gly Gly Asp Thr Ala Leu Ser Gly Asp Gly Asp Pro Pro Lys Pro Glu Arg Lys Gly Pro Glu Met Pro Arg Leu Phe Leu Asp Leu Gly Pro Pro Gln Gly Asn Ser Glu Gln Ile Lys Ala Arg Leu Ser Arg Leu Ser Leu Ala Leu Pro Pro Leu Thr Leu Thr Pro Phe Pro Gly Pro Gly Pro Arg Arg Pro Pro Trp Glu Gly Ala Asp Ala Gly Ala Ala Gly Gly Glu Ala Gly Gly Ala Gly Ala Pro Gly Pro Ala Glu Glu Asp Gly Glu Asp Glu Asp Glu Asp Glu Glu Glu Asp Glu Glu Ala Ala Ala Pro Gly Ala Ala Ala Gly Pro Arg Gly Pro Gly Arg Ala Arg Ala Ala Pro Val Pro Val Val Val Ser Ser Ala Asp Ala Asp Ala Ala Arg Pro Leu Arg Gly Leu Leu Lys Ser Pro Arg Gly Ala Asp Glu Pro Glu Asp Ser Glu Leu Glu Arg Lys Arg Lys Met Val Ser Phe His Gly Asp Val Thr Val Tyr Leu Phe Asp Gln Glu Thr Pro Thr Asn Glu Leu Ser Val Gln Ala Pro Pro Glu Gly Asp Thr Asp Pro Ser Thr Pro Pro Ala Pro Pro Thr Pro Pro His Pro Ala Thr Pro Gly Asp Gly Phe Pro Ser Asn Asp Ser Gly Phe Gly Gly Ser Phe Glu Trp Ala Glu Asp Phe Pro Leu Leu Pro Pro Pro Gly Pro Pro Leu Cys Phe Ser Arg Phe Ser Val Ser Pro Ala Leu Glu Thr Pro Gly Pro Pro Ala Arg Ala Pro Asp Ala Arg Pro Ala Gly Pro Val Glu Asn

Claims (60)

CLAIMS:

1. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) sequences provided in SEQ ID NO: 1-11, 19, 22-25, 27-31, 51, 53, 55, 63, 70, 72, 79, 80, 86, 87, 89, 90, 102-107, 109, 139, 143-149, 151-154 and 156-158;
(b) the complements of sequences provided in SEQ ID NO: 1-11, 19, 22-25, 27-31, 51, 53, 55, 63, 70, 72, 79, 80, 86, 87, 89, 90, 102-107, 109, 139, 143-149, 151-154 and 156-158; and (c) variants of the sequences of (a) and (b).

2. An isolated polypeptide comprising an immunogenic portion of a lung tumor protein or a variant thereof, wherein said protein comprises an amino acid sequence encoded by a polynucleotide of claim 1.

3. The isolated polypeptide of claim 2 wherein the polypeptide comprises a sequence selected from the group of sequences recited in SEQ ID NO: 182, 184-193 and 216.

4. A polynucleotide comprising a nucleotide sequence encoding the polypeptide of claim 3.

5. An expression vector comprising the polynucleotide of claims 1 or 4.

6. A host cell transformed with the expression vector of claim 5.

7. The host cell of claim 6 wherein the host cell is selected from the group consisting of E. coli, yeast and mammalian cell lines.

8. A pharmaceutical composition comprising the polypeptide of claim 2 and a physiologically acceptable carrier.

9. A vaccine comprising the polypeptide of claim 2 and an immune response enhancer.

10. The vaccine of claim 9 wherein the immune response enhancer is an adjuvant.

11. A vaccine comprising the polynucleotide of claims 1 or 4 and an immune response enhancer.

12. The vaccine of claim 11 wherein the immune response enhancer is an adjuvant.

13. A pharmaceutical composition for the treatment of lung cancer comprising a polypeptide and a physiologically acceptable carrier, the polypeptide comprising an immunogenic portion of a lung protein or of a variant thereof, wherein said protein comprises an amino acid sequence encoded by a polynucleotide comprising a sequence selected from the group consisting of:
(a) sequences recited in SEQ ID NO: 12-18, 20, 21, 26, 49, 50, 52, 54, 64, 66, 68, 69, 71, 78, 84, 85, 88, 91, 92, 116-120, 126-138, 140-142, 150, 155 and 159-181;
(b) sequences complementary to the sequences of SEQ ID NO: 12-18, 20, 21, 26, 49, 50, 52, 54, 64, 66, 68, 69, 71, 78, 84, 85, 88, 91, 92, 116-120, 126-138, 140-142, 150, 155 and 159-181; and (c) variants of the sequences of (a) and (b).

14. A vaccine for the treatment of lung cancer comprising a polypeptide and an immune response enhancer, said polypeptide comprising an immunogenic portion of a lung protein or of a variant thereof, wherein said protein comprises an amino acid sequence encoded by a polynucleotide comprising a sequence selected from the group consisting of (a) sequences recited in SEQ ID NO: 12-18, 20, 21, 26, 49, 50, 52, S4, 64, 66, 68, 69, 71, 78, 84, 85, 88, 91, 92, 116-120, 126-138, 140-142, 150, 155 and 159-181;

(b) sequences complementary to the sequences of SEQ ID NO: 12-18, 20, 21, 26, 49, 50, 52, 54, 64, 66, 68, 69, 71, 78, 84, 85, 88, 91, 92, 116-120, 126-138, 140-142, 150, 155 and 159-181; and (c) variants of the sequences of (a) and (b).

15. A vaccine for the treatment of lung cancer comprising a polynucleotide and an immune response enhancer, the polynucleotide comprising a sequence selected from the group consisting of:
(a) sequences recited-in SEQ ID NO: 12-18, 20, 21, 26, 49, 50, 52, 54, 64, 66, 68, 69, 71, 78, 84, 85, 88, 91, 92, 116-120, 126-138, 140-142, 150, 155 and 159-181;
(b) sequences complementary to the sequences of SEQ ID NO: 12-18, 20, 21, 26, 49, 50, 52, 54, 64, 66, 68, 69, 71, 78, 84, 85, 88, 91, 92, 116-120, 126-138, 140-142, 150, 155 and 159-181; and (c) variants of the sequences of (a) and (b).

16. A method for inhibiting the development of lung cancer in a patient, comprising administering to the patient an effective amount of the pharmaceutical composition of claims 8 or 13.

17. A method for inhibiting the development of lung cancer in a patient, comprising administering to the patient an effective amount of the vaccine of any one of claims 9, 11, 14 or 15.

18. A fusion protein comprising at least one polypeptide according to claim 2.

19. A fusion protein comprising at least two polypeptides according to claim 2.

20. A fusion protein comprising a polypeptide according to claim 2 and a known lung tumor antigen.

21. A pharmaceutical composition comprising a fusion protein according to any one of claims 18-20 and a physiologically acceptable carrier.

22. A vaccine comprising a fusion protein according to any one of claims 18-20 and an immune response enhancer.

23. The vaccine of claim 22 wherein the immune response enhancer is an adjuvant.

24. A method for inhibiting the development of lung cancer in a patient, comprising administering to the patient an effective amount of the pharmaceutical composition of claim 21.

25. A method for inhibiting the development of lung cancer in a patient, comprising administering to the patient an effective amount of the vaccine of claim 22.

26. A method for inhibiting the development of lung cancer in a patient, comprising administering to the patient a polynucleotide under conditions such that the polynucleotide enters a cell of the patient and is expressed therein, the polynucleotide having a sequence selected from the group consisting of:
(a) a sequence provided in SEQ ID NO: 102;
(b) sequences complementary to a sequence of SEQ ID NO: 102; and (c) variants of the sequence of SEQ ID NO: 102.

27. A method for detecting lung cancer in a patient, comprising:
(a) contacting a biological sample obtained from the patient with a binding agent which is capable of binding to a polypeptide, the polypeptide comprising an immunogenic portion of a lung tumor protein or a variant thereof, wherein said protein comprises an amino acid sequence encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of sequences provided in SEQ ID
NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181, the complements of said sequences and variants thereof; and (b) detecting in the sample a polypeptide that binds to the binding agent, thereby detecting lung cancer in the patient.

28. The method of claim 27 wherein the binding agent is a monoclonal antibody.

29. The method of claim 28 wherein the binding agent is a polyclonal antibody.

30. A method for monitoring the progression of lung cancer in a patient, comprising:
(a) contacting a biological sample obtained from the patient with a binding agent that is capable of binding to a polypeptide, said polypeptide comprising an immunogenic portion of a lung tumor protein or a variant thereof, wherein said protein comprises an amino acid sequence encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of sequences recited in SEQ ID NO:
1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181, the complements of said sequences and variants thereof;
(b) determining in the sample an amount of a polypeptide that binds to the binding agent;
(c) repeating steps (a) and (b); and (d) comparing the amount of polypeptide detected in steps (b) and (c) to monitor the progression of lung cancer in the patient.

31. A monoclonal antibody that binds to a polypeptide comprising an immunogenic portion of a lung tumor protein or a variant thereof,, wherein said protein comprises an amino acid sequence encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of:

(a) sequences recited in SEQ ID NO: 1-11, 19, 22-25, 27-31, 51, 53, 55, 63, 70, 72, 79, 80, 86, 87, 89, 90, 102-107, 109, 139, 143-149, 151-154 and 156-158;
(b) the complements of nucleotide sequences recited in SEQ ID NO: 1-11, 19, 22-25, 27-31, 51, 53, 55, 63, 70, 72, 79, 80, 86, 87, 89, 90, 102-107, 109, 139, 143-149, 151-154 and 156-158; and (c) variants of the sequences of (a) and (b).

32. A method for inhibiting the development of lung cancer in a patient, comprising administering to the patient a therapeutically effective amount of a monoclonal antibody according to claim 31.

33. The method of claim 32 wherein the monoclonal antibody is conjugated to a therapeutic agent.

34. A method for detecting lung cancer in a patient comprising:
(a) obtaining a biological sample from the patient;
(b) contacting the sample with at least two oligonucleotide primers in a polymerase chain reaction, wherein at least one of the oligonucleotides is specific for a polynucleotide encoding a polypeptide comprising an immunogenic portion of a lung tumor protein or a variant thereof, said protein comprising an amino acid sequence encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of sequences recited in SEQ ID NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181, the complements of said sequences and variants thereof;
and (c) detecting in the sample a DNA sequence that amplifies in the presence of the oligonucleotide primers, thereby detecting lung cancer.

35. The method of claim 34, wherein at least one of the oligonucleotide primers comprises at least about 10 contiguous nucleotides of a polynucleotide comprising a sequence selected from SEQ ID NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181.

36. A diagnostic kit comprising:
(a) one or more monoclonal antibodies according to claim 31; and (b) a detection reagent.

37. The kit of claim 36 wherein the monoclonal antibody is immobilized on a solid support.

38. The kit of claim 37 wherein the solid support comprises nitrocellulose, latex or a plastic material.

39. The kit of claim 36 wherein the detection reagent comprises a reporter group conjugated to a binding agent.

40. The kit of claim 39 wherein the binding agent is selected from the group consisting of anti-immunoglobulins, Protein G, Protein A and lectins.

41. The kit of claim 39 wherein the reporter group is selected from the group consisting of radioisotopes, fluorescent groups, luminescent groups, enzymes, biotin and dye particles.

42. A diagnostic kit comprising at least two oligonucleotide primers, at least one of the oligonucleotide primers being specific for a polynucleotide encoding a polypeptide comprising an immunogenic portion of a lung tumor protein or a variant thereof, said protein comprising an amino acid sequence encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of sequences recited in SEQ ID NO:
1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181, the complements of said sequences and variants thereof.

43. The diagnostic kit of claim 42 wherein at least one of the oligonucleotide primers comprises at least about 10 contiguous nucleotides of a polynucleotide having a nucleotide sequence selected from the group consisting of sequences provided in SEQ ID NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181, the complements of said sequences and variants thereof.

44. A method for detecting lung cancer in a patient, comprising:
(a) obtaining a biological sample from the patient;
(b) contacting the biological sample with an oligonucleotide probe specific for a polynucleotide encoding a polypeptide comprising an immunogenic portion of a lung tumor protein or a variant thereof, said protein comprising an amino acid sequence encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of sequences recited in SEQ ID NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181, the complements of said nucleotide sequences and variants thereof; and (c) detecting in the sample a DNA sequence that hybridizes to the oligonucleotide probe, thereby detecting lung cancer in the patient.

45. The method of claim 44 wherein the oligonucleotide probe comprises at least about 15 contiguous nucleotides of a polynucleotide having a nucleotide sequence selected from the group consisting of sequences recited in SEQ ID NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181, the complements of said nucleotide sequences and variants thereof.

46. A diagnostic kit comprising an oligonucleotide probe specific for a polynucleotide encoding a polypeptide comprising an immunogenic portion of a lung tumor protein or a variant thereof, said protein comprising an amino acid sequence encoded by a polynucleotide comprising a nucleotide sequence selected from the group consisting of sequences recited in SEQ ID NO: 1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92, 102-110, 116-120 and 126-181, the complements of said sequences and variants thereof.

47. The diagnostic kit of claim 46, wherein the oligonucleotide probe comprises at least about 15 contiguous nucleotides of a polynucleotide having a nucleotide sequence selected from the group consisting of sequences recited in SEQ ID NO:
1-31, 49-55, 63, 64, 66, 68-72, 78-80, 84-92 and 102-110, the complements of said sequences and variants thereof.

48. A method for treating lung cancer in a patient, comprising the steps of (a) obtaining peripheral blood cells from the patient;
(b) incubating the cells in the presence of at least one polypeptide of claim 2, such that T cells proliferate; and (c) administering the proliferated T cells to the patient.

49. A method for treating lung cancer in a patient. comprising the steps of:
(a) obtaining peripheral blood cells from the patient;
(b) incubating the cells in the presence of at least one polynucleotide of claim 1, such that T cells proliferate; and (c) administering to the patient the proliferated T cells.

50. The method of any one of claims 48 and 49 wherein the step of incubating the T cells is repeated one or more times.

51. The method of any one of claims 48 and 49 wherein step (a) further comprises separating T cells from the peripheral blood cells, and the cells incubated in step (b) are the T cells.

52. The method of any one of claims 48 and 49 wherein step (a) further comprises separating CD4+ cells or CD8+ cells from the peripheral blood cells, and the cells proliferated in step (b) are CD4+ or CD8+ T cells.

53. The method of any one of claims 48 and 49 wherein step (b) further comprises cloning one or more T cells that proliferated in the presence of the polypeptide.

54. A composition for the treatment of lung cancer in a patient, comprising T cells proliferated in the presence of a polypeptide of claim 2. in combination with a pharmaceutically acceptable carrier.

55. A composition for the treatment of lung cancer in a patient, comprising T cells proliferated in the presence of a polynucleotide of claim l, in combination with a pharmaceutically acceptable carrier.

56. A method for treating lung cancer in a patient, comprising the steps of (a) incubating antigen presenting cells in the presence of at least one polypeptide of claim 2; and (b) administering to the patient the incubated antigen presenting cells.

57. A method for treating lung cancer in a patient, comprising the steps of (a) incubating antigen presenting cells in the presence of at least one polynucleotide of claim 1; and (b) administering to the patient the incubated antigen presenting cells.

58. The method of claims 54 or 55 wherein the antigen presenting cells are selected from the group consisting of dendritic cells and macrophage cells.

59. A composition for the treatment of lung cancer in a patient, comprising antigen presenting cells incubated in the presence of a polypeptide of claim 2, in combination with a pharmaceutically acceptable carrier.

60. A composition for the treatment of lung cancer in a patient, comprising antigen presenting cells incubated in the presence of a polynucleotide of claim 1, in combination with a pharmaceutically acceptable carrier.