KR20220077916A - 세포를 형질세포양 수지상 세포 또는 인터페론 유형 i-생산 세포로 재프로그래밍하기 위한 조성물, 방법 및 이의 용도 - Google Patents
세포를 형질세포양 수지상 세포 또는 인터페론 유형 i-생산 세포로 재프로그래밍하기 위한 조성물, 방법 및 이의 용도 Download PDFInfo
- Publication number
- KR20220077916A KR20220077916A KR1020227013673A KR20227013673A KR20220077916A KR 20220077916 A KR20220077916 A KR 20220077916A KR 1020227013673 A KR1020227013673 A KR 1020227013673A KR 20227013673 A KR20227013673 A KR 20227013673A KR 20220077916 A KR20220077916 A KR 20220077916A
- Authority
- KR
- South Korea
- Prior art keywords
- seq
- cancer
- irf8
- spib
- cells
- Prior art date
Links
- 210000004027 cell Anatomy 0.000 title claims abstract description 328
- 239000000203 mixture Substances 0.000 title claims abstract description 153
- 238000000034 method Methods 0.000 title claims abstract description 121
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 title claims abstract description 112
- 102000002227 Interferon Type I Human genes 0.000 title claims abstract description 59
- 108010014726 Interferon Type I Proteins 0.000 title claims abstract description 59
- 230000008672 reprogramming Effects 0.000 title claims abstract description 43
- 239000013598 vector Substances 0.000 claims abstract description 129
- 102000040945 Transcription factor Human genes 0.000 claims abstract description 113
- 108091023040 Transcription factor Proteins 0.000 claims abstract description 113
- 210000001778 pluripotent stem cell Anatomy 0.000 claims abstract description 38
- 230000007416 antiviral immune response Effects 0.000 claims abstract description 6
- 102100038069 Interferon regulatory factor 8 Human genes 0.000 claims description 225
- 206010028980 Neoplasm Diseases 0.000 claims description 73
- 150000007523 nucleic acids Chemical group 0.000 claims description 69
- 230000001939 inductive effect Effects 0.000 claims description 68
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 60
- 241000282414 Homo sapiens Species 0.000 claims description 56
- 102100035051 TSC22 domain family protein 1 Human genes 0.000 claims description 55
- 201000011510 cancer Diseases 0.000 claims description 55
- 102100021123 Transcription factor 12 Human genes 0.000 claims description 49
- 102000039446 nucleic acids Human genes 0.000 claims description 49
- 108020004707 nucleic acids Proteins 0.000 claims description 49
- 101000825182 Homo sapiens Transcription factor Spi-B Proteins 0.000 claims description 47
- 210000004443 dendritic cell Anatomy 0.000 claims description 47
- 101001032345 Homo sapiens Interferon regulatory factor 8 Proteins 0.000 claims description 45
- 101001132819 Homo sapiens Protein CBFA2T3 Proteins 0.000 claims description 42
- 101000903703 Homo sapiens B-cell lymphoma/leukemia 11A Proteins 0.000 claims description 41
- 102100023489 Transcription factor 4 Human genes 0.000 claims description 41
- 102100022976 B-cell lymphoma/leukemia 11A Human genes 0.000 claims description 39
- 102100033812 Protein CBFA2T3 Human genes 0.000 claims description 39
- 241000700605 Viruses Species 0.000 claims description 39
- 101000745624 Homo sapiens Cyclic AMP-responsive element-binding protein 3-like protein 2 Proteins 0.000 claims description 38
- 101000792952 Homo sapiens AT-rich interactive domain-containing protein 5A Proteins 0.000 claims description 37
- 101000599038 Homo sapiens DNA-binding protein Ikaros Proteins 0.000 claims description 37
- 102100039299 Cyclic AMP-responsive element-binding protein 3-like protein 2 Human genes 0.000 claims description 35
- 102100030834 AT-rich interactive domain-containing protein 5A Human genes 0.000 claims description 34
- 102100037799 DNA-binding protein Ikaros Human genes 0.000 claims description 34
- 125000003729 nucleotide group Chemical group 0.000 claims description 30
- 230000003612 virological effect Effects 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
- 238000002560 therapeutic procedure Methods 0.000 claims description 27
- 208000015181 infectious disease Diseases 0.000 claims description 26
- 108020004999 messenger RNA Proteins 0.000 claims description 26
- 239000002773 nucleotide Substances 0.000 claims description 26
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 25
- 102000004127 Cytokines Human genes 0.000 claims description 24
- 108090000695 Cytokines Proteins 0.000 claims description 24
- 210000000130 stem cell Anatomy 0.000 claims description 19
- 108010047761 Interferon-alpha Proteins 0.000 claims description 18
- 102000006992 Interferon-alpha Human genes 0.000 claims description 18
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 18
- 108090000467 Interferon-beta Proteins 0.000 claims description 17
- 102100026720 Interferon beta Human genes 0.000 claims description 16
- 101000596334 Homo sapiens TSC22 domain family protein 1 Proteins 0.000 claims description 15
- 206010002022 amyloidosis Diseases 0.000 claims description 15
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 claims description 15
- 101001041525 Homo sapiens Transcription factor 12 Proteins 0.000 claims description 14
- 241000701161 unidentified adenovirus Species 0.000 claims description 14
- 239000013603 viral vector Substances 0.000 claims description 14
- 101000976959 Homo sapiens Transcription factor 4 Proteins 0.000 claims description 12
- 238000000338 in vitro Methods 0.000 claims description 12
- 101000876829 Homo sapiens Protein C-ets-1 Proteins 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 241000710929 Alphavirus Species 0.000 claims description 10
- 206010009944 Colon cancer Diseases 0.000 claims description 10
- 208000035473 Communicable disease Diseases 0.000 claims description 10
- 102000003814 Interleukin-10 Human genes 0.000 claims description 10
- 108090000174 Interleukin-10 Proteins 0.000 claims description 10
- 238000003745 diagnosis Methods 0.000 claims description 10
- 210000001616 monocyte Anatomy 0.000 claims description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- 238000009169 immunotherapy Methods 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 8
- 239000007924 injection Substances 0.000 claims description 8
- 230000001177 retroviral effect Effects 0.000 claims description 8
- 230000002463 transducing effect Effects 0.000 claims description 8
- 210000004881 tumor cell Anatomy 0.000 claims description 8
- 241001430294 unidentified retrovirus Species 0.000 claims description 8
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 7
- 206010060862 Prostate cancer Diseases 0.000 claims description 7
- 230000003115 biocidal effect Effects 0.000 claims description 7
- 201000005787 hematologic cancer Diseases 0.000 claims description 7
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 7
- 206010005003 Bladder cancer Diseases 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 241000710831 Flavivirus Species 0.000 claims description 6
- 206010019799 Hepatitis viral Diseases 0.000 claims description 6
- 208000009889 Herpes Simplex Diseases 0.000 claims description 6
- 241000701044 Human gammaherpesvirus 4 Species 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 6
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
- 206010039491 Sarcoma Diseases 0.000 claims description 6
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 6
- 230000001580 bacterial effect Effects 0.000 claims description 6
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 6
- 210000005260 human cell Anatomy 0.000 claims description 6
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 6
- 210000000056 organ Anatomy 0.000 claims description 6
- 201000002528 pancreatic cancer Diseases 0.000 claims description 6
- 230000007170 pathology Effects 0.000 claims description 6
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 5
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 5
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 5
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 5
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims description 5
- 208000007514 Herpes zoster Diseases 0.000 claims description 5
- 208000017604 Hodgkin disease Diseases 0.000 claims description 5
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 5
- 241000713666 Lentivirus Species 0.000 claims description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 208000030852 Parasitic disease Diseases 0.000 claims description 5
- 208000024777 Prion disease Diseases 0.000 claims description 5
- 201000000582 Retinoblastoma Diseases 0.000 claims description 5
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 5
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 5
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 5
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 5
- 201000010881 cervical cancer Diseases 0.000 claims description 5
- 208000029742 colonic neoplasm Diseases 0.000 claims description 5
- 238000007877 drug screening Methods 0.000 claims description 5
- 201000010175 gallbladder cancer Diseases 0.000 claims description 5
- 206010017758 gastric cancer Diseases 0.000 claims description 5
- 208000006454 hepatitis Diseases 0.000 claims description 5
- 231100000283 hepatitis Toxicity 0.000 claims description 5
- 230000002163 immunogen Effects 0.000 claims description 5
- 206010022000 influenza Diseases 0.000 claims description 5
- 208000032839 leukemia Diseases 0.000 claims description 5
- 201000007270 liver cancer Diseases 0.000 claims description 5
- 208000014018 liver neoplasm Diseases 0.000 claims description 5
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 5
- 230000004770 neurodegeneration Effects 0.000 claims description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
- 201000000849 skin cancer Diseases 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
- 241001529453 unidentified herpesvirus Species 0.000 claims description 5
- 241000712461 unidentified influenza virus Species 0.000 claims description 5
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 4
- 206010004593 Bile duct cancer Diseases 0.000 claims description 4
- 206010005949 Bone cancer Diseases 0.000 claims description 4
- 208000018084 Bone neoplasm Diseases 0.000 claims description 4
- 206010008263 Cervical dysplasia Diseases 0.000 claims description 4
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 4
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 4
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 4
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 4
- 208000021309 Germ cell tumor Diseases 0.000 claims description 4
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 4
- 241000701806 Human papillomavirus Species 0.000 claims description 4
- 206010061598 Immunodeficiency Diseases 0.000 claims description 4
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 4
- 102000013462 Interleukin-12 Human genes 0.000 claims description 4
- 108010065805 Interleukin-12 Proteins 0.000 claims description 4
- 108090000978 Interleukin-4 Proteins 0.000 claims description 4
- 102000004388 Interleukin-4 Human genes 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 206010023825 Laryngeal cancer Diseases 0.000 claims description 4
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 206010036105 Polyneuropathy Diseases 0.000 claims description 4
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 241000315672 SARS coronavirus Species 0.000 claims description 4
- 208000000277 Splenic Neoplasms Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 208000023915 Ureteral Neoplasms Diseases 0.000 claims description 4
- 206010046392 Ureteric cancer Diseases 0.000 claims description 4
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 4
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 4
- 208000026900 bile duct neoplasm Diseases 0.000 claims description 4
- 208000015114 central nervous system disease Diseases 0.000 claims description 4
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 4
- 201000004101 esophageal cancer Diseases 0.000 claims description 4
- 230000002538 fungal effect Effects 0.000 claims description 4
- 230000007813 immunodeficiency Effects 0.000 claims description 4
- 230000003308 immunostimulating effect Effects 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- 201000002313 intestinal cancer Diseases 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 206010023841 laryngeal neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 201000007275 lymphatic system cancer Diseases 0.000 claims description 4
- 208000002780 macular degeneration Diseases 0.000 claims description 4
- 208000025848 malignant tumor of nasopharynx Diseases 0.000 claims description 4
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 claims description 4
- 201000011216 nasopharynx carcinoma Diseases 0.000 claims description 4
- 208000027232 peripheral nervous system disease Diseases 0.000 claims description 4
- 230000007824 polyneuropathy Effects 0.000 claims description 4
- 206010038038 rectal cancer Diseases 0.000 claims description 4
- 201000001275 rectum cancer Diseases 0.000 claims description 4
- 201000002471 spleen cancer Diseases 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 206010044285 tracheal cancer Diseases 0.000 claims description 4
- 201000011294 ureter cancer Diseases 0.000 claims description 4
- 206010046766 uterine cancer Diseases 0.000 claims description 4
- 206010046885 vaginal cancer Diseases 0.000 claims description 4
- 208000013139 vaginal neoplasm Diseases 0.000 claims description 4
- 241000498849 Chlamydiales Species 0.000 claims description 3
- 208000005016 Intestinal Neoplasms Diseases 0.000 claims description 3
- 208000012902 Nervous system disease Diseases 0.000 claims description 3
- 239000003443 antiviral agent Substances 0.000 claims description 3
- 210000000621 bronchi Anatomy 0.000 claims description 3
- 210000003123 bronchiole Anatomy 0.000 claims description 3
- 239000007972 injectable composition Substances 0.000 claims description 3
- 201000004962 larynx cancer Diseases 0.000 claims description 3
- 210000004962 mammalian cell Anatomy 0.000 claims description 3
- 210000003716 mesoderm Anatomy 0.000 claims description 3
- 210000001685 thyroid gland Anatomy 0.000 claims description 3
- 201000001862 viral hepatitis Diseases 0.000 claims description 3
- 108010002217 Calcifying Nanoparticles Proteins 0.000 claims description 2
- 241000702421 Dependoparvovirus Species 0.000 claims description 2
- 108020004459 Small interfering RNA Proteins 0.000 claims description 2
- 230000000202 analgesic effect Effects 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 2
- 230000000973 chemotherapeutic effect Effects 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 230000001882 diuretic effect Effects 0.000 claims description 2
- 210000003981 ectoderm Anatomy 0.000 claims description 2
- 210000001900 endoderm Anatomy 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 210000004966 intestinal stem cell Anatomy 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 2
- 210000002894 multi-fate stem cell Anatomy 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000008685 targeting Effects 0.000 claims description 2
- 238000012360 testing method Methods 0.000 claims description 2
- 229960005486 vaccine Drugs 0.000 claims description 2
- 102100022281 Transcription factor Spi-B Human genes 0.000 claims 43
- 101000596771 Homo sapiens Transcription factor 7-like 2 Proteins 0.000 claims 9
- 102100035251 Protein C-ets-1 Human genes 0.000 claims 9
- 108010044012 STAT1 Transcription Factor Proteins 0.000 claims 9
- 102100029904 Signal transducer and activator of transcription 1-alpha/beta Human genes 0.000 claims 9
- 208000001528 Coronaviridae Infections Diseases 0.000 claims 1
- 208000007054 Medullary Carcinoma Diseases 0.000 claims 1
- 210000004602 germ cell Anatomy 0.000 claims 1
- 230000003053 immunization Effects 0.000 claims 1
- 238000002649 immunization Methods 0.000 claims 1
- 238000012487 in-house method Methods 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 claims 1
- 230000005975 antitumor immune response Effects 0.000 abstract description 2
- 108010051621 interferon regulatory factor-8 Proteins 0.000 description 188
- 210000004544 dc2 Anatomy 0.000 description 100
- 230000014509 gene expression Effects 0.000 description 62
- 108020004414 DNA Proteins 0.000 description 54
- 101710172149 TSC22 domain family protein 1 Proteins 0.000 description 43
- 101710119706 Transcription factor 12 Proteins 0.000 description 38
- 108010054624 red fluorescent protein Proteins 0.000 description 36
- 108010048992 Transcription Factor 4 Proteins 0.000 description 32
- 241000699660 Mus musculus Species 0.000 description 29
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 description 29
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 29
- 239000000427 antigen Substances 0.000 description 29
- 108091007433 antigens Proteins 0.000 description 28
- 102000036639 antigens Human genes 0.000 description 28
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 27
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 27
- 230000003394 haemopoietic effect Effects 0.000 description 24
- 108010026333 seryl-proline Proteins 0.000 description 22
- 108020004705 Codon Proteins 0.000 description 21
- 108090000623 proteins and genes Proteins 0.000 description 20
- 230000028327 secretion Effects 0.000 description 20
- 210000001082 somatic cell Anatomy 0.000 description 20
- 102000043131 MHC class II family Human genes 0.000 description 19
- 108091054438 MHC class II family Proteins 0.000 description 19
- 101150035137 Clec9a gene Proteins 0.000 description 18
- -1 STAT1 Proteins 0.000 description 18
- 230000004913 activation Effects 0.000 description 18
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 17
- 101001077568 Homo sapiens Homeobox protein Hox-A5 Proteins 0.000 description 16
- 150000001413 amino acids Chemical group 0.000 description 16
- 210000002950 fibroblast Anatomy 0.000 description 16
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 16
- 108090000765 processed proteins & peptides Proteins 0.000 description 15
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 14
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 14
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 14
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 14
- 210000000612 antigen-presenting cell Anatomy 0.000 description 14
- 239000012091 fetal bovine serum Substances 0.000 description 14
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 14
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 230000000638 stimulation Effects 0.000 description 14
- 102100025110 Homeobox protein Hox-A5 Human genes 0.000 description 13
- 108010077112 prolyl-proline Proteins 0.000 description 13
- 238000010361 transduction Methods 0.000 description 13
- 102000014150 Interferons Human genes 0.000 description 12
- 108010050904 Interferons Proteins 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 108010050848 glycylleucine Proteins 0.000 description 12
- 229920001184 polypeptide Polymers 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 230000026683 transduction Effects 0.000 description 12
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 11
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 11
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 11
- 210000001744 T-lymphocyte Anatomy 0.000 description 11
- 102000002689 Toll-like receptor Human genes 0.000 description 11
- 108020000411 Toll-like receptor Proteins 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000013604 expression vector Substances 0.000 description 11
- 238000000684 flow cytometry Methods 0.000 description 11
- 229940079322 interferon Drugs 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 10
- 102000019034 Chemokines Human genes 0.000 description 10
- 108010012236 Chemokines Proteins 0.000 description 10
- BUZMZDDKFCSKOT-CIUDSAMLSA-N Glu-Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O BUZMZDDKFCSKOT-CIUDSAMLSA-N 0.000 description 10
- 210000003719 b-lymphocyte Anatomy 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 244000052769 pathogen Species 0.000 description 10
- 108010031719 prolyl-serine Proteins 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 101100028791 Caenorhabditis elegans pbs-5 gene Proteins 0.000 description 9
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 9
- 101001032342 Homo sapiens Interferon regulatory factor 7 Proteins 0.000 description 9
- 102000004889 Interleukin-6 Human genes 0.000 description 9
- 108090001005 Interleukin-6 Proteins 0.000 description 9
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 9
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 9
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 9
- 108010005233 alanylglutamic acid Proteins 0.000 description 9
- 108010047495 alanylglycine Proteins 0.000 description 9
- 108010008355 arginyl-glutamine Proteins 0.000 description 9
- 108010068380 arginylarginine Proteins 0.000 description 9
- 108010093581 aspartyl-proline Proteins 0.000 description 9
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 230000002458 infectious effect Effects 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 8
- 101000599037 Homo sapiens Zinc finger protein Helios Proteins 0.000 description 8
- 108010087924 alanylproline Proteins 0.000 description 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 8
- 229960003722 doxycycline Drugs 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 108010015792 glycyllysine Proteins 0.000 description 8
- 229940100601 interleukin-6 Drugs 0.000 description 8
- 210000002540 macrophage Anatomy 0.000 description 8
- 239000003550 marker Substances 0.000 description 8
- 108010070643 prolylglutamic acid Proteins 0.000 description 8
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 101001036287 Homo sapiens DNA-binding protein inhibitor ID-3 Proteins 0.000 description 7
- 101001021503 Homo sapiens Hematopoietically-expressed homeobox protein HHEX Proteins 0.000 description 7
- 101000899255 Homo sapiens Histone deacetylase 5 Proteins 0.000 description 7
- 101000636213 Homo sapiens Transcriptional activator Myb Proteins 0.000 description 7
- 101000599042 Homo sapiens Zinc finger protein Aiolos Proteins 0.000 description 7
- 101001002579 Homo sapiens Zinc finger protein Pegasus Proteins 0.000 description 7
- 102100038070 Interferon regulatory factor 7 Human genes 0.000 description 7
- WHNJMTHJGCEKGA-ULQDDVLXSA-N Pro-Phe-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O WHNJMTHJGCEKGA-ULQDDVLXSA-N 0.000 description 7
- 208000036142 Viral infection Diseases 0.000 description 7
- 108010047857 aspartylglycine Proteins 0.000 description 7
- 108010049041 glutamylalanine Proteins 0.000 description 7
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 7
- 229940076144 interleukin-10 Drugs 0.000 description 7
- 108010034529 leucyl-lysine Proteins 0.000 description 7
- 108010064235 lysylglycine Proteins 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 230000037361 pathway Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 230000000770 proinflammatory effect Effects 0.000 description 7
- 230000009385 viral infection Effects 0.000 description 7
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 6
- CKRUHITYRFNUKW-WDSKDSINSA-N Glu-Asn-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O CKRUHITYRFNUKW-WDSKDSINSA-N 0.000 description 6
- KKBWDNZXYLGJEY-UHFFFAOYSA-N Gly-Arg-Pro Natural products NCC(=O)NC(CCNC(=N)N)C(=O)N1CCCC1C(=O)O KKBWDNZXYLGJEY-UHFFFAOYSA-N 0.000 description 6
- 108010065920 Insulin Lispro Proteins 0.000 description 6
- SBANPBVRHYIMRR-UHFFFAOYSA-N Leu-Ser-Pro Natural products CC(C)CC(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O SBANPBVRHYIMRR-UHFFFAOYSA-N 0.000 description 6
- PPGBXYKMUMHFBF-KATARQTJSA-N Leu-Ser-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PPGBXYKMUMHFBF-KATARQTJSA-N 0.000 description 6
- QSWKNJAPHQDAAS-MELADBBJSA-N Phe-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O QSWKNJAPHQDAAS-MELADBBJSA-N 0.000 description 6
- 102100037796 Zinc finger protein Helios Human genes 0.000 description 6
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 6
- 108010013835 arginine glutamate Proteins 0.000 description 6
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 6
- 210000001185 bone marrow Anatomy 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 238000012258 culturing Methods 0.000 description 6
- 108010016616 cysteinylglycine Proteins 0.000 description 6
- 230000002950 deficient Effects 0.000 description 6
- 108010078144 glutaminyl-glycine Proteins 0.000 description 6
- 108010077515 glycylproline Proteins 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 6
- 108010025306 histidylleucine Proteins 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000000411 inducer Substances 0.000 description 6
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 6
- 210000004698 lymphocyte Anatomy 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 108010093296 prolyl-prolyl-alanine Proteins 0.000 description 6
- 108010004914 prolylarginine Proteins 0.000 description 6
- 108010029020 prolylglycine Proteins 0.000 description 6
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 6
- 229950010550 resiquimod Drugs 0.000 description 6
- 230000003248 secreting effect Effects 0.000 description 6
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 210000000952 spleen Anatomy 0.000 description 6
- 238000001890 transfection Methods 0.000 description 6
- 102000015775 Core Binding Factor Alpha 1 Subunit Human genes 0.000 description 5
- 108010024682 Core Binding Factor Alpha 1 Subunit Proteins 0.000 description 5
- 102100039436 DNA-binding protein inhibitor ID-3 Human genes 0.000 description 5
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 5
- 102100035961 Hematopoietically-expressed homeobox protein HHEX Human genes 0.000 description 5
- 102100021453 Histone deacetylase 5 Human genes 0.000 description 5
- 206010020751 Hypersensitivity Diseases 0.000 description 5
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 5
- DZQMXBALGUHGJT-GUBZILKMSA-N Leu-Glu-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O DZQMXBALGUHGJT-GUBZILKMSA-N 0.000 description 5
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 5
- 102000055120 MEF2 Transcription Factors Human genes 0.000 description 5
- 108010018650 MEF2 Transcription Factors Proteins 0.000 description 5
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 5
- NMELOOXSGDRBRU-YUMQZZPRSA-N Pro-Glu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1 NMELOOXSGDRBRU-YUMQZZPRSA-N 0.000 description 5
- SBVPYBFMIGDIDX-SRVKXCTJSA-N Pro-Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)[C@H]2NCCC2)CCC1 SBVPYBFMIGDIDX-SRVKXCTJSA-N 0.000 description 5
- RCYUBVHMVUHEBM-RCWTZXSCSA-N Pro-Pro-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O RCYUBVHMVUHEBM-RCWTZXSCSA-N 0.000 description 5
- SNGZLPOXVRTNMB-LPEHRKFASA-N Pro-Ser-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N2CCC[C@@H]2C(=O)O SNGZLPOXVRTNMB-LPEHRKFASA-N 0.000 description 5
- MKGIILKDUGDRRO-FXQIFTODSA-N Pro-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 MKGIILKDUGDRRO-FXQIFTODSA-N 0.000 description 5
- UIUWGMRJTWHIJZ-ULQDDVLXSA-N Pro-Tyr-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCCCN)C(=O)O UIUWGMRJTWHIJZ-ULQDDVLXSA-N 0.000 description 5
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 5
- 102000004495 STAT3 Transcription Factor Human genes 0.000 description 5
- YQHZVYJAGWMHES-ZLUOBGJFSA-N Ser-Ala-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YQHZVYJAGWMHES-ZLUOBGJFSA-N 0.000 description 5
- 230000005867 T cell response Effects 0.000 description 5
- GBIUHAYJGWVNLN-UHFFFAOYSA-N Val-Ser-Pro Natural products CC(C)C(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O GBIUHAYJGWVNLN-UHFFFAOYSA-N 0.000 description 5
- 102100037798 Zinc finger protein Aiolos Human genes 0.000 description 5
- 102100020893 Zinc finger protein Pegasus Human genes 0.000 description 5
- 210000005006 adaptive immune system Anatomy 0.000 description 5
- 108010044940 alanylglutamine Proteins 0.000 description 5
- 230000007815 allergy Effects 0.000 description 5
- 108010052670 arginyl-glutamyl-glutamic acid Proteins 0.000 description 5
- 108010062796 arginyllysine Proteins 0.000 description 5
- 108010038633 aspartylglutamate Proteins 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000005860 defense response to virus Effects 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 5
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 108010057821 leucylproline Proteins 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 239000002777 nucleoside Substances 0.000 description 5
- 150000003833 nucleoside derivatives Chemical class 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- DEWWPUNXRNGMQN-LPEHRKFASA-N Ala-Met-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@@H]1C(=O)O)N DEWWPUNXRNGMQN-LPEHRKFASA-N 0.000 description 4
- RTZCUEHYUQZIDE-WHFBIAKZSA-N Ala-Ser-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RTZCUEHYUQZIDE-WHFBIAKZSA-N 0.000 description 4
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 4
- YVTHEZNOKSAWRW-DCAQKATOSA-N Arg-Lys-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O YVTHEZNOKSAWRW-DCAQKATOSA-N 0.000 description 4
- RIIVUOJDDQXHRV-SRVKXCTJSA-N Arg-Lys-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O RIIVUOJDDQXHRV-SRVKXCTJSA-N 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- SNLOOPZHAQDMJG-CIUDSAMLSA-N Gln-Glu-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SNLOOPZHAQDMJG-CIUDSAMLSA-N 0.000 description 4
- UTKUTMJSWKKHEM-WDSKDSINSA-N Glu-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O UTKUTMJSWKKHEM-WDSKDSINSA-N 0.000 description 4
- ZQIMMEYPEXIYBB-IUCAKERBSA-N Gly-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CN ZQIMMEYPEXIYBB-IUCAKERBSA-N 0.000 description 4
- LUJVWKKYHSLULQ-ZKWXMUAHSA-N Gly-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN LUJVWKKYHSLULQ-ZKWXMUAHSA-N 0.000 description 4
- NNCSJUBVFBDDLC-YUMQZZPRSA-N Gly-Leu-Ser Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O NNCSJUBVFBDDLC-YUMQZZPRSA-N 0.000 description 4
- GGLIDLCEPDHEJO-BQBZGAKWSA-N Gly-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)CN GGLIDLCEPDHEJO-BQBZGAKWSA-N 0.000 description 4
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 4
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 4
- 101000903609 Homo sapiens Basic leucine zipper transcriptional factor ATF-like 3 Proteins 0.000 description 4
- 102100022297 Integrin alpha-X Human genes 0.000 description 4
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 4
- CQQGCWPXDHTTNF-GUBZILKMSA-N Leu-Ala-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O CQQGCWPXDHTTNF-GUBZILKMSA-N 0.000 description 4
- XBBKIIGCUMBKCO-JXUBOQSCSA-N Leu-Ala-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XBBKIIGCUMBKCO-JXUBOQSCSA-N 0.000 description 4
- WQWSMEOYXJTFRU-GUBZILKMSA-N Leu-Glu-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O WQWSMEOYXJTFRU-GUBZILKMSA-N 0.000 description 4
- OXRLYTYUXAQTHP-YUMQZZPRSA-N Leu-Gly-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(O)=O OXRLYTYUXAQTHP-YUMQZZPRSA-N 0.000 description 4
- KYIIALJHAOIAHF-KKUMJFAQSA-N Leu-Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KYIIALJHAOIAHF-KKUMJFAQSA-N 0.000 description 4
- AAKRWBIIGKPOKQ-ONGXEEELSA-N Leu-Val-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O AAKRWBIIGKPOKQ-ONGXEEELSA-N 0.000 description 4
- 108010079364 N-glycylalanine Proteins 0.000 description 4
- DMKWYMWNEKIPFC-IUCAKERBSA-N Pro-Gly-Arg Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O DMKWYMWNEKIPFC-IUCAKERBSA-N 0.000 description 4
- FKLSMYYLJHYPHH-UWVGGRQHSA-N Pro-Gly-Leu Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O FKLSMYYLJHYPHH-UWVGGRQHSA-N 0.000 description 4
- UIMCLYYSUCIUJM-UWVGGRQHSA-N Pro-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 UIMCLYYSUCIUJM-UWVGGRQHSA-N 0.000 description 4
- KDBHVPXBQADZKY-GUBZILKMSA-N Pro-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KDBHVPXBQADZKY-GUBZILKMSA-N 0.000 description 4
- CGSOWZUPLOKYOR-AVGNSLFASA-N Pro-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 CGSOWZUPLOKYOR-AVGNSLFASA-N 0.000 description 4
- FDMKYQQYJKYCLV-GUBZILKMSA-N Pro-Pro-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 FDMKYQQYJKYCLV-GUBZILKMSA-N 0.000 description 4
- HRNQLKCLPVKZNE-CIUDSAMLSA-N Ser-Ala-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O HRNQLKCLPVKZNE-CIUDSAMLSA-N 0.000 description 4
- QWZIOCFPXMAXET-CIUDSAMLSA-N Ser-Arg-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O QWZIOCFPXMAXET-CIUDSAMLSA-N 0.000 description 4
- ADJDNJCSPNFFPI-FXQIFTODSA-N Ser-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO ADJDNJCSPNFFPI-FXQIFTODSA-N 0.000 description 4
- OVQZAFXWIWNYKA-GUBZILKMSA-N Ser-Pro-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)N OVQZAFXWIWNYKA-GUBZILKMSA-N 0.000 description 4
- AZWNCEBQZXELEZ-FXQIFTODSA-N Ser-Pro-Ser Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O AZWNCEBQZXELEZ-FXQIFTODSA-N 0.000 description 4
- CUXJENOFJXOSOZ-BIIVOSGPSA-N Ser-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CO)N)C(=O)O CUXJENOFJXOSOZ-BIIVOSGPSA-N 0.000 description 4
- ZSDXEKUKQAKZFE-XAVMHZPKSA-N Ser-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N)O ZSDXEKUKQAKZFE-XAVMHZPKSA-N 0.000 description 4
- MROIJTGJGIDEEJ-RCWTZXSCSA-N Thr-Pro-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 MROIJTGJGIDEEJ-RCWTZXSCSA-N 0.000 description 4
- TZQWJCGVCIJDMU-HEIBUPTGSA-N Thr-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)O)N)O TZQWJCGVCIJDMU-HEIBUPTGSA-N 0.000 description 4
- 102100027654 Transcription factor PU.1 Human genes 0.000 description 4
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 4
- 108010070944 alanylhistidine Proteins 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 4
- 238000001415 gene therapy Methods 0.000 description 4
- 108010082286 glycyl-seryl-alanine Proteins 0.000 description 4
- 108010037850 glycylvaline Proteins 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 108010028295 histidylhistidine Proteins 0.000 description 4
- 108010085325 histidylproline Proteins 0.000 description 4
- 108010018006 histidylserine Proteins 0.000 description 4
- 210000002865 immune cell Anatomy 0.000 description 4
- 108010009298 lysylglutamic acid Proteins 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 125000003835 nucleoside group Chemical group 0.000 description 4
- 210000005259 peripheral blood Anatomy 0.000 description 4
- 239000011886 peripheral blood Substances 0.000 description 4
- 108700042769 prolyl-leucyl-glycine Proteins 0.000 description 4
- 108010008929 proto-oncogene protein Spi-1 Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 108010071207 serylmethionine Proteins 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 108010061238 threonyl-glycine Proteins 0.000 description 4
- 230000009261 transgenic effect Effects 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 108010073969 valyllysine Proteins 0.000 description 4
- IDGZVZJLYFTXSL-UHFFFAOYSA-N 2-[[2-[(2-amino-4-methylpentanoyl)amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound CC(C)CC(N)C(=O)NC(CO)C(=O)NC(C(O)=O)CCCN=C(N)N IDGZVZJLYFTXSL-UHFFFAOYSA-N 0.000 description 3
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical group CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 3
- MQIGTEQXYCRLGK-BQBZGAKWSA-N Ala-Gly-Pro Chemical compound C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(O)=O MQIGTEQXYCRLGK-BQBZGAKWSA-N 0.000 description 3
- NBTGEURICRTMGL-WHFBIAKZSA-N Ala-Gly-Ser Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O NBTGEURICRTMGL-WHFBIAKZSA-N 0.000 description 3
- OYJCVIGKMXUVKB-GARJFASQSA-N Ala-Leu-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N OYJCVIGKMXUVKB-GARJFASQSA-N 0.000 description 3
- HYIDEIQUCBKIPL-CQDKDKBSSA-N Ala-Phe-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N HYIDEIQUCBKIPL-CQDKDKBSSA-N 0.000 description 3
- XWFWAXPOLRTDFZ-FXQIFTODSA-N Ala-Pro-Ser Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O XWFWAXPOLRTDFZ-FXQIFTODSA-N 0.000 description 3
- OEVCHROQUIVQFZ-YTLHQDLWSA-N Ala-Thr-Ala Chemical compound C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](C)C(O)=O OEVCHROQUIVQFZ-YTLHQDLWSA-N 0.000 description 3
- QOIGKCBMXUCDQU-KDXUFGMBSA-N Ala-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C)N)O QOIGKCBMXUCDQU-KDXUFGMBSA-N 0.000 description 3
- LVMUGODRNHFGRA-AVGNSLFASA-N Arg-Leu-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O LVMUGODRNHFGRA-AVGNSLFASA-N 0.000 description 3
- VRTWYUYCJGNFES-CIUDSAMLSA-N Arg-Ser-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O VRTWYUYCJGNFES-CIUDSAMLSA-N 0.000 description 3
- LFAUVOXPCGJKTB-DCAQKATOSA-N Arg-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N LFAUVOXPCGJKTB-DCAQKATOSA-N 0.000 description 3
- HBUJSDCLZCXXCW-YDHLFZDLSA-N Asn-Val-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HBUJSDCLZCXXCW-YDHLFZDLSA-N 0.000 description 3
- XYBJLTKSGFBLCS-QXEWZRGKSA-N Asp-Arg-Val Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC(O)=O XYBJLTKSGFBLCS-QXEWZRGKSA-N 0.000 description 3
- WCFCYFDBMNFSPA-ACZMJKKPSA-N Asp-Asp-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O WCFCYFDBMNFSPA-ACZMJKKPSA-N 0.000 description 3
- FANQWNCPNFEPGZ-WHFBIAKZSA-N Asp-Asp-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O FANQWNCPNFEPGZ-WHFBIAKZSA-N 0.000 description 3
- ZEDBMCPXPIYJLW-XHNCKOQMSA-N Asp-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)N)C(=O)O ZEDBMCPXPIYJLW-XHNCKOQMSA-N 0.000 description 3
- BRRPVTUFESPTCP-ACZMJKKPSA-N Asp-Ser-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O BRRPVTUFESPTCP-ACZMJKKPSA-N 0.000 description 3
- MGSVBZIBCCKGCY-ZLUOBGJFSA-N Asp-Ser-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MGSVBZIBCCKGCY-ZLUOBGJFSA-N 0.000 description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 102100023013 Basic leucine zipper transcriptional factor ATF-like 3 Human genes 0.000 description 3
- 102100039521 C-type lectin domain family 9 member A Human genes 0.000 description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 241000991587 Enterovirus C Species 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- MCAVASRGVBVPMX-FXQIFTODSA-N Gln-Glu-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O MCAVASRGVBVPMX-FXQIFTODSA-N 0.000 description 3
- IWUFOVSLWADEJC-AVGNSLFASA-N Gln-His-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O IWUFOVSLWADEJC-AVGNSLFASA-N 0.000 description 3
- DYFJZDDQPNIPAB-NHCYSSNCSA-N Glu-Arg-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O DYFJZDDQPNIPAB-NHCYSSNCSA-N 0.000 description 3
- MUSGDMDGNGXULI-DCAQKATOSA-N Glu-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O MUSGDMDGNGXULI-DCAQKATOSA-N 0.000 description 3
- PXXGVUVQWQGGIG-YUMQZZPRSA-N Glu-Gly-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N PXXGVUVQWQGGIG-YUMQZZPRSA-N 0.000 description 3
- HVYWQYLBVXMXSV-GUBZILKMSA-N Glu-Leu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O HVYWQYLBVXMXSV-GUBZILKMSA-N 0.000 description 3
- DNPCBMNFQVTHMA-DCAQKATOSA-N Glu-Leu-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O DNPCBMNFQVTHMA-DCAQKATOSA-N 0.000 description 3
- CQAHWYDHKUWYIX-YUMQZZPRSA-N Glu-Pro-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O CQAHWYDHKUWYIX-YUMQZZPRSA-N 0.000 description 3
- SYWCGQOIIARSIX-SRVKXCTJSA-N Glu-Pro-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O SYWCGQOIIARSIX-SRVKXCTJSA-N 0.000 description 3
- MFVQGXGQRIXBPK-WDSKDSINSA-N Gly-Ala-Glu Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MFVQGXGQRIXBPK-WDSKDSINSA-N 0.000 description 3
- UPOJUWHGMDJUQZ-IUCAKERBSA-N Gly-Arg-Arg Chemical compound NC(=N)NCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UPOJUWHGMDJUQZ-IUCAKERBSA-N 0.000 description 3
- KRRMJKMGWWXWDW-STQMWFEESA-N Gly-Arg-Phe Chemical compound NC(=N)NCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KRRMJKMGWWXWDW-STQMWFEESA-N 0.000 description 3
- FSPVILZGHUJOHS-QWRGUYRKSA-N Gly-His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CNC=N1 FSPVILZGHUJOHS-QWRGUYRKSA-N 0.000 description 3
- TWTPDFFBLQEBOE-IUCAKERBSA-N Gly-Leu-Gln Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O TWTPDFFBLQEBOE-IUCAKERBSA-N 0.000 description 3
- WDEHMRNSGHVNOH-VHSXEESVSA-N Gly-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)CN)C(=O)O WDEHMRNSGHVNOH-VHSXEESVSA-N 0.000 description 3
- LCRDMSSAKLTKBU-ZDLURKLDSA-N Gly-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN LCRDMSSAKLTKBU-ZDLURKLDSA-N 0.000 description 3
- 241000711549 Hepacivirus C Species 0.000 description 3
- 241000700721 Hepatitis B virus Species 0.000 description 3
- ZUPVLBAXUUGKKN-VHSXEESVSA-N His-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CC2=CN=CN2)N)C(=O)O ZUPVLBAXUUGKKN-VHSXEESVSA-N 0.000 description 3
- YYOCMTFVGKDNQP-IHRRRGAJSA-N His-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N YYOCMTFVGKDNQP-IHRRRGAJSA-N 0.000 description 3
- HYWZHNUGAYVEEW-KKUMJFAQSA-N His-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N HYWZHNUGAYVEEW-KKUMJFAQSA-N 0.000 description 3
- IXQGOKWTQPCIQM-YJRXYDGGSA-N His-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)O IXQGOKWTQPCIQM-YJRXYDGGSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000888548 Homo sapiens C-type lectin domain family 9 member A Proteins 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- JDAWAWXGAUZPNJ-ZPFDUUQYSA-N Ile-Glu-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N JDAWAWXGAUZPNJ-ZPFDUUQYSA-N 0.000 description 3
- HGCNKOLVKRAVHD-UHFFFAOYSA-N L-Met-L-Phe Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 HGCNKOLVKRAVHD-UHFFFAOYSA-N 0.000 description 3
- SENJXOPIZNYLHU-UHFFFAOYSA-N L-leucyl-L-arginine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-UHFFFAOYSA-N 0.000 description 3
- MJOZZTKJZQFKDK-GUBZILKMSA-N Leu-Ala-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(N)=O MJOZZTKJZQFKDK-GUBZILKMSA-N 0.000 description 3
- WNGVUZWBXZKQES-YUMQZZPRSA-N Leu-Ala-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O WNGVUZWBXZKQES-YUMQZZPRSA-N 0.000 description 3
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 3
- JLWZLIQRYCTYBD-IHRRRGAJSA-N Leu-Lys-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JLWZLIQRYCTYBD-IHRRRGAJSA-N 0.000 description 3
- RZXLZBIUTDQHJQ-SRVKXCTJSA-N Leu-Lys-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O RZXLZBIUTDQHJQ-SRVKXCTJSA-N 0.000 description 3
- DPURXCQCHSQPAN-AVGNSLFASA-N Leu-Pro-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DPURXCQCHSQPAN-AVGNSLFASA-N 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- XOQMURBBIXRRCR-SRVKXCTJSA-N Lys-Lys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN XOQMURBBIXRRCR-SRVKXCTJSA-N 0.000 description 3
- HVAUKHLDSDDROB-KKUMJFAQSA-N Lys-Lys-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O HVAUKHLDSDDROB-KKUMJFAQSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 3
- WUGMRIBZSVSJNP-UHFFFAOYSA-N N-L-alanyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C)C(O)=O)=CNC2=C1 WUGMRIBZSVSJNP-UHFFFAOYSA-N 0.000 description 3
- XZFYRXDAULDNFX-UHFFFAOYSA-N N-L-cysteinyl-L-phenylalanine Natural products SCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XZFYRXDAULDNFX-UHFFFAOYSA-N 0.000 description 3
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 3
- 241000711504 Paramyxoviridae Species 0.000 description 3
- HBXAOEBRGLCLIW-AVGNSLFASA-N Phe-Ser-Gln Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N HBXAOEBRGLCLIW-AVGNSLFASA-N 0.000 description 3
- 241000709664 Picornaviridae Species 0.000 description 3
- MCWHYUWXVNRXFV-RWMBFGLXSA-N Pro-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 MCWHYUWXVNRXFV-RWMBFGLXSA-N 0.000 description 3
- HBBBLSVBQGZKOZ-GUBZILKMSA-N Pro-Met-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O HBBBLSVBQGZKOZ-GUBZILKMSA-N 0.000 description 3
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 3
- FNGOXVQBBCMFKV-CIUDSAMLSA-N Pro-Ser-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O FNGOXVQBBCMFKV-CIUDSAMLSA-N 0.000 description 3
- BRKHVZNDAOMAHX-BIIVOSGPSA-N Ser-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N BRKHVZNDAOMAHX-BIIVOSGPSA-N 0.000 description 3
- UOLGINIHBRIECN-FXQIFTODSA-N Ser-Glu-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UOLGINIHBRIECN-FXQIFTODSA-N 0.000 description 3
- GZFAWAQTEYDKII-YUMQZZPRSA-N Ser-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO GZFAWAQTEYDKII-YUMQZZPRSA-N 0.000 description 3
- IAORETPTUDBBGV-CIUDSAMLSA-N Ser-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N IAORETPTUDBBGV-CIUDSAMLSA-N 0.000 description 3
- KCGIREHVWRXNDH-GARJFASQSA-N Ser-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N KCGIREHVWRXNDH-GARJFASQSA-N 0.000 description 3
- NNFMANHDYSVNIO-DCAQKATOSA-N Ser-Lys-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NNFMANHDYSVNIO-DCAQKATOSA-N 0.000 description 3
- FKYWFUYPVKLJLP-DCAQKATOSA-N Ser-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FKYWFUYPVKLJLP-DCAQKATOSA-N 0.000 description 3
- QUGRFWPMPVIAPW-IHRRRGAJSA-N Ser-Pro-Phe Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 QUGRFWPMPVIAPW-IHRRRGAJSA-N 0.000 description 3
- KQNDIKOYWZTZIX-FXQIFTODSA-N Ser-Ser-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KQNDIKOYWZTZIX-FXQIFTODSA-N 0.000 description 3
- NADLKBTYNKUJEP-KATARQTJSA-N Ser-Thr-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NADLKBTYNKUJEP-KATARQTJSA-N 0.000 description 3
- 241000194017 Streptococcus Species 0.000 description 3
- FHDLKMFZKRUQCE-HJGDQZAQSA-N Thr-Glu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FHDLKMFZKRUQCE-HJGDQZAQSA-N 0.000 description 3
- IVDFVBVIVLJJHR-LKXGYXEUSA-N Thr-Ser-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IVDFVBVIVLJJHR-LKXGYXEUSA-N 0.000 description 3
- OOEUVMFKKZYSRX-LEWSCRJBSA-N Tyr-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N OOEUVMFKKZYSRX-LEWSCRJBSA-N 0.000 description 3
- OPGWZDIYEYJVRX-AVGNSLFASA-N Val-His-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N OPGWZDIYEYJVRX-AVGNSLFASA-N 0.000 description 3
- BTWMICVCQLKKNR-DCAQKATOSA-N Val-Leu-Ser Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C([O-])=O BTWMICVCQLKKNR-DCAQKATOSA-N 0.000 description 3
- YQYFYUSYEDNLSD-YEPSODPASA-N Val-Thr-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O YQYFYUSYEDNLSD-YEPSODPASA-N 0.000 description 3
- 108010024078 alanyl-glycyl-serine Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000006023 anti-tumor response Effects 0.000 description 3
- 230000014102 antigen processing and presentation of exogenous peptide antigen via MHC class I Effects 0.000 description 3
- 108010043240 arginyl-leucyl-glycine Proteins 0.000 description 3
- 108010077245 asparaginyl-proline Proteins 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229940104302 cytosine Drugs 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 108010054813 diprotin B Proteins 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 108091006047 fluorescent proteins Proteins 0.000 description 3
- 102000034287 fluorescent proteins Human genes 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000001476 gene delivery Methods 0.000 description 3
- 108010000434 glycyl-alanyl-leucine Proteins 0.000 description 3
- 108010010147 glycylglutamine Proteins 0.000 description 3
- 210000003714 granulocyte Anatomy 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 210000005007 innate immune system Anatomy 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 108010000761 leucylarginine Proteins 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 210000003563 lymphoid tissue Anatomy 0.000 description 3
- 108010057952 lysyl-phenylalanyl-lysine Proteins 0.000 description 3
- 108010017391 lysylvaline Proteins 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 210000003593 megakaryocyte Anatomy 0.000 description 3
- 108010068488 methionylphenylalanine Proteins 0.000 description 3
- 210000000822 natural killer cell Anatomy 0.000 description 3
- 230000005868 ontogenesis Effects 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 244000045947 parasite Species 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 230000037452 priming Effects 0.000 description 3
- 108010007513 prolyl-glycyl-prolyl-leucine Proteins 0.000 description 3
- 108010025826 prolyl-leucyl-arginine Proteins 0.000 description 3
- 108010087846 prolyl-prolyl-glycine Proteins 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000003362 replicative effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 230000000392 somatic effect Effects 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 108010031491 threonyl-lysyl-glutamic acid Proteins 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 229940035893 uracil Drugs 0.000 description 3
- SXUXMRMBWZCMEN-UHFFFAOYSA-N 2'-O-methyl uridine Natural products COC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-UHFFFAOYSA-N 0.000 description 2
- GJTBSTBJLVYKAU-XVFCMESISA-N 2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C=C1 GJTBSTBJLVYKAU-XVFCMESISA-N 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- CXRCVCURMBFFOL-FXQIFTODSA-N Ala-Ala-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O CXRCVCURMBFFOL-FXQIFTODSA-N 0.000 description 2
- YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 description 2
- KVWLTGNCJYDJET-LSJOCFKGSA-N Ala-Arg-His Chemical compound C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N KVWLTGNCJYDJET-LSJOCFKGSA-N 0.000 description 2
- YSMPVONNIWLJML-FXQIFTODSA-N Ala-Asp-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(O)=O YSMPVONNIWLJML-FXQIFTODSA-N 0.000 description 2
- UQJUGHFKNKGHFQ-VZFHVOOUSA-N Ala-Cys-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UQJUGHFKNKGHFQ-VZFHVOOUSA-N 0.000 description 2
- CSAHOYQKNHGDHX-ACZMJKKPSA-N Ala-Gln-Asn Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O CSAHOYQKNHGDHX-ACZMJKKPSA-N 0.000 description 2
- BLGHHPHXVJWCNK-GUBZILKMSA-N Ala-Gln-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O BLGHHPHXVJWCNK-GUBZILKMSA-N 0.000 description 2
- WKOBSJOZRJJVRZ-FXQIFTODSA-N Ala-Glu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WKOBSJOZRJJVRZ-FXQIFTODSA-N 0.000 description 2
- BLIMFWGRQKRCGT-YUMQZZPRSA-N Ala-Gly-Lys Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN BLIMFWGRQKRCGT-YUMQZZPRSA-N 0.000 description 2
- GRPHQEMIFDPKOE-HGNGGELXSA-N Ala-His-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O GRPHQEMIFDPKOE-HGNGGELXSA-N 0.000 description 2
- 108010076441 Ala-His-His Proteins 0.000 description 2
- CCDFBRZVTDDJNM-GUBZILKMSA-N Ala-Leu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O CCDFBRZVTDDJNM-GUBZILKMSA-N 0.000 description 2
- VCSABYLVNWQYQE-UHFFFAOYSA-N Ala-Lys-Lys Natural products NCCCCC(NC(=O)C(N)C)C(=O)NC(CCCCN)C(O)=O VCSABYLVNWQYQE-UHFFFAOYSA-N 0.000 description 2
- BLTRAARCJYVJKV-QEJZJMRPSA-N Ala-Lys-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(O)=O BLTRAARCJYVJKV-QEJZJMRPSA-N 0.000 description 2
- MDNAVFBZPROEHO-UHFFFAOYSA-N Ala-Lys-Val Natural products CC(C)C(C(O)=O)NC(=O)C(NC(=O)C(C)N)CCCCN MDNAVFBZPROEHO-UHFFFAOYSA-N 0.000 description 2
- OSRZOHXQCUFIQG-FPMFFAJLSA-N Ala-Phe-Pro Chemical compound C([C@H](NC(=O)[C@@H]([NH3+])C)C(=O)N1[C@H](CCC1)C([O-])=O)C1=CC=CC=C1 OSRZOHXQCUFIQG-FPMFFAJLSA-N 0.000 description 2
- YCRAFFCYWOUEOF-DLOVCJGASA-N Ala-Phe-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 YCRAFFCYWOUEOF-DLOVCJGASA-N 0.000 description 2
- IPZQNYYAYVRKKK-FXQIFTODSA-N Ala-Pro-Ala Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O IPZQNYYAYVRKKK-FXQIFTODSA-N 0.000 description 2
- MMLHRUJLOUSRJX-CIUDSAMLSA-N Ala-Ser-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN MMLHRUJLOUSRJX-CIUDSAMLSA-N 0.000 description 2
- REWSWYIDQIELBE-FXQIFTODSA-N Ala-Val-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O REWSWYIDQIELBE-FXQIFTODSA-N 0.000 description 2
- GXCSUJQOECMKPV-CIUDSAMLSA-N Arg-Ala-Gln Chemical compound C[C@H](NC(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O GXCSUJQOECMKPV-CIUDSAMLSA-N 0.000 description 2
- RKRSYHCNPFGMTA-CIUDSAMLSA-N Arg-Glu-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O RKRSYHCNPFGMTA-CIUDSAMLSA-N 0.000 description 2
- PNQWAUXQDBIJDY-GUBZILKMSA-N Arg-Glu-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PNQWAUXQDBIJDY-GUBZILKMSA-N 0.000 description 2
- NKBQZKVMKJJDLX-SRVKXCTJSA-N Arg-Glu-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NKBQZKVMKJJDLX-SRVKXCTJSA-N 0.000 description 2
- PPPXVIBMLFWNSK-BQBZGAKWSA-N Arg-Gly-Cys Chemical compound C(C[C@@H](C(=O)NCC(=O)N[C@@H](CS)C(=O)O)N)CN=C(N)N PPPXVIBMLFWNSK-BQBZGAKWSA-N 0.000 description 2
- OQCWXQJLCDPRHV-UWVGGRQHSA-N Arg-Gly-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O OQCWXQJLCDPRHV-UWVGGRQHSA-N 0.000 description 2
- YKBHOXLMMPZPHQ-GMOBBJLQSA-N Arg-Ile-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O YKBHOXLMMPZPHQ-GMOBBJLQSA-N 0.000 description 2
- GNYUVVJYGJFKHN-RVMXOQNASA-N Arg-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N GNYUVVJYGJFKHN-RVMXOQNASA-N 0.000 description 2
- FNXCAFKDGBROCU-STECZYCISA-N Arg-Ile-Tyr Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 FNXCAFKDGBROCU-STECZYCISA-N 0.000 description 2
- NIUDXSFNLBIWOB-DCAQKATOSA-N Arg-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N NIUDXSFNLBIWOB-DCAQKATOSA-N 0.000 description 2
- IGFJVXOATGZTHD-UHFFFAOYSA-N Arg-Phe-His Natural products NC(CCNC(=N)N)C(=O)NC(Cc1ccccc1)C(=O)NC(Cc2c[nH]cn2)C(=O)O IGFJVXOATGZTHD-UHFFFAOYSA-N 0.000 description 2
- AOHKLEBWKMKITA-IHRRRGAJSA-N Arg-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N AOHKLEBWKMKITA-IHRRRGAJSA-N 0.000 description 2
- KXOPYFNQLVUOAQ-FXQIFTODSA-N Arg-Ser-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O KXOPYFNQLVUOAQ-FXQIFTODSA-N 0.000 description 2
- ADPACBMPYWJJCE-FXQIFTODSA-N Arg-Ser-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O ADPACBMPYWJJCE-FXQIFTODSA-N 0.000 description 2
- ICRHGPYYXMWHIE-LPEHRKFASA-N Arg-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ICRHGPYYXMWHIE-LPEHRKFASA-N 0.000 description 2
- DDBMKOCQWNFDBH-RHYQMDGZSA-N Arg-Thr-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O DDBMKOCQWNFDBH-RHYQMDGZSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- ZDOQDYFZNGASEY-BIIVOSGPSA-N Asn-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)N)N)C(=O)O ZDOQDYFZNGASEY-BIIVOSGPSA-N 0.000 description 2
- ZMWDUIIACVLIHK-GHCJXIJMSA-N Asn-Cys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)N)N ZMWDUIIACVLIHK-GHCJXIJMSA-N 0.000 description 2
- FTCGGKNCJZOPNB-WHFBIAKZSA-N Asn-Gly-Ser Chemical compound NC(=O)C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O FTCGGKNCJZOPNB-WHFBIAKZSA-N 0.000 description 2
- BZWRLDPIWKOVKB-ZPFDUUQYSA-N Asn-Leu-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BZWRLDPIWKOVKB-ZPFDUUQYSA-N 0.000 description 2
- NCFJQJRLQJEECD-NHCYSSNCSA-N Asn-Leu-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O NCFJQJRLQJEECD-NHCYSSNCSA-N 0.000 description 2
- COWITDLVHMZSIW-CIUDSAMLSA-N Asn-Lys-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O COWITDLVHMZSIW-CIUDSAMLSA-N 0.000 description 2
- VHQSGALUSWIYOD-QXEWZRGKSA-N Asn-Pro-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O VHQSGALUSWIYOD-QXEWZRGKSA-N 0.000 description 2
- ZUFPUBYQYWCMDB-NUMRIWBASA-N Asn-Thr-Glu Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZUFPUBYQYWCMDB-NUMRIWBASA-N 0.000 description 2
- KRXIWXCXOARFNT-ZLUOBGJFSA-N Asp-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O KRXIWXCXOARFNT-ZLUOBGJFSA-N 0.000 description 2
- UQBGYPFHWFZMCD-ZLUOBGJFSA-N Asp-Asn-Asn Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O UQBGYPFHWFZMCD-ZLUOBGJFSA-N 0.000 description 2
- VPSHHQXIWLGVDD-ZLUOBGJFSA-N Asp-Asp-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O VPSHHQXIWLGVDD-ZLUOBGJFSA-N 0.000 description 2
- XAJRHVUUVUPFQL-ACZMJKKPSA-N Asp-Glu-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XAJRHVUUVUPFQL-ACZMJKKPSA-N 0.000 description 2
- GHODABZPVZMWCE-FXQIFTODSA-N Asp-Glu-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O GHODABZPVZMWCE-FXQIFTODSA-N 0.000 description 2
- PDECQIHABNQRHN-GUBZILKMSA-N Asp-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(O)=O PDECQIHABNQRHN-GUBZILKMSA-N 0.000 description 2
- POTCZYQVVNXUIG-BQBZGAKWSA-N Asp-Gly-Pro Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(O)=O POTCZYQVVNXUIG-BQBZGAKWSA-N 0.000 description 2
- SVABRQFIHCSNCI-FOHZUACHSA-N Asp-Gly-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O SVABRQFIHCSNCI-FOHZUACHSA-N 0.000 description 2
- OGTCOKZFOJIZFG-CIUDSAMLSA-N Asp-His-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(O)=O OGTCOKZFOJIZFG-CIUDSAMLSA-N 0.000 description 2
- LIVXPXUVXFRWNY-CIUDSAMLSA-N Asp-Lys-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O LIVXPXUVXFRWNY-CIUDSAMLSA-N 0.000 description 2
- GKWFMNNNYZHJHV-SRVKXCTJSA-N Asp-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC(O)=O GKWFMNNNYZHJHV-SRVKXCTJSA-N 0.000 description 2
- RPUYTJJZXQBWDT-SRVKXCTJSA-N Asp-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N RPUYTJJZXQBWDT-SRVKXCTJSA-N 0.000 description 2
- HRVQDZOWMLFAOD-BIIVOSGPSA-N Asp-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N)C(=O)O HRVQDZOWMLFAOD-BIIVOSGPSA-N 0.000 description 2
- IQCJOIHDVFJQFV-LKXGYXEUSA-N Asp-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O IQCJOIHDVFJQFV-LKXGYXEUSA-N 0.000 description 2
- GXIUDSXIUSTSLO-QXEWZRGKSA-N Asp-Val-Met Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC(=O)O)N GXIUDSXIUSTSLO-QXEWZRGKSA-N 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 102100037086 Bone marrow stromal antigen 2 Human genes 0.000 description 2
- 102100036170 C-X-C motif chemokine 9 Human genes 0.000 description 2
- 210000003967 CLP Anatomy 0.000 description 2
- 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 2
- 102000001327 Chemokine CCL5 Human genes 0.000 description 2
- 108010055166 Chemokine CCL5 Proteins 0.000 description 2
- 241000710777 Classical swine fever virus Species 0.000 description 2
- 241000186227 Corynebacterium diphtheriae Species 0.000 description 2
- 241000710127 Cricket paralysis virus Species 0.000 description 2
- AMRLSQGGERHDHJ-FXQIFTODSA-N Cys-Ala-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AMRLSQGGERHDHJ-FXQIFTODSA-N 0.000 description 2
- OIMUAKUQOUEPCZ-WHFBIAKZSA-N Cys-Asn-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O OIMUAKUQOUEPCZ-WHFBIAKZSA-N 0.000 description 2
- UPJGYXRAPJWIHD-CIUDSAMLSA-N Cys-Asn-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O UPJGYXRAPJWIHD-CIUDSAMLSA-N 0.000 description 2
- NIPJKKSXHSBEMX-CIUDSAMLSA-N Cys-Asp-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)N NIPJKKSXHSBEMX-CIUDSAMLSA-N 0.000 description 2
- MWZSCEAYQCMROW-GUBZILKMSA-N Cys-Gln-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CS)N MWZSCEAYQCMROW-GUBZILKMSA-N 0.000 description 2
- HQZGVYJBRSISDT-BQBZGAKWSA-N Cys-Gly-Arg Chemical compound [H]N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O HQZGVYJBRSISDT-BQBZGAKWSA-N 0.000 description 2
- WVLZTXGTNGHPBO-SRVKXCTJSA-N Cys-Leu-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O WVLZTXGTNGHPBO-SRVKXCTJSA-N 0.000 description 2
- SWJYSDXMTPMBHO-FXQIFTODSA-N Cys-Pro-Ser Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O SWJYSDXMTPMBHO-FXQIFTODSA-N 0.000 description 2
- NXQCSPVUPLUTJH-WHFBIAKZSA-N Cys-Ser-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O NXQCSPVUPLUTJH-WHFBIAKZSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 241000709661 Enterovirus Species 0.000 description 2
- 241000214054 Equine rhinitis A virus Species 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 2
- IGNGBUVODQLMRJ-CIUDSAMLSA-N Gln-Ala-Met Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(O)=O IGNGBUVODQLMRJ-CIUDSAMLSA-N 0.000 description 2
- XXLBHPPXDUWYAG-XQXXSGGOSA-N Gln-Ala-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XXLBHPPXDUWYAG-XQXXSGGOSA-N 0.000 description 2
- LZRMPXRYLLTAJX-GUBZILKMSA-N Gln-Arg-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O LZRMPXRYLLTAJX-GUBZILKMSA-N 0.000 description 2
- PRBLYKYHAJEABA-SRVKXCTJSA-N Gln-Arg-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O PRBLYKYHAJEABA-SRVKXCTJSA-N 0.000 description 2
- XFKUFUJECJUQTQ-CIUDSAMLSA-N Gln-Gln-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XFKUFUJECJUQTQ-CIUDSAMLSA-N 0.000 description 2
- IVCOYUURLWQDJQ-LPEHRKFASA-N Gln-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O IVCOYUURLWQDJQ-LPEHRKFASA-N 0.000 description 2
- QQAPDATZKKTBIY-YUMQZZPRSA-N Gln-Gly-Met Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O QQAPDATZKKTBIY-YUMQZZPRSA-N 0.000 description 2
- ZBKUIQNCRIYVGH-SDDRHHMPSA-N Gln-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N ZBKUIQNCRIYVGH-SDDRHHMPSA-N 0.000 description 2
- YPMDZWPZFOZYFG-GUBZILKMSA-N Gln-Leu-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YPMDZWPZFOZYFG-GUBZILKMSA-N 0.000 description 2
- HSHCEAUPUPJPTE-JYJNAYRXSA-N Gln-Leu-Tyr Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N HSHCEAUPUPJPTE-JYJNAYRXSA-N 0.000 description 2
- MSHXWFKYXJTLEZ-CIUDSAMLSA-N Gln-Met-Asn Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N MSHXWFKYXJTLEZ-CIUDSAMLSA-N 0.000 description 2
- QBEWLBKBGXVVPD-RYUDHWBXSA-N Gln-Phe-Gly Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCC(=O)N)N QBEWLBKBGXVVPD-RYUDHWBXSA-N 0.000 description 2
- UESYBOXFJWJVSB-AVGNSLFASA-N Gln-Phe-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O UESYBOXFJWJVSB-AVGNSLFASA-N 0.000 description 2
- MQJDLNRXBOELJW-KKUMJFAQSA-N Gln-Pro-Phe Chemical compound N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(O)=O MQJDLNRXBOELJW-KKUMJFAQSA-N 0.000 description 2
- QGWXAMDECCKGRU-XVKPBYJWSA-N Gln-Val-Gly Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCC(N)=O)C(=O)NCC(O)=O QGWXAMDECCKGRU-XVKPBYJWSA-N 0.000 description 2
- VEYGCDYMOXHJLS-GVXVVHGQSA-N Gln-Val-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O VEYGCDYMOXHJLS-GVXVVHGQSA-N 0.000 description 2
- UTKICHUQEQBDGC-ACZMJKKPSA-N Glu-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N UTKICHUQEQBDGC-ACZMJKKPSA-N 0.000 description 2
- LKDIBBOKUAASNP-FXQIFTODSA-N Glu-Ala-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LKDIBBOKUAASNP-FXQIFTODSA-N 0.000 description 2
- RLZBLVSJDFHDBL-KBIXCLLPSA-N Glu-Ala-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RLZBLVSJDFHDBL-KBIXCLLPSA-N 0.000 description 2
- NLKVNZUFDPWPNL-YUMQZZPRSA-N Glu-Arg-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O NLKVNZUFDPWPNL-YUMQZZPRSA-N 0.000 description 2
- OJGLIOXAKGFFDW-SRVKXCTJSA-N Glu-Arg-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)O)N OJGLIOXAKGFFDW-SRVKXCTJSA-N 0.000 description 2
- XHUCVVHRLNPZSZ-CIUDSAMLSA-N Glu-Gln-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XHUCVVHRLNPZSZ-CIUDSAMLSA-N 0.000 description 2
- PVBBEKPHARMPHX-DCAQKATOSA-N Glu-Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCC(O)=O PVBBEKPHARMPHX-DCAQKATOSA-N 0.000 description 2
- CGOHAEBMDSEKFB-FXQIFTODSA-N Glu-Glu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O CGOHAEBMDSEKFB-FXQIFTODSA-N 0.000 description 2
- HNVFSTLPVJWIDV-CIUDSAMLSA-N Glu-Glu-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HNVFSTLPVJWIDV-CIUDSAMLSA-N 0.000 description 2
- SJPMNHCEWPTRBR-BQBZGAKWSA-N Glu-Glu-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O SJPMNHCEWPTRBR-BQBZGAKWSA-N 0.000 description 2
- KASDBWKLWJKTLJ-GUBZILKMSA-N Glu-Glu-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(O)=O KASDBWKLWJKTLJ-GUBZILKMSA-N 0.000 description 2
- QJCKNLPMTPXXEM-AUTRQRHGSA-N Glu-Glu-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O QJCKNLPMTPXXEM-AUTRQRHGSA-N 0.000 description 2
- XIKYNVKEUINBGL-IUCAKERBSA-N Glu-His-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)NCC(O)=O XIKYNVKEUINBGL-IUCAKERBSA-N 0.000 description 2
- NJPQBTJSYCKCNS-HVTMNAMFSA-N Glu-His-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCC(=O)O)N NJPQBTJSYCKCNS-HVTMNAMFSA-N 0.000 description 2
- QLPYYTDOUQNJGQ-AVGNSLFASA-N Glu-His-Lys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N QLPYYTDOUQNJGQ-AVGNSLFASA-N 0.000 description 2
- WVTIBGWZUMJBFY-GUBZILKMSA-N Glu-His-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O WVTIBGWZUMJBFY-GUBZILKMSA-N 0.000 description 2
- PJBVXVBTTFZPHJ-GUBZILKMSA-N Glu-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)O)N PJBVXVBTTFZPHJ-GUBZILKMSA-N 0.000 description 2
- JHSRJMUJOGLIHK-GUBZILKMSA-N Glu-Met-Glu Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)O)N JHSRJMUJOGLIHK-GUBZILKMSA-N 0.000 description 2
- LHIPZASLKPYDPI-AVGNSLFASA-N Glu-Phe-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O LHIPZASLKPYDPI-AVGNSLFASA-N 0.000 description 2
- RXESHTOTINOODU-JYJNAYRXSA-N Glu-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CCC(=O)O)N RXESHTOTINOODU-JYJNAYRXSA-N 0.000 description 2
- QJVZSVUYZFYLFQ-CIUDSAMLSA-N Glu-Pro-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O QJVZSVUYZFYLFQ-CIUDSAMLSA-N 0.000 description 2
- AAJHGGDRKHYSDH-GUBZILKMSA-N Glu-Pro-Gln Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O AAJHGGDRKHYSDH-GUBZILKMSA-N 0.000 description 2
- MRWYPDWDZSLWJM-ACZMJKKPSA-N Glu-Ser-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O MRWYPDWDZSLWJM-ACZMJKKPSA-N 0.000 description 2
- YPHPEHMXOYTEQG-LAEOZQHASA-N Glu-Val-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCC(O)=O YPHPEHMXOYTEQG-LAEOZQHASA-N 0.000 description 2
- HQTDNEZTGZUWSY-XVKPBYJWSA-N Glu-Val-Gly Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCC(O)=O)C(=O)NCC(O)=O HQTDNEZTGZUWSY-XVKPBYJWSA-N 0.000 description 2
- RMWAOBGCZZSJHE-UMNHJUIQSA-N Glu-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N RMWAOBGCZZSJHE-UMNHJUIQSA-N 0.000 description 2
- PUUYVMYCMIWHFE-BQBZGAKWSA-N Gly-Ala-Arg Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PUUYVMYCMIWHFE-BQBZGAKWSA-N 0.000 description 2
- VSVZIEVNUYDAFR-YUMQZZPRSA-N Gly-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN VSVZIEVNUYDAFR-YUMQZZPRSA-N 0.000 description 2
- LJPIRKICOISLKN-WHFBIAKZSA-N Gly-Ala-Ser Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O LJPIRKICOISLKN-WHFBIAKZSA-N 0.000 description 2
- QSDKBRMVXSWAQE-BFHQHQDPSA-N Gly-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN QSDKBRMVXSWAQE-BFHQHQDPSA-N 0.000 description 2
- DWUKOTKSTDWGAE-BQBZGAKWSA-N Gly-Asn-Arg Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DWUKOTKSTDWGAE-BQBZGAKWSA-N 0.000 description 2
- FMNHBTKMRFVGRO-FOHZUACHSA-N Gly-Asn-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CN FMNHBTKMRFVGRO-FOHZUACHSA-N 0.000 description 2
- XBWMTPAIUQIWKA-BYULHYEWSA-N Gly-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CN XBWMTPAIUQIWKA-BYULHYEWSA-N 0.000 description 2
- YZACQYVWLCQWBT-BQBZGAKWSA-N Gly-Cys-Arg Chemical compound [H]NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O YZACQYVWLCQWBT-BQBZGAKWSA-N 0.000 description 2
- VUUOMYFPWDYETE-WDSKDSINSA-N Gly-Gln-Cys Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN VUUOMYFPWDYETE-WDSKDSINSA-N 0.000 description 2
- GNPVTZJUUBPZKW-WDSKDSINSA-N Gly-Gln-Ser Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GNPVTZJUUBPZKW-WDSKDSINSA-N 0.000 description 2
- XMPXVJIDADUOQB-RCOVLWMOSA-N Gly-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C([O-])=O)NC(=O)CNC(=O)C[NH3+] XMPXVJIDADUOQB-RCOVLWMOSA-N 0.000 description 2
- XPJBQTCXPJNIFE-ZETCQYMHSA-N Gly-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)CN XPJBQTCXPJNIFE-ZETCQYMHSA-N 0.000 description 2
- TVDHVLGFJSHPAX-UWVGGRQHSA-N Gly-His-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 TVDHVLGFJSHPAX-UWVGGRQHSA-N 0.000 description 2
- BHPQOIPBLYJNAW-NGZCFLSTSA-N Gly-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN BHPQOIPBLYJNAW-NGZCFLSTSA-N 0.000 description 2
- MHZXESQPPXOING-KBPBESRZSA-N Gly-Lys-Phe Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O MHZXESQPPXOING-KBPBESRZSA-N 0.000 description 2
- JJGBXTYGTKWGAT-YUMQZZPRSA-N Gly-Pro-Glu Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O JJGBXTYGTKWGAT-YUMQZZPRSA-N 0.000 description 2
- NSVOVKWEKGEOQB-LURJTMIESA-N Gly-Pro-Gly Chemical compound NCC(=O)N1CCC[C@H]1C(=O)NCC(O)=O NSVOVKWEKGEOQB-LURJTMIESA-N 0.000 description 2
- OOCFXNOVSLSHAB-IUCAKERBSA-N Gly-Pro-Pro Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OOCFXNOVSLSHAB-IUCAKERBSA-N 0.000 description 2
- HAOUOFNNJJLVNS-BQBZGAKWSA-N Gly-Pro-Ser Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O HAOUOFNNJJLVNS-BQBZGAKWSA-N 0.000 description 2
- YOBGUCWZPXJHTN-BQBZGAKWSA-N Gly-Ser-Arg Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YOBGUCWZPXJHTN-BQBZGAKWSA-N 0.000 description 2
- SOEGEPHNZOISMT-BYPYZUCNSA-N Gly-Ser-Gly Chemical compound NCC(=O)N[C@@H](CO)C(=O)NCC(O)=O SOEGEPHNZOISMT-BYPYZUCNSA-N 0.000 description 2
- WNGHUXFWEWTKAO-YUMQZZPRSA-N Gly-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN WNGHUXFWEWTKAO-YUMQZZPRSA-N 0.000 description 2
- POJJAZJHBGXEGM-YUMQZZPRSA-N Gly-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)CN POJJAZJHBGXEGM-YUMQZZPRSA-N 0.000 description 2
- JSLVAHYTAJJEQH-QWRGUYRKSA-N Gly-Ser-Phe Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JSLVAHYTAJJEQH-QWRGUYRKSA-N 0.000 description 2
- ZLCLYFGMKFCDCN-XPUUQOCRSA-N Gly-Ser-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(O)=O ZLCLYFGMKFCDCN-XPUUQOCRSA-N 0.000 description 2
- BAYQNCWLXIDLHX-ONGXEEELSA-N Gly-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CN BAYQNCWLXIDLHX-ONGXEEELSA-N 0.000 description 2
- 208000015023 Graves' disease Diseases 0.000 description 2
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 2
- 241000590002 Helicobacter pylori Species 0.000 description 2
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 2
- DCRODRAURLJOFY-XPUUQOCRSA-N His-Ala-Gly Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)NCC(O)=O DCRODRAURLJOFY-XPUUQOCRSA-N 0.000 description 2
- PROLDOGUBQJNPG-RWMBFGLXSA-N His-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC2=CN=CN2)N)C(=O)O PROLDOGUBQJNPG-RWMBFGLXSA-N 0.000 description 2
- TVRMJKNELJKNRS-GUBZILKMSA-N His-Glu-Asn Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N TVRMJKNELJKNRS-GUBZILKMSA-N 0.000 description 2
- PGTISAJTWZPFGN-PEXQALLHSA-N His-Gly-Ile Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O PGTISAJTWZPFGN-PEXQALLHSA-N 0.000 description 2
- RGPWUJOMKFYFSR-QWRGUYRKSA-N His-Gly-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O RGPWUJOMKFYFSR-QWRGUYRKSA-N 0.000 description 2
- JBSLJUPMTYLLFH-MELADBBJSA-N His-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC3=CN=CN3)N)C(=O)O JBSLJUPMTYLLFH-MELADBBJSA-N 0.000 description 2
- FSOXZQBMPBQKGJ-QSFUFRPTSA-N His-Ile-Ala Chemical compound [O-]C(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]([NH3+])CC1=CN=CN1 FSOXZQBMPBQKGJ-QSFUFRPTSA-N 0.000 description 2
- ORERHHPZDDEMSC-VGDYDELISA-N His-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N ORERHHPZDDEMSC-VGDYDELISA-N 0.000 description 2
- VFBZWZXKCVBTJR-SRVKXCTJSA-N His-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N VFBZWZXKCVBTJR-SRVKXCTJSA-N 0.000 description 2
- GJMHMDKCJPQJOI-IHRRRGAJSA-N His-Lys-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CN=CN1 GJMHMDKCJPQJOI-IHRRRGAJSA-N 0.000 description 2
- CKRJBQJIGOEKMC-SRVKXCTJSA-N His-Lys-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O CKRJBQJIGOEKMC-SRVKXCTJSA-N 0.000 description 2
- BZAQOPHNBFOOJS-DCAQKATOSA-N His-Pro-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O BZAQOPHNBFOOJS-DCAQKATOSA-N 0.000 description 2
- KAXZXLSXFWSNNZ-XVYDVKMFSA-N His-Ser-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O KAXZXLSXFWSNNZ-XVYDVKMFSA-N 0.000 description 2
- 101000740785 Homo sapiens Bone marrow stromal antigen 2 Proteins 0.000 description 2
- 101000962077 Homo sapiens Myocyte-specific enhancer factor 2C Proteins 0.000 description 2
- 101000857682 Homo sapiens Runt-related transcription factor 2 Proteins 0.000 description 2
- 101000585484 Homo sapiens Signal transducer and activator of transcription 1-alpha/beta Proteins 0.000 description 2
- 101000826373 Homo sapiens Signal transducer and activator of transcription 3 Proteins 0.000 description 2
- DVRDRICMWUSCBN-UKJIMTQDSA-N Ile-Gln-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N DVRDRICMWUSCBN-UKJIMTQDSA-N 0.000 description 2
- TVSPLSZTKTUYLV-ZPFDUUQYSA-N Ile-Glu-Met Chemical compound N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)O TVSPLSZTKTUYLV-ZPFDUUQYSA-N 0.000 description 2
- KTNGVMMGIQWIDV-OSUNSFLBSA-N Ile-Pro-Thr Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O KTNGVMMGIQWIDV-OSUNSFLBSA-N 0.000 description 2
- ZNOBVZFCHNHKHA-KBIXCLLPSA-N Ile-Ser-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N ZNOBVZFCHNHKHA-KBIXCLLPSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 102000000646 Interleukin-3 Human genes 0.000 description 2
- IBMVEYRWAWIOTN-UHFFFAOYSA-N L-Leucyl-L-Arginyl-L-Proline Natural products CC(C)CC(N)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(O)=O IBMVEYRWAWIOTN-UHFFFAOYSA-N 0.000 description 2
- UGTHTQWIQKEDEH-BQBZGAKWSA-N L-alanyl-L-prolylglycine zwitterion Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UGTHTQWIQKEDEH-BQBZGAKWSA-N 0.000 description 2
- LZDNBBYBDGBADK-UHFFFAOYSA-N L-valyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C(C)C)C(O)=O)=CNC2=C1 LZDNBBYBDGBADK-UHFFFAOYSA-N 0.000 description 2
- 241000880493 Leptailurus serval Species 0.000 description 2
- KWTVLKBOQATPHJ-SRVKXCTJSA-N Leu-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(C)C)N KWTVLKBOQATPHJ-SRVKXCTJSA-N 0.000 description 2
- NTRAGDHVSGKUSF-AVGNSLFASA-N Leu-Arg-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NTRAGDHVSGKUSF-AVGNSLFASA-N 0.000 description 2
- GRZSCTXVCDUIPO-SRVKXCTJSA-N Leu-Arg-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O GRZSCTXVCDUIPO-SRVKXCTJSA-N 0.000 description 2
- KSZCCRIGNVSHFH-UWVGGRQHSA-N Leu-Arg-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O KSZCCRIGNVSHFH-UWVGGRQHSA-N 0.000 description 2
- QUAAUWNLWMLERT-IHRRRGAJSA-N Leu-Arg-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(C)C)C(O)=O QUAAUWNLWMLERT-IHRRRGAJSA-N 0.000 description 2
- FIJMQLGQLBLBOL-HJGDQZAQSA-N Leu-Asn-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FIJMQLGQLBLBOL-HJGDQZAQSA-N 0.000 description 2
- PIHFVNPEAHFNLN-KKUMJFAQSA-N Leu-Cys-Tyr Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N PIHFVNPEAHFNLN-KKUMJFAQSA-N 0.000 description 2
- DXYBNWJZJVSZAE-GUBZILKMSA-N Leu-Gln-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N DXYBNWJZJVSZAE-GUBZILKMSA-N 0.000 description 2
- DPWGZWUMUUJQDT-IUCAKERBSA-N Leu-Gln-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O DPWGZWUMUUJQDT-IUCAKERBSA-N 0.000 description 2
- BOFAFKVZQUMTID-AVGNSLFASA-N Leu-Gln-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N BOFAFKVZQUMTID-AVGNSLFASA-N 0.000 description 2
- CQGSYZCULZMEDE-SRVKXCTJSA-N Leu-Gln-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(O)=O CQGSYZCULZMEDE-SRVKXCTJSA-N 0.000 description 2
- CQGSYZCULZMEDE-UHFFFAOYSA-N Leu-Gln-Pro Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)N1CCCC1C(O)=O CQGSYZCULZMEDE-UHFFFAOYSA-N 0.000 description 2
- HFBCHNRFRYLZNV-GUBZILKMSA-N Leu-Glu-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HFBCHNRFRYLZNV-GUBZILKMSA-N 0.000 description 2
- HQUXQAMSWFIRET-AVGNSLFASA-N Leu-Glu-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN HQUXQAMSWFIRET-AVGNSLFASA-N 0.000 description 2
- YFBBUHJJUXXZOF-UWVGGRQHSA-N Leu-Gly-Pro Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(O)=O YFBBUHJJUXXZOF-UWVGGRQHSA-N 0.000 description 2
- POZULHZYLPGXMR-ONGXEEELSA-N Leu-Gly-Val Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O POZULHZYLPGXMR-ONGXEEELSA-N 0.000 description 2
- LKXANTUNFMVCNF-IHPCNDPISA-N Leu-His-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O LKXANTUNFMVCNF-IHPCNDPISA-N 0.000 description 2
- QLDHBYRUNQZIJQ-DKIMLUQUSA-N Leu-Ile-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QLDHBYRUNQZIJQ-DKIMLUQUSA-N 0.000 description 2
- TVEOVCYCYGKVPP-HSCHXYMDSA-N Leu-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC(C)C)N TVEOVCYCYGKVPP-HSCHXYMDSA-N 0.000 description 2
- PDQDCFBVYXEFSD-SRVKXCTJSA-N Leu-Leu-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O PDQDCFBVYXEFSD-SRVKXCTJSA-N 0.000 description 2
- XVZCXCTYGHPNEM-UHFFFAOYSA-N Leu-Leu-Pro Natural products CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O XVZCXCTYGHPNEM-UHFFFAOYSA-N 0.000 description 2
- IEWBEPKLKUXQBU-VOAKCMCISA-N Leu-Leu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IEWBEPKLKUXQBU-VOAKCMCISA-N 0.000 description 2
- LVTJJOJKDCVZGP-QWRGUYRKSA-N Leu-Lys-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O LVTJJOJKDCVZGP-QWRGUYRKSA-N 0.000 description 2
- AKVBOOKXVAMKSS-GUBZILKMSA-N Leu-Ser-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O AKVBOOKXVAMKSS-GUBZILKMSA-N 0.000 description 2
- AMSSKPUHBUQBOQ-SRVKXCTJSA-N Leu-Ser-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N AMSSKPUHBUQBOQ-SRVKXCTJSA-N 0.000 description 2
- ICYRCNICGBJLGM-HJGDQZAQSA-N Leu-Thr-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(O)=O ICYRCNICGBJLGM-HJGDQZAQSA-N 0.000 description 2
- AIQWYVFNBNNOLU-RHYQMDGZSA-N Leu-Thr-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O AIQWYVFNBNNOLU-RHYQMDGZSA-N 0.000 description 2
- ZGGVHTQAPHVMKM-IHPCNDPISA-N Leu-Trp-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CCCCN)C(=O)O)N ZGGVHTQAPHVMKM-IHPCNDPISA-N 0.000 description 2
- AXVIGSRGTMNSJU-YESZJQIVSA-N Leu-Tyr-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N2CCC[C@@H]2C(=O)O)N AXVIGSRGTMNSJU-YESZJQIVSA-N 0.000 description 2
- XZNJZXJZBMBGGS-NHCYSSNCSA-N Leu-Val-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O XZNJZXJZBMBGGS-NHCYSSNCSA-N 0.000 description 2
- MPOHDJKRBLVGCT-CIUDSAMLSA-N Lys-Ala-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N MPOHDJKRBLVGCT-CIUDSAMLSA-N 0.000 description 2
- YRWCPXOFBKTCFY-NUTKFTJISA-N Lys-Ala-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CCCCN)N YRWCPXOFBKTCFY-NUTKFTJISA-N 0.000 description 2
- CLBGMWIYPYAZPR-AVGNSLFASA-N Lys-Arg-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O CLBGMWIYPYAZPR-AVGNSLFASA-N 0.000 description 2
- VHNOAIFVYUQOOY-XUXIUFHCSA-N Lys-Arg-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VHNOAIFVYUQOOY-XUXIUFHCSA-N 0.000 description 2
- NQCJGQHHYZNUDK-DCAQKATOSA-N Lys-Arg-Ser Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CCCN=C(N)N NQCJGQHHYZNUDK-DCAQKATOSA-N 0.000 description 2
- OVIVOCSURJYCTM-GUBZILKMSA-N Lys-Asp-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O OVIVOCSURJYCTM-GUBZILKMSA-N 0.000 description 2
- MWVUEPNEPWMFBD-SRVKXCTJSA-N Lys-Cys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CCCCN MWVUEPNEPWMFBD-SRVKXCTJSA-N 0.000 description 2
- GGNOBVSOZPHLCE-GUBZILKMSA-N Lys-Gln-Asp Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O GGNOBVSOZPHLCE-GUBZILKMSA-N 0.000 description 2
- GJJQCBVRWDGLMQ-GUBZILKMSA-N Lys-Glu-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O GJJQCBVRWDGLMQ-GUBZILKMSA-N 0.000 description 2
- GCMWRRQAKQXDED-IUCAKERBSA-N Lys-Glu-Gly Chemical compound [NH3+]CCCC[C@H]([NH3+])C(=O)N[C@@H](CCC([O-])=O)C(=O)NCC([O-])=O GCMWRRQAKQXDED-IUCAKERBSA-N 0.000 description 2
- GQZMPWBZQALKJO-UWVGGRQHSA-N Lys-Gly-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O GQZMPWBZQALKJO-UWVGGRQHSA-N 0.000 description 2
- QZONCCHVHCOBSK-YUMQZZPRSA-N Lys-Gly-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O QZONCCHVHCOBSK-YUMQZZPRSA-N 0.000 description 2
- RFQATBGBLDAKGI-VHSXEESVSA-N Lys-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCCCN)N)C(=O)O RFQATBGBLDAKGI-VHSXEESVSA-N 0.000 description 2
- SKRGVGLIRUGANF-AVGNSLFASA-N Lys-Leu-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SKRGVGLIRUGANF-AVGNSLFASA-N 0.000 description 2
- RBEATVHTWHTHTJ-KKUMJFAQSA-N Lys-Leu-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O RBEATVHTWHTHTJ-KKUMJFAQSA-N 0.000 description 2
- XIZQPFCRXLUNMK-BZSNNMDCSA-N Lys-Leu-Phe Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCCCN)N XIZQPFCRXLUNMK-BZSNNMDCSA-N 0.000 description 2
- WBSCNDJQPKSPII-KKUMJFAQSA-N Lys-Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O WBSCNDJQPKSPII-KKUMJFAQSA-N 0.000 description 2
- JMNRXRPBHFGXQX-GUBZILKMSA-N Lys-Ser-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O JMNRXRPBHFGXQX-GUBZILKMSA-N 0.000 description 2
- ZUGVARDEGWMMLK-SRVKXCTJSA-N Lys-Ser-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN ZUGVARDEGWMMLK-SRVKXCTJSA-N 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 2
- YRAWWKUTNBILNT-FXQIFTODSA-N Met-Ala-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O YRAWWKUTNBILNT-FXQIFTODSA-N 0.000 description 2
- OGAZPKJHHZPYFK-GARJFASQSA-N Met-Glu-Pro Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N OGAZPKJHHZPYFK-GARJFASQSA-N 0.000 description 2
- AFFKUNVPPLQUGA-DCAQKATOSA-N Met-Leu-Ala Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O AFFKUNVPPLQUGA-DCAQKATOSA-N 0.000 description 2
- XPVCDCMPKCERFT-GUBZILKMSA-N Met-Ser-Arg Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XPVCDCMPKCERFT-GUBZILKMSA-N 0.000 description 2
- KPVLLNDCBYXKNV-CYDGBPFRSA-N Met-Val-Ile Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KPVLLNDCBYXKNV-CYDGBPFRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000003250 Mixed connective tissue disease Diseases 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000714177 Murine leukemia virus Species 0.000 description 2
- 101100323954 Mus musculus Arid5a gene Proteins 0.000 description 2
- 101100493742 Mus musculus Bcl11a gene Proteins 0.000 description 2
- 101100346717 Mus musculus Cbfa2t3 gene Proteins 0.000 description 2
- 101100114767 Mus musculus Creb3l2 gene Proteins 0.000 description 2
- 101100226191 Mus musculus Ets1 gene Proteins 0.000 description 2
- 101100230659 Mus musculus Hdac5 gene Proteins 0.000 description 2
- 101100338879 Mus musculus Hhex gene Proteins 0.000 description 2
- 101100451911 Mus musculus Hoxa5 gene Proteins 0.000 description 2
- 101100340263 Mus musculus Id3 gene Proteins 0.000 description 2
- 101100452381 Mus musculus Ikzf1 gene Proteins 0.000 description 2
- 101100452384 Mus musculus Ikzf2 gene Proteins 0.000 description 2
- 101100452387 Mus musculus Ikzf3 gene Proteins 0.000 description 2
- 101100232852 Mus musculus Ikzf5 gene Proteins 0.000 description 2
- 101100341162 Mus musculus Irf7 gene Proteins 0.000 description 2
- 101100290705 Mus musculus Mef2c gene Proteins 0.000 description 2
- 101100459253 Mus musculus Myb gene Proteins 0.000 description 2
- 101100476217 Mus musculus Runx2 gene Proteins 0.000 description 2
- 101100366419 Mus musculus Spib gene Proteins 0.000 description 2
- 101100096914 Mus musculus Stat1 gene Proteins 0.000 description 2
- 101100366881 Mus musculus Stat3 gene Proteins 0.000 description 2
- 101100178756 Mus musculus Tcf12 gene Proteins 0.000 description 2
- 101100126599 Mus musculus Tcf4 gene Proteins 0.000 description 2
- 101100099163 Mus musculus Tcf7l2 gene Proteins 0.000 description 2
- 101100098616 Mus musculus Tsc22d1 gene Proteins 0.000 description 2
- 241000186367 Mycobacterium avium Species 0.000 description 2
- 241000187484 Mycobacterium gordonae Species 0.000 description 2
- 241000186364 Mycobacterium intracellulare Species 0.000 description 2
- PESQCPHRXOFIPX-UHFFFAOYSA-N N-L-methionyl-L-tyrosine Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 PESQCPHRXOFIPX-UHFFFAOYSA-N 0.000 description 2
- 108010066427 N-valyltryptophan Proteins 0.000 description 2
- 108010047562 NGR peptide Proteins 0.000 description 2
- BQVUABVGYYSDCJ-UHFFFAOYSA-N Nalpha-L-Leucyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-UHFFFAOYSA-N 0.000 description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
- VHWOBXIWBDWZHK-IHRRRGAJSA-N Phe-Arg-Asp Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](CC(O)=O)C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 VHWOBXIWBDWZHK-IHRRRGAJSA-N 0.000 description 2
- PLNHHOXNVSYKOB-JYJNAYRXSA-N Phe-Arg-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC1=CC=CC=C1)N PLNHHOXNVSYKOB-JYJNAYRXSA-N 0.000 description 2
- ALHULIGNEXGFRM-QWRGUYRKSA-N Phe-Cys-Gly Chemical compound OC(=O)CNC(=O)[C@H](CS)NC(=O)[C@@H](N)CC1=CC=CC=C1 ALHULIGNEXGFRM-QWRGUYRKSA-N 0.000 description 2
- IDUCUXTUHHIQIP-SOUVJXGZSA-N Phe-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O IDUCUXTUHHIQIP-SOUVJXGZSA-N 0.000 description 2
- OPEVYHFJXLCCRT-AVGNSLFASA-N Phe-Gln-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O OPEVYHFJXLCCRT-AVGNSLFASA-N 0.000 description 2
- JEBWZLWTRPZQRX-QWRGUYRKSA-N Phe-Gly-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O JEBWZLWTRPZQRX-QWRGUYRKSA-N 0.000 description 2
- ZLGQEBCCANLYRA-RYUDHWBXSA-N Phe-Gly-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O ZLGQEBCCANLYRA-RYUDHWBXSA-N 0.000 description 2
- CMHTUJQZQXFNTQ-OEAJRASXSA-N Phe-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)N)O CMHTUJQZQXFNTQ-OEAJRASXSA-N 0.000 description 2
- TXJJXEXCZBHDNA-ACRUOGEOSA-N Phe-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC3=CN=CN3)C(=O)O)N TXJJXEXCZBHDNA-ACRUOGEOSA-N 0.000 description 2
- WWPAHTZOWURIMR-ULQDDVLXSA-N Phe-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 WWPAHTZOWURIMR-ULQDDVLXSA-N 0.000 description 2
- SHUFSZDAIPLZLF-BEAPCOKYSA-N Phe-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N)O SHUFSZDAIPLZLF-BEAPCOKYSA-N 0.000 description 2
- BAONJAHBAUDJKA-BZSNNMDCSA-N Phe-Tyr-Asp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(O)=O)C(O)=O)C1=CC=CC=C1 BAONJAHBAUDJKA-BZSNNMDCSA-N 0.000 description 2
- RGMLUHANLDVMPB-ULQDDVLXSA-N Phe-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N RGMLUHANLDVMPB-ULQDDVLXSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- DRVIASBABBMZTF-GUBZILKMSA-N Pro-Ala-Met Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@@H]1CCCN1 DRVIASBABBMZTF-GUBZILKMSA-N 0.000 description 2
- CGBYDGAJHSOGFQ-LPEHRKFASA-N Pro-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 CGBYDGAJHSOGFQ-LPEHRKFASA-N 0.000 description 2
- SSSFPISOZOLQNP-GUBZILKMSA-N Pro-Arg-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O SSSFPISOZOLQNP-GUBZILKMSA-N 0.000 description 2
- IHCXPSYCHXFXKT-DCAQKATOSA-N Pro-Arg-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O IHCXPSYCHXFXKT-DCAQKATOSA-N 0.000 description 2
- QBFONMUYNSNKIX-AVGNSLFASA-N Pro-Arg-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O QBFONMUYNSNKIX-AVGNSLFASA-N 0.000 description 2
- ORPZXBQTEHINPB-SRVKXCTJSA-N Pro-Arg-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H]1CCCN1)C(O)=O ORPZXBQTEHINPB-SRVKXCTJSA-N 0.000 description 2
- HXOLCSYHGRNXJJ-IHRRRGAJSA-N Pro-Asp-Phe Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HXOLCSYHGRNXJJ-IHRRRGAJSA-N 0.000 description 2
- HJSCRFZVGXAGNG-SRVKXCTJSA-N Pro-Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1 HJSCRFZVGXAGNG-SRVKXCTJSA-N 0.000 description 2
- LHALYDBUDCWMDY-CIUDSAMLSA-N Pro-Glu-Ala Chemical compound C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1)C(O)=O LHALYDBUDCWMDY-CIUDSAMLSA-N 0.000 description 2
- VYWNORHENYEQDW-YUMQZZPRSA-N Pro-Gly-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 VYWNORHENYEQDW-YUMQZZPRSA-N 0.000 description 2
- FEVDNIBDCRKMER-IUCAKERBSA-N Pro-Gly-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1 FEVDNIBDCRKMER-IUCAKERBSA-N 0.000 description 2
- LCUOTSLIVGSGAU-AVGNSLFASA-N Pro-His-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O LCUOTSLIVGSGAU-AVGNSLFASA-N 0.000 description 2
- YXHYJEPDKSYPSQ-AVGNSLFASA-N Pro-Leu-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 YXHYJEPDKSYPSQ-AVGNSLFASA-N 0.000 description 2
- CLJLVCYFABNTHP-DCAQKATOSA-N Pro-Leu-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O CLJLVCYFABNTHP-DCAQKATOSA-N 0.000 description 2
- GURGCNUWVSDYTP-SRVKXCTJSA-N Pro-Leu-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GURGCNUWVSDYTP-SRVKXCTJSA-N 0.000 description 2
- XYSXOCIWCPFOCG-IHRRRGAJSA-N Pro-Leu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O XYSXOCIWCPFOCG-IHRRRGAJSA-N 0.000 description 2
- FKYKZHOKDOPHSA-DCAQKATOSA-N Pro-Leu-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O FKYKZHOKDOPHSA-DCAQKATOSA-N 0.000 description 2
- INDVYIOKMXFQFM-SRVKXCTJSA-N Pro-Lys-Gln Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)O INDVYIOKMXFQFM-SRVKXCTJSA-N 0.000 description 2
- ULWBBFKQBDNGOY-RWMBFGLXSA-N Pro-Lys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@@H]2C(=O)O ULWBBFKQBDNGOY-RWMBFGLXSA-N 0.000 description 2
- QGLFRQCECIWXFA-RCWTZXSCSA-N Pro-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1)O QGLFRQCECIWXFA-RCWTZXSCSA-N 0.000 description 2
- VGVCNKSUVSZEIE-IHRRRGAJSA-N Pro-Phe-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O VGVCNKSUVSZEIE-IHRRRGAJSA-N 0.000 description 2
- GFHXZNVJIKMAGO-IHRRRGAJSA-N Pro-Phe-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O GFHXZNVJIKMAGO-IHRRRGAJSA-N 0.000 description 2
- LEIKGVHQTKHOLM-IUCAKERBSA-N Pro-Pro-Gly Chemical compound OC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 LEIKGVHQTKHOLM-IUCAKERBSA-N 0.000 description 2
- SEZGGSHLMROBFX-CIUDSAMLSA-N Pro-Ser-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O SEZGGSHLMROBFX-CIUDSAMLSA-N 0.000 description 2
- KIDXAAQVMNLJFQ-KZVJFYERSA-N Pro-Thr-Ala Chemical compound C[C@@H](O)[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](C)C(O)=O KIDXAAQVMNLJFQ-KZVJFYERSA-N 0.000 description 2
- IURWWZYKYPEANQ-HJGDQZAQSA-N Pro-Thr-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O IURWWZYKYPEANQ-HJGDQZAQSA-N 0.000 description 2
- AIOWVDNPESPXRB-YTWAJWBKSA-N Pro-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2)O AIOWVDNPESPXRB-YTWAJWBKSA-N 0.000 description 2
- FYXCBXDAMPEHIQ-FHWLQOOXSA-N Pro-Trp-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CCCCN)C(=O)O FYXCBXDAMPEHIQ-FHWLQOOXSA-N 0.000 description 2
- OOZJHTXCLJUODH-QXEWZRGKSA-N Pro-Val-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 OOZJHTXCLJUODH-QXEWZRGKSA-N 0.000 description 2
- ZMLRZBWCXPQADC-TUAOUCFPSA-N Pro-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 ZMLRZBWCXPQADC-TUAOUCFPSA-N 0.000 description 2
- YDTUEBLEAVANFH-RCWTZXSCSA-N Pro-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 YDTUEBLEAVANFH-RCWTZXSCSA-N 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- SRTCFKGBYBZRHA-ACZMJKKPSA-N Ser-Ala-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SRTCFKGBYBZRHA-ACZMJKKPSA-N 0.000 description 2
- BTKUIVBNGBFTTP-WHFBIAKZSA-N Ser-Ala-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)NCC(O)=O BTKUIVBNGBFTTP-WHFBIAKZSA-N 0.000 description 2
- IDQFQFVEWMWRQQ-DLOVCJGASA-N Ser-Ala-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O IDQFQFVEWMWRQQ-DLOVCJGASA-N 0.000 description 2
- YUSRGTQIPCJNHQ-CIUDSAMLSA-N Ser-Arg-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O YUSRGTQIPCJNHQ-CIUDSAMLSA-N 0.000 description 2
- HQTKVSCNCDLXSX-BQBZGAKWSA-N Ser-Arg-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O HQTKVSCNCDLXSX-BQBZGAKWSA-N 0.000 description 2
- WDXYVIIVDIDOSX-DCAQKATOSA-N Ser-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N WDXYVIIVDIDOSX-DCAQKATOSA-N 0.000 description 2
- VAUMZJHYZQXZBQ-WHFBIAKZSA-N Ser-Asn-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O VAUMZJHYZQXZBQ-WHFBIAKZSA-N 0.000 description 2
- QPFJSHSJFIYDJZ-GHCJXIJMSA-N Ser-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CO QPFJSHSJFIYDJZ-GHCJXIJMSA-N 0.000 description 2
- WTPKKLMBNBCCNL-ACZMJKKPSA-N Ser-Cys-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N WTPKKLMBNBCCNL-ACZMJKKPSA-N 0.000 description 2
- OJPHFSOMBZKQKQ-GUBZILKMSA-N Ser-Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CO OJPHFSOMBZKQKQ-GUBZILKMSA-N 0.000 description 2
- DGPGKMKUNGKHPK-QEJZJMRPSA-N Ser-Gln-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N DGPGKMKUNGKHPK-QEJZJMRPSA-N 0.000 description 2
- SQBLRDDJTUJDMV-ACZMJKKPSA-N Ser-Glu-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O SQBLRDDJTUJDMV-ACZMJKKPSA-N 0.000 description 2
- BRGQQXQKPUCUJQ-KBIXCLLPSA-N Ser-Glu-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BRGQQXQKPUCUJQ-KBIXCLLPSA-N 0.000 description 2
- GZBKRJVCRMZAST-XKBZYTNZSA-N Ser-Glu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZBKRJVCRMZAST-XKBZYTNZSA-N 0.000 description 2
- AEGUWTFAQQWVLC-BQBZGAKWSA-N Ser-Gly-Arg Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O AEGUWTFAQQWVLC-BQBZGAKWSA-N 0.000 description 2
- SFTZWNJFZYOLBD-ZDLURKLDSA-N Ser-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO SFTZWNJFZYOLBD-ZDLURKLDSA-N 0.000 description 2
- LWMQRHDTXHQQOV-MXAVVETBSA-N Ser-Ile-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LWMQRHDTXHQQOV-MXAVVETBSA-N 0.000 description 2
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 2
- XUDRHBPSPAPDJP-SRVKXCTJSA-N Ser-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CO XUDRHBPSPAPDJP-SRVKXCTJSA-N 0.000 description 2
- ZGFRMNZZTOVBOU-CIUDSAMLSA-N Ser-Met-Gln Chemical compound N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)O ZGFRMNZZTOVBOU-CIUDSAMLSA-N 0.000 description 2
- ASGYVPAVFNDZMA-GUBZILKMSA-N Ser-Met-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)N ASGYVPAVFNDZMA-GUBZILKMSA-N 0.000 description 2
- ZKBKUWQVDWWSRI-BZSNNMDCSA-N Ser-Phe-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZKBKUWQVDWWSRI-BZSNNMDCSA-N 0.000 description 2
- BSXKBOUZDAZXHE-CIUDSAMLSA-N Ser-Pro-Glu Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O BSXKBOUZDAZXHE-CIUDSAMLSA-N 0.000 description 2
- RHAPJNVNWDBFQI-BQBZGAKWSA-N Ser-Pro-Gly Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O RHAPJNVNWDBFQI-BQBZGAKWSA-N 0.000 description 2
- FLONGDPORFIVQW-XGEHTFHBSA-N Ser-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FLONGDPORFIVQW-XGEHTFHBSA-N 0.000 description 2
- HHJFMHQYEAAOBM-ZLUOBGJFSA-N Ser-Ser-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O HHJFMHQYEAAOBM-ZLUOBGJFSA-N 0.000 description 2
- GYDFRTRSSXOZCR-ACZMJKKPSA-N Ser-Ser-Glu Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O GYDFRTRSSXOZCR-ACZMJKKPSA-N 0.000 description 2
- KKKVOZNCLALMPV-XKBZYTNZSA-N Ser-Thr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O KKKVOZNCLALMPV-XKBZYTNZSA-N 0.000 description 2
- SNXUIBACCONSOH-BWBBJGPYSA-N Ser-Thr-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CO)C(O)=O SNXUIBACCONSOH-BWBBJGPYSA-N 0.000 description 2
- KIEIJCFVGZCUAS-MELADBBJSA-N Ser-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CO)N)C(=O)O KIEIJCFVGZCUAS-MELADBBJSA-N 0.000 description 2
- PMTWIUBUQRGCSB-FXQIFTODSA-N Ser-Val-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O PMTWIUBUQRGCSB-FXQIFTODSA-N 0.000 description 2
- UKKROEYWYIHWBD-ZKWXMUAHSA-N Ser-Val-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O UKKROEYWYIHWBD-ZKWXMUAHSA-N 0.000 description 2
- HSWXBJCBYSWBPT-GUBZILKMSA-N Ser-Val-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)C(O)=O HSWXBJCBYSWBPT-GUBZILKMSA-N 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 241000193996 Streptococcus pyogenes Species 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- DWYAUVCQDTZIJI-VZFHVOOUSA-N Thr-Ala-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DWYAUVCQDTZIJI-VZFHVOOUSA-N 0.000 description 2
- ONNSECRQFSTMCC-XKBZYTNZSA-N Thr-Glu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O ONNSECRQFSTMCC-XKBZYTNZSA-N 0.000 description 2
- AQAMPXBRJJWPNI-JHEQGTHGSA-N Thr-Gly-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O AQAMPXBRJJWPNI-JHEQGTHGSA-N 0.000 description 2
- FDALPRWYVKJCLL-PMVVWTBXSA-N Thr-His-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)NCC(O)=O FDALPRWYVKJCLL-PMVVWTBXSA-N 0.000 description 2
- KLCCPYZXGXHAGS-QTKMDUPCSA-N Thr-His-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCSC)C(=O)O)N)O KLCCPYZXGXHAGS-QTKMDUPCSA-N 0.000 description 2
- XTCNBOBTROGWMW-RWRJDSDZSA-N Thr-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N XTCNBOBTROGWMW-RWRJDSDZSA-N 0.000 description 2
- NCXVJIQMWSGRHY-KXNHARMFSA-N Thr-Leu-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O NCXVJIQMWSGRHY-KXNHARMFSA-N 0.000 description 2
- VGYVVSQFSSKZRJ-OEAJRASXSA-N Thr-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@H](O)C)CC1=CC=CC=C1 VGYVVSQFSSKZRJ-OEAJRASXSA-N 0.000 description 2
- NDXSOKGYKCGYKT-VEVYYDQMSA-N Thr-Pro-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O NDXSOKGYKCGYKT-VEVYYDQMSA-N 0.000 description 2
- XKWABWFMQXMUMT-HJGDQZAQSA-N Thr-Pro-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XKWABWFMQXMUMT-HJGDQZAQSA-N 0.000 description 2
- VTMGKRABARCZAX-OSUNSFLBSA-N Thr-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)[C@@H](C)O VTMGKRABARCZAX-OSUNSFLBSA-N 0.000 description 2
- FWTFAZKJORVTIR-VZFHVOOUSA-N Thr-Ser-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O FWTFAZKJORVTIR-VZFHVOOUSA-N 0.000 description 2
- VUXIQSUQQYNLJP-XAVMHZPKSA-N Thr-Ser-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N)O VUXIQSUQQYNLJP-XAVMHZPKSA-N 0.000 description 2
- WPSKTVVMQCXPRO-BWBBJGPYSA-N Thr-Ser-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O WPSKTVVMQCXPRO-BWBBJGPYSA-N 0.000 description 2
- BBPCSGKKPJUYRB-UVOCVTCTSA-N Thr-Thr-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O BBPCSGKKPJUYRB-UVOCVTCTSA-N 0.000 description 2
- MYNYCUXMIIWUNW-IEGACIPQSA-N Thr-Trp-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MYNYCUXMIIWUNW-IEGACIPQSA-N 0.000 description 2
- KAJRRNHOVMZYBL-IRIUXVKKSA-N Thr-Tyr-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O KAJRRNHOVMZYBL-IRIUXVKKSA-N 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- WKCFCVBOFKEVKY-HSCHXYMDSA-N Trp-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N WKCFCVBOFKEVKY-HSCHXYMDSA-N 0.000 description 2
- PWPJLBWYRTVYQS-PMVMPFDFSA-N Trp-Phe-Leu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O PWPJLBWYRTVYQS-PMVMPFDFSA-N 0.000 description 2
- RPTAWXPQXXCUGL-OYDLWJJNSA-N Trp-Trp-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](N)Cc1c[nH]c2ccccc12)C(O)=O RPTAWXPQXXCUGL-OYDLWJJNSA-N 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- VCXWRWYFJLXITF-AUTRQRHGSA-N Tyr-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 VCXWRWYFJLXITF-AUTRQRHGSA-N 0.000 description 2
- NOOMDULIORCDNF-IRXDYDNUSA-N Tyr-Gly-Phe Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O NOOMDULIORCDNF-IRXDYDNUSA-N 0.000 description 2
- SZEIFUXUTBBQFQ-STQMWFEESA-N Tyr-Pro-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O SZEIFUXUTBBQFQ-STQMWFEESA-N 0.000 description 2
- QFHRUCJIRVILCK-YJRXYDGGSA-N Tyr-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O QFHRUCJIRVILCK-YJRXYDGGSA-N 0.000 description 2
- 241000700618 Vaccinia virus Species 0.000 description 2
- ZLFHAAGHGQBQQN-GUBZILKMSA-N Val-Ala-Pro Natural products CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O ZLFHAAGHGQBQQN-GUBZILKMSA-N 0.000 description 2
- HNWQUBBOBKSFQV-AVGNSLFASA-N Val-Arg-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N HNWQUBBOBKSFQV-AVGNSLFASA-N 0.000 description 2
- UDNYEPLJTRDMEJ-RCOVLWMOSA-N Val-Asn-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)NCC(=O)O)N UDNYEPLJTRDMEJ-RCOVLWMOSA-N 0.000 description 2
- BMGOFDMKDVVGJG-NHCYSSNCSA-N Val-Asp-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N BMGOFDMKDVVGJG-NHCYSSNCSA-N 0.000 description 2
- UZDHNIJRRTUKKC-DLOVCJGASA-N Val-Gln-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N UZDHNIJRRTUKKC-DLOVCJGASA-N 0.000 description 2
- DJEVQCWNMQOABE-RCOVLWMOSA-N Val-Gly-Asp Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)O)N DJEVQCWNMQOABE-RCOVLWMOSA-N 0.000 description 2
- BZMIYHIJVVJPCK-QSFUFRPTSA-N Val-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N BZMIYHIJVVJPCK-QSFUFRPTSA-N 0.000 description 2
- LKUDRJSNRWVGMS-QSFUFRPTSA-N Val-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N LKUDRJSNRWVGMS-QSFUFRPTSA-N 0.000 description 2
- JZWZACGUZVCQPS-RNJOBUHISA-N Val-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N JZWZACGUZVCQPS-RNJOBUHISA-N 0.000 description 2
- BMOFUVHDBROBSE-DCAQKATOSA-N Val-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C(C)C)N BMOFUVHDBROBSE-DCAQKATOSA-N 0.000 description 2
- UMPVMAYCLYMYGA-ONGXEEELSA-N Val-Leu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O UMPVMAYCLYMYGA-ONGXEEELSA-N 0.000 description 2
- ZHQWPWQNVRCXAX-XQQFMLRXSA-N Val-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N ZHQWPWQNVRCXAX-XQQFMLRXSA-N 0.000 description 2
- GVJUTBOZZBTBIG-AVGNSLFASA-N Val-Lys-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N GVJUTBOZZBTBIG-AVGNSLFASA-N 0.000 description 2
- JAKHAONCJJZVHT-DCAQKATOSA-N Val-Lys-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)O)N JAKHAONCJJZVHT-DCAQKATOSA-N 0.000 description 2
- MHHAWNPHDLCPLF-ULQDDVLXSA-N Val-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CC=CC=C1 MHHAWNPHDLCPLF-ULQDDVLXSA-N 0.000 description 2
- RYQUMYBMOJYYDK-NHCYSSNCSA-N Val-Pro-Glu Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)O)N RYQUMYBMOJYYDK-NHCYSSNCSA-N 0.000 description 2
- NHXZRXLFOBFMDM-AVGNSLFASA-N Val-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)C(C)C NHXZRXLFOBFMDM-AVGNSLFASA-N 0.000 description 2
- LTTQCQRTSHJPPL-ZKWXMUAHSA-N Val-Ser-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)N LTTQCQRTSHJPPL-ZKWXMUAHSA-N 0.000 description 2
- QTPQHINADBYBNA-DCAQKATOSA-N Val-Ser-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN QTPQHINADBYBNA-DCAQKATOSA-N 0.000 description 2
- GBIUHAYJGWVNLN-AEJSXWLSSA-N Val-Ser-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N GBIUHAYJGWVNLN-AEJSXWLSSA-N 0.000 description 2
- JXCOEPXCBVCTRD-JYJNAYRXSA-N Val-Tyr-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N JXCOEPXCBVCTRD-JYJNAYRXSA-N 0.000 description 2
- ZHWZDZFWBXWPDW-GUBZILKMSA-N Val-Val-Cys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(O)=O ZHWZDZFWBXWPDW-GUBZILKMSA-N 0.000 description 2
- AEFJNECXZCODJM-UWVGGRQHSA-N Val-Val-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](C(C)C)C(=O)NCC([O-])=O AEFJNECXZCODJM-UWVGGRQHSA-N 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 108010078114 alanyl-tryptophyl-alanine Proteins 0.000 description 2
- 108010045350 alanyl-tyrosyl-alanine Proteins 0.000 description 2
- 239000013566 allergen Substances 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 108010001271 arginyl-glutamyl-arginine Proteins 0.000 description 2
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 2
- 108010091092 arginyl-glycyl-proline Proteins 0.000 description 2
- 108010038850 arginyl-isoleucyl-tyrosine Proteins 0.000 description 2
- 108010029539 arginyl-prolyl-proline Proteins 0.000 description 2
- 108010060035 arginylproline Proteins 0.000 description 2
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 2
- 108010068265 aspartyltyrosine Proteins 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- FPUGCISOLXNPPC-IOSLPCCCSA-N cordysinin B Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 FPUGCISOLXNPPC-IOSLPCCCSA-N 0.000 description 2
- 108010060199 cysteinylproline Proteins 0.000 description 2
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 210000002257 embryonic structure Anatomy 0.000 description 2
- 230000001973 epigenetic effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 108010085059 glutamyl-arginyl-proline Proteins 0.000 description 2
- 108010080575 glutamyl-aspartyl-alanine Proteins 0.000 description 2
- 108010008237 glutamyl-valyl-glycine Proteins 0.000 description 2
- JYPCXBJRLBHWME-UHFFFAOYSA-N glycyl-L-prolyl-L-arginine Natural products NCC(=O)N1CCCC1C(=O)NC(CCCN=C(N)N)C(O)=O JYPCXBJRLBHWME-UHFFFAOYSA-N 0.000 description 2
- 108010027668 glycyl-alanyl-valine Proteins 0.000 description 2
- 108010023364 glycyl-histidyl-arginine Proteins 0.000 description 2
- 108010077435 glycyl-phenylalanyl-glycine Proteins 0.000 description 2
- 108010079413 glycyl-prolyl-glutamic acid Proteins 0.000 description 2
- 108010081551 glycylphenylalanine Proteins 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 108010040030 histidinoalanine Proteins 0.000 description 2
- 108010050343 histidyl-alanyl-glutamine Proteins 0.000 description 2
- 108010092114 histidylphenylalanine Proteins 0.000 description 2
- 102000051265 human ARID5A Human genes 0.000 description 2
- 102000052096 human BCL11A Human genes 0.000 description 2
- 102000055117 human CBFA2T3 Human genes 0.000 description 2
- 102000055537 human CREB3L2 Human genes 0.000 description 2
- 102000051882 human ETS1 Human genes 0.000 description 2
- 102000048596 human HDAC5 Human genes 0.000 description 2
- 102000057807 human HHEX Human genes 0.000 description 2
- 102000052252 human HOXA5 Human genes 0.000 description 2
- 102000058048 human ID3 Human genes 0.000 description 2
- 102000055354 human IKZF1 Human genes 0.000 description 2
- 102000045754 human IKZF2 Human genes 0.000 description 2
- 102000044015 human IKZF3 Human genes 0.000 description 2
- 102000056824 human IKZF5 Human genes 0.000 description 2
- 102000053956 human IRF7 Human genes 0.000 description 2
- 102000043473 human MEF2C Human genes 0.000 description 2
- 102000056573 human MYB Human genes 0.000 description 2
- 102000050251 human RUNX2 Human genes 0.000 description 2
- 102000050009 human SPIB Human genes 0.000 description 2
- 102000051839 human STAT1 Human genes 0.000 description 2
- 102000051841 human STAT3 Human genes 0.000 description 2
- 102000051603 human TCF12 Human genes 0.000 description 2
- 102000047493 human TCF4 Human genes 0.000 description 2
- 102000057610 human TSC22D1 Human genes 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 244000000056 intracellular parasite Species 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 108010083708 leucyl-aspartyl-valine Proteins 0.000 description 2
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 2
- 108010090333 leucyl-lysyl-proline Proteins 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 108010072591 lysyl-leucyl-alanyl-arginine Proteins 0.000 description 2
- 108010038320 lysylphenylalanine Proteins 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 108010005942 methionylglycine Proteins 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 206010028417 myasthenia gravis Diseases 0.000 description 2
- 210000003643 myeloid progenitor cell Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 208000021255 pancreatic insulinoma Diseases 0.000 description 2
- 108010024654 phenylalanyl-prolyl-alanine Proteins 0.000 description 2
- 108010051242 phenylalanylserine Proteins 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 108010014614 prolyl-glycyl-proline Proteins 0.000 description 2
- 108010079317 prolyl-tyrosine Proteins 0.000 description 2
- 108010090894 prolylleucine Proteins 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000001172 regenerating effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 108010048818 seryl-histidine Proteins 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000004988 splenocyte Anatomy 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000004114 suspension culture Methods 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- 108010080629 tryptophan-leucine Proteins 0.000 description 2
- 108010029384 tryptophyl-histidine Proteins 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 2
- 230000014567 type I interferon production Effects 0.000 description 2
- 108010035534 tyrosyl-leucyl-alanine Proteins 0.000 description 2
- 108010051110 tyrosyl-lysine Proteins 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 108010027345 wheylin-1 peptide Proteins 0.000 description 2
- GJLXVWOMRRWCIB-MERZOTPQSA-N (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanamide Chemical compound C([C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=C(O)C=C1 GJLXVWOMRRWCIB-MERZOTPQSA-N 0.000 description 1
- GRYSXUXXBDSYRT-WOUKDFQISA-N (2r,3r,4r,5r)-2-(hydroxymethyl)-4-methoxy-5-[6-(methylamino)purin-9-yl]oxolan-3-ol Chemical compound C1=NC=2C(NC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1OC GRYSXUXXBDSYRT-WOUKDFQISA-N 0.000 description 1
- XVZCXCTYGHPNEM-IHRRRGAJSA-N (2s)-1-[(2s)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(O)=O XVZCXCTYGHPNEM-IHRRRGAJSA-N 0.000 description 1
- BRPMXFSTKXXNHF-IUCAKERBSA-N (2s)-1-[2-[[(2s)-pyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H]1NCCC1 BRPMXFSTKXXNHF-IUCAKERBSA-N 0.000 description 1
- NOUIAHOPEGZYFE-JPLJXNOCSA-N (3S)-4-[[(2S)-1-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-[[(2S)-2,6-diaminohexanoyl]amino]-4-oxobutanoic acid Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NOUIAHOPEGZYFE-JPLJXNOCSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- OTFGHFBGGZEXEU-PEBGCTIMSA-N 1-[(2r,3r,4r,5r)-4-hydroxy-5-(hydroxymethyl)-3-methoxyoxolan-2-yl]-3-methylpyrimidine-2,4-dione Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N(C)C(=O)C=C1 OTFGHFBGGZEXEU-PEBGCTIMSA-N 0.000 description 1
- QPHRQMAYYMYWFW-FJGDRVTGSA-N 1-[(2r,3s,4r,5r)-3-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 QPHRQMAYYMYWFW-FJGDRVTGSA-N 0.000 description 1
- FPUGCISOLXNPPC-UHFFFAOYSA-N 2'-O-Methyladenosine Natural products COC1C(O)C(CO)OC1N1C2=NC=NC(N)=C2N=C1 FPUGCISOLXNPPC-UHFFFAOYSA-N 0.000 description 1
- RFCQJGFZUQFYRF-UHFFFAOYSA-N 2'-O-Methylcytidine Natural products COC1C(O)C(CO)OC1N1C(=O)N=C(N)C=C1 RFCQJGFZUQFYRF-UHFFFAOYSA-N 0.000 description 1
- OVYNGSFVYRPRCG-UHFFFAOYSA-N 2'-O-Methylguanosine Natural products COC1C(O)C(CO)OC1N1C(NC(N)=NC2=O)=C2N=C1 OVYNGSFVYRPRCG-UHFFFAOYSA-N 0.000 description 1
- RFCQJGFZUQFYRF-ZOQUXTDFSA-N 2'-O-methylcytidine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 RFCQJGFZUQFYRF-ZOQUXTDFSA-N 0.000 description 1
- OVYNGSFVYRPRCG-KQYNXXCUSA-N 2'-O-methylguanosine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=C(N)NC2=O)=C2N=C1 OVYNGSFVYRPRCG-KQYNXXCUSA-N 0.000 description 1
- 101800001779 2'-O-methyltransferase Proteins 0.000 description 1
- SXUXMRMBWZCMEN-ZOQUXTDFSA-N 2'-O-methyluridine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-ZOQUXTDFSA-N 0.000 description 1
- MXHRCPNRJAMMIM-BBVRLYRLSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-BBVRLYRLSA-N 0.000 description 1
- SCPRYBYMKVYVND-UHFFFAOYSA-N 2-[[2-[[1-(2-amino-4-methylpentanoyl)pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoic acid Chemical compound CC(C)CC(N)C(=O)N1CCCC1C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(O)=O SCPRYBYMKVYVND-UHFFFAOYSA-N 0.000 description 1
- LDHYTBAFXANWKM-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one Chemical compound O=C1NC(N)=NC2=C1NC=N2.O=C1NC(N)=NC2=C1N=CN2 LDHYTBAFXANWKM-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 238000010600 3H thymidine incorporation assay Methods 0.000 description 1
- ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 description 1
- ZLOIGESWDJYCTF-XVFCMESISA-N 4-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-XVFCMESISA-N 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- IPRQAJTUSRLECG-UHFFFAOYSA-N 5-[6-(dimethylamino)purin-9-yl]-2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound COC1C(O)C(CO)OC1N1C2=NC=NC(N(C)C)=C2N=C1 IPRQAJTUSRLECG-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- OGHAROSJZRTIOK-KQYNXXCUSA-O 7-methylguanosine Chemical compound C1=2N=C(N)NC(=O)C=2[N+](C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OGHAROSJZRTIOK-KQYNXXCUSA-O 0.000 description 1
- 102100030841 AT-rich interactive domain-containing protein 4A Human genes 0.000 description 1
- 241000186041 Actinomyces israelii Species 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 241000701242 Adenoviridae Species 0.000 description 1
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 description 1
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 1
- 241000701386 African swine fever virus Species 0.000 description 1
- SBGXWWCLHIOABR-UHFFFAOYSA-N Ala Ala Gly Ala Chemical compound CC(N)C(=O)NC(C)C(=O)NCC(=O)NC(C)C(O)=O SBGXWWCLHIOABR-UHFFFAOYSA-N 0.000 description 1
- HHGYNJRJIINWAK-FXQIFTODSA-N Ala-Ala-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N HHGYNJRJIINWAK-FXQIFTODSA-N 0.000 description 1
- BUANFPRKJKJSRR-ACZMJKKPSA-N Ala-Ala-Gln Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](C)C(=O)N[C@H](C([O-])=O)CCC(N)=O BUANFPRKJKJSRR-ACZMJKKPSA-N 0.000 description 1
- RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 description 1
- WQVFQXXBNHHPLX-ZKWXMUAHSA-N Ala-Ala-His Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O WQVFQXXBNHHPLX-ZKWXMUAHSA-N 0.000 description 1
- JBVSSSZFNTXJDX-YTLHQDLWSA-N Ala-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N JBVSSSZFNTXJDX-YTLHQDLWSA-N 0.000 description 1
- UGLPMYSCWHTZQU-AUTRQRHGSA-N Ala-Ala-Tyr Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](C)C(=O)N[C@H](C([O-])=O)CC1=CC=C(O)C=C1 UGLPMYSCWHTZQU-AUTRQRHGSA-N 0.000 description 1
- ODWSTKXGQGYHSH-FXQIFTODSA-N Ala-Arg-Ala Chemical compound C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O ODWSTKXGQGYHSH-FXQIFTODSA-N 0.000 description 1
- QDRGPQWIVZNJQD-CIUDSAMLSA-N Ala-Arg-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O QDRGPQWIVZNJQD-CIUDSAMLSA-N 0.000 description 1
- LWUWMHIOBPTZBA-DCAQKATOSA-N Ala-Arg-Lys Chemical compound NC(=N)NCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CCCCN)C(O)=O LWUWMHIOBPTZBA-DCAQKATOSA-N 0.000 description 1
- JAMAWBXXKFGFGX-KZVJFYERSA-N Ala-Arg-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JAMAWBXXKFGFGX-KZVJFYERSA-N 0.000 description 1
- WYPUMLRSQMKIJU-BPNCWPANSA-N Ala-Arg-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WYPUMLRSQMKIJU-BPNCWPANSA-N 0.000 description 1
- HGRBNYQIMKTUNT-XVYDVKMFSA-N Ala-Asn-His Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N HGRBNYQIMKTUNT-XVYDVKMFSA-N 0.000 description 1
- PBAMJJXWDQXOJA-FXQIFTODSA-N Ala-Asp-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PBAMJJXWDQXOJA-FXQIFTODSA-N 0.000 description 1
- BTYTYHBSJKQBQA-GCJQMDKQSA-N Ala-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)N)O BTYTYHBSJKQBQA-GCJQMDKQSA-N 0.000 description 1
- DECCMEWNXSNSDO-ZLUOBGJFSA-N Ala-Cys-Ala Chemical compound C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O DECCMEWNXSNSDO-ZLUOBGJFSA-N 0.000 description 1
- ZRGNRZLDMUACOW-HERUPUMHSA-N Ala-Cys-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N ZRGNRZLDMUACOW-HERUPUMHSA-N 0.000 description 1
- CXQODNIBUNQWAS-CIUDSAMLSA-N Ala-Gln-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N CXQODNIBUNQWAS-CIUDSAMLSA-N 0.000 description 1
- OQCPATDFWYYDDX-HGNGGELXSA-N Ala-Gln-His Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O OQCPATDFWYYDDX-HGNGGELXSA-N 0.000 description 1
- ZDYNWWQXFRUOEO-XDTLVQLUSA-N Ala-Gln-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZDYNWWQXFRUOEO-XDTLVQLUSA-N 0.000 description 1
- FUSPCLTUKXQREV-ACZMJKKPSA-N Ala-Glu-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O FUSPCLTUKXQREV-ACZMJKKPSA-N 0.000 description 1
- OMMDTNGURYRDAC-NRPADANISA-N Ala-Glu-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O OMMDTNGURYRDAC-NRPADANISA-N 0.000 description 1
- LJFNNUBZSZCZFN-WHFBIAKZSA-N Ala-Gly-Cys Chemical compound N[C@@H](C)C(=O)NCC(=O)N[C@@H](CS)C(=O)O LJFNNUBZSZCZFN-WHFBIAKZSA-N 0.000 description 1
- VGPWRRFOPXVGOH-BYPYZUCNSA-N Ala-Gly-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)NCC(O)=O VGPWRRFOPXVGOH-BYPYZUCNSA-N 0.000 description 1
- ATAKEVCGTRZKLI-UWJYBYFXSA-N Ala-His-His Chemical compound C([C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 ATAKEVCGTRZKLI-UWJYBYFXSA-N 0.000 description 1
- KMGOBAQSCKTBGD-DLOVCJGASA-N Ala-His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CN=CN1 KMGOBAQSCKTBGD-DLOVCJGASA-N 0.000 description 1
- FAJIYNONGXEXAI-CQDKDKBSSA-N Ala-His-Phe Chemical compound C([C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 FAJIYNONGXEXAI-CQDKDKBSSA-N 0.000 description 1
- PNALXAODQKTNLV-JBDRJPRFSA-N Ala-Ile-Ala Chemical compound C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O PNALXAODQKTNLV-JBDRJPRFSA-N 0.000 description 1
- OKIKVSXTXVVFDV-MMWGEVLESA-N Ala-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C)N OKIKVSXTXVVFDV-MMWGEVLESA-N 0.000 description 1
- VNYMOTCMNHJGTG-JBDRJPRFSA-N Ala-Ile-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O VNYMOTCMNHJGTG-JBDRJPRFSA-N 0.000 description 1
- MNZHHDPWDWQJCQ-YUMQZZPRSA-N Ala-Leu-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O MNZHHDPWDWQJCQ-YUMQZZPRSA-N 0.000 description 1
- ZKEHTYWGPMMGBC-XUXIUFHCSA-N Ala-Leu-Leu-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O ZKEHTYWGPMMGBC-XUXIUFHCSA-N 0.000 description 1
- OPZJWMJPCNNZNT-DCAQKATOSA-N Ala-Leu-Met Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)O)N OPZJWMJPCNNZNT-DCAQKATOSA-N 0.000 description 1
- MEFILNJXAVSUTO-JXUBOQSCSA-N Ala-Leu-Thr Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MEFILNJXAVSUTO-JXUBOQSCSA-N 0.000 description 1
- LDLSENBXQNDTPB-DCAQKATOSA-N Ala-Lys-Arg Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N LDLSENBXQNDTPB-DCAQKATOSA-N 0.000 description 1
- SDZRIBWEVVRDQI-CIUDSAMLSA-N Ala-Lys-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O SDZRIBWEVVRDQI-CIUDSAMLSA-N 0.000 description 1
- MFMDKJIPHSWSBM-GUBZILKMSA-N Ala-Lys-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O MFMDKJIPHSWSBM-GUBZILKMSA-N 0.000 description 1
- PMQXMXAASGFUDX-SRVKXCTJSA-N Ala-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CCCCN PMQXMXAASGFUDX-SRVKXCTJSA-N 0.000 description 1
- FUKFQILQFQKHLE-DCAQKATOSA-N Ala-Lys-Met Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(O)=O FUKFQILQFQKHLE-DCAQKATOSA-N 0.000 description 1
- MDNAVFBZPROEHO-DCAQKATOSA-N Ala-Lys-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O MDNAVFBZPROEHO-DCAQKATOSA-N 0.000 description 1
- BFMIRJBURUXDRG-DLOVCJGASA-N Ala-Phe-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 BFMIRJBURUXDRG-DLOVCJGASA-N 0.000 description 1
- ZBLQIYPCUWZSRZ-QEJZJMRPSA-N Ala-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=CC=C1 ZBLQIYPCUWZSRZ-QEJZJMRPSA-N 0.000 description 1
- DYJJJCHDHLEFDW-FXQIFTODSA-N Ala-Pro-Cys Chemical compound C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(=O)O)N DYJJJCHDHLEFDW-FXQIFTODSA-N 0.000 description 1
- XAXHGSOBFPIRFG-LSJOCFKGSA-N Ala-Pro-His Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O XAXHGSOBFPIRFG-LSJOCFKGSA-N 0.000 description 1
- WQLDNOCHHRISMS-NAKRPEOUSA-N Ala-Pro-Ile Chemical compound [H]N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WQLDNOCHHRISMS-NAKRPEOUSA-N 0.000 description 1
- ADSGHMXEAZJJNF-DCAQKATOSA-N Ala-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N ADSGHMXEAZJJNF-DCAQKATOSA-N 0.000 description 1
- DCVYRWFAMZFSDA-ZLUOBGJFSA-N Ala-Ser-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O DCVYRWFAMZFSDA-ZLUOBGJFSA-N 0.000 description 1
- VJVQKGYHIZPSNS-FXQIFTODSA-N Ala-Ser-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N VJVQKGYHIZPSNS-FXQIFTODSA-N 0.000 description 1
- YYAVDNKUWLAFCV-ACZMJKKPSA-N Ala-Ser-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O YYAVDNKUWLAFCV-ACZMJKKPSA-N 0.000 description 1
- HOVPGJUNRLMIOZ-CIUDSAMLSA-N Ala-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N HOVPGJUNRLMIOZ-CIUDSAMLSA-N 0.000 description 1
- WQKAQKZRDIZYNV-VZFHVOOUSA-N Ala-Ser-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WQKAQKZRDIZYNV-VZFHVOOUSA-N 0.000 description 1
- VRTOMXFZHGWHIJ-KZVJFYERSA-N Ala-Thr-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VRTOMXFZHGWHIJ-KZVJFYERSA-N 0.000 description 1
- AENHOIXXHKNIQL-AUTRQRHGSA-N Ala-Tyr-Ala Chemical compound [O-]C(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]([NH3+])C)CC1=CC=C(O)C=C1 AENHOIXXHKNIQL-AUTRQRHGSA-N 0.000 description 1
- MTDDMSUUXNQMKK-BPNCWPANSA-N Ala-Tyr-Arg Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N MTDDMSUUXNQMKK-BPNCWPANSA-N 0.000 description 1
- XAXMJQUMRJAFCH-CQDKDKBSSA-N Ala-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 XAXMJQUMRJAFCH-CQDKDKBSSA-N 0.000 description 1
- ZXKNLCPUNZPFGY-LEWSCRJBSA-N Ala-Tyr-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N2CCC[C@@H]2C(=O)O)N ZXKNLCPUNZPFGY-LEWSCRJBSA-N 0.000 description 1
- XSLGWYYNOSUMRM-ZKWXMUAHSA-N Ala-Val-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O XSLGWYYNOSUMRM-ZKWXMUAHSA-N 0.000 description 1
- YJHKTAMKPGFJCT-NRPADANISA-N Ala-Val-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O YJHKTAMKPGFJCT-NRPADANISA-N 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 206010001742 Allergy to animal Diseases 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 241000712892 Arenaviridae Species 0.000 description 1
- YYOVLDPHIJAOSY-DCAQKATOSA-N Arg-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N YYOVLDPHIJAOSY-DCAQKATOSA-N 0.000 description 1
- QEKBCDODJBBWHV-GUBZILKMSA-N Arg-Arg-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O QEKBCDODJBBWHV-GUBZILKMSA-N 0.000 description 1
- JGDGLDNAQJJGJI-AVGNSLFASA-N Arg-Arg-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)N JGDGLDNAQJJGJI-AVGNSLFASA-N 0.000 description 1
- OVVUNXXROOFSIM-SDDRHHMPSA-N Arg-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O OVVUNXXROOFSIM-SDDRHHMPSA-N 0.000 description 1
- UISQLSIBJKEJSS-GUBZILKMSA-N Arg-Arg-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(O)=O UISQLSIBJKEJSS-GUBZILKMSA-N 0.000 description 1
- JTKLCCFLSLCCST-SZMVWBNQSA-N Arg-Arg-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)N)C(O)=O)=CNC2=C1 JTKLCCFLSLCCST-SZMVWBNQSA-N 0.000 description 1
- NONSEUUPKITYQT-BQBZGAKWSA-N Arg-Asn-Gly Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)NCC(=O)O)N)CN=C(N)N NONSEUUPKITYQT-BQBZGAKWSA-N 0.000 description 1
- OTUQSEPIIVBYEM-IHRRRGAJSA-N Arg-Asn-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O OTUQSEPIIVBYEM-IHRRRGAJSA-N 0.000 description 1
- XVLLUZMFSAYKJV-GUBZILKMSA-N Arg-Asp-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XVLLUZMFSAYKJV-GUBZILKMSA-N 0.000 description 1
- ASQYTJJWAMDISW-BPUTZDHNSA-N Arg-Asp-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N ASQYTJJWAMDISW-BPUTZDHNSA-N 0.000 description 1
- DQNLFLGFZAUIOW-FXQIFTODSA-N Arg-Cys-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O DQNLFLGFZAUIOW-FXQIFTODSA-N 0.000 description 1
- JVMKBJNSRZWDBO-FXQIFTODSA-N Arg-Cys-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O JVMKBJNSRZWDBO-FXQIFTODSA-N 0.000 description 1
- QQJSJIBESHAJPM-IHRRRGAJSA-N Arg-Cys-Tyr Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 QQJSJIBESHAJPM-IHRRRGAJSA-N 0.000 description 1
- FEZJJKXNPSEYEV-CIUDSAMLSA-N Arg-Gln-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O FEZJJKXNPSEYEV-CIUDSAMLSA-N 0.000 description 1
- GIVWETPOBCRTND-DCAQKATOSA-N Arg-Gln-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O GIVWETPOBCRTND-DCAQKATOSA-N 0.000 description 1
- VNFWDYWTSHFRRG-SRVKXCTJSA-N Arg-Gln-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O VNFWDYWTSHFRRG-SRVKXCTJSA-N 0.000 description 1
- QAODJPUKWNNNRP-DCAQKATOSA-N Arg-Glu-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O QAODJPUKWNNNRP-DCAQKATOSA-N 0.000 description 1
- XLWSGICNBZGYTA-CIUDSAMLSA-N Arg-Glu-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XLWSGICNBZGYTA-CIUDSAMLSA-N 0.000 description 1
- NYZGVTGOMPHSJW-CIUDSAMLSA-N Arg-Glu-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N)CN=C(N)N NYZGVTGOMPHSJW-CIUDSAMLSA-N 0.000 description 1
- SKTGPBFTMNLIHQ-KKUMJFAQSA-N Arg-Glu-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SKTGPBFTMNLIHQ-KKUMJFAQSA-N 0.000 description 1
- ZATRYQNPUHGXCU-DTWKUNHWSA-N Arg-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ZATRYQNPUHGXCU-DTWKUNHWSA-N 0.000 description 1
- WVNFNPGXYADPPO-BQBZGAKWSA-N Arg-Gly-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O WVNFNPGXYADPPO-BQBZGAKWSA-N 0.000 description 1
- KRQSPVKUISQQFS-FJXKBIBVSA-N Arg-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N KRQSPVKUISQQFS-FJXKBIBVSA-N 0.000 description 1
- YBIAYFFIVAZXPK-AVGNSLFASA-N Arg-His-Arg Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O YBIAYFFIVAZXPK-AVGNSLFASA-N 0.000 description 1
- OTZMRMHZCMZOJZ-SRVKXCTJSA-N Arg-Leu-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O OTZMRMHZCMZOJZ-SRVKXCTJSA-N 0.000 description 1
- COXMUHNBYCVVRG-DCAQKATOSA-N Arg-Leu-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O COXMUHNBYCVVRG-DCAQKATOSA-N 0.000 description 1
- JEOCWTUOMKEEMF-RHYQMDGZSA-N Arg-Leu-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JEOCWTUOMKEEMF-RHYQMDGZSA-N 0.000 description 1
- OGSQONVYSTZIJB-WDSOQIARSA-N Arg-Leu-Trp Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CCCN=C(N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O OGSQONVYSTZIJB-WDSOQIARSA-N 0.000 description 1
- FSNVAJOPUDVQAR-AVGNSLFASA-N Arg-Lys-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FSNVAJOPUDVQAR-AVGNSLFASA-N 0.000 description 1
- CVXXSWQORBZAAA-SRVKXCTJSA-N Arg-Lys-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N CVXXSWQORBZAAA-SRVKXCTJSA-N 0.000 description 1
- NGTYEHIRESTSRX-UWVGGRQHSA-N Arg-Lys-Gly Chemical compound NCCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N NGTYEHIRESTSRX-UWVGGRQHSA-N 0.000 description 1
- CLICCYPMVFGUOF-IHRRRGAJSA-N Arg-Lys-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O CLICCYPMVFGUOF-IHRRRGAJSA-N 0.000 description 1
- PAPSMOYMQDWIOR-AVGNSLFASA-N Arg-Lys-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O PAPSMOYMQDWIOR-AVGNSLFASA-N 0.000 description 1
- AFNHFVVOJZBIJD-GUBZILKMSA-N Arg-Met-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O AFNHFVVOJZBIJD-GUBZILKMSA-N 0.000 description 1
- UGZUVYDKAYNCII-ULQDDVLXSA-N Arg-Phe-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O UGZUVYDKAYNCII-ULQDDVLXSA-N 0.000 description 1
- FOQFHANLUJDQEE-GUBZILKMSA-N Arg-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCCN=C(N)N)N)C(=O)N[C@@H](CS)C(=O)O FOQFHANLUJDQEE-GUBZILKMSA-N 0.000 description 1
- HGKHPCFTRQDHCU-IUCAKERBSA-N Arg-Pro-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O HGKHPCFTRQDHCU-IUCAKERBSA-N 0.000 description 1
- STHNZYKCJHWULY-AVGNSLFASA-N Arg-Pro-His Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCCN=C(N)N)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O STHNZYKCJHWULY-AVGNSLFASA-N 0.000 description 1
- YFHATWYGAAXQCF-JYJNAYRXSA-N Arg-Pro-Phe Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YFHATWYGAAXQCF-JYJNAYRXSA-N 0.000 description 1
- YCYXHLZRUSJITQ-SRVKXCTJSA-N Arg-Pro-Pro Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 YCYXHLZRUSJITQ-SRVKXCTJSA-N 0.000 description 1
- ATABBWFGOHKROJ-GUBZILKMSA-N Arg-Pro-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O ATABBWFGOHKROJ-GUBZILKMSA-N 0.000 description 1
- AUIJUTGLPVHIRT-FXQIFTODSA-N Arg-Ser-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N)CN=C(N)N AUIJUTGLPVHIRT-FXQIFTODSA-N 0.000 description 1
- JOTRDIXZHNQYGP-DCAQKATOSA-N Arg-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N JOTRDIXZHNQYGP-DCAQKATOSA-N 0.000 description 1
- LRPZJPMQGKGHSG-XGEHTFHBSA-N Arg-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)O LRPZJPMQGKGHSG-XGEHTFHBSA-N 0.000 description 1
- RYQSYXFGFOTJDJ-RHYQMDGZSA-N Arg-Thr-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O RYQSYXFGFOTJDJ-RHYQMDGZSA-N 0.000 description 1
- UGJLILSJKSBVIR-ZFWWWQNUSA-N Arg-Trp-Gly Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCN=C(N)N)N)C(=O)NCC(O)=O)=CNC2=C1 UGJLILSJKSBVIR-ZFWWWQNUSA-N 0.000 description 1
- BFDDUDQCPJWQRQ-IHRRRGAJSA-N Arg-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O BFDDUDQCPJWQRQ-IHRRRGAJSA-N 0.000 description 1
- QHUOOCKNNURZSL-IHRRRGAJSA-N Arg-Tyr-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O QHUOOCKNNURZSL-IHRRRGAJSA-N 0.000 description 1
- ISVACHFCVRKIDG-SRVKXCTJSA-N Arg-Val-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O ISVACHFCVRKIDG-SRVKXCTJSA-N 0.000 description 1
- ULBHWNVWSCJLCO-NHCYSSNCSA-N Arg-Val-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N ULBHWNVWSCJLCO-NHCYSSNCSA-N 0.000 description 1
- SUMJNGAMIQSNGX-TUAOUCFPSA-N Arg-Val-Pro Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCCNC(N)=N)C(=O)N1CCC[C@@H]1C(O)=O SUMJNGAMIQSNGX-TUAOUCFPSA-N 0.000 description 1
- 241000244185 Ascaris lumbricoides Species 0.000 description 1
- YNDLOUMBVDVALC-ZLUOBGJFSA-N Asn-Ala-Ala Chemical compound C[C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CC(=O)N)N YNDLOUMBVDVALC-ZLUOBGJFSA-N 0.000 description 1
- MFFOYNGMOYFPBD-DCAQKATOSA-N Asn-Arg-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O MFFOYNGMOYFPBD-DCAQKATOSA-N 0.000 description 1
- ZWASIOHRQWRWAS-UGYAYLCHSA-N Asn-Asp-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ZWASIOHRQWRWAS-UGYAYLCHSA-N 0.000 description 1
- RRVBEKYEFMCDIF-WHFBIAKZSA-N Asn-Cys-Gly Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)O)N)C(=O)N RRVBEKYEFMCDIF-WHFBIAKZSA-N 0.000 description 1
- SPIPSJXLZVTXJL-ZLUOBGJFSA-N Asn-Cys-Ser Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O SPIPSJXLZVTXJL-ZLUOBGJFSA-N 0.000 description 1
- NNMUHYLAYUSTTN-FXQIFTODSA-N Asn-Gln-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O NNMUHYLAYUSTTN-FXQIFTODSA-N 0.000 description 1
- DMLSCRJBWUEALP-LAEOZQHASA-N Asn-Glu-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O DMLSCRJBWUEALP-LAEOZQHASA-N 0.000 description 1
- GJFYPBDMUGGLFR-NKWVEPMBSA-N Asn-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CC(=O)N)N)C(=O)O GJFYPBDMUGGLFR-NKWVEPMBSA-N 0.000 description 1
- GLWFAWNYGWBMOC-SRVKXCTJSA-N Asn-Leu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GLWFAWNYGWBMOC-SRVKXCTJSA-N 0.000 description 1
- FHETWELNCBMRMG-HJGDQZAQSA-N Asn-Leu-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FHETWELNCBMRMG-HJGDQZAQSA-N 0.000 description 1
- FTSAJSADJCMDHH-CIUDSAMLSA-N Asn-Lys-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N FTSAJSADJCMDHH-CIUDSAMLSA-N 0.000 description 1
- ORJQQZIXTOYGGH-SRVKXCTJSA-N Asn-Lys-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O ORJQQZIXTOYGGH-SRVKXCTJSA-N 0.000 description 1
- CDGHMJJJHYKMPA-DLOVCJGASA-N Asn-Phe-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)N)N CDGHMJJJHYKMPA-DLOVCJGASA-N 0.000 description 1
- ZJIFRAPZHAGLGR-MELADBBJSA-N Asn-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(=O)N)N)C(=O)O ZJIFRAPZHAGLGR-MELADBBJSA-N 0.000 description 1
- YXVAESUIQFDBHN-SRVKXCTJSA-N Asn-Phe-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O YXVAESUIQFDBHN-SRVKXCTJSA-N 0.000 description 1
- BKFXFUPYETWGGA-XVSYOHENSA-N Asn-Phe-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BKFXFUPYETWGGA-XVSYOHENSA-N 0.000 description 1
- QXOPPIDJKPEKCW-GUBZILKMSA-N Asn-Pro-Arg Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O QXOPPIDJKPEKCW-GUBZILKMSA-N 0.000 description 1
- GMUOCGCDOYYWPD-FXQIFTODSA-N Asn-Pro-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O GMUOCGCDOYYWPD-FXQIFTODSA-N 0.000 description 1
- JWQWPRCDYWNVNM-ACZMJKKPSA-N Asn-Ser-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N JWQWPRCDYWNVNM-ACZMJKKPSA-N 0.000 description 1
- GZXOUBTUAUAVHD-ACZMJKKPSA-N Asn-Ser-Glu Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O GZXOUBTUAUAVHD-ACZMJKKPSA-N 0.000 description 1
- CBHVAFXKOYAHOY-NHCYSSNCSA-N Asn-Val-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O CBHVAFXKOYAHOY-NHCYSSNCSA-N 0.000 description 1
- XEDQMTWEYFBOIK-ACZMJKKPSA-N Asp-Ala-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O XEDQMTWEYFBOIK-ACZMJKKPSA-N 0.000 description 1
- XBQSLMACWDXWLJ-GHCJXIJMSA-N Asp-Ala-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XBQSLMACWDXWLJ-GHCJXIJMSA-N 0.000 description 1
- VPPXTHJNTYDNFJ-CIUDSAMLSA-N Asp-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N VPPXTHJNTYDNFJ-CIUDSAMLSA-N 0.000 description 1
- KVMPVNGOKHTUHZ-GCJQMDKQSA-N Asp-Ala-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KVMPVNGOKHTUHZ-GCJQMDKQSA-N 0.000 description 1
- QHAJMRDEWNAIBQ-FXQIFTODSA-N Asp-Arg-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O QHAJMRDEWNAIBQ-FXQIFTODSA-N 0.000 description 1
- ZLGKHJHFYSRUBH-FXQIFTODSA-N Asp-Arg-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLGKHJHFYSRUBH-FXQIFTODSA-N 0.000 description 1
- WSOKZUVWBXVJHX-CIUDSAMLSA-N Asp-Arg-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O WSOKZUVWBXVJHX-CIUDSAMLSA-N 0.000 description 1
- FAEIQWHBRBWUBN-FXQIFTODSA-N Asp-Arg-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N)CN=C(N)N FAEIQWHBRBWUBN-FXQIFTODSA-N 0.000 description 1
- CELPEWWLSXMVPH-CIUDSAMLSA-N Asp-Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(O)=O CELPEWWLSXMVPH-CIUDSAMLSA-N 0.000 description 1
- ZSJFGGSPCCHMNE-LAEOZQHASA-N Asp-Gln-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)O)N ZSJFGGSPCCHMNE-LAEOZQHASA-N 0.000 description 1
- VAWNQIGQPUOPQW-ACZMJKKPSA-N Asp-Glu-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O VAWNQIGQPUOPQW-ACZMJKKPSA-N 0.000 description 1
- HSWYMWGDMPLTTH-FXQIFTODSA-N Asp-Glu-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HSWYMWGDMPLTTH-FXQIFTODSA-N 0.000 description 1
- YDJVIBMKAMQPPP-LAEOZQHASA-N Asp-Glu-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O YDJVIBMKAMQPPP-LAEOZQHASA-N 0.000 description 1
- YNCHFVRXEQFPBY-BQBZGAKWSA-N Asp-Gly-Arg Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N YNCHFVRXEQFPBY-BQBZGAKWSA-N 0.000 description 1
- SNDBKTFJWVEVPO-WHFBIAKZSA-N Asp-Gly-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SNDBKTFJWVEVPO-WHFBIAKZSA-N 0.000 description 1
- WSGVTKZFVJSJOG-RCOVLWMOSA-N Asp-Gly-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O WSGVTKZFVJSJOG-RCOVLWMOSA-N 0.000 description 1
- KTTCQQNRRLCIBC-GHCJXIJMSA-N Asp-Ile-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O KTTCQQNRRLCIBC-GHCJXIJMSA-N 0.000 description 1
- LDLZOAJRXXBVGF-GMOBBJLQSA-N Asp-Ile-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC(=O)O)N LDLZOAJRXXBVGF-GMOBBJLQSA-N 0.000 description 1
- IVPNEDNYYYFAGI-GARJFASQSA-N Asp-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N IVPNEDNYYYFAGI-GARJFASQSA-N 0.000 description 1
- SARSTIZOZFBDOM-FXQIFTODSA-N Asp-Met-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O SARSTIZOZFBDOM-FXQIFTODSA-N 0.000 description 1
- YTXCCDCOHIYQFC-GUBZILKMSA-N Asp-Met-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O YTXCCDCOHIYQFC-GUBZILKMSA-N 0.000 description 1
- DJCAHYVLMSRBFR-QXEWZRGKSA-N Asp-Met-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CC(O)=O DJCAHYVLMSRBFR-QXEWZRGKSA-N 0.000 description 1
- PWAIZUBWHRHYKS-MELADBBJSA-N Asp-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(=O)O)N)C(=O)O PWAIZUBWHRHYKS-MELADBBJSA-N 0.000 description 1
- USNJAPJZSGTTPX-XVSYOHENSA-N Asp-Phe-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O USNJAPJZSGTTPX-XVSYOHENSA-N 0.000 description 1
- YFGUZQQCSDZRBN-DCAQKATOSA-N Asp-Pro-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O YFGUZQQCSDZRBN-DCAQKATOSA-N 0.000 description 1
- WMLFFCRUSPNENW-ZLUOBGJFSA-N Asp-Ser-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O WMLFFCRUSPNENW-ZLUOBGJFSA-N 0.000 description 1
- CUQDCPXNZPDYFQ-ZLUOBGJFSA-N Asp-Ser-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O CUQDCPXNZPDYFQ-ZLUOBGJFSA-N 0.000 description 1
- QSFHZPQUAAQHAQ-CIUDSAMLSA-N Asp-Ser-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O QSFHZPQUAAQHAQ-CIUDSAMLSA-N 0.000 description 1
- VNXQRBXEQXLERQ-CIUDSAMLSA-N Asp-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N VNXQRBXEQXLERQ-CIUDSAMLSA-N 0.000 description 1
- YIDFBWRHIYOYAA-LKXGYXEUSA-N Asp-Ser-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O YIDFBWRHIYOYAA-LKXGYXEUSA-N 0.000 description 1
- UTLCRGFJFSZWAW-OLHMAJIHSA-N Asp-Thr-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O UTLCRGFJFSZWAW-OLHMAJIHSA-N 0.000 description 1
- XAPPCWUWHNWCPQ-PBCZWWQYSA-N Asp-Thr-His Chemical compound N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O XAPPCWUWHNWCPQ-PBCZWWQYSA-N 0.000 description 1
- NAAAPCLFJPURAM-HJGDQZAQSA-N Asp-Thr-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O NAAAPCLFJPURAM-HJGDQZAQSA-N 0.000 description 1
- GCACQYDBDHRVGE-LKXGYXEUSA-N Asp-Thr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CC(O)=O GCACQYDBDHRVGE-LKXGYXEUSA-N 0.000 description 1
- MRYDJCIIVRXVGG-QEJZJMRPSA-N Asp-Trp-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O MRYDJCIIVRXVGG-QEJZJMRPSA-N 0.000 description 1
- WOKXEQLPBLLWHC-IHRRRGAJSA-N Asp-Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 WOKXEQLPBLLWHC-IHRRRGAJSA-N 0.000 description 1
- XQFLFQWOBXPMHW-NHCYSSNCSA-N Asp-Val-His Chemical compound N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O XQFLFQWOBXPMHW-NHCYSSNCSA-N 0.000 description 1
- QPDUWAUSSWGJSB-NGZCFLSTSA-N Asp-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N QPDUWAUSSWGJSB-NGZCFLSTSA-N 0.000 description 1
- GYNUXDMCDILYIQ-QRTARXTBSA-N Asp-Val-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC(=O)O)N GYNUXDMCDILYIQ-QRTARXTBSA-N 0.000 description 1
- 208000004300 Atrophic Gastritis Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 241001455947 Babesia divergens Species 0.000 description 1
- 241000223848 Babesia microti Species 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 241001148536 Bacteroides sp. Species 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 208000027496 Behcet disease Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 102100021277 Beta-secretase 2 Human genes 0.000 description 1
- 101710150190 Beta-secretase 2 Proteins 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 241000702628 Birnaviridae Species 0.000 description 1
- 241000228405 Blastomyces dermatitidis Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000244038 Brugia malayi Species 0.000 description 1
- 241000143302 Brugia timori Species 0.000 description 1
- 101150080672 Bst2 gene Proteins 0.000 description 1
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 1
- 101710085500 C-X-C motif chemokine 9 Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 101150077194 CAP1 gene Proteins 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 101100298998 Caenorhabditis elegans pbs-3 gene Proteins 0.000 description 1
- 241000589994 Campylobacter sp. Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 241000710190 Cardiovirus Species 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 241000193449 Clostridium tetani Species 0.000 description 1
- 241000223205 Coccidioides immitis Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 102000000503 Collagen Type II Human genes 0.000 description 1
- 108010041390 Collagen Type II Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 241000186249 Corynebacterium sp. Species 0.000 description 1
- 241000709687 Coxsackievirus Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 201000007336 Cryptococcosis Diseases 0.000 description 1
- 241000221204 Cryptococcus neoformans Species 0.000 description 1
- NOCCABSVTRONIN-CIUDSAMLSA-N Cys-Ala-Leu Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CS)N NOCCABSVTRONIN-CIUDSAMLSA-N 0.000 description 1
- PRXCTTWKGJAPMT-ZLUOBGJFSA-N Cys-Ala-Ser Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O PRXCTTWKGJAPMT-ZLUOBGJFSA-N 0.000 description 1
- MBPKYKSYUAPLMY-DCAQKATOSA-N Cys-Arg-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O MBPKYKSYUAPLMY-DCAQKATOSA-N 0.000 description 1
- HRJLVSQKBLZHSR-ZLUOBGJFSA-N Cys-Asn-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O HRJLVSQKBLZHSR-ZLUOBGJFSA-N 0.000 description 1
- UUERSUCTHOZPMG-SRVKXCTJSA-N Cys-Asn-Tyr Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 UUERSUCTHOZPMG-SRVKXCTJSA-N 0.000 description 1
- MBILEVLLOHJZMG-FXQIFTODSA-N Cys-Gln-Glu Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CS)N MBILEVLLOHJZMG-FXQIFTODSA-N 0.000 description 1
- KEBJBKIASQVRJS-WDSKDSINSA-N Cys-Gln-Gly Chemical compound C(CC(=O)N)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N KEBJBKIASQVRJS-WDSKDSINSA-N 0.000 description 1
- UCMIKRLLIOVDRJ-XKBZYTNZSA-N Cys-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CS)N)O UCMIKRLLIOVDRJ-XKBZYTNZSA-N 0.000 description 1
- KABHAOSDMIYXTR-GUBZILKMSA-N Cys-Glu-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CS)N KABHAOSDMIYXTR-GUBZILKMSA-N 0.000 description 1
- UCSXXFRXHGUXCQ-SRVKXCTJSA-N Cys-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CS)N UCSXXFRXHGUXCQ-SRVKXCTJSA-N 0.000 description 1
- CIVXDCMSSFGWAL-YUMQZZPRSA-N Cys-Lys-Gly Chemical compound C(CCN)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N CIVXDCMSSFGWAL-YUMQZZPRSA-N 0.000 description 1
- VOBMMKMWSIVIOA-SRVKXCTJSA-N Cys-Lys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N VOBMMKMWSIVIOA-SRVKXCTJSA-N 0.000 description 1
- XMVZMBGFIOQONW-GARJFASQSA-N Cys-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N)C(=O)O XMVZMBGFIOQONW-GARJFASQSA-N 0.000 description 1
- HJGUQJJJXQGXGJ-FXQIFTODSA-N Cys-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CS)N HJGUQJJJXQGXGJ-FXQIFTODSA-N 0.000 description 1
- OETOANMAHTWESF-KKUMJFAQSA-N Cys-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CS)N OETOANMAHTWESF-KKUMJFAQSA-N 0.000 description 1
- JEKIARHEWURQRJ-BZSNNMDCSA-N Cys-Phe-Tyr Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)NC(=O)[C@H](CS)N JEKIARHEWURQRJ-BZSNNMDCSA-N 0.000 description 1
- SMEYEQDCCBHTEF-FXQIFTODSA-N Cys-Pro-Ala Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O SMEYEQDCCBHTEF-FXQIFTODSA-N 0.000 description 1
- MBRWOKXNHTUJMB-CIUDSAMLSA-N Cys-Pro-Glu Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O MBRWOKXNHTUJMB-CIUDSAMLSA-N 0.000 description 1
- DQUWSUWXPWGTQT-DCAQKATOSA-N Cys-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CS DQUWSUWXPWGTQT-DCAQKATOSA-N 0.000 description 1
- YWEHYKGJWHPGPY-XGEHTFHBSA-N Cys-Thr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CS)N)O YWEHYKGJWHPGPY-XGEHTFHBSA-N 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- 206010012468 Dermatitis herpetiformis Diseases 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- 241000710188 Encephalomyocarditis virus Species 0.000 description 1
- 102100027723 Endogenous retrovirus group K member 6 Rec protein Human genes 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 241001495410 Enterococcus sp. Species 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 208000000832 Equine Encephalomyelitis Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000186810 Erysipelothrix rhusiopathiae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 241000711950 Filoviridae Species 0.000 description 1
- 208000004262 Food Hypersensitivity Diseases 0.000 description 1
- 206010016946 Food allergy Diseases 0.000 description 1
- 241000605986 Fusobacterium nucleatum Species 0.000 description 1
- 101150005295 GATA2 gene Proteins 0.000 description 1
- 208000036495 Gastritis atrophic Diseases 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- SHERTACNJPYHAR-ACZMJKKPSA-N Gln-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O SHERTACNJPYHAR-ACZMJKKPSA-N 0.000 description 1
- WOACHWLUOFZLGJ-GUBZILKMSA-N Gln-Arg-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O WOACHWLUOFZLGJ-GUBZILKMSA-N 0.000 description 1
- ZPDVKYLJTOFQJV-WDSKDSINSA-N Gln-Asn-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O ZPDVKYLJTOFQJV-WDSKDSINSA-N 0.000 description 1
- WLODHVXYKYHLJD-ACZMJKKPSA-N Gln-Asp-Ser Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)O)N WLODHVXYKYHLJD-ACZMJKKPSA-N 0.000 description 1
- AJDMYLOISOCHHC-YVNDNENWSA-N Gln-Gln-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O AJDMYLOISOCHHC-YVNDNENWSA-N 0.000 description 1
- MADFVRSKEIEZHZ-DCAQKATOSA-N Gln-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N MADFVRSKEIEZHZ-DCAQKATOSA-N 0.000 description 1
- LVNILKSSFHCSJZ-IHRRRGAJSA-N Gln-Gln-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N LVNILKSSFHCSJZ-IHRRRGAJSA-N 0.000 description 1
- KCJJFESQRXGTGC-BQBZGAKWSA-N Gln-Glu-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O KCJJFESQRXGTGC-BQBZGAKWSA-N 0.000 description 1
- VOLVNCMGXWDDQY-LPEHRKFASA-N Gln-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N)C(=O)O VOLVNCMGXWDDQY-LPEHRKFASA-N 0.000 description 1
- IKFZXRLDMYWNBU-YUMQZZPRSA-N Gln-Gly-Arg Chemical compound NC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N IKFZXRLDMYWNBU-YUMQZZPRSA-N 0.000 description 1
- FGYPOQPQTUNESW-IUCAKERBSA-N Gln-Gly-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)N FGYPOQPQTUNESW-IUCAKERBSA-N 0.000 description 1
- ORYMMTRPKVTGSJ-XVKPBYJWSA-N Gln-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O ORYMMTRPKVTGSJ-XVKPBYJWSA-N 0.000 description 1
- KHGGWBRVRPHFMH-PEFMBERDSA-N Gln-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N KHGGWBRVRPHFMH-PEFMBERDSA-N 0.000 description 1
- JXBZEDIQFFCHPZ-PEFMBERDSA-N Gln-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N JXBZEDIQFFCHPZ-PEFMBERDSA-N 0.000 description 1
- HXOLDXKNWKLDMM-YVNDNENWSA-N Gln-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N HXOLDXKNWKLDMM-YVNDNENWSA-N 0.000 description 1
- ZNTDJIMJKNNSLR-RWRJDSDZSA-N Gln-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N ZNTDJIMJKNNSLR-RWRJDSDZSA-N 0.000 description 1
- QBLMTCRYYTVUQY-GUBZILKMSA-N Gln-Leu-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O QBLMTCRYYTVUQY-GUBZILKMSA-N 0.000 description 1
- LGIKBBLQVSWUGK-DCAQKATOSA-N Gln-Leu-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LGIKBBLQVSWUGK-DCAQKATOSA-N 0.000 description 1
- CAXXTYYGFYTBPV-IUCAKERBSA-N Gln-Leu-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O CAXXTYYGFYTBPV-IUCAKERBSA-N 0.000 description 1
- MLSKFHLRFVGNLL-WDCWCFNPSA-N Gln-Leu-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MLSKFHLRFVGNLL-WDCWCFNPSA-N 0.000 description 1
- IHSGESFHTMFHRB-GUBZILKMSA-N Gln-Lys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(N)=O IHSGESFHTMFHRB-GUBZILKMSA-N 0.000 description 1
- FKXCBKCOSVIGCT-AVGNSLFASA-N Gln-Lys-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O FKXCBKCOSVIGCT-AVGNSLFASA-N 0.000 description 1
- YGNPTRVNRUKVLA-DCAQKATOSA-N Gln-Met-Met Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CCC(=O)N)N YGNPTRVNRUKVLA-DCAQKATOSA-N 0.000 description 1
- SWDSRANUCKNBLA-AVGNSLFASA-N Gln-Phe-Asp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N SWDSRANUCKNBLA-AVGNSLFASA-N 0.000 description 1
- WHVLABLIJYGVEK-QEWYBTABSA-N Gln-Phe-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WHVLABLIJYGVEK-QEWYBTABSA-N 0.000 description 1
- XZUUUKNKNWVPHQ-JYJNAYRXSA-N Gln-Phe-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O XZUUUKNKNWVPHQ-JYJNAYRXSA-N 0.000 description 1
- ZVQZXPADLZIQFF-FHWLQOOXSA-N Gln-Phe-Tyr Chemical compound C([C@H](NC(=O)[C@H](CCC(N)=O)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 ZVQZXPADLZIQFF-FHWLQOOXSA-N 0.000 description 1
- DOQUICBEISTQHE-CIUDSAMLSA-N Gln-Pro-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O DOQUICBEISTQHE-CIUDSAMLSA-N 0.000 description 1
- SYZZMPFLOLSMHL-XHNCKOQMSA-N Gln-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N)C(=O)O SYZZMPFLOLSMHL-XHNCKOQMSA-N 0.000 description 1
- JILRMFFFCHUUTJ-ACZMJKKPSA-N Gln-Ser-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O JILRMFFFCHUUTJ-ACZMJKKPSA-N 0.000 description 1
- PAOHIZNRJNIXQY-XQXXSGGOSA-N Gln-Thr-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O PAOHIZNRJNIXQY-XQXXSGGOSA-N 0.000 description 1
- SYTFJIQPBRJSOK-NKIYYHGXSA-N Gln-Thr-His Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 SYTFJIQPBRJSOK-NKIYYHGXSA-N 0.000 description 1
- NHMRJKKAVMENKJ-WDCWCFNPSA-N Gln-Thr-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NHMRJKKAVMENKJ-WDCWCFNPSA-N 0.000 description 1
- VLOLPWWCNKWRNB-LOKLDPHHSA-N Gln-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O VLOLPWWCNKWRNB-LOKLDPHHSA-N 0.000 description 1
- STHSGOZLFLFGSS-SUSMZKCASA-N Gln-Thr-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O STHSGOZLFLFGSS-SUSMZKCASA-N 0.000 description 1
- OEIDWQHTRYEYGG-QEJZJMRPSA-N Gln-Trp-Asp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N OEIDWQHTRYEYGG-QEJZJMRPSA-N 0.000 description 1
- JKDBRTNMYXYLHO-JYJNAYRXSA-N Gln-Tyr-Leu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 JKDBRTNMYXYLHO-JYJNAYRXSA-N 0.000 description 1
- VCUNGPMMPNJSGS-JYJNAYRXSA-N Gln-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O VCUNGPMMPNJSGS-JYJNAYRXSA-N 0.000 description 1
- ZMXZGYLINVNTKH-DZKIICNBSA-N Gln-Val-Phe Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZMXZGYLINVNTKH-DZKIICNBSA-N 0.000 description 1
- HNAUFGBKJLTWQE-IFFSRLJSSA-N Gln-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(=O)N)N)O HNAUFGBKJLTWQE-IFFSRLJSSA-N 0.000 description 1
- RUFHOVYUYSNDNY-ACZMJKKPSA-N Glu-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O RUFHOVYUYSNDNY-ACZMJKKPSA-N 0.000 description 1
- IRDASPPCLZIERZ-XHNCKOQMSA-N Glu-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N IRDASPPCLZIERZ-XHNCKOQMSA-N 0.000 description 1
- KBKGRMNVKPSQIF-XDTLVQLUSA-N Glu-Ala-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KBKGRMNVKPSQIF-XDTLVQLUSA-N 0.000 description 1
- AVZHGSCDKIQZPQ-CIUDSAMLSA-N Glu-Arg-Ala Chemical compound C[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CCC(O)=O)C(O)=O AVZHGSCDKIQZPQ-CIUDSAMLSA-N 0.000 description 1
- DIXKFOPPGWKZLY-CIUDSAMLSA-N Glu-Arg-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O DIXKFOPPGWKZLY-CIUDSAMLSA-N 0.000 description 1
- PBEQPAZRHDVJQI-SRVKXCTJSA-N Glu-Arg-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)O)N PBEQPAZRHDVJQI-SRVKXCTJSA-N 0.000 description 1
- VPKBCVUDBNINAH-GARJFASQSA-N Glu-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)O)N)C(=O)O VPKBCVUDBNINAH-GARJFASQSA-N 0.000 description 1
- YKLNMGJYMNPBCP-ACZMJKKPSA-N Glu-Asn-Asp Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N YKLNMGJYMNPBCP-ACZMJKKPSA-N 0.000 description 1
- YYOBUPFZLKQUAX-FXQIFTODSA-N Glu-Asn-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YYOBUPFZLKQUAX-FXQIFTODSA-N 0.000 description 1
- RDPOETHPAQEGDP-ACZMJKKPSA-N Glu-Asp-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O RDPOETHPAQEGDP-ACZMJKKPSA-N 0.000 description 1
- JPHYJQHPILOKHC-ACZMJKKPSA-N Glu-Asp-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O JPHYJQHPILOKHC-ACZMJKKPSA-N 0.000 description 1
- IESFZVCAVACGPH-PEFMBERDSA-N Glu-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCC(O)=O IESFZVCAVACGPH-PEFMBERDSA-N 0.000 description 1
- JVSBYEDSSRZQGV-GUBZILKMSA-N Glu-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCC(O)=O JVSBYEDSSRZQGV-GUBZILKMSA-N 0.000 description 1
- PAQUJCSYVIBPLC-AVGNSLFASA-N Glu-Asp-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PAQUJCSYVIBPLC-AVGNSLFASA-N 0.000 description 1
- FKGNJUCQKXQNRA-NRPADANISA-N Glu-Cys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCC(O)=O FKGNJUCQKXQNRA-NRPADANISA-N 0.000 description 1
- OXEMJGCAJFFREE-FXQIFTODSA-N Glu-Gln-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O OXEMJGCAJFFREE-FXQIFTODSA-N 0.000 description 1
- UMIRPYLZFKOEOH-YVNDNENWSA-N Glu-Gln-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O UMIRPYLZFKOEOH-YVNDNENWSA-N 0.000 description 1
- AUTNXSQEVVHSJK-YVNDNENWSA-N Glu-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O AUTNXSQEVVHSJK-YVNDNENWSA-N 0.000 description 1
- KUTPGXNAAOQSPD-LPEHRKFASA-N Glu-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)N)C(=O)O KUTPGXNAAOQSPD-LPEHRKFASA-N 0.000 description 1
- QYPKJXSMLMREKF-BPUTZDHNSA-N Glu-Glu-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)N QYPKJXSMLMREKF-BPUTZDHNSA-N 0.000 description 1
- LYCDZGLXQBPNQU-WDSKDSINSA-N Glu-Gly-Cys Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CS)C(O)=O LYCDZGLXQBPNQU-WDSKDSINSA-N 0.000 description 1
- KRGZZKWSBGPLKL-IUCAKERBSA-N Glu-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)N KRGZZKWSBGPLKL-IUCAKERBSA-N 0.000 description 1
- ZWQVYZXPYSYPJD-RYUDHWBXSA-N Glu-Gly-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZWQVYZXPYSYPJD-RYUDHWBXSA-N 0.000 description 1
- RAUDKMVXNOWDLS-WDSKDSINSA-N Glu-Gly-Ser Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O RAUDKMVXNOWDLS-WDSKDSINSA-N 0.000 description 1
- HILMIYALTUQTRC-XVKPBYJWSA-N Glu-Gly-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HILMIYALTUQTRC-XVKPBYJWSA-N 0.000 description 1
- QIQABBIDHGQXGA-ZPFDUUQYSA-N Glu-Ile-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O QIQABBIDHGQXGA-ZPFDUUQYSA-N 0.000 description 1
- VMKCPNBBPGGQBJ-GUBZILKMSA-N Glu-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N VMKCPNBBPGGQBJ-GUBZILKMSA-N 0.000 description 1
- VGBSZQSKQRMLHD-MNXVOIDGSA-N Glu-Leu-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VGBSZQSKQRMLHD-MNXVOIDGSA-N 0.000 description 1
- MWMJCGBSIORNCD-AVGNSLFASA-N Glu-Leu-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O MWMJCGBSIORNCD-AVGNSLFASA-N 0.000 description 1
- FBEJIDRSQCGFJI-GUBZILKMSA-N Glu-Leu-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O FBEJIDRSQCGFJI-GUBZILKMSA-N 0.000 description 1
- BCYGDJXHAGZNPQ-DCAQKATOSA-N Glu-Lys-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O BCYGDJXHAGZNPQ-DCAQKATOSA-N 0.000 description 1
- YGLCLCMAYUYZSG-AVGNSLFASA-N Glu-Lys-His Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 YGLCLCMAYUYZSG-AVGNSLFASA-N 0.000 description 1
- ILWHFUZZCFYSKT-AVGNSLFASA-N Glu-Lys-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O ILWHFUZZCFYSKT-AVGNSLFASA-N 0.000 description 1
- RBXSZQRSEGYDFG-GUBZILKMSA-N Glu-Lys-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O RBXSZQRSEGYDFG-GUBZILKMSA-N 0.000 description 1
- QDMVXRNLOPTPIE-WDCWCFNPSA-N Glu-Lys-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QDMVXRNLOPTPIE-WDCWCFNPSA-N 0.000 description 1
- NPMSEUWUMOSEFM-CIUDSAMLSA-N Glu-Met-Asn Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N NPMSEUWUMOSEFM-CIUDSAMLSA-N 0.000 description 1
- CBWKURKPYSLMJV-SOUVJXGZSA-N Glu-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCC(=O)O)N)C(=O)O CBWKURKPYSLMJV-SOUVJXGZSA-N 0.000 description 1
- PAZQYODKOZHXGA-SRVKXCTJSA-N Glu-Pro-His Chemical compound N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O PAZQYODKOZHXGA-SRVKXCTJSA-N 0.000 description 1
- WIKMTDVSCUJIPJ-CIUDSAMLSA-N Glu-Ser-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N WIKMTDVSCUJIPJ-CIUDSAMLSA-N 0.000 description 1
- GTFYQOVVVJASOA-ACZMJKKPSA-N Glu-Ser-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N GTFYQOVVVJASOA-ACZMJKKPSA-N 0.000 description 1
- RFTVTKBHDXCEEX-WDSKDSINSA-N Glu-Ser-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RFTVTKBHDXCEEX-WDSKDSINSA-N 0.000 description 1
- HMJULNMJWOZNFI-XHNCKOQMSA-N Glu-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)N)C(=O)O HMJULNMJWOZNFI-XHNCKOQMSA-N 0.000 description 1
- GPSHCSTUYOQPAI-JHEQGTHGSA-N Glu-Thr-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O GPSHCSTUYOQPAI-JHEQGTHGSA-N 0.000 description 1
- ZQNCUVODKOBSSO-XEGUGMAKSA-N Glu-Trp-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(O)=O ZQNCUVODKOBSSO-XEGUGMAKSA-N 0.000 description 1
- YOTHMZZSJKKEHZ-SZMVWBNQSA-N Glu-Trp-Lys Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](N)CCC(O)=O)=CNC2=C1 YOTHMZZSJKKEHZ-SZMVWBNQSA-N 0.000 description 1
- QEJKKJNDDDPSMU-KKUMJFAQSA-N Glu-Tyr-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCSC)C(O)=O QEJKKJNDDDPSMU-KKUMJFAQSA-N 0.000 description 1
- UZWUBBRJWFTHTD-LAEOZQHASA-N Glu-Val-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCC(O)=O UZWUBBRJWFTHTD-LAEOZQHASA-N 0.000 description 1
- LZEUDRYSAZAJIO-AUTRQRHGSA-N Glu-Val-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LZEUDRYSAZAJIO-AUTRQRHGSA-N 0.000 description 1
- VIPDPMHGICREIS-GVXVVHGQSA-N Glu-Val-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O VIPDPMHGICREIS-GVXVVHGQSA-N 0.000 description 1
- ZYRXTRTUCAVNBQ-GVXVVHGQSA-N Glu-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZYRXTRTUCAVNBQ-GVXVVHGQSA-N 0.000 description 1
- SOYWRINXUSUWEQ-DLOVCJGASA-N Glu-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCC(O)=O SOYWRINXUSUWEQ-DLOVCJGASA-N 0.000 description 1
- UGVQELHRNUDMAA-BYPYZUCNSA-N Gly-Ala-Gly Chemical compound [NH3+]CC(=O)N[C@@H](C)C(=O)NCC([O-])=O UGVQELHRNUDMAA-BYPYZUCNSA-N 0.000 description 1
- FKJQNJCQTKUBCD-XPUUQOCRSA-N Gly-Ala-His Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O FKJQNJCQTKUBCD-XPUUQOCRSA-N 0.000 description 1
- JBRBACJPBZNFMF-YUMQZZPRSA-N Gly-Ala-Lys Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN JBRBACJPBZNFMF-YUMQZZPRSA-N 0.000 description 1
- QXPRJQPCFXMCIY-NKWVEPMBSA-N Gly-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN QXPRJQPCFXMCIY-NKWVEPMBSA-N 0.000 description 1
- QIZJOTQTCAGKPU-KWQFWETISA-N Gly-Ala-Tyr Chemical compound [NH3+]CC(=O)N[C@@H](C)C(=O)N[C@H](C([O-])=O)CC1=CC=C(O)C=C1 QIZJOTQTCAGKPU-KWQFWETISA-N 0.000 description 1
- OVSKVOOUFAKODB-UWVGGRQHSA-N Gly-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N OVSKVOOUFAKODB-UWVGGRQHSA-N 0.000 description 1
- WKJKBELXHCTHIJ-WPRPVWTQSA-N Gly-Arg-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N WKJKBELXHCTHIJ-WPRPVWTQSA-N 0.000 description 1
- UXJHNZODTMHWRD-WHFBIAKZSA-N Gly-Asn-Ala Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O UXJHNZODTMHWRD-WHFBIAKZSA-N 0.000 description 1
- JVWPPCWUDRJGAE-YUMQZZPRSA-N Gly-Asn-Leu Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JVWPPCWUDRJGAE-YUMQZZPRSA-N 0.000 description 1
- KQDMENMTYNBWMR-WHFBIAKZSA-N Gly-Asp-Ala Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O KQDMENMTYNBWMR-WHFBIAKZSA-N 0.000 description 1
- FUTAPPOITCCWTH-WHFBIAKZSA-N Gly-Asp-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O FUTAPPOITCCWTH-WHFBIAKZSA-N 0.000 description 1
- ZRZILYKEJBMFHY-BQBZGAKWSA-N Gly-Asp-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CN ZRZILYKEJBMFHY-BQBZGAKWSA-N 0.000 description 1
- PEZZSFLFXXFUQD-XPUUQOCRSA-N Gly-Cys-Val Chemical compound [H]NCC(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O PEZZSFLFXXFUQD-XPUUQOCRSA-N 0.000 description 1
- CQZDZKRHFWJXDF-WDSKDSINSA-N Gly-Gln-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CN CQZDZKRHFWJXDF-WDSKDSINSA-N 0.000 description 1
- XLFHCWHXKSFVIB-BQBZGAKWSA-N Gly-Gln-Gln Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O XLFHCWHXKSFVIB-BQBZGAKWSA-N 0.000 description 1
- LXXANCRPFBSSKS-IUCAKERBSA-N Gly-Gln-Leu Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LXXANCRPFBSSKS-IUCAKERBSA-N 0.000 description 1
- NPSWCZIRBAYNSB-JHEQGTHGSA-N Gly-Gln-Thr Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NPSWCZIRBAYNSB-JHEQGTHGSA-N 0.000 description 1
- DHDOADIPGZTAHT-YUMQZZPRSA-N Gly-Glu-Arg Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DHDOADIPGZTAHT-YUMQZZPRSA-N 0.000 description 1
- FIQQRCFQXGLOSZ-WDSKDSINSA-N Gly-Glu-Asp Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O FIQQRCFQXGLOSZ-WDSKDSINSA-N 0.000 description 1
- HFXJIZNEXNIZIJ-BQBZGAKWSA-N Gly-Glu-Gln Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HFXJIZNEXNIZIJ-BQBZGAKWSA-N 0.000 description 1
- CCQOOWAONKGYKQ-BYPYZUCNSA-N Gly-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)CN CCQOOWAONKGYKQ-BYPYZUCNSA-N 0.000 description 1
- UFPXDFOYHVEIPI-BYPYZUCNSA-N Gly-Gly-Asp Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O UFPXDFOYHVEIPI-BYPYZUCNSA-N 0.000 description 1
- QITBQGJOXQYMOA-ZETCQYMHSA-N Gly-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)CN QITBQGJOXQYMOA-ZETCQYMHSA-N 0.000 description 1
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 1
- UESJMAMHDLEHGM-NHCYSSNCSA-N Gly-Ile-Leu Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O UESJMAMHDLEHGM-NHCYSSNCSA-N 0.000 description 1
- ZOTGXWMKUFSKEU-QXEWZRGKSA-N Gly-Ile-Met Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCSC)C(O)=O ZOTGXWMKUFSKEU-QXEWZRGKSA-N 0.000 description 1
- PAWIVEIWWYGBAM-YUMQZZPRSA-N Gly-Leu-Ala Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O PAWIVEIWWYGBAM-YUMQZZPRSA-N 0.000 description 1
- ULZCYBYDTUMHNF-IUCAKERBSA-N Gly-Leu-Glu Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ULZCYBYDTUMHNF-IUCAKERBSA-N 0.000 description 1
- UHPAZODVFFYEEL-QWRGUYRKSA-N Gly-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)CN UHPAZODVFFYEEL-QWRGUYRKSA-N 0.000 description 1
- LLZXNUUIBOALNY-QWRGUYRKSA-N Gly-Leu-Lys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCCN LLZXNUUIBOALNY-QWRGUYRKSA-N 0.000 description 1
- LPHQAFLNEHWKFF-QXEWZRGKSA-N Gly-Met-Ile Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LPHQAFLNEHWKFF-QXEWZRGKSA-N 0.000 description 1
- UWQDKRIZSROAKS-FJXKBIBVSA-N Gly-Met-Thr Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UWQDKRIZSROAKS-FJXKBIBVSA-N 0.000 description 1
- GGAPHLIUUTVYMX-QWRGUYRKSA-N Gly-Phe-Ser Chemical compound OC[C@@H](C([O-])=O)NC(=O)[C@@H](NC(=O)C[NH3+])CC1=CC=CC=C1 GGAPHLIUUTVYMX-QWRGUYRKSA-N 0.000 description 1
- JYPCXBJRLBHWME-IUCAKERBSA-N Gly-Pro-Arg Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JYPCXBJRLBHWME-IUCAKERBSA-N 0.000 description 1
- WDXLKVQATNEAJQ-BQBZGAKWSA-N Gly-Pro-Asp Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O WDXLKVQATNEAJQ-BQBZGAKWSA-N 0.000 description 1
- YABRDIBSPZONIY-BQBZGAKWSA-N Gly-Ser-Met Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(O)=O YABRDIBSPZONIY-BQBZGAKWSA-N 0.000 description 1
- YXTFLTJYLIAZQG-FJXKBIBVSA-N Gly-Thr-Arg Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YXTFLTJYLIAZQG-FJXKBIBVSA-N 0.000 description 1
- MYXNLWDWWOTERK-BHNWBGBOSA-N Gly-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN)O MYXNLWDWWOTERK-BHNWBGBOSA-N 0.000 description 1
- BNMRSWQOHIQTFL-JSGCOSHPSA-N Gly-Val-Phe Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 BNMRSWQOHIQTFL-JSGCOSHPSA-N 0.000 description 1
- 208000024869 Goodpasture syndrome Diseases 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
- RVKIPWVMZANZLI-UHFFFAOYSA-N H-Lys-Trp-OH Natural products C1=CC=C2C(CC(NC(=O)C(N)CCCCN)C(O)=O)=CNC2=C1 RVKIPWVMZANZLI-UHFFFAOYSA-N 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 206010061192 Haemorrhagic fever Diseases 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 241000700739 Hepadnaviridae Species 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 208000037262 Hepatitis delta Diseases 0.000 description 1
- 241000709721 Hepatovirus A Species 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- SYMSVYVUSPSAAO-IHRRRGAJSA-N His-Arg-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O SYMSVYVUSPSAAO-IHRRRGAJSA-N 0.000 description 1
- LIEIYPBMQJLASB-SRVKXCTJSA-N His-Gln-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC1=CN=CN1 LIEIYPBMQJLASB-SRVKXCTJSA-N 0.000 description 1
- YADRBUZBKHHDAO-XPUUQOCRSA-N His-Gly-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](C)C(O)=O YADRBUZBKHHDAO-XPUUQOCRSA-N 0.000 description 1
- PYNUBZSXKQKAHL-UWVGGRQHSA-N His-Gly-Arg Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O PYNUBZSXKQKAHL-UWVGGRQHSA-N 0.000 description 1
- CZXKZMQKXQZDEX-YUMQZZPRSA-N His-Gly-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)NCC(=O)N[C@@H](CS)C(=O)O)N CZXKZMQKXQZDEX-YUMQZZPRSA-N 0.000 description 1
- FDQYIRHBVVUTJF-ZETCQYMHSA-N His-Gly-Gly Chemical compound [O-]C(=O)CNC(=O)CNC(=O)[C@@H]([NH3+])CC1=CN=CN1 FDQYIRHBVVUTJF-ZETCQYMHSA-N 0.000 description 1
- ORZGPQXISSXQGW-IHRRRGAJSA-N His-His-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C(C)C)C(O)=O ORZGPQXISSXQGW-IHRRRGAJSA-N 0.000 description 1
- ZRSJXIKQXUGKRB-TUBUOCAGSA-N His-Ile-Thr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZRSJXIKQXUGKRB-TUBUOCAGSA-N 0.000 description 1
- JENKOCSDMSVWPY-SRVKXCTJSA-N His-Leu-Asn Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O JENKOCSDMSVWPY-SRVKXCTJSA-N 0.000 description 1
- AIPUZFXMXAHZKY-QWRGUYRKSA-N His-Leu-Gly Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O AIPUZFXMXAHZKY-QWRGUYRKSA-N 0.000 description 1
- BPOHQCZZSFBSON-KKUMJFAQSA-N His-Leu-His Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)Cc1cnc[nH]1)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O BPOHQCZZSFBSON-KKUMJFAQSA-N 0.000 description 1
- SKOKHBGDXGTDDP-MELADBBJSA-N His-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N SKOKHBGDXGTDDP-MELADBBJSA-N 0.000 description 1
- LVXFNTIIGOQBMD-SRVKXCTJSA-N His-Leu-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O LVXFNTIIGOQBMD-SRVKXCTJSA-N 0.000 description 1
- TWROVBNEHJSXDG-IHRRRGAJSA-N His-Leu-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O TWROVBNEHJSXDG-IHRRRGAJSA-N 0.000 description 1
- JUIOPCXACJLRJK-AVGNSLFASA-N His-Lys-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N JUIOPCXACJLRJK-AVGNSLFASA-N 0.000 description 1
- UXSATKFPUVZVDK-KKUMJFAQSA-N His-Lys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CN=CN1)N UXSATKFPUVZVDK-KKUMJFAQSA-N 0.000 description 1
- YIGCZZKZFMNSIU-RWMBFGLXSA-N His-Met-Pro Chemical compound CSCC[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N YIGCZZKZFMNSIU-RWMBFGLXSA-N 0.000 description 1
- XJFITURPHAKKAI-SRVKXCTJSA-N His-Pro-Gln Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(O)=O)C1=CN=CN1 XJFITURPHAKKAI-SRVKXCTJSA-N 0.000 description 1
- PBVQWNDMFFCPIZ-ULQDDVLXSA-N His-Pro-Phe Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CN=CN1 PBVQWNDMFFCPIZ-ULQDDVLXSA-N 0.000 description 1
- OWYIDJCNRWRSJY-QTKMDUPCSA-N His-Pro-Thr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O OWYIDJCNRWRSJY-QTKMDUPCSA-N 0.000 description 1
- FLXCRBXJRJSDHX-AVGNSLFASA-N His-Pro-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O FLXCRBXJRJSDHX-AVGNSLFASA-N 0.000 description 1
- STGQSBKUYSPPIG-CIUDSAMLSA-N His-Ser-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CN=CN1 STGQSBKUYSPPIG-CIUDSAMLSA-N 0.000 description 1
- PLCAEMGSYOYIPP-GUBZILKMSA-N His-Ser-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CN=CN1 PLCAEMGSYOYIPP-GUBZILKMSA-N 0.000 description 1
- PZAJPILZRFPYJJ-SRVKXCTJSA-N His-Ser-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O PZAJPILZRFPYJJ-SRVKXCTJSA-N 0.000 description 1
- FFKJUTZARGRVTH-KKUMJFAQSA-N His-Ser-Tyr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O FFKJUTZARGRVTH-KKUMJFAQSA-N 0.000 description 1
- UPJODPVSKKWGDQ-KLHWPWHYSA-N His-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)O UPJODPVSKKWGDQ-KLHWPWHYSA-N 0.000 description 1
- UIRUVUUGUYCMBY-KCTSRDHCSA-N His-Trp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC3=CN=CN3)N UIRUVUUGUYCMBY-KCTSRDHCSA-N 0.000 description 1
- CSRRMQFXMBPSIL-SIXJUCDHSA-N His-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC3=CN=CN3)N CSRRMQFXMBPSIL-SIXJUCDHSA-N 0.000 description 1
- FRDFAWHTPDKRHG-ULQDDVLXSA-N His-Tyr-Arg Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C1=CN=CN1 FRDFAWHTPDKRHG-ULQDDVLXSA-N 0.000 description 1
- ZHMZWSFQRUGLEC-JYJNAYRXSA-N His-Tyr-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZHMZWSFQRUGLEC-JYJNAYRXSA-N 0.000 description 1
- WSAILOWUJZEAGC-DCAQKATOSA-N His-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N WSAILOWUJZEAGC-DCAQKATOSA-N 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 241000228404 Histoplasma capsulatum Species 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000792933 Homo sapiens AT-rich interactive domain-containing protein 4A Proteins 0.000 description 1
- 101000740067 Homo sapiens Barrier-to-autointegration factor Proteins 0.000 description 1
- 101000947172 Homo sapiens C-X-C motif chemokine 9 Proteins 0.000 description 1
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 1
- 101000666730 Homo sapiens T-complex protein 1 subunit alpha Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 101001057744 Human cytomegalovirus (strain AD169) Uncharacterized protein IRL9 Proteins 0.000 description 1
- 241000722343 Human papillomavirus types Species 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 102000043138 IRF family Human genes 0.000 description 1
- 108091054729 IRF family Proteins 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- UAVQIQOOBXFKRC-BYULHYEWSA-N Ile-Asn-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O UAVQIQOOBXFKRC-BYULHYEWSA-N 0.000 description 1
- XENGULNPUDGALZ-ZPFDUUQYSA-N Ile-Asn-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)O)N XENGULNPUDGALZ-ZPFDUUQYSA-N 0.000 description 1
- AWTDTFXPVCTHAK-BJDJZHNGSA-N Ile-Cys-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)O)N AWTDTFXPVCTHAK-BJDJZHNGSA-N 0.000 description 1
- VQUCKIAECLVLAD-SVSWQMSJSA-N Ile-Cys-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N VQUCKIAECLVLAD-SVSWQMSJSA-N 0.000 description 1
- ZDNORQNHCJUVOV-KBIXCLLPSA-N Ile-Gln-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O ZDNORQNHCJUVOV-KBIXCLLPSA-N 0.000 description 1
- KMBPQYKVZBMRMH-PEFMBERDSA-N Ile-Gln-Asn Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O KMBPQYKVZBMRMH-PEFMBERDSA-N 0.000 description 1
- LPFBXFILACZHIB-LAEOZQHASA-N Ile-Gly-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)O)N LPFBXFILACZHIB-LAEOZQHASA-N 0.000 description 1
- RWYCOSAAAJBJQL-KCTSRDHCSA-N Ile-Gly-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N RWYCOSAAAJBJQL-KCTSRDHCSA-N 0.000 description 1
- UASTVUQJMLZWGG-PEXQALLHSA-N Ile-His-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)NCC(=O)O)N UASTVUQJMLZWGG-PEXQALLHSA-N 0.000 description 1
- UWLHDGMRWXHFFY-HPCHECBXSA-N Ile-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1CCC[C@@H]1C(=O)O)N UWLHDGMRWXHFFY-HPCHECBXSA-N 0.000 description 1
- PMMMQRVUMVURGJ-XUXIUFHCSA-N Ile-Leu-Pro Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(O)=O PMMMQRVUMVURGJ-XUXIUFHCSA-N 0.000 description 1
- DSDPLOODKXISDT-XUXIUFHCSA-N Ile-Leu-Val Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O DSDPLOODKXISDT-XUXIUFHCSA-N 0.000 description 1
- ADDYYRVQQZFIMW-MNXVOIDGSA-N Ile-Lys-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N ADDYYRVQQZFIMW-MNXVOIDGSA-N 0.000 description 1
- YSGBJIQXTIVBHZ-AJNGGQMLSA-N Ile-Lys-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O YSGBJIQXTIVBHZ-AJNGGQMLSA-N 0.000 description 1
- CKRFDMPBSWYOBT-PPCPHDFISA-N Ile-Lys-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N CKRFDMPBSWYOBT-PPCPHDFISA-N 0.000 description 1
- NPAYJTAXWXJKLO-NAKRPEOUSA-N Ile-Met-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)O)N NPAYJTAXWXJKLO-NAKRPEOUSA-N 0.000 description 1
- NURNJECQNNCRBK-FLBSBUHZSA-N Ile-Thr-Thr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NURNJECQNNCRBK-FLBSBUHZSA-N 0.000 description 1
- ZUWSVOYKBCHLRR-MGHWNKPDSA-N Ile-Tyr-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCCN)C(=O)O)N ZUWSVOYKBCHLRR-MGHWNKPDSA-N 0.000 description 1
- RQZFWBLDTBDEOF-RNJOBUHISA-N Ile-Val-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N RQZFWBLDTBDEOF-RNJOBUHISA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 102100040019 Interferon alpha-1/13 Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108090000171 Interleukin-18 Proteins 0.000 description 1
- 108050009288 Interleukin-19 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 241000701377 Iridoviridae Species 0.000 description 1
- 239000007760 Iscove's Modified Dulbecco's Medium Substances 0.000 description 1
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 241000588915 Klebsiella aerogenes Species 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 208000007811 Latex Hypersensitivity Diseases 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000222740 Leishmania braziliensis Species 0.000 description 1
- 241000222727 Leishmania donovani Species 0.000 description 1
- 241000222732 Leishmania major Species 0.000 description 1
- 241000222736 Leishmania tropica Species 0.000 description 1
- 241000589902 Leptospira Species 0.000 description 1
- LJHGALIOHLRRQN-DCAQKATOSA-N Leu-Ala-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N LJHGALIOHLRRQN-DCAQKATOSA-N 0.000 description 1
- BQSLGJHIAGOZCD-CIUDSAMLSA-N Leu-Ala-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O BQSLGJHIAGOZCD-CIUDSAMLSA-N 0.000 description 1
- SUPVSFFZWVOEOI-UHFFFAOYSA-N Leu-Ala-Tyr Natural products CC(C)CC(N)C(=O)NC(C)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 SUPVSFFZWVOEOI-UHFFFAOYSA-N 0.000 description 1
- HBJZFCIVFIBNSV-DCAQKATOSA-N Leu-Arg-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(O)=O HBJZFCIVFIBNSV-DCAQKATOSA-N 0.000 description 1
- CNNQBZRGQATKNY-DCAQKATOSA-N Leu-Arg-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N CNNQBZRGQATKNY-DCAQKATOSA-N 0.000 description 1
- HASRFYOMVPJRPU-SRVKXCTJSA-N Leu-Arg-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HASRFYOMVPJRPU-SRVKXCTJSA-N 0.000 description 1
- IBMVEYRWAWIOTN-RWMBFGLXSA-N Leu-Arg-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(O)=O IBMVEYRWAWIOTN-RWMBFGLXSA-N 0.000 description 1
- VCSBGUACOYUIGD-CIUDSAMLSA-N Leu-Asn-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O VCSBGUACOYUIGD-CIUDSAMLSA-N 0.000 description 1
- WGNOPSQMIQERPK-GARJFASQSA-N Leu-Asn-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N WGNOPSQMIQERPK-GARJFASQSA-N 0.000 description 1
- WGNOPSQMIQERPK-UHFFFAOYSA-N Leu-Asn-Pro Natural products CC(C)CC(N)C(=O)NC(CC(=O)N)C(=O)N1CCCC1C(=O)O WGNOPSQMIQERPK-UHFFFAOYSA-N 0.000 description 1
- OGCQGUIWMSBHRZ-CIUDSAMLSA-N Leu-Asn-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O OGCQGUIWMSBHRZ-CIUDSAMLSA-N 0.000 description 1
- ILJREDZFPHTUIE-GUBZILKMSA-N Leu-Asp-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ILJREDZFPHTUIE-GUBZILKMSA-N 0.000 description 1
- MMEDVBWCMGRKKC-GARJFASQSA-N Leu-Asp-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N MMEDVBWCMGRKKC-GARJFASQSA-N 0.000 description 1
- HUEBCHPSXSQUGN-GARJFASQSA-N Leu-Cys-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N HUEBCHPSXSQUGN-GARJFASQSA-N 0.000 description 1
- VQPPIMUZCZCOIL-GUBZILKMSA-N Leu-Gln-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O VQPPIMUZCZCOIL-GUBZILKMSA-N 0.000 description 1
- KAFOIVJDVSZUMD-UHFFFAOYSA-N Leu-Gln-Gln Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(O)=O KAFOIVJDVSZUMD-UHFFFAOYSA-N 0.000 description 1
- QDSKNVXKLPQNOJ-GVXVVHGQSA-N Leu-Gln-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O QDSKNVXKLPQNOJ-GVXVVHGQSA-N 0.000 description 1
- RVVBWTWPNFDYBE-SRVKXCTJSA-N Leu-Glu-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RVVBWTWPNFDYBE-SRVKXCTJSA-N 0.000 description 1
- WIDZHJTYKYBLSR-DCAQKATOSA-N Leu-Glu-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WIDZHJTYKYBLSR-DCAQKATOSA-N 0.000 description 1
- QVFGXCVIXXBFHO-AVGNSLFASA-N Leu-Glu-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O QVFGXCVIXXBFHO-AVGNSLFASA-N 0.000 description 1
- HVJVUYQWFYMGJS-GVXVVHGQSA-N Leu-Glu-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O HVJVUYQWFYMGJS-GVXVVHGQSA-N 0.000 description 1
- KGCLIYGPQXUNLO-IUCAKERBSA-N Leu-Gly-Glu Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O KGCLIYGPQXUNLO-IUCAKERBSA-N 0.000 description 1
- VWHGTYCRDRBSFI-ZETCQYMHSA-N Leu-Gly-Gly Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)NCC(O)=O VWHGTYCRDRBSFI-ZETCQYMHSA-N 0.000 description 1
- KEVYYIMVELOXCT-KBPBESRZSA-N Leu-Gly-Phe Chemical compound CC(C)C[C@H]([NH3+])C(=O)NCC(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 KEVYYIMVELOXCT-KBPBESRZSA-N 0.000 description 1
- VGPCJSXPPOQPBK-YUMQZZPRSA-N Leu-Gly-Ser Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O VGPCJSXPPOQPBK-YUMQZZPRSA-N 0.000 description 1
- KUIDCYNIEJBZBU-AJNGGQMLSA-N Leu-Ile-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O KUIDCYNIEJBZBU-AJNGGQMLSA-N 0.000 description 1
- LIINDKYIGYTDLG-PPCPHDFISA-N Leu-Ile-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LIINDKYIGYTDLG-PPCPHDFISA-N 0.000 description 1
- DSFYPIUSAMSERP-IHRRRGAJSA-N Leu-Leu-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DSFYPIUSAMSERP-IHRRRGAJSA-N 0.000 description 1
- QNBVTHNJGCOVFA-AVGNSLFASA-N Leu-Leu-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O QNBVTHNJGCOVFA-AVGNSLFASA-N 0.000 description 1
- RXGLHDWAZQECBI-SRVKXCTJSA-N Leu-Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O RXGLHDWAZQECBI-SRVKXCTJSA-N 0.000 description 1
- RTIRBWJPYJYTLO-MELADBBJSA-N Leu-Lys-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N RTIRBWJPYJYTLO-MELADBBJSA-N 0.000 description 1
- FIICHHJDINDXKG-IHPCNDPISA-N Leu-Lys-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O FIICHHJDINDXKG-IHPCNDPISA-N 0.000 description 1
- NHRINZSPIUXYQZ-DCAQKATOSA-N Leu-Met-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CS)C(=O)O)N NHRINZSPIUXYQZ-DCAQKATOSA-N 0.000 description 1
- POMXSEDNUXYPGK-IHRRRGAJSA-N Leu-Met-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N POMXSEDNUXYPGK-IHRRRGAJSA-N 0.000 description 1
- GNRPTBRHRRZCMA-RWMBFGLXSA-N Leu-Met-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@@H]1C(=O)O)N GNRPTBRHRRZCMA-RWMBFGLXSA-N 0.000 description 1
- QMKFDEUJGYNFMC-AVGNSLFASA-N Leu-Pro-Arg Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O QMKFDEUJGYNFMC-AVGNSLFASA-N 0.000 description 1
- BMVFXOQHDQZAQU-DCAQKATOSA-N Leu-Pro-Asp Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)O)N BMVFXOQHDQZAQU-DCAQKATOSA-N 0.000 description 1
- UCBPDSYUVAAHCD-UWVGGRQHSA-N Leu-Pro-Gly Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UCBPDSYUVAAHCD-UWVGGRQHSA-N 0.000 description 1
- MUCIDQMDOYQYBR-IHRRRGAJSA-N Leu-Pro-His Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N MUCIDQMDOYQYBR-IHRRRGAJSA-N 0.000 description 1
- KWLWZYMNUZJKMZ-IHRRRGAJSA-N Leu-Pro-Leu Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O KWLWZYMNUZJKMZ-IHRRRGAJSA-N 0.000 description 1
- CHJKEDSZNSONPS-DCAQKATOSA-N Leu-Pro-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O CHJKEDSZNSONPS-DCAQKATOSA-N 0.000 description 1
- JDBQSGMJBMPNFT-AVGNSLFASA-N Leu-Pro-Val Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O JDBQSGMJBMPNFT-AVGNSLFASA-N 0.000 description 1
- RGUXWMDNCPMQFB-YUMQZZPRSA-N Leu-Ser-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RGUXWMDNCPMQFB-YUMQZZPRSA-N 0.000 description 1
- SBANPBVRHYIMRR-GARJFASQSA-N Leu-Ser-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N SBANPBVRHYIMRR-GARJFASQSA-N 0.000 description 1
- ZDJQVSIPFLMNOX-RHYQMDGZSA-N Leu-Thr-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N ZDJQVSIPFLMNOX-RHYQMDGZSA-N 0.000 description 1
- HGLKOTPFWOMPOB-MEYUZBJRSA-N Leu-Thr-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HGLKOTPFWOMPOB-MEYUZBJRSA-N 0.000 description 1
- VHTIZYYHIUHMCA-JYJNAYRXSA-N Leu-Tyr-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O VHTIZYYHIUHMCA-JYJNAYRXSA-N 0.000 description 1
- BTEMNFBEAAOGBR-BZSNNMDCSA-N Leu-Tyr-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCCN)C(=O)O)N BTEMNFBEAAOGBR-BZSNNMDCSA-N 0.000 description 1
- AIMGJYMCTAABEN-GVXVVHGQSA-N Leu-Val-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AIMGJYMCTAABEN-GVXVVHGQSA-N 0.000 description 1
- FDBTVENULFNTAL-XQQFMLRXSA-N Leu-Val-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N FDBTVENULFNTAL-XQQFMLRXSA-N 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 241000712899 Lymphocytic choriomeningitis mammarenavirus Species 0.000 description 1
- 206010025280 Lymphocytosis Diseases 0.000 description 1
- VHFFQUSNFFIZBT-CIUDSAMLSA-N Lys-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCCN)N VHFFQUSNFFIZBT-CIUDSAMLSA-N 0.000 description 1
- UWKNTTJNVSYXPC-CIUDSAMLSA-N Lys-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN UWKNTTJNVSYXPC-CIUDSAMLSA-N 0.000 description 1
- IRNSXVOWSXSULE-DCAQKATOSA-N Lys-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN IRNSXVOWSXSULE-DCAQKATOSA-N 0.000 description 1
- GAOJCVKPIGHTGO-UWVGGRQHSA-N Lys-Arg-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O GAOJCVKPIGHTGO-UWVGGRQHSA-N 0.000 description 1
- YNNPKXBBRZVIRX-IHRRRGAJSA-N Lys-Arg-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O YNNPKXBBRZVIRX-IHRRRGAJSA-N 0.000 description 1
- SJNZALDHDUYDBU-IHRRRGAJSA-N Lys-Arg-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(O)=O SJNZALDHDUYDBU-IHRRRGAJSA-N 0.000 description 1
- CKSXSQUVEYCDIW-AVGNSLFASA-N Lys-Arg-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)N CKSXSQUVEYCDIW-AVGNSLFASA-N 0.000 description 1
- LZWNAOIMTLNMDW-NHCYSSNCSA-N Lys-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)N LZWNAOIMTLNMDW-NHCYSSNCSA-N 0.000 description 1
- ZAENPHCEQXALHO-GUBZILKMSA-N Lys-Cys-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZAENPHCEQXALHO-GUBZILKMSA-N 0.000 description 1
- NNCDAORZCMPZPX-GUBZILKMSA-N Lys-Gln-Ser Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N NNCDAORZCMPZPX-GUBZILKMSA-N 0.000 description 1
- IRRZDAIFYHNIIN-JYJNAYRXSA-N Lys-Gln-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IRRZDAIFYHNIIN-JYJNAYRXSA-N 0.000 description 1
- DRCILAJNUJKAHC-SRVKXCTJSA-N Lys-Glu-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O DRCILAJNUJKAHC-SRVKXCTJSA-N 0.000 description 1
- ZXEUFAVXODIPHC-GUBZILKMSA-N Lys-Glu-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZXEUFAVXODIPHC-GUBZILKMSA-N 0.000 description 1
- PBIPLDMFHAICIP-DCAQKATOSA-N Lys-Glu-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PBIPLDMFHAICIP-DCAQKATOSA-N 0.000 description 1
- DCRWPTBMWMGADO-AVGNSLFASA-N Lys-Glu-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O DCRWPTBMWMGADO-AVGNSLFASA-N 0.000 description 1
- PAMDBWYMLWOELY-SDDRHHMPSA-N Lys-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)N)C(=O)O PAMDBWYMLWOELY-SDDRHHMPSA-N 0.000 description 1
- VEGLGAOVLFODGC-GUBZILKMSA-N Lys-Glu-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O VEGLGAOVLFODGC-GUBZILKMSA-N 0.000 description 1
- ULUQBUKAPDUKOC-GVXVVHGQSA-N Lys-Glu-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O ULUQBUKAPDUKOC-GVXVVHGQSA-N 0.000 description 1
- XNKDCYABMBBEKN-IUCAKERBSA-N Lys-Gly-Gln Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O XNKDCYABMBBEKN-IUCAKERBSA-N 0.000 description 1
- ISHNZELVUVPCHY-ZETCQYMHSA-N Lys-Gly-Gly Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O ISHNZELVUVPCHY-ZETCQYMHSA-N 0.000 description 1
- GQFDWEDHOQRNLC-QWRGUYRKSA-N Lys-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN GQFDWEDHOQRNLC-QWRGUYRKSA-N 0.000 description 1
- HAUUXTXKJNVIFY-ONGXEEELSA-N Lys-Gly-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HAUUXTXKJNVIFY-ONGXEEELSA-N 0.000 description 1
- PRCHKVGXZVTALR-KKUMJFAQSA-N Lys-His-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CCCCN)N PRCHKVGXZVTALR-KKUMJFAQSA-N 0.000 description 1
- OWRUUFUVXFREBD-KKUMJFAQSA-N Lys-His-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O OWRUUFUVXFREBD-KKUMJFAQSA-N 0.000 description 1
- YXTKSLRSRXKXNV-IHRRRGAJSA-N Lys-His-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCCCN)N YXTKSLRSRXKXNV-IHRRRGAJSA-N 0.000 description 1
- OVAOHZIOUBEQCJ-IHRRRGAJSA-N Lys-Leu-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OVAOHZIOUBEQCJ-IHRRRGAJSA-N 0.000 description 1
- VMTYLUGCXIEDMV-QWRGUYRKSA-N Lys-Leu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCCCN VMTYLUGCXIEDMV-QWRGUYRKSA-N 0.000 description 1
- WRODMZBHNNPRLN-SRVKXCTJSA-N Lys-Leu-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O WRODMZBHNNPRLN-SRVKXCTJSA-N 0.000 description 1
- VUTWYNQUSJWBHO-BZSNNMDCSA-N Lys-Leu-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O VUTWYNQUSJWBHO-BZSNNMDCSA-N 0.000 description 1
- BEGQVWUZFXLNHZ-IHPCNDPISA-N Lys-Lys-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(O)=O)=CNC2=C1 BEGQVWUZFXLNHZ-IHPCNDPISA-N 0.000 description 1
- URGPVYGVWLIRGT-DCAQKATOSA-N Lys-Met-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O URGPVYGVWLIRGT-DCAQKATOSA-N 0.000 description 1
- ZCWWVXAXWUAEPZ-SRVKXCTJSA-N Lys-Met-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZCWWVXAXWUAEPZ-SRVKXCTJSA-N 0.000 description 1
- AFLBTVGQCQLOFJ-AVGNSLFASA-N Lys-Pro-Arg Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O AFLBTVGQCQLOFJ-AVGNSLFASA-N 0.000 description 1
- WGILOYIKJVQUPT-DCAQKATOSA-N Lys-Pro-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O WGILOYIKJVQUPT-DCAQKATOSA-N 0.000 description 1
- HYSVGEAWTGPMOA-IHRRRGAJSA-N Lys-Pro-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O HYSVGEAWTGPMOA-IHRRRGAJSA-N 0.000 description 1
- LUTDBHBIHHREDC-IHRRRGAJSA-N Lys-Pro-Lys Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(O)=O LUTDBHBIHHREDC-IHRRRGAJSA-N 0.000 description 1
- YSPZCHGIWAQVKQ-AVGNSLFASA-N Lys-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCCN YSPZCHGIWAQVKQ-AVGNSLFASA-N 0.000 description 1
- CTJUSALVKAWFFU-CIUDSAMLSA-N Lys-Ser-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N CTJUSALVKAWFFU-CIUDSAMLSA-N 0.000 description 1
- UWHCKWNPWKTMBM-WDCWCFNPSA-N Lys-Thr-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O UWHCKWNPWKTMBM-WDCWCFNPSA-N 0.000 description 1
- QVTDVTONTRSQMF-WDCWCFNPSA-N Lys-Thr-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H]([C@H](O)C)NC(=O)[C@@H](N)CCCCN QVTDVTONTRSQMF-WDCWCFNPSA-N 0.000 description 1
- JHNOXVASMSXSNB-WEDXCCLWSA-N Lys-Thr-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O JHNOXVASMSXSNB-WEDXCCLWSA-N 0.000 description 1
- WAAZECNCPVGPIV-RHYQMDGZSA-N Lys-Thr-Met Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(O)=O WAAZECNCPVGPIV-RHYQMDGZSA-N 0.000 description 1
- NROQVSYLPRLJIP-PMVMPFDFSA-N Lys-Trp-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NROQVSYLPRLJIP-PMVMPFDFSA-N 0.000 description 1
- NYTDJEZBAAFLLG-IHRRRGAJSA-N Lys-Val-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(O)=O NYTDJEZBAAFLLG-IHRRRGAJSA-N 0.000 description 1
- TXTZMVNJIRZABH-ULQDDVLXSA-N Lys-Val-Phe Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 TXTZMVNJIRZABH-ULQDDVLXSA-N 0.000 description 1
- OZVXDDFYCQOPFD-XQQFMLRXSA-N Lys-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N OZVXDDFYCQOPFD-XQQFMLRXSA-N 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- GAELMDJMQDUDLJ-BQBZGAKWSA-N Met-Ala-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O GAELMDJMQDUDLJ-BQBZGAKWSA-N 0.000 description 1
- MUYQDMBLDFEVRJ-LSJOCFKGSA-N Met-Ala-His Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 MUYQDMBLDFEVRJ-LSJOCFKGSA-N 0.000 description 1
- VTKPSXWRUGCOAC-GUBZILKMSA-N Met-Ala-Met Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCSC VTKPSXWRUGCOAC-GUBZILKMSA-N 0.000 description 1
- ACYHZNZHIZWLQF-BQBZGAKWSA-N Met-Asn-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O ACYHZNZHIZWLQF-BQBZGAKWSA-N 0.000 description 1
- FBQMBZLJHOQAIH-GUBZILKMSA-N Met-Asp-Met Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(O)=O FBQMBZLJHOQAIH-GUBZILKMSA-N 0.000 description 1
- HGKJFNCLOHKEHS-FXQIFTODSA-N Met-Cys-Asp Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC(O)=O HGKJFNCLOHKEHS-FXQIFTODSA-N 0.000 description 1
- YLLWCSDBVGZLOW-CIUDSAMLSA-N Met-Gln-Ala Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O YLLWCSDBVGZLOW-CIUDSAMLSA-N 0.000 description 1
- UYAKZHGIPRCGPF-CIUDSAMLSA-N Met-Glu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)N UYAKZHGIPRCGPF-CIUDSAMLSA-N 0.000 description 1
- OOSPRDCGTLQLBP-NHCYSSNCSA-N Met-Glu-Val Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O OOSPRDCGTLQLBP-NHCYSSNCSA-N 0.000 description 1
- XPCLRYNQMZOOFB-ULQDDVLXSA-N Met-His-Phe Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)N XPCLRYNQMZOOFB-ULQDDVLXSA-N 0.000 description 1
- LNXGEYIEEUZGGH-JYJNAYRXSA-N Met-Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CCSC)CC1=CC=CC=C1 LNXGEYIEEUZGGH-JYJNAYRXSA-N 0.000 description 1
- JQHYVIKEFYETEW-IHRRRGAJSA-N Met-Phe-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CC1=CC=CC=C1 JQHYVIKEFYETEW-IHRRRGAJSA-N 0.000 description 1
- VQILILSLEFDECU-GUBZILKMSA-N Met-Pro-Ala Chemical compound [H]N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O VQILILSLEFDECU-GUBZILKMSA-N 0.000 description 1
- MQASRXPTQJJNFM-JYJNAYRXSA-N Met-Pro-Phe Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MQASRXPTQJJNFM-JYJNAYRXSA-N 0.000 description 1
- ZDJICAUBMUKVEJ-CIUDSAMLSA-N Met-Ser-Gln Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O ZDJICAUBMUKVEJ-CIUDSAMLSA-N 0.000 description 1
- NSMXRFMGZYTFEX-KJEVXHAQSA-N Met-Thr-Tyr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CCSC)N)O NSMXRFMGZYTFEX-KJEVXHAQSA-N 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 1
- 101100245221 Mus musculus Prss8 gene Proteins 0.000 description 1
- 241000186363 Mycobacterium kansasii Species 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 1
- 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 1
- 206010028665 Myxoedema Diseases 0.000 description 1
- IYYIBFCJILKPCO-WOUKDFQISA-O N(2),N(2),N(7)-trimethylguanosine Chemical compound C1=2NC(N(C)C)=NC(=O)C=2N(C)C=[N+]1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O IYYIBFCJILKPCO-WOUKDFQISA-O 0.000 description 1
- ZBYRSRLCXTUFLJ-IOSLPCCCSA-O N(2),N(7)-dimethylguanosine Chemical compound CNC=1NC(C=2[N+](=CN([C@H]3[C@H](O)[C@H](O)[C@@H](CO)O3)C=2N=1)C)=O ZBYRSRLCXTUFLJ-IOSLPCCCSA-O 0.000 description 1
- VQAYFKKCNSOZKM-IOSLPCCCSA-N N(6)-methyladenosine Chemical compound C1=NC=2C(NC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VQAYFKKCNSOZKM-IOSLPCCCSA-N 0.000 description 1
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 241000588650 Neisseria meningitidis Species 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000243985 Onchocerca volvulus Species 0.000 description 1
- 241000702259 Orbivirus Species 0.000 description 1
- 241000712464 Orthomyxoviridae Species 0.000 description 1
- 241000150218 Orthonairovirus Species 0.000 description 1
- 101150012195 PREB gene Proteins 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 241000606580 Pasteurella sp. Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000031845 Pernicious anaemia Diseases 0.000 description 1
- LGBVMDMZZFYSFW-HJWJTTGWSA-N Phe-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC1=CC=CC=C1)N LGBVMDMZZFYSFW-HJWJTTGWSA-N 0.000 description 1
- MQVFHOPCKNTHGT-MELADBBJSA-N Phe-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O MQVFHOPCKNTHGT-MELADBBJSA-N 0.000 description 1
- WFDAEEUZPZSMOG-SRVKXCTJSA-N Phe-Cys-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O WFDAEEUZPZSMOG-SRVKXCTJSA-N 0.000 description 1
- SFKOEHXABNPLRT-KBPBESRZSA-N Phe-His-Gly Chemical compound N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)NCC(O)=O SFKOEHXABNPLRT-KBPBESRZSA-N 0.000 description 1
- YZJKNDCEPDDIDA-BZSNNMDCSA-N Phe-His-Lys Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CN=CN1 YZJKNDCEPDDIDA-BZSNNMDCSA-N 0.000 description 1
- YTILBRIUASDGBL-BZSNNMDCSA-N Phe-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 YTILBRIUASDGBL-BZSNNMDCSA-N 0.000 description 1
- YCCUXNNKXDGMAM-KKUMJFAQSA-N Phe-Leu-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YCCUXNNKXDGMAM-KKUMJFAQSA-N 0.000 description 1
- INHMISZWLJZQGH-ULQDDVLXSA-N Phe-Leu-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 INHMISZWLJZQGH-ULQDDVLXSA-N 0.000 description 1
- MJAYDXWQQUOURZ-JYJNAYRXSA-N Phe-Lys-Gln Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O MJAYDXWQQUOURZ-JYJNAYRXSA-N 0.000 description 1
- AUJWXNGCAQWLEI-KBPBESRZSA-N Phe-Lys-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O AUJWXNGCAQWLEI-KBPBESRZSA-N 0.000 description 1
- FUAIIFPQELBNJF-ULQDDVLXSA-N Phe-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N FUAIIFPQELBNJF-ULQDDVLXSA-N 0.000 description 1
- OXKJSGGTHFMGDT-UFYCRDLUSA-N Phe-Phe-Arg Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C1=CC=CC=C1 OXKJSGGTHFMGDT-UFYCRDLUSA-N 0.000 description 1
- GPLWGAYGROGDEN-BZSNNMDCSA-N Phe-Phe-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O GPLWGAYGROGDEN-BZSNNMDCSA-N 0.000 description 1
- AAERWTUHZKLDLC-IHRRRGAJSA-N Phe-Pro-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O AAERWTUHZKLDLC-IHRRRGAJSA-N 0.000 description 1
- XOHJOMKCRLHGCY-UNQGMJICSA-N Phe-Pro-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOHJOMKCRLHGCY-UNQGMJICSA-N 0.000 description 1
- WEDZFLRYSIDIRX-IHRRRGAJSA-N Phe-Ser-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=CC=C1 WEDZFLRYSIDIRX-IHRRRGAJSA-N 0.000 description 1
- YMIZSYUAZJSOFL-SRVKXCTJSA-N Phe-Ser-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O YMIZSYUAZJSOFL-SRVKXCTJSA-N 0.000 description 1
- BONHGTUEEPIMPM-AVGNSLFASA-N Phe-Ser-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O BONHGTUEEPIMPM-AVGNSLFASA-N 0.000 description 1
- MCIXMYKSPQUMJG-SRVKXCTJSA-N Phe-Ser-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MCIXMYKSPQUMJG-SRVKXCTJSA-N 0.000 description 1
- BSKMOCNNLNDIMU-CDMKHQONSA-N Phe-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O BSKMOCNNLNDIMU-CDMKHQONSA-N 0.000 description 1
- SJRQWEDYTKYHHL-SLFFLAALSA-N Phe-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CC=CC=C3)N)C(=O)O SJRQWEDYTKYHHL-SLFFLAALSA-N 0.000 description 1
- KIQUCMUULDXTAZ-HJOGWXRNSA-N Phe-Tyr-Tyr Chemical compound N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O KIQUCMUULDXTAZ-HJOGWXRNSA-N 0.000 description 1
- BQMFWUKNOCJDNV-HJWJTTGWSA-N Phe-Val-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BQMFWUKNOCJDNV-HJWJTTGWSA-N 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 241000223801 Plasmodium knowlesi Species 0.000 description 1
- 241000223821 Plasmodium malariae Species 0.000 description 1
- 241001505293 Plasmodium ovale Species 0.000 description 1
- 108091036407 Polyadenylation Proteins 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 108010076039 Polyproteins Proteins 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- ALJGSKMBIUEJOB-FXQIFTODSA-N Pro-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@@H]1CCCN1 ALJGSKMBIUEJOB-FXQIFTODSA-N 0.000 description 1
- AJLVKXCNXIJHDV-CIUDSAMLSA-N Pro-Ala-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O AJLVKXCNXIJHDV-CIUDSAMLSA-N 0.000 description 1
- IWNOFCGBMSFTBC-CIUDSAMLSA-N Pro-Ala-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O IWNOFCGBMSFTBC-CIUDSAMLSA-N 0.000 description 1
- KIZQGKLMXKGDIV-BQBZGAKWSA-N Pro-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 KIZQGKLMXKGDIV-BQBZGAKWSA-N 0.000 description 1
- FCCBQBZXIAZNIG-LSJOCFKGSA-N Pro-Ala-His Chemical compound C[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O FCCBQBZXIAZNIG-LSJOCFKGSA-N 0.000 description 1
- XQLBWXHVZVBNJM-FXQIFTODSA-N Pro-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 XQLBWXHVZVBNJM-FXQIFTODSA-N 0.000 description 1
- HFZNNDWPHBRNPV-KZVJFYERSA-N Pro-Ala-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O HFZNNDWPHBRNPV-KZVJFYERSA-N 0.000 description 1
- LCRSGSIRKLXZMZ-BPNCWPANSA-N Pro-Ala-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LCRSGSIRKLXZMZ-BPNCWPANSA-N 0.000 description 1
- OOLOTUZJUBOMAX-GUBZILKMSA-N Pro-Ala-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O OOLOTUZJUBOMAX-GUBZILKMSA-N 0.000 description 1
- OCSACVPBMIYNJE-GUBZILKMSA-N Pro-Arg-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O OCSACVPBMIYNJE-GUBZILKMSA-N 0.000 description 1
- QSKCKTUQPICLSO-AVGNSLFASA-N Pro-Arg-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O QSKCKTUQPICLSO-AVGNSLFASA-N 0.000 description 1
- CYQQWUPHIZVCNY-GUBZILKMSA-N Pro-Arg-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CYQQWUPHIZVCNY-GUBZILKMSA-N 0.000 description 1
- ZSKJPKFTPQCPIH-RCWTZXSCSA-N Pro-Arg-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZSKJPKFTPQCPIH-RCWTZXSCSA-N 0.000 description 1
- XROLYVMNVIKVEM-BQBZGAKWSA-N Pro-Asn-Gly Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O XROLYVMNVIKVEM-BQBZGAKWSA-N 0.000 description 1
- MTHRMUXESFIAMS-DCAQKATOSA-N Pro-Asn-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O MTHRMUXESFIAMS-DCAQKATOSA-N 0.000 description 1
- WPQKSRHDTMRSJM-CIUDSAMLSA-N Pro-Asp-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 WPQKSRHDTMRSJM-CIUDSAMLSA-N 0.000 description 1
- GDXZRWYXJSGWIV-GMOBBJLQSA-N Pro-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1 GDXZRWYXJSGWIV-GMOBBJLQSA-N 0.000 description 1
- YFNOUBWUIIJQHF-LPEHRKFASA-N Pro-Asp-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N2CCC[C@@H]2C(=O)O YFNOUBWUIIJQHF-LPEHRKFASA-N 0.000 description 1
- ZCXQTRXYZOSGJR-FXQIFTODSA-N Pro-Asp-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O ZCXQTRXYZOSGJR-FXQIFTODSA-N 0.000 description 1
- SFECXGVELZFBFJ-VEVYYDQMSA-N Pro-Asp-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SFECXGVELZFBFJ-VEVYYDQMSA-N 0.000 description 1
- TUYWCHPXKQTISF-LPEHRKFASA-N Pro-Cys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N2CCC[C@@H]2C(=O)O TUYWCHPXKQTISF-LPEHRKFASA-N 0.000 description 1
- HQVPQXMCQKXARZ-FXQIFTODSA-N Pro-Cys-Ser Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O HQVPQXMCQKXARZ-FXQIFTODSA-N 0.000 description 1
- JFNPBBOGGNMSRX-CIUDSAMLSA-N Pro-Gln-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O JFNPBBOGGNMSRX-CIUDSAMLSA-N 0.000 description 1
- ODPIUQVTULPQEP-CIUDSAMLSA-N Pro-Gln-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H]1CCCN1 ODPIUQVTULPQEP-CIUDSAMLSA-N 0.000 description 1
- FRKBNXCFJBPJOL-GUBZILKMSA-N Pro-Glu-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O FRKBNXCFJBPJOL-GUBZILKMSA-N 0.000 description 1
- VPFGPKIWSDVTOY-SRVKXCTJSA-N Pro-Glu-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O VPFGPKIWSDVTOY-SRVKXCTJSA-N 0.000 description 1
- WVOXLKUUVCCCSU-ZPFDUUQYSA-N Pro-Glu-Ile Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WVOXLKUUVCCCSU-ZPFDUUQYSA-N 0.000 description 1
- LXVLKXPFIDDHJG-CIUDSAMLSA-N Pro-Glu-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O LXVLKXPFIDDHJG-CIUDSAMLSA-N 0.000 description 1
- CLNJSLSHKJECME-BQBZGAKWSA-N Pro-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]1CCCN1 CLNJSLSHKJECME-BQBZGAKWSA-N 0.000 description 1
- HAAQQNHQZBOWFO-LURJTMIESA-N Pro-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1 HAAQQNHQZBOWFO-LURJTMIESA-N 0.000 description 1
- AFXCXDQNRXTSBD-FJXKBIBVSA-N Pro-Gly-Thr Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O AFXCXDQNRXTSBD-FJXKBIBVSA-N 0.000 description 1
- YTWNSIDWAFSEEI-RWMBFGLXSA-N Pro-His-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N3CCC[C@@H]3C(=O)O YTWNSIDWAFSEEI-RWMBFGLXSA-N 0.000 description 1
- XFFIGWGYMUFCCQ-ULQDDVLXSA-N Pro-His-Tyr Chemical compound C1=CC(O)=CC=C1C[C@@H](C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H]1[NH2+]CCC1)CC1=CN=CN1 XFFIGWGYMUFCCQ-ULQDDVLXSA-N 0.000 description 1
- AQGUSRZKDZYGGV-GMOBBJLQSA-N Pro-Ile-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O AQGUSRZKDZYGGV-GMOBBJLQSA-N 0.000 description 1
- UREQLMJCKFLLHM-NAKRPEOUSA-N Pro-Ile-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O UREQLMJCKFLLHM-NAKRPEOUSA-N 0.000 description 1
- FMLRRBDLBJLJIK-DCAQKATOSA-N Pro-Leu-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 FMLRRBDLBJLJIK-DCAQKATOSA-N 0.000 description 1
- RUDOLGWDSKQQFF-DCAQKATOSA-N Pro-Leu-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O RUDOLGWDSKQQFF-DCAQKATOSA-N 0.000 description 1
- FYPGHGXAOZTOBO-IHRRRGAJSA-N Pro-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@@H]2CCCN2 FYPGHGXAOZTOBO-IHRRRGAJSA-N 0.000 description 1
- MRYUJHGPZQNOAD-IHRRRGAJSA-N Pro-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1 MRYUJHGPZQNOAD-IHRRRGAJSA-N 0.000 description 1
- VTFXTWDFPTWNJY-RHYQMDGZSA-N Pro-Leu-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VTFXTWDFPTWNJY-RHYQMDGZSA-N 0.000 description 1
- RMODQFBNDDENCP-IHRRRGAJSA-N Pro-Lys-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O RMODQFBNDDENCP-IHRRRGAJSA-N 0.000 description 1
- WIPAMEKBSHNFQE-IUCAKERBSA-N Pro-Met-Gly Chemical compound CSCC[C@@H](C(=O)NCC(=O)O)NC(=O)[C@@H]1CCCN1 WIPAMEKBSHNFQE-IUCAKERBSA-N 0.000 description 1
- XYAFCOJKICBRDU-JYJNAYRXSA-N Pro-Phe-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O XYAFCOJKICBRDU-JYJNAYRXSA-N 0.000 description 1
- FYKUEXMZYFIZKA-DCAQKATOSA-N Pro-Pro-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O FYKUEXMZYFIZKA-DCAQKATOSA-N 0.000 description 1
- POQFNPILEQEODH-FXQIFTODSA-N Pro-Ser-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O POQFNPILEQEODH-FXQIFTODSA-N 0.000 description 1
- GOMUXSCOIWIJFP-GUBZILKMSA-N Pro-Ser-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GOMUXSCOIWIJFP-GUBZILKMSA-N 0.000 description 1
- LNICFEXCAHIJOR-DCAQKATOSA-N Pro-Ser-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O LNICFEXCAHIJOR-DCAQKATOSA-N 0.000 description 1
- BJCXXMGGPHRSHV-GUBZILKMSA-N Pro-Ser-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 BJCXXMGGPHRSHV-GUBZILKMSA-N 0.000 description 1
- AJJDPGVVNPUZCR-RHYQMDGZSA-N Pro-Thr-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1)O AJJDPGVVNPUZCR-RHYQMDGZSA-N 0.000 description 1
- JDJMFMVVJHLWDP-UNQGMJICSA-N Pro-Thr-Phe Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JDJMFMVVJHLWDP-UNQGMJICSA-N 0.000 description 1
- RMJZWERKFFNNNS-XGEHTFHBSA-N Pro-Thr-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O RMJZWERKFFNNNS-XGEHTFHBSA-N 0.000 description 1
- GZNYIXWOIUFLGO-ZJDVBMNYSA-N Pro-Thr-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZNYIXWOIUFLGO-ZJDVBMNYSA-N 0.000 description 1
- VVAWNPIOYXAMAL-KJEVXHAQSA-N Pro-Thr-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O VVAWNPIOYXAMAL-KJEVXHAQSA-N 0.000 description 1
- CWZUFLWPEFHWEI-IHRRRGAJSA-N Pro-Tyr-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O CWZUFLWPEFHWEI-IHRRRGAJSA-N 0.000 description 1
- FZXSYIPVAFVYBH-KKUMJFAQSA-N Pro-Tyr-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O FZXSYIPVAFVYBH-KKUMJFAQSA-N 0.000 description 1
- IALSFJSONJZBKB-HRCADAONSA-N Pro-Tyr-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N3CCC[C@@H]3C(=O)O IALSFJSONJZBKB-HRCADAONSA-N 0.000 description 1
- WWXNZNWZNZPDIF-SRVKXCTJSA-N Pro-Val-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 WWXNZNWZNZPDIF-SRVKXCTJSA-N 0.000 description 1
- STGVYUTZKGPRCI-GUBZILKMSA-N Pro-Val-Cys Chemical compound SC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 STGVYUTZKGPRCI-GUBZILKMSA-N 0.000 description 1
- IIRBTQHFVNGPMQ-AVGNSLFASA-N Pro-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@@H]1CCCN1 IIRBTQHFVNGPMQ-AVGNSLFASA-N 0.000 description 1
- FIODMZKLZFLYQP-GUBZILKMSA-N Pro-Val-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O FIODMZKLZFLYQP-GUBZILKMSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 108010018070 Proto-Oncogene Proteins c-ets Proteins 0.000 description 1
- 102000004053 Proto-Oncogene Proteins c-ets Human genes 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 241000589774 Pseudomonas sp. Species 0.000 description 1
- 229930185560 Pseudouridine Natural products 0.000 description 1
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 238000003559 RNA-seq method Methods 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 241000702247 Reoviridae Species 0.000 description 1
- 241000702263 Reovirus sp. Species 0.000 description 1
- 102000018779 Replication Protein C Human genes 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- 206010039251 Rubber sensitivity Diseases 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- 241000607149 Salmonella sp. Species 0.000 description 1
- 241000242680 Schistosoma mansoni Species 0.000 description 1
- 206010048908 Seasonal allergy Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- ZUGXSSFMTXKHJS-ZLUOBGJFSA-N Ser-Ala-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O ZUGXSSFMTXKHJS-ZLUOBGJFSA-N 0.000 description 1
- FIXILCYTSAUERA-FXQIFTODSA-N Ser-Ala-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FIXILCYTSAUERA-FXQIFTODSA-N 0.000 description 1
- LVVBAKCGXXUHFO-ZLUOBGJFSA-N Ser-Ala-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O LVVBAKCGXXUHFO-ZLUOBGJFSA-N 0.000 description 1
- IDCKUIWEIZYVSO-WFBYXXMGSA-N Ser-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C)C(O)=O)=CNC2=C1 IDCKUIWEIZYVSO-WFBYXXMGSA-N 0.000 description 1
- QEDMOZUJTGEIBF-FXQIFTODSA-N Ser-Arg-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O QEDMOZUJTGEIBF-FXQIFTODSA-N 0.000 description 1
- VQBLHWSPVYYZTB-DCAQKATOSA-N Ser-Arg-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CO)N VQBLHWSPVYYZTB-DCAQKATOSA-N 0.000 description 1
- QFBNNYNWKYKVJO-DCAQKATOSA-N Ser-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N QFBNNYNWKYKVJO-DCAQKATOSA-N 0.000 description 1
- NRCJWSGXMAPYQX-LPEHRKFASA-N Ser-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CO)N)C(=O)O NRCJWSGXMAPYQX-LPEHRKFASA-N 0.000 description 1
- OBXVZEAMXFSGPU-FXQIFTODSA-N Ser-Asn-Arg Chemical compound C(C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)N)CN=C(N)N OBXVZEAMXFSGPU-FXQIFTODSA-N 0.000 description 1
- KNZQGAUEYZJUSQ-ZLUOBGJFSA-N Ser-Asp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)N KNZQGAUEYZJUSQ-ZLUOBGJFSA-N 0.000 description 1
- CNIIKZQXBBQHCX-FXQIFTODSA-N Ser-Asp-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O CNIIKZQXBBQHCX-FXQIFTODSA-N 0.000 description 1
- FTVRVZNYIYWJGB-ACZMJKKPSA-N Ser-Asp-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O FTVRVZNYIYWJGB-ACZMJKKPSA-N 0.000 description 1
- MMAPOBOTRUVNKJ-ZLUOBGJFSA-N Ser-Asp-Ser Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CO)N)C(=O)O MMAPOBOTRUVNKJ-ZLUOBGJFSA-N 0.000 description 1
- RNFKSBPHLTZHLU-WHFBIAKZSA-N Ser-Cys-Gly Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)O)N)O RNFKSBPHLTZHLU-WHFBIAKZSA-N 0.000 description 1
- DSSOYPJWSWFOLK-CIUDSAMLSA-N Ser-Cys-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O DSSOYPJWSWFOLK-CIUDSAMLSA-N 0.000 description 1
- RFBKULCUBJAQFT-BIIVOSGPSA-N Ser-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CO)N)C(=O)O RFBKULCUBJAQFT-BIIVOSGPSA-N 0.000 description 1
- GRRAECZXRONTEE-UBHSHLNASA-N Ser-Cys-Trp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O GRRAECZXRONTEE-UBHSHLNASA-N 0.000 description 1
- DGHFNYXVIXNNMC-GUBZILKMSA-N Ser-Gln-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N DGHFNYXVIXNNMC-GUBZILKMSA-N 0.000 description 1
- KJMOINFQVCCSDX-XKBZYTNZSA-N Ser-Gln-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KJMOINFQVCCSDX-XKBZYTNZSA-N 0.000 description 1
- SMIDBHKWSYUBRZ-ACZMJKKPSA-N Ser-Glu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O SMIDBHKWSYUBRZ-ACZMJKKPSA-N 0.000 description 1
- HJEBZBMOTCQYDN-ACZMJKKPSA-N Ser-Glu-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HJEBZBMOTCQYDN-ACZMJKKPSA-N 0.000 description 1
- YRBGKVIWMNEVCZ-WDSKDSINSA-N Ser-Glu-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O YRBGKVIWMNEVCZ-WDSKDSINSA-N 0.000 description 1
- LALNXSXEYFUUDD-GUBZILKMSA-N Ser-Glu-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LALNXSXEYFUUDD-GUBZILKMSA-N 0.000 description 1
- QKQDTEYDEIJPNK-GUBZILKMSA-N Ser-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO QKQDTEYDEIJPNK-GUBZILKMSA-N 0.000 description 1
- VQBCMLMPEWPUTB-ACZMJKKPSA-N Ser-Glu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O VQBCMLMPEWPUTB-ACZMJKKPSA-N 0.000 description 1
- BPMRXBZYPGYPJN-WHFBIAKZSA-N Ser-Gly-Asn Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O BPMRXBZYPGYPJN-WHFBIAKZSA-N 0.000 description 1
- SVWQEIRZHHNBIO-WHFBIAKZSA-N Ser-Gly-Cys Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CS)C(O)=O SVWQEIRZHHNBIO-WHFBIAKZSA-N 0.000 description 1
- WSTIOCFMWXNOCX-YUMQZZPRSA-N Ser-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N WSTIOCFMWXNOCX-YUMQZZPRSA-N 0.000 description 1
- ZFVFHHZBCVNLGD-GUBZILKMSA-N Ser-His-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZFVFHHZBCVNLGD-GUBZILKMSA-N 0.000 description 1
- QGAHMVHBORDHDC-YUMQZZPRSA-N Ser-His-Gly Chemical compound OC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CN=CN1 QGAHMVHBORDHDC-YUMQZZPRSA-N 0.000 description 1
- CICQXRWZNVXFCU-SRVKXCTJSA-N Ser-His-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O CICQXRWZNVXFCU-SRVKXCTJSA-N 0.000 description 1
- CAOYHZOWXFFAIR-CIUDSAMLSA-N Ser-His-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O CAOYHZOWXFFAIR-CIUDSAMLSA-N 0.000 description 1
- JEHPKECJCALLRW-CUJWVEQBSA-N Ser-His-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JEHPKECJCALLRW-CUJWVEQBSA-N 0.000 description 1
- FUMGHWDRRFCKEP-CIUDSAMLSA-N Ser-Leu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O FUMGHWDRRFCKEP-CIUDSAMLSA-N 0.000 description 1
- QYSFWUIXDFJUDW-DCAQKATOSA-N Ser-Leu-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QYSFWUIXDFJUDW-DCAQKATOSA-N 0.000 description 1
- KCNSGAMPBPYUAI-CIUDSAMLSA-N Ser-Leu-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O KCNSGAMPBPYUAI-CIUDSAMLSA-N 0.000 description 1
- ZIFYDQAFEMIZII-GUBZILKMSA-N Ser-Leu-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZIFYDQAFEMIZII-GUBZILKMSA-N 0.000 description 1
- VMLONWHIORGALA-SRVKXCTJSA-N Ser-Leu-Leu Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]([NH3+])CO VMLONWHIORGALA-SRVKXCTJSA-N 0.000 description 1
- SRKMDKACHDVPMD-SRVKXCTJSA-N Ser-Lys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N SRKMDKACHDVPMD-SRVKXCTJSA-N 0.000 description 1
- CRJZZXMAADSBBQ-SRVKXCTJSA-N Ser-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CO CRJZZXMAADSBBQ-SRVKXCTJSA-N 0.000 description 1
- UGGWCAFQPKANMW-FXQIFTODSA-N Ser-Met-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O UGGWCAFQPKANMW-FXQIFTODSA-N 0.000 description 1
- GDUZTEQRAOXYJS-SRVKXCTJSA-N Ser-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CO)N GDUZTEQRAOXYJS-SRVKXCTJSA-N 0.000 description 1
- UGTZYIPOBYXWRW-SRVKXCTJSA-N Ser-Phe-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O UGTZYIPOBYXWRW-SRVKXCTJSA-N 0.000 description 1
- RRVFEDGUXSYWOW-BZSNNMDCSA-N Ser-Phe-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RRVFEDGUXSYWOW-BZSNNMDCSA-N 0.000 description 1
- QMCDMHWAKMUGJE-IHRRRGAJSA-N Ser-Phe-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O QMCDMHWAKMUGJE-IHRRRGAJSA-N 0.000 description 1
- DINQYZRMXGWWTG-GUBZILKMSA-N Ser-Pro-Pro Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DINQYZRMXGWWTG-GUBZILKMSA-N 0.000 description 1
- CKDXFSPMIDSMGV-GUBZILKMSA-N Ser-Pro-Val Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O CKDXFSPMIDSMGV-GUBZILKMSA-N 0.000 description 1
- VFWQQZMRKFOGLE-ZLUOBGJFSA-N Ser-Ser-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N)O VFWQQZMRKFOGLE-ZLUOBGJFSA-N 0.000 description 1
- FZXOPYUEQGDGMS-ACZMJKKPSA-N Ser-Ser-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O FZXOPYUEQGDGMS-ACZMJKKPSA-N 0.000 description 1
- NVNPWELENFJOHH-CIUDSAMLSA-N Ser-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)N NVNPWELENFJOHH-CIUDSAMLSA-N 0.000 description 1
- AABIBDJHSKIMJK-FXQIFTODSA-N Ser-Ser-Met Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(O)=O AABIBDJHSKIMJK-FXQIFTODSA-N 0.000 description 1
- ILZAUMFXKSIUEF-SRVKXCTJSA-N Ser-Ser-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ILZAUMFXKSIUEF-SRVKXCTJSA-N 0.000 description 1
- VGQVAVQWKJLIRM-FXQIFTODSA-N Ser-Ser-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O VGQVAVQWKJLIRM-FXQIFTODSA-N 0.000 description 1
- SOACHCFYJMCMHC-BWBBJGPYSA-N Ser-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N)O SOACHCFYJMCMHC-BWBBJGPYSA-N 0.000 description 1
- SZRNDHWMVSFPSP-XKBZYTNZSA-N Ser-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CO)N)O SZRNDHWMVSFPSP-XKBZYTNZSA-N 0.000 description 1
- PURRNJBBXDDWLX-ZDLURKLDSA-N Ser-Thr-Gly Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CO)N)O PURRNJBBXDDWLX-ZDLURKLDSA-N 0.000 description 1
- FGBLCMLXHRPVOF-IHRRRGAJSA-N Ser-Tyr-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FGBLCMLXHRPVOF-IHRRRGAJSA-N 0.000 description 1
- JGUWRQWULDWNCM-FXQIFTODSA-N Ser-Val-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O JGUWRQWULDWNCM-FXQIFTODSA-N 0.000 description 1
- SIEBDTCABMZCLF-XGEHTFHBSA-N Ser-Val-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SIEBDTCABMZCLF-XGEHTFHBSA-N 0.000 description 1
- ODRUTDLAONAVDV-IHRRRGAJSA-N Ser-Val-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ODRUTDLAONAVDV-IHRRRGAJSA-N 0.000 description 1
- 102000054727 Serum Amyloid A Human genes 0.000 description 1
- 108700028909 Serum Amyloid A Proteins 0.000 description 1
- 241000713311 Simian immunodeficiency virus Species 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 241000295644 Staphylococcaceae Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 102000015215 Stem Cell Factor Human genes 0.000 description 1
- 108010039445 Stem Cell Factor Proteins 0.000 description 1
- 206010072148 Stiff-Person syndrome Diseases 0.000 description 1
- 241001478880 Streptobacillus moniliformis Species 0.000 description 1
- 241000193985 Streptococcus agalactiae Species 0.000 description 1
- 241000194049 Streptococcus equinus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000194022 Streptococcus sp. Species 0.000 description 1
- 241001505901 Streptococcus sp. 'group A' Species 0.000 description 1
- 241000193990 Streptococcus sp. 'group B' Species 0.000 description 1
- 208000027522 Sydenham chorea Diseases 0.000 description 1
- 206010042742 Sympathetic ophthalmia Diseases 0.000 description 1
- 102100038410 T-complex protein 1 subunit alpha Human genes 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 101150100033 TSC22D1 gene Proteins 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 241001420369 Thosea Species 0.000 description 1
- LVHHEVGYAZGXDE-KDXUFGMBSA-N Thr-Ala-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(=O)O)N)O LVHHEVGYAZGXDE-KDXUFGMBSA-N 0.000 description 1
- XYEXCEPTALHNEV-RCWTZXSCSA-N Thr-Arg-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XYEXCEPTALHNEV-RCWTZXSCSA-N 0.000 description 1
- TWLMXDWFVNEFFK-FJXKBIBVSA-N Thr-Arg-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O TWLMXDWFVNEFFK-FJXKBIBVSA-N 0.000 description 1
- VFEHSAJCWWHDBH-RHYQMDGZSA-N Thr-Arg-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O VFEHSAJCWWHDBH-RHYQMDGZSA-N 0.000 description 1
- JBHMLZSKIXMVFS-XVSYOHENSA-N Thr-Asn-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JBHMLZSKIXMVFS-XVSYOHENSA-N 0.000 description 1
- VXMHQKHDKCATDV-VEVYYDQMSA-N Thr-Asp-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VXMHQKHDKCATDV-VEVYYDQMSA-N 0.000 description 1
- DHPPWTOLRWYIDS-XKBZYTNZSA-N Thr-Cys-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O DHPPWTOLRWYIDS-XKBZYTNZSA-N 0.000 description 1
- KWQBJOUOSNJDRR-XAVMHZPKSA-N Thr-Cys-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N)O KWQBJOUOSNJDRR-XAVMHZPKSA-N 0.000 description 1
- UZJDBCHMIQXLOQ-HEIBUPTGSA-N Thr-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O UZJDBCHMIQXLOQ-HEIBUPTGSA-N 0.000 description 1
- DIPIPFHFLPTCLK-LOKLDPHHSA-N Thr-Gln-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N)O DIPIPFHFLPTCLK-LOKLDPHHSA-N 0.000 description 1
- CQNFRKAKGDSJFR-NUMRIWBASA-N Thr-Glu-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)O CQNFRKAKGDSJFR-NUMRIWBASA-N 0.000 description 1
- GKWNLDNXMMLRMC-GLLZPBPUSA-N Thr-Glu-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O GKWNLDNXMMLRMC-GLLZPBPUSA-N 0.000 description 1
- SHOMROOOQBDGRL-JHEQGTHGSA-N Thr-Glu-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O SHOMROOOQBDGRL-JHEQGTHGSA-N 0.000 description 1
- BNGDYRRHRGOPHX-IFFSRLJSSA-N Thr-Glu-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)[C@@H](C)O)C(O)=O BNGDYRRHRGOPHX-IFFSRLJSSA-N 0.000 description 1
- DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-N 0.000 description 1
- JKGGPMOUIAAJAA-YEPSODPASA-N Thr-Gly-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O JKGGPMOUIAAJAA-YEPSODPASA-N 0.000 description 1
- GXUWHVZYDAHFSV-FLBSBUHZSA-N Thr-Ile-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GXUWHVZYDAHFSV-FLBSBUHZSA-N 0.000 description 1
- RRRRCRYTLZVCEN-HJGDQZAQSA-N Thr-Leu-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O RRRRCRYTLZVCEN-HJGDQZAQSA-N 0.000 description 1
- HOVLHEKTGVIKAP-WDCWCFNPSA-N Thr-Leu-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O HOVLHEKTGVIKAP-WDCWCFNPSA-N 0.000 description 1
- RFKVQLIXNVEOMB-WEDXCCLWSA-N Thr-Leu-Gly Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)O)N)O RFKVQLIXNVEOMB-WEDXCCLWSA-N 0.000 description 1
- YOOAQCZYZHGUAZ-KATARQTJSA-N Thr-Leu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YOOAQCZYZHGUAZ-KATARQTJSA-N 0.000 description 1
- VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 description 1
- KRDSCBLRHORMRK-JXUBOQSCSA-N Thr-Lys-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O KRDSCBLRHORMRK-JXUBOQSCSA-N 0.000 description 1
- XSEPSRUDSPHMPX-KATARQTJSA-N Thr-Lys-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O XSEPSRUDSPHMPX-KATARQTJSA-N 0.000 description 1
- XNTVWRJTUIOGQO-RHYQMDGZSA-N Thr-Met-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O XNTVWRJTUIOGQO-RHYQMDGZSA-N 0.000 description 1
- WTMPKZWHRCMMMT-KZVJFYERSA-N Thr-Pro-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O WTMPKZWHRCMMMT-KZVJFYERSA-N 0.000 description 1
- NYQIZWROIMIQSL-VEVYYDQMSA-N Thr-Pro-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O NYQIZWROIMIQSL-VEVYYDQMSA-N 0.000 description 1
- MXDOAJQRJBMGMO-FJXKBIBVSA-N Thr-Pro-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O MXDOAJQRJBMGMO-FJXKBIBVSA-N 0.000 description 1
- DEGCBBCMYWNJNA-RHYQMDGZSA-N Thr-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)[C@@H](C)O DEGCBBCMYWNJNA-RHYQMDGZSA-N 0.000 description 1
- DOBIBIXIHJKVJF-XKBZYTNZSA-N Thr-Ser-Gln Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O DOBIBIXIHJKVJF-XKBZYTNZSA-N 0.000 description 1
- VBMOVTMNHWPZJR-SUSMZKCASA-N Thr-Thr-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O VBMOVTMNHWPZJR-SUSMZKCASA-N 0.000 description 1
- GRIUMVXCJDKVPI-IZPVPAKOSA-N Thr-Thr-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O GRIUMVXCJDKVPI-IZPVPAKOSA-N 0.000 description 1
- LXXCHJKHJYRMIY-FQPOAREZSA-N Thr-Tyr-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O LXXCHJKHJYRMIY-FQPOAREZSA-N 0.000 description 1
- CYCGARJWIQWPQM-YJRXYDGGSA-N Thr-Tyr-Ser Chemical compound C[C@@H](O)[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CO)C([O-])=O)CC1=CC=C(O)C=C1 CYCGARJWIQWPQM-YJRXYDGGSA-N 0.000 description 1
- QGVBFDIREUUSHX-IFFSRLJSSA-N Thr-Val-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O QGVBFDIREUUSHX-IFFSRLJSSA-N 0.000 description 1
- QNXZCKMXHPULME-ZNSHCXBVSA-N Thr-Val-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O QNXZCKMXHPULME-ZNSHCXBVSA-N 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 208000005485 Thrombocytosis Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000033781 Thyroid carcinoma Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 241000710924 Togaviridae Species 0.000 description 1
- 241000223997 Toxoplasma gondii Species 0.000 description 1
- 102100030780 Transcriptional activator Myb Human genes 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 241000589886 Treponema Species 0.000 description 1
- 241000589904 Treponema pallidum subsp. pertenue Species 0.000 description 1
- 241000243777 Trichinella spiralis Species 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- MQVGIFJSFFVGFW-XEGUGMAKSA-N Trp-Ala-Glu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MQVGIFJSFFVGFW-XEGUGMAKSA-N 0.000 description 1
- MVHHTXAUJCIOMZ-WDSOQIARSA-N Trp-Arg-Lys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N MVHHTXAUJCIOMZ-WDSOQIARSA-N 0.000 description 1
- GUWJWCHZNGDKBG-UBHSHLNASA-N Trp-Asn-Cys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N GUWJWCHZNGDKBG-UBHSHLNASA-N 0.000 description 1
- DEZKIRSBKKXUEV-NYVOZVTQSA-N Trp-Asp-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)O)N DEZKIRSBKKXUEV-NYVOZVTQSA-N 0.000 description 1
- YRXXUYPYPHRJPB-RXVVDRJESA-N Trp-Gly-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)NCC(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)O)N YRXXUYPYPHRJPB-RXVVDRJESA-N 0.000 description 1
- ORQGVWIUHICVKE-KCTSRDHCSA-N Trp-His-Ala Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(O)=O ORQGVWIUHICVKE-KCTSRDHCSA-N 0.000 description 1
- OSYOKZZRVGUDMO-HSCHXYMDSA-N Trp-Lys-Ile Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O OSYOKZZRVGUDMO-HSCHXYMDSA-N 0.000 description 1
- CUHBVKUVJIXRFK-DVXDUOKCSA-N Trp-Trp-Ala Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC=3C4=CC=CC=C4NC=3)C(=O)N[C@@H](C)C(O)=O)=CNC2=C1 CUHBVKUVJIXRFK-DVXDUOKCSA-N 0.000 description 1
- BABINGWMZBWXIX-BPUTZDHNSA-N Trp-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N BABINGWMZBWXIX-BPUTZDHNSA-N 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 241000223104 Trypanosoma Species 0.000 description 1
- 241001442399 Trypanosoma brucei gambiense Species 0.000 description 1
- 241001442397 Trypanosoma brucei rhodesiense Species 0.000 description 1
- 241000223109 Trypanosoma cruzi Species 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- ZWZOCUWOXSDYFZ-CQDKDKBSSA-N Tyr-Ala-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 ZWZOCUWOXSDYFZ-CQDKDKBSSA-N 0.000 description 1
- NOXKHHXSHQFSGJ-FQPOAREZSA-N Tyr-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NOXKHHXSHQFSGJ-FQPOAREZSA-N 0.000 description 1
- AKXBNSZMYAOGLS-STQMWFEESA-N Tyr-Arg-Gly Chemical compound NC(N)=NCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AKXBNSZMYAOGLS-STQMWFEESA-N 0.000 description 1
- MBFJIHUHHCJBSN-AVGNSLFASA-N Tyr-Asn-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MBFJIHUHHCJBSN-AVGNSLFASA-N 0.000 description 1
- GAYLGYUVTDMLKC-UWJYBYFXSA-N Tyr-Asp-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 GAYLGYUVTDMLKC-UWJYBYFXSA-N 0.000 description 1
- YGKVNUAKYPGORG-AVGNSLFASA-N Tyr-Asp-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YGKVNUAKYPGORG-AVGNSLFASA-N 0.000 description 1
- FQNUWOHNGJWNLM-QWRGUYRKSA-N Tyr-Cys-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)NCC(O)=O FQNUWOHNGJWNLM-QWRGUYRKSA-N 0.000 description 1
- FFCRCJZJARTYCG-KKUMJFAQSA-N Tyr-Cys-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)O)N)O FFCRCJZJARTYCG-KKUMJFAQSA-N 0.000 description 1
- FXYOYUMPUJONGW-FHWLQOOXSA-N Tyr-Gln-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 FXYOYUMPUJONGW-FHWLQOOXSA-N 0.000 description 1
- NQJDICVXXIMMMB-XDTLVQLUSA-N Tyr-Glu-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O NQJDICVXXIMMMB-XDTLVQLUSA-N 0.000 description 1
- XQYHLZNPOTXRMQ-KKUMJFAQSA-N Tyr-Glu-Arg Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XQYHLZNPOTXRMQ-KKUMJFAQSA-N 0.000 description 1
- NZFCWALTLNFHHC-JYJNAYRXSA-N Tyr-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NZFCWALTLNFHHC-JYJNAYRXSA-N 0.000 description 1
- HIINQLBHPIQYHN-JTQLQIEISA-N Tyr-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 HIINQLBHPIQYHN-JTQLQIEISA-N 0.000 description 1
- JAGGEZACYAAMIL-CQDKDKBSSA-N Tyr-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=C(C=C1)O)N JAGGEZACYAAMIL-CQDKDKBSSA-N 0.000 description 1
- CWVHKVVKAQIJKY-ACRUOGEOSA-N Tyr-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CC=C(C=C2)O)N CWVHKVVKAQIJKY-ACRUOGEOSA-N 0.000 description 1
- GYBVHTWOQJMYAM-HRCADAONSA-N Tyr-Met-Pro Chemical compound CSCC[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N GYBVHTWOQJMYAM-HRCADAONSA-N 0.000 description 1
- SYFHQHYTNCQCCN-MELADBBJSA-N Tyr-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O SYFHQHYTNCQCCN-MELADBBJSA-N 0.000 description 1
- KLQPIEVIKOQRAW-IZPVPAKOSA-N Tyr-Thr-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O KLQPIEVIKOQRAW-IZPVPAKOSA-N 0.000 description 1
- OBKOPLHSRDATFO-XHSDSOJGSA-N Tyr-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N OBKOPLHSRDATFO-XHSDSOJGSA-N 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- ASQFIHTXXMFENG-XPUUQOCRSA-N Val-Ala-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O ASQFIHTXXMFENG-XPUUQOCRSA-N 0.000 description 1
- ZLFHAAGHGQBQQN-AEJSXWLSSA-N Val-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N ZLFHAAGHGQBQQN-AEJSXWLSSA-N 0.000 description 1
- IVXJODPZRWHCCR-JYJNAYRXSA-N Val-Arg-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N IVXJODPZRWHCCR-JYJNAYRXSA-N 0.000 description 1
- DNOOLPROHJWCSQ-RCWTZXSCSA-N Val-Arg-Thr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DNOOLPROHJWCSQ-RCWTZXSCSA-N 0.000 description 1
- ZMDCGGKHRKNWKD-LAEOZQHASA-N Val-Asn-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N ZMDCGGKHRKNWKD-LAEOZQHASA-N 0.000 description 1
- ISERLACIZUGCDX-ZKWXMUAHSA-N Val-Asp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)N ISERLACIZUGCDX-ZKWXMUAHSA-N 0.000 description 1
- YODDULVCGFQRFZ-ZKWXMUAHSA-N Val-Asp-Ser Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O YODDULVCGFQRFZ-ZKWXMUAHSA-N 0.000 description 1
- XGJLNBNZNMVJRS-NRPADANISA-N Val-Glu-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O XGJLNBNZNMVJRS-NRPADANISA-N 0.000 description 1
- ZXAGTABZUOMUDO-GVXVVHGQSA-N Val-Glu-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N ZXAGTABZUOMUDO-GVXVVHGQSA-N 0.000 description 1
- WDIGUPHXPBMODF-UMNHJUIQSA-N Val-Glu-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N WDIGUPHXPBMODF-UMNHJUIQSA-N 0.000 description 1
- OQWNEUXPKHIEJO-NRPADANISA-N Val-Glu-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)O)N OQWNEUXPKHIEJO-NRPADANISA-N 0.000 description 1
- KVRLNEILGGVBJX-IHRRRGAJSA-N Val-His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CN=CN1 KVRLNEILGGVBJX-IHRRRGAJSA-N 0.000 description 1
- OTJMMKPMLUNTQT-AVGNSLFASA-N Val-Leu-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](C(C)C)N OTJMMKPMLUNTQT-AVGNSLFASA-N 0.000 description 1
- FEXILLGKGGTLRI-NHCYSSNCSA-N Val-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N FEXILLGKGGTLRI-NHCYSSNCSA-N 0.000 description 1
- IJGPOONOTBNTFS-GVXVVHGQSA-N Val-Lys-Glu Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O IJGPOONOTBNTFS-GVXVVHGQSA-N 0.000 description 1
- YQMILNREHKTFBS-IHRRRGAJSA-N Val-Phe-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)O)N YQMILNREHKTFBS-IHRRRGAJSA-N 0.000 description 1
- UZFNHAXYMICTBU-DZKIICNBSA-N Val-Phe-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N UZFNHAXYMICTBU-DZKIICNBSA-N 0.000 description 1
- YTNGABPUXFEOGU-SRVKXCTJSA-N Val-Pro-Arg Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O YTNGABPUXFEOGU-SRVKXCTJSA-N 0.000 description 1
- VSCIANXXVZOYOC-AVGNSLFASA-N Val-Pro-His Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N VSCIANXXVZOYOC-AVGNSLFASA-N 0.000 description 1
- DOFAQXCYFQKSHT-SRVKXCTJSA-N Val-Pro-Pro Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DOFAQXCYFQKSHT-SRVKXCTJSA-N 0.000 description 1
- JQTYTBPCSOAZHI-FXQIFTODSA-N Val-Ser-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N JQTYTBPCSOAZHI-FXQIFTODSA-N 0.000 description 1
- RYHUIHUOYRNNIE-NRPADANISA-N Val-Ser-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N RYHUIHUOYRNNIE-NRPADANISA-N 0.000 description 1
- VHIZXDZMTDVFGX-DCAQKATOSA-N Val-Ser-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N VHIZXDZMTDVFGX-DCAQKATOSA-N 0.000 description 1
- MNSSBIHFEUUXNW-RCWTZXSCSA-N Val-Thr-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N MNSSBIHFEUUXNW-RCWTZXSCSA-N 0.000 description 1
- QHSSPPHOHJSTML-HOCLYGCPSA-N Val-Trp-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)NCC(=O)O)N QHSSPPHOHJSTML-HOCLYGCPSA-N 0.000 description 1
- HOZAIQIEJTWWDG-HJOGWXRNSA-N Val-Trp-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)O)N HOZAIQIEJTWWDG-HJOGWXRNSA-N 0.000 description 1
- PMKQKNBISAOSRI-XHSDSOJGSA-N Val-Tyr-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N2CCC[C@@H]2C(=O)O)N PMKQKNBISAOSRI-XHSDSOJGSA-N 0.000 description 1
- JSOXWWFKRJKTMT-WOPDTQHZSA-N Val-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N JSOXWWFKRJKTMT-WOPDTQHZSA-N 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108010087302 Viral Structural Proteins Proteins 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 241000244005 Wuchereria bancrofti Species 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 208000017733 acquired polycythemia vera Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 108700010877 adenoviridae proteins Proteins 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 201000005179 adrenal carcinoma Diseases 0.000 description 1
- 208000020990 adrenal cortex carcinoma Diseases 0.000 description 1
- 201000005188 adrenal gland cancer Diseases 0.000 description 1
- 201000006966 adult T-cell leukemia Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 108010087049 alanyl-alanyl-prolyl-valine Proteins 0.000 description 1
- 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 1
- 108010045023 alanyl-prolyl-tyrosine Proteins 0.000 description 1
- 108010041407 alanylaspartic acid Proteins 0.000 description 1
- 108010011559 alanylphenylalanine Proteins 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000028004 allergic respiratory disease Diseases 0.000 description 1
- 238000011224 anti-cancer immunotherapy Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 108010010430 asparagine-proline-alanine Proteins 0.000 description 1
- 108010027234 aspartyl-glycyl-glutamyl-alanine Proteins 0.000 description 1
- 108010092854 aspartyllysine Proteins 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 244000309743 astrovirus Species 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000008668 cellular reprogramming Effects 0.000 description 1
- 210000002230 centromere Anatomy 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000003021 clonogenic effect Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000009073 conformational modification Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 210000003515 double negative t cell Anatomy 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000012645 endogenous antigen Substances 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940092559 enterobacter aerogenes Drugs 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 108700014844 flt3 ligand Proteins 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000020932 food allergy Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 201000011587 gastric lymphoma Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 108010057083 glutamyl-aspartyl-leucine Proteins 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 108010062266 glycyl-glycyl-argininal Proteins 0.000 description 1
- 108010025801 glycyl-prolyl-arginine Proteins 0.000 description 1
- 108010074027 glycyl-seryl-phenylalanine Proteins 0.000 description 1
- 108010089804 glycyl-threonine Proteins 0.000 description 1
- 108010087823 glycyltyrosine Proteins 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 201000003911 head and neck carcinoma Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000002064 heart cell Anatomy 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 208000029570 hepatitis D virus infection Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 108010045383 histidyl-glycyl-glutamic acid Proteins 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000006054 immunological memory Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 238000002743 insertional mutagenesis Methods 0.000 description 1
- 229960001388 interferon-beta Drugs 0.000 description 1
- 230000014828 interferon-gamma production Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 108090000681 interleukin 20 Proteins 0.000 description 1
- 230000006662 intracellular pathway Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 1
- 108010027338 isoleucylcysteine Proteins 0.000 description 1
- 108010053037 kyotorphin Proteins 0.000 description 1
- 201000005391 latex allergy Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 108010087810 leucyl-seryl-glutamyl-leucine Proteins 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 210000003738 lymphoid progenitor cell Anatomy 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 108010054155 lysyllysine Proteins 0.000 description 1
- 201000000564 macroglobulinemia Diseases 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 239000012577 media supplement Substances 0.000 description 1
- 239000012913 medium supplement Substances 0.000 description 1
- 210000000135 megakaryocyte-erythroid progenitor cell Anatomy 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 108010056582 methionylglutamic acid Proteins 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 210000003887 myelocyte Anatomy 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 208000009091 myxoma Diseases 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 230000031942 natural killer cell mediated cytotoxicity Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 108010073101 phenylalanylleucine Proteins 0.000 description 1
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229940118768 plasmodium malariae Drugs 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 201000004338 pollen allergy Diseases 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 208000037244 polycythemia vera Diseases 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 208000017805 post-transplant lymphoproliferative disease Diseases 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 108010015796 prolylisoleucine Proteins 0.000 description 1
- 108010053725 prolylvaline Proteins 0.000 description 1
- 210000004765 promyelocyte Anatomy 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000007388 punch biopsy Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000003439 radiotherapeutic effect Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 201000004335 respiratory allergy Diseases 0.000 description 1
- 230000008593 response to virus Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 108010005652 splenotritin Proteins 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 108010071097 threonyl-lysyl-proline Proteins 0.000 description 1
- 108010072986 threonyl-seryl-lysine Proteins 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 208000005057 thyrotoxicosis Diseases 0.000 description 1
- 230000003614 tolerogenic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 229940096911 trichinella spiralis Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 108010038745 tryptophylglycine Proteins 0.000 description 1
- 230000005851 tumor immunogenicity Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 230000007189 type III interferon production Effects 0.000 description 1
- 108010079202 tyrosyl-alanyl-cysteine Proteins 0.000 description 1
- 108010020532 tyrosyl-proline Proteins 0.000 description 1
- 108010003137 tyrosyltyrosine Proteins 0.000 description 1
- 241000724775 unclassified viruses Species 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 210000002444 unipotent stem cell Anatomy 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 108010027510 vaccinia virus capping enzyme Proteins 0.000 description 1
- IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 1
- 108010015385 valyl-prolyl-proline Proteins 0.000 description 1
- 108010009962 valyltyrosine Proteins 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
- 210000000605 viral structure Anatomy 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0639—Dendritic cells, e.g. Langherhans cells in the epidermis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4615—Dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4621—Cellular immunotherapy characterized by the effect or the function of the cells immunosuppressive or immunotolerising
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/46433—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/464838—Viral antigens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/60—Transcription factors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Cell Biology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Hematology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Marine Sciences & Fisheries (AREA)
- Toxicology (AREA)
- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Developmental Biology & Embryology (AREA)
Abstract
본 개시는 세포를 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포로 재프로그래밍하기 위한 조성물, 작제물 및 벡터, 이의 방법 및 용도에 관한 것이다. 본 개시는, 단리된/합성 전사 인자를 도입 및 발현함으로써 분화된, 다분화능 또는 다능성 줄기 세포로부터 항바이러스 및 항종양 면역 반응을 촉진하는 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포를 제조하는 방법의 개발에 관한 것이다. 보다 구체적으로, 본 개시는 놀랍게도 특정 전사 인자의 조합을 사용하여 직접적인 세포 재프로그래밍에 의해 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포를 수득하는 방법을 제공한다.
Description
본 개시는 세포를 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포로 재프로그래밍(reprogramming)하기 위한 조성물, 방법 및 이의 용도에 관한 것이다.
본 개시는 단리된/합성 전사 인자(transcription factor)를 도입하고 발현함으로써 분화된, 다분화능(multipotent) 또는 다능성(pluripotent) 줄기 세포로부터 면역 항바이러스 및 항종양 반응을 촉진하는 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포를 제조하는 방법의 개발에 관한 것이다. 보다 구체적으로, 본 개시는 특정 전사 인자의 조합을 놀랍게도 유익한 사용으로 직접 세포 재프로그래밍함으로써 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포를 수득하는 방법을 제공한다.
세포 재프로그래밍은 하나의 세포 상태의 후성유전적 및 전사 네트워크를 상이한 세포 유형의 네트워크로 재배선하는 것에 의존한다. 전사 인자(TF)-형질도입 실험은 성체 체세포 또는 분화 세포의 가소성을 강조하여 임의의 목적하는 세포 유형을 생성하기 위한 새로운 기술을 제공한다. TF의 강제 발현에 의해, 체세포 또는 분화된 세포(differentiated cell)를 배아 줄기 세포와 현저하게 유사한 유도 다능성 줄기 세포(iPSC)로 재프로그래밍하는 것이 가능하다[참조: Takahashi et al., 2006; Takahashi et al., 2007]. 대안적으로, 체세포는 다른 특수화된 세포 유형으로 전환될 수도 있다[참조: Pereira et al., 2012]. 직접 계통 전환은 표적 세포의 동일성을 지정하는 TF를 사용하여 마우스 및 인간 섬유아세포를 뉴런, 심근세포 및 간세포 등의 몇몇 세포 유형으로 재프로그래밍하는 데 성공적인 것으로 입증되었다[참조: Xu et al., 2015]. 계통 전환은 또한 조혈 시스템에서도 입증되었고, 여기서 TF의 강제 발현은 B 세포 및 섬유아세포에서 마크로파지의 운명을 유도하고[참조: Xie et al., 2004], 마우스 섬유아세포를 클론원성 조혈 전구 세포로 직접 재프로그래밍하는 것은 전사 인자 Gata2, Gfi1b, cFos 및 Etv6로 달성되었다[참조: Pereira et al., 2013]. 이 4개의 TF는 내피-유사 중간체를 통해 진행되는 동적 다단계 조혈 프로세스를 유도하여, 시험관내에서 발달 조혈을 반복한다[참조: Pereira et al., 2016].
재프로그래밍된 세포는 재생 의학을 위한 매우 유망한 치료 도구이고, iPSC의 분화에 의해 수득되는 세포는 이미 임상 연구에서 시험되고 있다.
세포 재프로그래밍 전략은 체세포를 다능성으로 전환하기 위해 세포형-특이적 TF를 사용할 수 있는 가능성을 구비한 세포 운명의 유연성을 강조했다. 하나의 분화된 세포 유형을 다른 세포 유형으로 직접 계통 전환하는 것도 입증되어 있고, 세포 생물학 메커니즘을 설명하고 재생 의학 목적을 위해 조사되었다. 최근, 항원 제시 수지상 세포(DC)가 TF의 작은 조합에 의해 관련 없는 세포 유형으로부터 재프로그래밍될 수 있음을 입증했다[참조: Rosa et al., 2018]. 고전적으로, 골수성 DC 관여 전구체는 기능적으로 상이한 DC 서브세트: 종래의 DC(cDC) 및 형질세포양 DC(pDC)를 생성하는 것으로 생각된다. cDC는 항원 특이적 면역 반응을 유도하는 전문 항원 제시 세포(APC)인 반면, pDC는 바이러스 감염시의 유형 I 인터페론의 전문 생산자이다. 이들은 자연 면역 기능과 적응 면역 기능을 모두 나타내고, T 세포 반응에 직접 영향을 미치는 APC로 기능할 수 있다. DC 개발 중의 다양한 서브세트의 분기를 규제하는 시기와 정확한 메커니즘은 아직 확립되지 않았다.
문헌 EP 제3 385 373호는, 세포 유도 또는 세포를 종래의 수지상 세포 또는 항원 제시 세포 상태로 재프로그래밍하기 위한 조성물, 핵산 작제물(construct), 방법 및 키트(kit)에 관한 것이고, 부분적으로는, 분화 또는 미분화 세포의 DC 또는 APC로의 유도 또는 재프로그래밍을 가능하게 하는 전사 인자 조합의 사용에 대한 이 문서에 기재된 신규의 놀라운 효과에 기초한다.
문서 EP 제3 385 373호에 기재된 전사 인자의 조합은 DC의 cDC1 서브세트에 특징적인 표면 표현형, 전사 특징 및 기능적 특성을 갖는 DC를 유도한다. 인터페론 유형 I, 예를 들면, 인터페론 알파(IFN-α) 및 베타(IFN-β)를 분비하는 능력은 이전에 기재되지 않았다.
본 명세서에 기재된 유도된 pDC 또는 인터페론 유형 I-생산 세포는 핵산을 검출하고 유형 I 인터페론을 분비함으로써 반응하는 전형적 pDC 기능적 특성을 요약한다[참조: Reizis 2019].
이러한 사실은 본 개시에 의해 해결되는 기술적 과제를 설명하기 위해 개시되어 있다.
본 주제는, 분화된 세포, 다분화능 또는 다능성 줄기 세포를 시험관내, 생체외 또는 생체내에서 pDC 또는 인터페론 유형 I-생산 세포로 놀랍게도 재프로그래밍하거나 유도하는 몇몇 단리된 전사 인자를 특정한다.
놀랍게도, 본 개시에 기재된 바와 같이 재프로그래밍에 의해 생성된 유도된 pDC 또는 인터페론 유형 I-생산 세포는 항바이러스 또는 항종양 반응을 유도하는 데 필요한 유형 I 인터페론을 본질적으로 분비할 수 있다.
놀랍게도, 본 개시에 기재된 바와 같이 재프로그래밍에 의해 생성된 유도된 pDC 또는 인터페론 유형 I-생산 세포는 증가된 양의 유형 I 인터페론, 예를 들면, 항바이러스 반응을 유도하기 위해 필요한 인터페론 알파(IFN-α) 및 베타(IFN-β)를 분비함으로써 톨-유사 수용체 7(TLR7) 및 TLR9 리간드에 본질적으로 반응할 수 있다.
DC는 선천 면역계와 적응 면역계의 경계에서 기능하는 신체 전체에 위치한 전문 APC이다. DC는 주요 조직적합성 복합체(MHC) 클래스 I 및 MHC 클래스 II 분자에 로딩된 항원을 포획, 처리 및 T 세포에 제시하고, 이들을 상이한 유형의 면역 반응에 대해 표적으로 하는 능력을 통해 외부 환경과 적응 면역계 사이에 중요한 연결을 제공할 수 있다. 첫째, DC는 항원을 포획하고 주요 조직적합성 복합체(MHC) 클래스 I 및 MHC 클래스 II를 통해 항원을 처리해야 한다. 이들의 활성화 후, DC는 적응 면역의 중요한 특징인 복수의 B 세포 및 T 세포 반응을 프라이밍하는 국소적 유입 림프절을 향해 이동할 수 있다. 초기 보호 효능은 주로 B 림프구에 의해 생성된 항원 특이적 항체의 유도에 의해 부여된다. 특정 항원에 대한 장기적 보호에는 특정 항체의 지속성과 후속 항원 노출 후에 신속하고 효율적인 반응을 제공할 수 있는 면역학적 기억의 생성이 필요하다. DC는, 전문 APC로서, 항원을 교차 제시하는 능력을 갖고, 이는, MHC 클래스 II에 외인성 항원을 제시하고 MHC 클래스 I에 내인성 항원을 제시하는 고전적 능력에 추가하여, 또한 세포독성 T 림프구 반응(CTL)을 생성하기 위한 중요한 단계인 MHC 클래스 I에 외인성 항원을 제시할 수 있음을 의미한다.
DC가 위치하는 개체 발생 및/또는 미세 환경은 DC에 의한 표면 수용체의 상이한 조합의 발현을 초래할 수 있다. 예를 들면, 표현형 기준을 통해 마우스 DC를 상이한 서브세트로 분류할 수 있다. 이들 중 림프 조직의 cDC는 전통적으로 cDC1 및 cDC2의 서브세트으로 세분화된다. 상이한 DC 서브세트가 특정 병원체의 특정 인식에 관여하고/하거나, 상이한 면역 반응, 예를 들면, Th1 또는 Th2(면역) 또는 조절 T 세포(내성)를 조절할 수 있다고 주장되어 왔다. 그러나, DC의 표현형 및 기능적 행동은 또한 외부 활성화 자극에 의해 유의하게 조절되어, 유의한 가소성을 나타낸다. cDC1 및 cDC2 서브세트는 생체내에서 Th1 및 Th2 반응을 차등적으로 프라이밍한다. 암에 대한 면역 요법은 종양 제거를 촉진하는 Th1 또는 세포독성 T 림프구 반응을 프라이밍하기 위해 DC를 이용하는 것에 의존한다. cDC와 함께, pDC는 바이러스 감염 또는 TLR7 및 TLR9를 통한 자가 핵산 인식 후에 유형 I 인터페론(IFN) 생산에 특화된 DC의 고유한 서브세트로서 등장했다. 항바이러스성 면역에 기여하는 것에 추가하여, pDC는, 자가면역 질환 및 암의 병리(pathology)에 연루되어 있는, 면역원성 및 관용원성 둘 다의 적응 면역 반응의 프라이밍에 참가할 수 있다.
pDC는 바이러스 및/또는 바이러스 유래 핵산에 반응하여 기타 세포 유형보다 더 많은 유형 I 인터페론을 생성하는 독특한 특징을 갖고 있다. TLR7 및 9는 세포내 엔도솜 구획의 pDC에서 고도로 발현된다. TLR7은 바이러스 단일 가닥(single strand) RNA를 인식하고, TLR9는 비메틸화된 CpG 올리고뉴클레오티드가 풍부한 바이러스 이중 가닥(double strand) DNA를 검출한다. 바이러스 핵산으로 활성화되면, 어댑터 단백질 MyD88 및 2개의 주요 TLR7/9 세포내 신호전달 경로의 자극 및 동원을 유도한다. 첫 번째 경로는 유형 I 인터페론 생산을 유도하고, 이는 IFN-α 및 IFN-β 전사 및 분비를 촉진하는 핵에 대한 IRF7의 전위를 필요로 한다. 핵산에 의한 활성화시에 pDC에 의해 분비되는 유형 I 인터페론은 선천성 면역계와 후천성 면역계를 연결하여, 장기 T 세포의 생존 및 기억, Th1 분극화, CD8 T 세포의 세포용해 활성, NK 세포 매개 세포독성 및 B 세포의 성장 및 분화를 촉진한다. 또는, 두 번째 경로의 활성화는 프로-염증성 사이토카인, TNF-α 및 IL-6, 게다가 케모카인, 예를 들면, CXCL9(MIG), CXCL10(IP-10), CCL3(MIP-1a), CCL4(MIP-1b) 및 CCL5(RANTES)의 발현의 NF-kb 의존적 염증 유발을 유도한다. 이들은 이어서 활성화된 CD4 및 CD8 T 세포를 염증 부위로 유인할 수 있다.
현재, DC 기반 면역요법은 자가 DC 전구체: 덜 효율적 DC의 생산과 관련된 단핵구 또는 매우 적은 수로 단리된 조혈 전구세포 중 하나에 의존한다. 또한, 이러한 전구 세포는 암을 갖는 환자에서는 일반적으로 손상되어, 기능 장애 및 불균일한 DC의 혼합물을 생성한다. 대조적으로, 섬유아세포 등의 비-조혈 세포-유형은 통상 영향을 받지 않는다. 인간 피부 섬유아세포(HDF)는 또한 기타 경쟁 우위를 나타내고; 이들은 작은 피부 펀치 생검으로부터 용이하게 수득될 수 있고, 시험관내에서 수계대에 걸쳐 용이하게 확장될 수 있고(4주 후에 1,500만 내지 2,000만 세포), 동결 보존되어 주문형으로 사용할 수 있다. 선천 면역계와 적응 면역계의 경계에서 기능하는 DC의 기본적 역할을 감안할 때, 항원 특이적 반응을 프라이밍하기 위해 기능적 pDC의 균질한 집단을 생성하기 위한 대체 전략을 찾기 위한 임상적 필요성이 남아 있다.
최근, pDC는 대량의 IFN을 생성하고 T 세포를 프라이밍하는 능력으로 인해 특별한 관심을 받았다. pDC 결핍 마우스는 CD4+ 및 CD8+ T 세포 반응의 손상으로 인해 림프구성 맥락수막염 바이러스를 효율적으로 제거할 수 없는 것으로 밝혀졌다[참조: Cervantes-Barragan et al., 2012]. 유사하게는, 환자에서 IRF7 눌(null) 돌연변이는 pDC에 의한 유형 I 및 유형 III IFN 생성에 부정적인 영향을 미치고, 심각한 인플루엔자 감염을 유도하는 것으로 보고되었다[참조: Ciancanelli et al., 2015]. 이러한 발견은 특히 초기 단계[참조: Swiecki and Colonna, 2015]에서 바이러스 감염과 싸우기 위해 pDC가 중요하다는 것을 나타내고, 여기서 IFN 생산이 바이러스 복제를 제한할 수 있다. 더욱이, 몇몇 임상 시험에서는 pDC가 항종양 면역 반응을 유도하는 가능성을 조사했다[참조: Tel et al., 2013]. 그러나, pDC의 치료적 사용은 혈액에서 순환하는 이들 세포의 수가 적기 때문에 제한되는 것으로 보인다. 따라서, DC 특히 pDC의 대체 공급원은 치료 요구를 충족하기 위해 필요하다.
일부 실시형태에서, 폴리펩티드 서열(서열번호 49 내지 서열번호 96)을 갖는 참조 폴리펩티드 또는 서열번호 1 내지 서열번호 48에 의해 코딩되는 폴리펩티드와 동일한 또는 유사한 활성을 갖는 폴리펩티드 변이체 또는 패밀리 구성원은 본 명세서에 기재된 조성물, 방법 및 키트에 사용될 수 있다. 일반적으로, 본 명세서에 기재된 조성물, 벡터(vector), 작제물, 방법 및 키트에 사용하기 위한 pDC-유도 인자를 코딩하는(encoding) 특정 폴리펩티드의 변이체는, 본 명세서에 기재되고 당업자에게 공지되어 있는 서열 정렬 프로그램 및 파라미터에 의해 결정되는 바와 같이, 특정 참조 폴리뉴클레오티드 또는 폴리펩티드에 대해 적어도 약 90%, 적어도 약 91%, 적어도 약 92%, 적어도 약 93%, 적어도 약 94%, 적어도 약 95%, 적어도 약 96%, 적어도 약 97%, 적어도 약 98%, 적어도 약 99%의 서열 동일성을 가질 것이다.
비교를 위한 서열의 정렬 방법은 당해 기술분야에 공지되어 있고, 이러한 방법에는 GAP, BESTFIT, BLAST, FASTA 및 TFASTA가 포함된다. GAP는 니들만 및 운쉬(Needleman and Wunsch)[참조: (1970) J Mol Biol 48: 443-453]의 알고리즘을 사용하여, 일치 수를 최대화하고 갭 수를 최소화하는 2개 서열의 전체(전체 서열에 대해) 정렬을 찾는 것이다. BLAST 알고리즘[참조: Altschul et al.(1990) J Mol Biol 215: 403-10]은 서열 동일성 퍼센트를 계산하고, 2개 서열 간의 유사성에 대한 통계적 분석을 수행한다. BLAST 분석을 수행하기 위한 소프트웨어는 미국 국립 바이오테크놀로지 정보 센터(National Center for Biotechnology Information; NCBI)를 통해 공개적으로 제공된다. 유사성 및 동일성의 전체 백분율은 MatGAT 소프트웨어 패키지[참조: Campanella et al., BMC Bioinformatics. 2003 Jul 10; 4:29. MatGAT: 단백질 또는 DNA 서열을 사용하여 유사성/동일성 매트릭스를 생성하는 어플리케이션)에서 이용 가능한 방법 중 하나를 사용하여 결정할 수도 있다. 당업자에게 명백한 바와 같이, 보존된 모티프 사이의 정렬을 최적화하기 위해 약간의 수동 편집이 수행될 수 있다. 본 주제에서 백분율로 표시되는 서열 동일성 값은 디폴트 파라미터로 BLAST를 사용하여 전체 아미노산 또는 뉴클레오티드 서열에 대해 결정되었다.
보다 양호한 결과를 위한 일 실시형태에서, 전사 인자는 IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4), ARID5A(서열번호 5, 서열번호 6), BCL11A(서열번호 7, 서열번호 8), CBFA2T3(서열번호 9, 서열번호 10), CREB3L2(서열번호 11, 서열번호 12), ETS1(서열번호 13, 서열번호 14), HDAC5(서열번호 15, 서열번호 16), HHEX(서열번호 17, 서열번호 18), HOXA5(서열번호 19, 서열번호 20), ID3(서열번호 21, 서열번호 22), IKZF1(서열번호 23, 서열번호 24), IKZF2(서열번호 25, 서열번호 26), IKZF3(서열번호 27, 서열번호 28), IKZF5(서열번호 29, 서열번호 30), IRF7(서열번호 31, 서열번호 32), MEF2C(서열번호 33, 서열번호 34), MYB(서열번호 35, 서열번호 36), RUNX2(서열번호 37, 서열번호 38), STAT3(서열번호 39, 서열번호 40), TCF4(서열번호 41, 서열번호 42), TCF12(서열번호 43, 서열번호 44), STAT1(서열번호 45, 서열번호 46), 및 TSC22D1(서열번호 47, 서열번호 48)로 이루어진 그룹으로부터 선택된 폴리뉴클레오티드에 의해 코딩될 수 있다.
본 발명의 일 실시형태에 있어서, 상기 전사 인자는 IRF8(서열번호 49, 서열번호 50), SPIB(서열번호 51, 서열번호 52), ARID5A(서열번호 53, 서열번호 54), BCL11A(서열번호 55, 서열번호 56), CBFA2T3(서열번호 57, 서열번호 58), CREB3L2(서열번호 59, 서열번호 60), ETS1(서열번호 61, 서열번호 62), HDAC5(서열번호 63, 서열번호 64), HHEX(서열번호 65, 서열번호 66), HOXA5(서열번호 67, 서열번호 68), ID3(서열번호 69, 서열번호 70), IKZF1(서열번호 71, 서열번호 72), IKZF2(서열번호 73, 서열번호 74), IKZF3(서열번호 75, 서열번호 76), IKZF5(서열번호 77, 서열번호 78), IRF7(서열번호 79, 서열번호 80), MEF2C(서열번호 81, 서열번호 82), MYB(서열번호 83, 서열번호 84), RUNX2(서열번호 85, 서열번호 86), STAT3(서열번호 87, 서열번호 88), TCF4(서열번호 89, 서열번호 90), TCF12(서열번호 91, 서열번호 92), STAT1(서열번호 93, 서열번호 94), 및 TSC22D1(서열번호 95, 서열번호 96)으로 이루어진 그룹으로부터 선택될 수 있다.
일 실시형태에서, 본 개시의 전사 인자는 수의학 또는 인간 의약, 특히 감염성 질환, 또는 바이러스성 질환, 또는 바이러스성 유발성 질환, 또는 암, 또는 자가면역 질환 또는 신경퇴행성 질환에서 사용될 수 있다.
보다 양호한 결과를 위한 일 실시형태에서, 세포는, 다능성 줄기 세포, 다분화능 줄기 세포, 조혈 줄기 세포, 분화 세포, 종양 세포, 암 세포, 세포주, 특히 단핵구 세포주 등의 중배엽-유래 세포주, 및 이의 혼합물로 이루어진 그룹으로부터 선택될 수 있다. 특히, 포유동물 세포, 보다 특히 마우스 또는 인간 세포.
보다 양호한 결과를 위한 일 실시형태에서, 본 개시의 전사 인자는 수지상 세포 또는 인터페론 유형 I 생산 세포 또는 항원 제시 세포, 바람직하게는 수지상 세포 또는 인터페론 유형 I-생산 세포 내로 다능성 줄기 세포, 또는 다분화능 줄기 세포, 또는 분화 세포 및 이의 혼합물로 이루어진 그룹으로부터 선택된 세포의 재프로그래밍 또는 유도 인자로서 사용될 수 있다.
보다 양호한 결과를 위한 일 실시형태에서, 본 개시의 전사 인자는 수지상 세포 또는 인터페론 유형 I-생산 세포 내로 다능성 줄기 세포, 또는 다분화능 줄기 세포, 또는 분화된 세포, 및 이들의 혼합물로 이루어진 그룹으로부터 선택된 세포의 재프로그래밍 또는 유도 인자로서 사용될 수 있다.
보다 양호한 결과를 위한 일 실시형태에서, 본 개시의 전사 인자는 항원 제시 세포 내로 종양 세포, 암 세포, 및 이들의 혼합물로 이루어진 그룹으로부터 선택된 세포의 재프로그래밍 또는 유도 인자로서 사용될 수 있다.
일 실시형태에서, 본 개시의 결과는, Clec9a 리포터 마우스에서, pDC가 tdTomato 형광 단백질로 표지되어, 이 모델을 pDC-유도 인자의 스크리닝에 적합한 것으로 되게 하는 것을 나타낸다. IRF8은 cDC1 및 pDC 사양에서 중요한 역할을 하는 것으로 설명되었고, DC 서브세트에서 모두 고도로 발현된다. 따라서, 본 발명은 IRF8을 개별 24개의 후보 각각과 조합하고, Clec9a 리포터 마우스 배아 섬유아세포(MEF)에서 점진적 부가 스크리닝을 수행했다.
일 실시형태에서, 놀랍게도, SPIB와 조합된 IRF8은 리포터 활성화를 유도하기에 충분하다. 더욱이, IRF8 및 SPIB가 BCL11A, CBFA2T3, CREB3L2, ETS1, STAT1, TCF4, TCF12 또는 TSC22D1과 조합될 때 리포터의 활성화 효율이 놀랍게도 증가한다. DC 기능에 중요한 주요 조직적합성 복합체(MHC) 클래스 II 분자의 발현은 또한 pDC 유도 TF의 IRF8- 및 IRF8+SPIB 기반 조합에 의해 유도된다.
일 실시형태에서, IRF8 및 SPIB의 발현은 조혈 마커 CD45의 표면 발현을 유도하기에 충분하다. 놀랍게도, IRF8 및 SPIB를 IKZF1 또는 IKZF2와 조합시키면, CD45의 표면 발현이 놀랍게도 증가한다.
일 실시형태에서, IRF8 및 SPIB는, pDC의 특징적 표현형 특성인 TLR7 및 TLR9 리간드로 자극한 후, 항-염증 IL-10이 아닌 인터페론 유형 I, 즉 IFN-α 및 IFN-β를 분비하는 능력을 유도할 수 있다. IRF8 및 SPIB를 BCL11A, CBFA2T3, CREB3L2, ETS1, STAT1, TCF4, TCF12 또는 TSC22D1과 조합시키면, 인터페론 분비가 추가로 증가한다. PU.1, IRF8 및 BATF3 TF로 생성된 유도 DC는 유형 I 인터페론을 분비하는 능력을 나타내지 않는다.
일 실시형태에서, IRF8 및 SPIB는, pDC의 특징적 표현형 특성인 TLR7 및 TLR9 리간드로 자극한 후, 프로-염증성 사이토카인, 특히 IL-6 및 TNF-α를 분비하는 능력을 유도할 수 있다. IRF8 및 SPIB를 ETS1, STAT1, TCF12 또는 TSC22D1과 조합시키면, 사이토카인 분비가 추가로 증가한다.
일 실시형태에서, IRF8 및 SPIB는, pDC의 특징적 표현형 특성인 TLR7 및 TLR9 리간드로 자극한 후, 케모카인, 즉 CCL5 및 CXCL10을 분비하는 능력을 유도할 수 있다. IRF8 및 SPIB를 HOXA5, STAT1, TCF12 또는 TSC22D1과 조합시키면, 케모카인 분비가 추가로 증가한다.
본 주제의 양태는,
대상체에서 줄기 세포 또는 분화 세포 또는 이의 혼합물을 형질세포양 수지상 세포(plasmacytoid dendritic cell) 또는 인터페론 생산 세포 또는 항원-제시 세포, 바람직하게는 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포 내로 재프로그래밍할 때에 사용하기 위한,
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4), ARID5A(서열번호 5, 서열번호 6), BCL11A(서열번호 7, 서열번호 8), CBFA2T3(서열번호 9, 서열번호 10), CREB3L2(서열번호 11, 서열번호 12), ETS1(서열번호 13, 서열번호 14), IKZF1(서열번호 23, 서열번호 24), STAT1(서열번호 45, 서열번호 46), TCF4(서열번호 41, 서열번호 42), TCF12(서열번호 43, 서열번호 44), TSC22D1(서열번호 47, 서열번호 48), 및 이들의 혼합물로 이루어진 목록으로부터 선택된 전사 인자로 이루어진 목록으로부터의 서열과 적어도 90% 동일한 단리된 또는 합성 서열에 의해 코딩된 적어도 2개의 전사 인자의 조합을 포함하는 조성물에 관한 것이다.
본 주제의 일 양태는, 대상체에서 줄기 세포 또는 분화된 세포, 또는 이들의 혼합물을 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포 내로 재프로그래밍할 때에 사용하기 위한, 적어도 2개의 전사 인자 IRF8 및 SPIB를 포함하는 조성물에 관한 것이다.
일 실시형태에서, 본 개시의 조성물은 본 명세서에 기재된 바와 같은 적어도 2개의 전사 인자를 포함하고, 단, 단리될 수 있거나 합성 전사 인자일 수 있는 적어도 2개의 전사 인자의 조합은 TCF4(서열번호 41, 서열번호 42) 및 IRF8(서열번호 1, 서열번호 2)이 아니다.
일 실시형태에서, 본 개시의 조성물은 ARID5A, BCL11A, CBFA2T3, CREB3L2, ETS1, IKZF1, STAT1, TCF4, TCF12 및 TSC22D1, 바람직하게는 BCL11A, CBFA2T3, CREB3L2, ETS1, IKZF1, TCF4, TCF12 및 TSC22D1으로 이루어진 그룹으로부터 선택된 하나 이상의 전사 인자를 추가로 포함한다.
일 실시형태에서, 본 개시의 조성물은, IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4), ARID5A(서열번호 5, 서열번호 6), BCL11A(서열번호 7, 서열번호 8), CBFA2T3(서열번호 9, 서열번호 10), CREB3L2(서열번호 11, 서열번호 12), ETS1(서열번호 13, 서열번호 14), IKZF1(서열번호 23, 서열번호 24), STAT1(서열번호 45, 서열번호 46), TCF4(서열번호 41, 서열번호 42), TCF12(서열번호 43, 서열번호 44), TSC22D1(서열번호 47, 서열번호 48), 및 이들의 혼합물로 이루어진 그룹으로부터의 선택된 TF로 이루어진 그룹으로부터의 서열과 적어도 95% 동일한, 바람직하게는 96%, 97%, 98%; 99% 동일한 단리된 또는 합성 서열에 의해 코딩된 적어도 2개의 전사 인자의 조합을 포함한다.
본 개시의 일 실시형태에서, 전사 인자는 IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4), ARID5A(서열번호 5, 서열번호 6), BCL11A(서열번호 7, 서열번호 8), CBFA2T3(서열번호 9, 서열번호 10), CREB3L2(서열번호 11, 서열번호 12), ETS1(서열번호 13, 서열번호 14), IKZF1(서열번호 23, 서열번호 24), STAT1(서열번호 45, 서열번호 46), TCF4(서열번호 41, 서열번호 42), TCF12(서열번호 X, 서열번호 X), TSC22D1(서열번호 47, 서열번호 48), 및 이들의 혼합물로 이루어진 그룹으로부터 선택된 서열과 적어도 90% 동일한, 바람직하게는 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 동일하다.
일 실시형태에서, 본 개시의 조성물은 하기 조합으로부터 선택된 전사 인자의 조합을 포함할 수 있다:
IRF8(서열번호 1, 서열번호 2) 및 SPIB(서열번호 3, 서열번호 4);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 ARID5A(서열번호 5, 서열번호 6);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 5, 서열번호 6) 및 BCL11A(서열번호 7, 서열번호 8);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 CBFA2T3(서열번호 9, 서열번호 10);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 CREB3L2(서열번호 11, 서열번호 12);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 ETS1(서열번호 13, 서열번호 14);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 IKZF1(서열번호 23, 서열번호 24);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 STAT1(서열번호 45, 서열번호 46);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 TCF4(서열번호 41, 서열번호 42);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 TCF12(서열번호 43, 서열번호 44);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 TSC22D1(서열번호 47, 서열번호 48), 및 이들의 혼합물.
일 실시형태에서, 본 개시의 조성물은 하기 조합으로부터 선택된 전사 인자의 조합을 포함할 수 있다:
IRF8 및 SPIB;
IRF8, SPIB 및 ARID5A;
IRF8, SPIB 및 BCL11A;
IRF8, SPIB 및 CBFA2T3;
IRF8, SPIB 및 CREB3L2;
IRF8, SPIB 및 ETS1;
IRF8, SPIB 및 IKZF1;
IRF8, SPIB 및 STAT1;
IRF8, SPIB 및 TCF4;
IRF8, SPIB 및 TCF12;
IRF8, SPIB 및 TSC22D1; 및 이들의 혼합물.
일 실시형태에서, 본 개시의 조성물은, 조합이 IRF8(서열번호 1, 서열번호 2) 및 SPIB(서열번호 3, 서열번호 4), 또는 IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 TCF12(서열번호 43, 서열번호 44)인 전사 인자의 조합을 포함할 수 있다.
일 실시형태에서, 본 개시의 조성물은, 조합이 IRF8, SPIB 및 TCF12인 전사 인자의 조합을 포함할 수 있다.
일 실시형태에서, 본 개시의 조성물은, 조합이 IRF8, SPIB 및 TSC22D1인 전사 인자의 조합을 포함할 수 있다.
일 실시형태에서, 본 개시의 조성물은 다능성 줄기 세포, 또는 다분화능 줄기 세포, 분화된 세포, 및 이들의 혼합물을 포함할 수 있다.
일 실시형태에서, 본 개시의 조성물은 종양 세포, 암 세포 및 이들의 혼합물로 이루어진 그룹으로부터 선택된 세포의 인터페론 유형 I-생산 세포로의 재프로그래밍 또는 유도 인자로서 사용할 수 있다.
일 실시형태에서, 본 개시의 조성물은 pDC의 재프로그래밍 또는 유도 인자로서 사용될 수 있고, 여기서 항원은 암 항원, 자가-항원, 알레르겐, 병원성 및/또는 감염성 생물로부터의 항원이다.
일 실시형태에서, 본 개시의 전사 인자의 조합의 사용에 의해 수득된 세포는 TLR7 및 TLR9 자극에 반응하는 능력을 갖고/갖거나, 세포는 인터페론 유형 I 사이토카인, 즉 IFN-α 및 IFN-β를 분비하는 능력을 갖는다.
본 개시의 또 다른 양태는 수의학적 또는 인간 의약, 특히 면역요법에서, 또는 신경퇴행성 또는 노화 질환, 또는 암 또는 감염성 질환에서, 또는 약물 스크리닝(drug screening)으로서 본 개시의 조성물의 용도에 관한 것이다.
본 개시의 또 다른 양태는 암, 항바이러스성 면역 반응 및 면역 병리, 특히 자가면역 질환 및 면역결핍 상태의 진단, 요법 또는 치료에서 본 개시의 조성물의 용도에 관한 것이다.
일 실시형태에서, 다능성 줄기 세포, 다분화능 줄기 세포 또는 분화된 세포는 포유동물 다능성 줄기 세포, 다분화능 줄기 세포 또는 분화된 세포, 특히 마우스 또는 인간 세포이다.
일 실시형태에서, 본 개시의 조성물은 감염성 질환, 바이러스성 질환 또는 바이러스-유도된 질환의 치료, 요법 또는 진단에 사용될 수 있다.
일 실시형태에서, 본 발명의 조성물은 항바이러스제 또는 면역원성 조성물로서 사용될 수 있다.
본 개시의 또 다른 양태는, 본 개시에 기재된 2개의 단리된 전사 인자의 적어도 조합, 바람직하게는 3개의 전사 인자, 보다 바람직하게는 4개의 전사 인자의 코딩된 조합을 코딩하는 작제물 또는 벡터에 관한 것이다.
일 실시형태에서, 적어도 2개의 단리된 전사 인자의 조합은 5'로부터 3'까지 하기의 연속 순서로 존재한다:
SPIB(서열번호 3, 서열번호 4) 및 IRF8(서열번호 1, 서열번호 2);
IRF8(서열번호 1, 서열번호 2) 및 SPIB(서열번호 3, 서열번호 4);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 ARID5A(서열번호 5, 서열번호 6);
SPIB(서열번호 5, 서열번호 6), IRF8(서열번호 1, 서열번호 2) 및 BCL11A(서열번호 7, 서열번호 8);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 CBFA2T3(서열번호 9, 서열번호 10);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 CREB3L2(서열번호 11, 서열번호 12);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 ETS1(서열번호 13, 서열번호 14);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 IKZF1(서열번호 23, 서열번호 24);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 STAT1(서열번호 45, 서열번호 46);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 TCF4(서열번호 41, 서열번호 42);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 TCF12(서열번호 43, 서열번호 44);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 TSC22D1(서열번호 47, 서열번호 48).
본 개시의 또 다른 양태는, 본 개시에 기재된 2개의 단리된 전사 인자의 적어도 조합, 바람직하게는 3개의 전사 인자의 코딩된 조합을 코딩하는 작제물 또는 벡터에 관한 것이고, 여기서 적어도 2개의 단리된 전사 인자의 조합은 5'으로부터 3'까지 하기의 연속 순서로 존재한다:
SPIB(서열번호 3, 서열번호 4) 및 IRF8(서열번호 1, 서열번호 2);
IRF8(서열번호 1, 서열번호 2) 및 SPIB(서열번호 3, 서열번호 4);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 ARID5A(서열번호 5, 서열번호 6);
SPIB(서열번호 5, 서열번호 6), IRF8(서열번호 1, 서열번호 2) 및 BCL11A(서열번호 7, 서열번호 8);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 CBFA2T3(서열번호 9, 서열번호 10);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 CREB3L2(서열번호 11, 서열번호 12);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 ETS1(서열번호 13, 서열번호 14);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 IKZF1(서열번호 23, 서열번호 24);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 STAT1(서열번호 45, 서열번호 46);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 TCF4(서열번호 41, 서열번호 42);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 TCF12(서열번호 43, 서열번호 44);
SPIB(서열번호 3, 서열번호 4), IRF8(서열번호 1, 서열번호 2) 및 TSC22D1(서열번호 47, 서열번호 48).
일 실시형태에서, 벡터는 바이러스 벡터; 특히 레트로바이러스, 아데노바이러스, 렌티바이러스, 헤르페스 바이러스, 수두 바이러스, 파라믹소바이러스(paramyxoviral), 랍도바이러스, 알파바이러스, 플라바이러스 또는 아데노-연관 바이러스 벡터이다.
일 실시형태에서, 벡터 또는 작제물은 합성 mRNA, 네이키드(naked) 알파바이러스 RNA 레플리콘(replicon) 또는 네이키드 플라비바이러스 RNA 레플리콘이다.
본 개시의 일 양태에서, 하나 이상의 벡터는 대상체에서 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포 내로 줄기 세포 또는 분화된 세포, 또는 이들의 혼합물의 재프로그래밍에 사용하기 위한, 적어도 2개의 전사 인자 IRF 및 SPIB를 코딩하는 적어도 2개의 폴리뉴클레오티드 서열을 포함한다.
본 개시의 일 실시형태에서, 하나 이상의 벡터는, ARID5A, BCL11A, CBFA2T3, CREB3L2, ETS1, IKZF1, STAT1, TCF4, TCF12 및 TSC22D1, 바람직하게는 BCL11A, CBFA2T3, CREB3L2, ETS1, IKZF1, TCF4, TCF12 및 TSC22D1로 이루어진 그룹으로부터 선택된 하나 이상의 전사 인자를 추가로 코딩한다.
본 개시의 일 실시형태에서, 하나 이상의 벡터의 전사 인자는, IRF8(서열번호 49, 서열번호 50), SPIB(서열번호 51, 서열번호 52), ARID5A(서열번호 53, 서열번호 54), BCL11A(서열번호 55, 서열번호 56), CBFA2T3(서열번호 57, 서열번호 58), CREB3L2(서열번호 59, 서열번호 60), ETS1(서열번호 61, 서열번호 62), IKZF1(서열번호 71, 서열번호 72), TCF4(서열번호 89, 서열번호 90), TCF12(서열번호 91, 서열번호 92), STAT1(서열번호 93, 서열번호 94), 및 TSC22D1(서열번호 95, 서열번호 96)으로 이루어진 그룹으로부터 선택된 서열과 개별적으로 적어도 90% 동일하다.
본 개시의 일 실시형태에서, 하나 이상의 벡터의 전사 인자의 조합은 하기 조합으로부터 선택된다:
IRF8 및 SPIB;
IRF8, SPIB 및 ARID5A;
IRF8, SPIB 및 BCL11A;
IRF8, SPIB 및 CBFA2T3;
IRF8, SPIB 및 CREB3L2;
IRF8, SPIB 및 ETS1;
IRF8, SPIB 및 IKZF1;
IRF8, SPIB 및 STAT1;
IRF8, SPIB 및 TCF4;
IRF8, SPIB 및 TCF12; 및
IRF8, SPIB 및 TSC22D1.
본 개시의 일 실시형태에서, 하나 이상의 벡터의 전사 인자의 조합은 IRF8, SPIB 및 TCF12의 조합이다.
본 개시의 일 실시형태에서, 하나 이상의 벡터의 전사 인자의 조합은 IRF8, SPIB 및 TSC22D1의 조합이다.
본 개시의 일 실시형태에서, 하나 이상의 벡터를 사용한 재프로그래밍에 사용되는 세포는 다능성 줄기 세포, 다분화능 줄기 세포, 분화된 세포, 종양 세포, 암 세포 및 이들의 혼합물로 이루어진 그룹으로부터 선택된다.
본 개시의 실시형태에서, 하나 이상의 벡터는, 수의학 또는 인간 의약, 특히 항바이러스성 면역 반응 및 면역 병리, 특히 자가면역 질환 및 면역결핍 상태, 신생물, 특히 암, 즉 고형 또는 혈액 종양, 양성 종양(benign tumour), 악성 종양(malignant tumour), 초기 암(early cancer), 기저 세포 암종(basal cell carcinoma), 자궁경부 이형성증(cervical dysplasia), 연조직 육종(soft tissue sarcoma), 생식 세포 종양(germ cell tumour), 망막모세포종(retinoblastoma), 연령 관련 황반 변성(age-related macular degeneration), 호지킨 림프종(Hodgkin's lymphoma), 혈액암(blood cancer), 전립선암(prostate cancer), 난소암(ovarian cancer), 자궁경부암(cervix cancer), 자궁암(uterus cancer), 질암(vaginal cancer), 유방암(breast cancer), 비인두암(naso-pharynx cancer), 기관암(trachea cancer), 후두암(larynx cancer), 기관지암(bronchi cancer), 세기관지암(bronchioles cancer), 폐암(lung cancer), 중공 장기암(hollow organs cancer), 식도암(esophagus cancer), 위암(stomach cancer), 담관암(bile duct cancer), 장암(intestine cancer), 결장암(colon cancer), 대장암(colorectum cancer), 직장암(rectum cancer), 방광암(bladder cancer), 요관암(ureter cancer), 신장암(kidney cancer), 간암(liver cancer), 담낭암(gall bladder cancer,), 비장암(spleen cancer), 뇌암(brain cancer), 림프계암(lymphatic system cancer), 골암(bone cancer), 췌장암(pancreatic cancer), 백혈병(leukaemia), 피부암(skin cancer) 또는 골수종(myeloma), 감염성 질환(infectious disease), 바이러스성 질환(viral disease) 또는 바이러스성 유발 질환(viral induced disease), 중추 및 말초 신경계 장애(central and peripheral nervous system disorder), 진균(fungal), 세균(viral), 클라미디아(chlamydial), 박테리아(bacterial), 나노박테리아(nanobacterial) 또는 기생충(parasitic) 감염 질환 또는 바이러스성 질환, 또는 바이러스 유발 질환의 진단, 요법 또는 치료에서, 항바이러스제로서 또는 면역원성 조성물로서, 면역요법으로서, 또는 신경퇴행성 질환의 치료 또는 요법에서, 암의 치료 또는 요법에서, 또는 감염성 질환의 치료 또는 요법에서, 또는 바이러스 질환, 또는 바이러스 유도 질환, 피내 및 경피 요법, HIV, SARS 코로나바이러스에 의한 감염, 아시아 독감 바이러스(Asian flu virus), 단순 포진(herpes simplex), 인플루엔자 바이러스, 대상 포진(herpes zoster), 간염(hepatitis), 인간 유두종 바이러스(human papillomavirus), 엡스타인-바르 바이러스(Epstein-Barr virus), 인간 T-림프성 바이러스 또는 바이러스 간염, 아밀로이드 질환, 특히 아밀로이드 질환 A 아밀로이드증(amyloidosis), 알츠하이머병(Alzheimer's disease), 경쇄(AL) 아밀로이드증(Light-Chain (AL) amyloidosis), 제2형 당뇨병(Type-2 Diabetes), 갑상선 수질암(Medullary Carcinoma of the Thyroid), 파킨슨병(Parkinson's disease), 다발성 신경병증(Polyneuropathy), 또는 해면상 뇌병증(Spongiform Encephalopathy)(크로이츠펠트 야콥병(Creutzfeldt Jakob disease)) 또는 약물 스크리닝에 사용하기 위한 것이다.
본 개시의 또 다른 양태는, 세포를 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포로 재프로그래밍하거나 유도하는 방법으로서,
줄기 세포 또는 분화 세포, 및 이들의 혼합물로 이루어진 그룹으로부터 선택된 세포를
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4), ARID5A(서열번호 5, 서열번호 6), BCL11A(서열번호 7, 서열번호 8), CBFA2T3(서열번호 9, 서열번호 10), CREB3L2(서열번호 11, 서열번호 12), ETS1(서열번호 13, 서열번호 14), IKZF1(서열번호 23, 서열번호 24), TCF4(서열번호 41, 서열번호 42), TCF12(서열번호 43, 서열번호 44), STAT1(서열번호 45, 서열번호 46), TSC22D1(서열번호 47, 서열번호 48) 및 이들의 혼합물로 이루어진 그룹으로부터 선택된 서열과 적어도 90% 동일한, 바람직하게는 적어도 95% 동일한 서열을 코딩하는 적어도 2개의 핵산 서열을 포함하는 하나 이상의 벡터로
형질도입하는 단계;
형질도입된 세포를, 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포의 성장을 서포트하는 세포 배지에서 배양하는 단계를 포함하는, 방법에 관한 것이다.
본 개시의 또 다른 양태는, 세포를 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포로 재프로그래밍하거나 유도하기 위한 시험관내 방법으로서,
줄기 세포 또는 분화 세포, 및 이들의 혼합물로 이루어진 그룹으로부터 선택된 세포를
적어도 2개의 전사 인자 IRF8 및 SPIB를 포함하는 하나 이상의 벡터로
형질도입하는 단계, 및
형질도입된 세포를, 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포의 성장을 서포트하는 세포 배지에서 배양하는 단계를 포함하는, 방법에 관한 것이다.
일 실시형태에서, 서열은 하기로 이루어진 조합의 그룹으로부터 선택된다:
IRF8(서열번호 1, 서열번호 2) 및 SPIB(서열번호 3, 서열번호 4);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 ARID5A(서열번호 5, 서열번호 6);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 5, 서열번호 6) 및 BCL11A(서열번호 7, 서열번호 8);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 CBFA2T3(서열번호 9, 서열번호 10);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 CREB3L2(서열번호 11, 서열번호 12);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 ETS1(서열번호 13, 서열번호 14);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 IKZF1(서열번호 23, 서열번호 24);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 STAT1(서열번호 45, 서열번호 46);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 TCF4(서열번호 41, 서열번호 42);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 TCF12(서열번호 43, 서열번호 44);
IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4) 및 TSC22D1(서열번호 47, 서열번호 48) 및 이들의 혼합물.
일 실시형태에서, 서열은 하기로 이루어진 조합의 그룹으로부터 선택된다:
IRF8 및 SPIB;
IRF8, SPIB 및 ARID5A;
IRF8, SPIB 및 BCL11A;
IRF8, SPIB 및 CBFA2T3;
IRF8, SPIB 및 CREB3L2;
IRF8, SPIB 및 ETS1;
IRF8, SPIB 및 IKZF1;
IRF8, SPIB 및 STAT1;
IRF8, SPIB 및 TCF4;
IRF8, SPIB 및 TCF12;
IRF8, SPIB 및 TSC22D1, 및 이들의 혼합물.
일 실시형태에서, 이 방법은 형질도입된 세포를 적어도 2일, 바람직하게는 적어도 5일, 보다 바람직하게는 적어도 8일, 보다 더 바람직하게는 적어도 9일 동안 배양하는 단계를 포함할 수 있다.
일 실시형태에서, 형질도입 단계는 IL-12를 코딩하는 핵산 서열; IL-4를 코딩하는 핵산 서열; IFN-α를 코딩하는 핵산 서열; IFN-β를 코딩하는 핵산 서열; IFN-γ를 코딩하는 핵산 서열; TNF를 코딩하는 핵산 서열; GM-CSF를 코딩하는 핵산 서열; IL-10 RNA를 표적으로 하는 siRNA를 코딩하는 핵산 서열, 및 이들의 혼합물로 이루어진 그룹으로부터 선택된 적어도 하나의 벡터를 추가로 포함한다.
일 실시형태에서, 형질도입 단계는 면역자극성 사이토카인을 코딩하는 핵산을 포함하는 적어도 하나의 벡터를 추가로 포함한다.
일 실시형태에서, 세포는 다능성 줄기 세포, 다분화능 줄기 세포, 또는 분화된 세포, 및 이들의 혼합물; 특히 포유동물 세포로 이루어진 그룹으로부터 선택된다.
일 실시형태에서, 다능성 줄기 세포, 다분화능 줄기 세포, 또는 분화된 세포는 내배엽-유래 세포, 중배엽-유래 세포, 외배엽-유래 세포, 중간엽 줄기 세포를 포함하는 다분화능 줄기 세포, 조혈 줄기 세포, 장 줄기 세포, 다능성 줄기 세포 및 세포주로 이루어진 그룹으로부터 선택된다.
일 실시형태에서, 세포는 인간 또는 비-인간이다. 또 다른 실시형태에서, 세포는 마우스 세포이다.
본 개시의 또 다른 양태는, 본 개시에 기재된 시험관내 방법에 의해 수득된 유도 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포 또는 항원 제시 세포, 바람직하게는 유도 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포에 관한 것이다.
본 개시의 또 다른 양태는, 치료학적 유효량의 본 개시에 기재된 형질세포양 수지상 세포, 또는 인터페론 유형 I-생산 세포, 또는 항원 제시 세포, 바람직하게는 유도된 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포 및 약제학적으로 허용되는 부형제를 포함하는 조성물에 관한 것이다.
일 실시형태에서, 조성물은 수의학 또는 인간 의약에 사용될 수 있다.
일 실시형태에서, 조성물은 면역요법, 또는 신경퇴행성 질환의 치료 또는 요법, 또는 암의 치료 또는 요법, 또는 감염성 질환의 치료 또는 요법에 사용될 수 있다.
일 실시형태에서, 조성물은 진통제, 항염증제, 화학요법제, 방사선요법제, 항생제, 이뇨제, 또는 이들의 혼합물을 추가로 포함할 수 있다.
일 실시형태에서, 조성물은 충전제, 결합제, 붕해제(disintegrant), 또는 윤활제, 또는 이들의 혼합물을 추가로 포함할 수 있다.
일 실시형태에서, 조성물은 피내 및 경피 요법에 사용될 수 있다.
일 실시형태에서, 조성물은 주사가능한 제형, 바람직하게는 원위치 주사제(in-situ injection)일 수 있다.
일 실시형태에서, 조성물은 수의학 또는 인간 의약, 또는 약물 스크리닝에 사용될 수 있다.
일 실시형태에서, 조성물은 중추 및 말초 신경계 장애의 치료, 요법 또는 진단에 사용될 수 있다.
일 실시형태에서, 조성물은 신생물, 특히 고형 종양 또는 혈액 종양 등의 암의 치료, 요법 또는 진단에 사용될 수 있다.
일 실시형태에서, 조성물, 벡터 또는 작제물은 양성 종양, 악성 종양, 초기 암, 기저 세포 암종, 자궁경부 이형성증, 연조직 육종, 생식 세포 종양, 망막모세포종, 노화 관련 황반변성, 호지킨 림프종, 혈액암, 전립선암, 난소암, 자궁경부암, 자궁암, 질암, 유방암, 비인두암, 기관암, 후두암, 기관지암, 세기관지암, 폐암, 중공 장기암, 식도암, 위암, 담관암, 장암, 결장암, 결장직장암, 직장암, 방광암, 요관암, 신장암, 간암, 담낭암, 비장암, 뇌암, 림프계암, 골암, 췌장암, 백혈병, 피부암 또는 골수종의 치료, 진단 또는 요법에 사용될 수 있다.
일 실시형태에서, 조성물, 벡터, 또는 작제물은 진균, 바이러스, 클라미디아, 세균, 나노박테리아 또는 기생충 감염 질환, 또는 바이러스 질환, 또는 바이러스 유발 질환의 치료, 요법 또는 진단에 사용될 수 있다.
일 실시형태에서, 조성물, 벡터 또는 작제물은 HIV, SARS 코로나바이러스, 아시아 독감 바이러스, 단순 포진, 인플루엔자 바이러스, 대상포진, 간염, 인간 유두종바이러스, 엡스타인-바르 바이러스, 인간 T-림프성 바이러스 또는 바이러스성 간염에 의한 감염의 치료, 요법 또는 진단에 사용될 수 있다.
일 실시형태에서, 조성물, 벡터 또는 작제물은 아밀로이드 질환, 특히 아밀로이드 A 아밀로이드증, 알츠하이머병, 경쇄(AL) 아밀로이드증, 유형-2 당뇨병, 갑상선의 수질암종, 파킨슨병, 다발성 신경병증 또는 크로이츠펠트 야콥병 등의 해면상 뇌병증의 치료, 요법 또는 진단에 사용될 수 있다.
본 개시의 또 다른 양태는, 본 개시에 기재된 조성물, 벡터 또는 작제물, 및/또는 기재된 바와 같은 유도 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포 또는 본 개시에 기재된 항원 제시 세포 또는 이들의 혼합물을 포함하는 백신 또는 주사가능한 제형에 관한 것이다.
본 개시의 또 다른 양태는 하기 성분들 중 적어도 하나를 포함하는 키트에 관한 것이다:
본 개시의 유도된 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포 또는 항원 제시 세포;
본 개시에 기재된 조성물;
본 개시에 기재된 하나 이상의 벡터 또는 작제물; 또는 이들의 혼합물.
본 개시의 또 다른 양태는 하기 성분들 중 적어도 하나를 포함하는 키트에 관한 것이다:
본 개시의 유도된 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포;
본 개시에 기재된 조성물;
본 개시에 기재된 하나 이상의 벡터 또는 작제물; 또는 이들의 혼합물.
일 실시형태에서, 본 개시는 IRF8이 SPIB와 조합된 경우에, 섬유아세포에서 pDC 프로그램을 개시한다는 증거를 제공한다. 이러한 발견은 pDC 사양에 대한 귀중한 통찰을 제공한다. 장래에, 직접 재프로그래밍에 의한 pDC의 생성은 자가 조작된 세포로 항바이러스성 면역 반응을 유도할 수 있는 길을 열어준다.
하기 도면은 본 개시를 설명하기 위한 바람직한 실시형태를 제공하는 것이고, 본 발명의 범위를 한정하는 것으로 간주되어서는 안 된다.
도 1. 수지상 세포의 주요 서브세트의 개체 발생. 종래의 수지상 세포 유형 1(cDC1) 및 유형 2(cDC2)는 일반적 수지상 세포 전구체(CDP)로부터 유래하는 DC 이전 집단으로부터 출현하지만, 형질세포양 수지상 세포(pDC)는 일반적 림프구 전구체(CLP) 또는 CDP로부터 유래할 수 있다. pDC는, 바이러스 감염 후의 유형 I 인터페론(IFN)의 생산에 특화된 DC의 고유한 서브세트로 출현한다. cDC1은 교차-제시를 수행하고, 세포독성 T 세포 반응을 유도하고, T 헬퍼 1 반응을 우선적으로 극성화하는 능력에 탁월하다. cDC2는 T 헬퍼 2 또는 17 반응을 극성화하는 T 헬퍼 세포에 항원을 제시하는 데 탁월하다.
도 2. 직접적 세포 재프로그래밍에 의한 pDC 또는 인터페론(IFN) 유형 I 생산 세포 생성. 다능성 줄기 세포, 다분화능 줄기 세포 및 체세포, 예를 들면, 섬유아세포로부터 pDC의 유도에 관한 본 주제에서 전사 인자(TF) 조합 개시의 효과 관찰. pDC는 유형 I IFN 생산에 특화되어 있기 때문에, 개별화 면역요법의 맥락에서 적용될 것이다. 유도된 pDC 또는 pDC-유도 TF 조합은 바이러스 감염 및 암을 포함한 명확한 병변 상황에서 면역을 유도하기 위해 사용될 것이다.
도 3. Clec9a, Irf8, Tlr7 및 Tlr9의 발현은 pDC로 제한된다. 개체 발생에 근접하는 pDC 및 기타 면역 세포, 특히 cDC1 및 cDC2, 마크로파지 및 단핵구에서 Clec9a, Irf8, Tlr7 및 Tlr9의 발현 수준을 나타내는 히트 맵. 발현 프로파일은 이뮤놀로지컬 게놈 프로젝트(Immunological Genome Project)(www.immgen.com)에서 입수 가능한 데이터로부터 수득되었다.
도 4. pDC를 유도하는 TF 후보. cDC1 및 cDC2와 비교한 경우, 22개의 후보 TF는 pDC가 고도로 풍부하다. 이뮤놀로지컬 게놈 프로젝트에서 이용 가능한 데이터로부터 추출한 유전자 발현 프로파일을 나타내는 히트 맵.
도 5. Clec9a는 pDC에서 발현된다. 이중 유전자도입 Clec9a-Cre x Rosa26-STOP-tdTomato의 비장으로부터 단리된 pDC(CD11clow BST2+ B220+ Siglec-H+ 세포로서 게이팅됨)의 92%에서 tdTomato의 발현.
도 6. SPIB와 조합된 IRF8은 Clec9a 리포터의 활성화를 유도한다. 이중 유전자도입 Clec9a-tdTomato 마우스로부터 단리된 마우스 배아 섬유아세포(MEF)에, IRF8을 단독으로 코딩하는 유도성 렌티바이러스 벡터 풀을 형질도입하거나, 추가 pDC 유도 TF와 조합하여, Dox의 첨가 5일 후에 유세포 분석으로 분석했다. IRF8 단독 또는 개별 pDC 유도 후보 TF와의 조합에 의한 형질도입 후의 tdTomato+ 세포의 정량화. M2rtTA-형질도입된 세포를 대조군으로 포함시켰다.
도 7. 유도된 pDC는 세포 표면에서 항원 제시 분자를 발현한다. 8일차에 IRF8 및 SPIB의 과발현 후에 생성된 tdTomato+ 세포의 주요 조직적합성 복합체 클래스 II(MHC-II) 발현의 유세포 분석.
도 8. 추가 pDC 유도 TF와 IRF8 및 SPIB의 조합은 Clec9a 리포터 활성화의 효율성을 증가시킨다. IRF8 및 SPIB를 단독 또는 개별 pDC 유도 인자와의 조합에 의한 이중 유전자도입 Clec9a-tdTomato MEF의 형질도입 후의 tdTomato+ 세포의 정량화. 유세포 분석은 8일차에 수행했다. M2rtTa-형질도입된 세포를 대조군으로 포함시켰다.
도 9. 추가 pDC 유도 TF와 IRF8 및 SPIB의 조합은 세포 표면에서 MHC-II의 발현을 증가시킨다. 8일차에, M2rtTA, IRF8+SPIB 단독으로 또는 개별 pDC 유도 TF와의 조합에 의해 형질도입된 MEF의 MHC-II 발현에 대한 유세포 분석. MHC-II 수준의 정량화는 tdTomato 음성(tdT-) 및 양성(tdT+) 집단에 대해 제시된다.
도 10. 유도된 pDC는 TLR7 및 TLR9 자극시에 유형 I 인터페론을 분비한다. MEF는 M2rtTA, PIB(PU.1, IRF8 및 BATF3), IRF8 및 SPIB 단독으로 또는 ARID5A, BCL11A, CBFA2T3, ETS1, HOXA5, TCF4 및 TCF12와의 조합에 의해 형질도입하고, tdTomato+ 세포를 독시사이클린 첨가 후 9일차에 선별했다. 정제된 tdTomato+ 세포를 TLR7(R848) 및 TLR9(CpG ODN 1668)와 함께 밤새 인큐베이팅하고, IFN-α(A), IFN-β(B) 및 IL-10(C) 사이토카인 분비를 세포계측 비드 어레이를 사용하여 상청액에서 정량화했다.
도 11. pDC를 유도하기 위한 추가 TF 후보. Stat1(A) 및 Tsc22d1(B)은 cDC1 및 cDC2와 비교한 경우 pDC가 풍부하다. 이뮤놀로지컬 게놈 프로젝트에서 이용 가능한 데이터로부터 추출한 유전자 발현 프로파일.
도 12. 추가 pDC 유도 TF와 IRF8 및 SPIB와의 조합은 Clec9a 리포터 활성화 및 MHC-II 표면 발현의 효율성을 증가시킨다. (A) Clec9a 리포터 활성화 및 (B) M2rtTA(M2), IRF8+SPIB 단독으로 또는 STAT1 또는 TSC22D1과의 조합에 의해 형질도입된 MEF의 MHC-II 발현의 유세포 분석. 유세포 분석은 5일차에 수행했다. M2rtTa-형질도입된 세포를 대조군으로 포함시켰다.
도 13. 유도된 pDC는 TLR7 및 TLR9 자극시에 유형 I 인터페론을 분비한다. MEF는 M2rtTA, IRF8 및 SPIB 단독으로 또는 STAT1 및 TSC22D1과의 조합에 의해 형질도입되고, 독시사이클린의 첨가 후 9일차에 tdTomato+ 세포를 선별했다. 정제된 tdTomato+ 세포는 TLR7(R848) 및 TLR9(CpG ODN 1668)의 트리거와 함께 밤새 인큐베이팅하고, IFN-α(A), IFN-β(B) 및 IL-10(C) 사이토카인 분비가 세포계측 비드 어레이를 사용하여 상청액에서 정량화되었다.
도 14. 유도된 pDC는 세포 표면에서 CD45를 발현한다. 5일차에, M2rtTA, PIB(PU.1, IRF8 및 BATF3), IRF8+SPIB 단독 또는 개별 pDC-유도 TF와의 조합에 의해 형질도입된 MEF의 CD45 발현의 유세포 분석. M2rtTa(M2)-형질도입된 세포를 대조군으로 포함시켰다.
도 15. 유도된 pDC는 TLR7 및 TLR9 자극시에 프로-염증성 사이토카인과 케모카인을 분비한다. MEF는 M2rtTA, IRF8 및 SPIB 단독으로, 또는 ARID4A, BCL11A, CBFA2T3, ETS1, HOXA5, STAT1, TCF4, TCF12 및 TSC22D1과의 조합에 의해 형질도입하고, tdTomato+ 세포는 독시사이클린 첨가 후 9일차에 선별했다. 정제된 tdTomato+ 세포는 TLR7(R848) 및 TLR9(CpG ODN 1668)와 함께 밤새 인큐베이팅하고, IL-6(A), TNF-α(B), CCL5(C) 및 CXCL10(D) 사이토카인 분비는 세포계측 비드 어레이를 사용하여 상청액에서 정량화했다.
도 1. 수지상 세포의 주요 서브세트의 개체 발생. 종래의 수지상 세포 유형 1(cDC1) 및 유형 2(cDC2)는 일반적 수지상 세포 전구체(CDP)로부터 유래하는 DC 이전 집단으로부터 출현하지만, 형질세포양 수지상 세포(pDC)는 일반적 림프구 전구체(CLP) 또는 CDP로부터 유래할 수 있다. pDC는, 바이러스 감염 후의 유형 I 인터페론(IFN)의 생산에 특화된 DC의 고유한 서브세트로 출현한다. cDC1은 교차-제시를 수행하고, 세포독성 T 세포 반응을 유도하고, T 헬퍼 1 반응을 우선적으로 극성화하는 능력에 탁월하다. cDC2는 T 헬퍼 2 또는 17 반응을 극성화하는 T 헬퍼 세포에 항원을 제시하는 데 탁월하다.
도 2. 직접적 세포 재프로그래밍에 의한 pDC 또는 인터페론(IFN) 유형 I 생산 세포 생성. 다능성 줄기 세포, 다분화능 줄기 세포 및 체세포, 예를 들면, 섬유아세포로부터 pDC의 유도에 관한 본 주제에서 전사 인자(TF) 조합 개시의 효과 관찰. pDC는 유형 I IFN 생산에 특화되어 있기 때문에, 개별화 면역요법의 맥락에서 적용될 것이다. 유도된 pDC 또는 pDC-유도 TF 조합은 바이러스 감염 및 암을 포함한 명확한 병변 상황에서 면역을 유도하기 위해 사용될 것이다.
도 3. Clec9a, Irf8, Tlr7 및 Tlr9의 발현은 pDC로 제한된다. 개체 발생에 근접하는 pDC 및 기타 면역 세포, 특히 cDC1 및 cDC2, 마크로파지 및 단핵구에서 Clec9a, Irf8, Tlr7 및 Tlr9의 발현 수준을 나타내는 히트 맵. 발현 프로파일은 이뮤놀로지컬 게놈 프로젝트(Immunological Genome Project)(www.immgen.com)에서 입수 가능한 데이터로부터 수득되었다.
도 4. pDC를 유도하는 TF 후보. cDC1 및 cDC2와 비교한 경우, 22개의 후보 TF는 pDC가 고도로 풍부하다. 이뮤놀로지컬 게놈 프로젝트에서 이용 가능한 데이터로부터 추출한 유전자 발현 프로파일을 나타내는 히트 맵.
도 5. Clec9a는 pDC에서 발현된다. 이중 유전자도입 Clec9a-Cre x Rosa26-STOP-tdTomato의 비장으로부터 단리된 pDC(CD11clow BST2+ B220+ Siglec-H+ 세포로서 게이팅됨)의 92%에서 tdTomato의 발현.
도 6. SPIB와 조합된 IRF8은 Clec9a 리포터의 활성화를 유도한다. 이중 유전자도입 Clec9a-tdTomato 마우스로부터 단리된 마우스 배아 섬유아세포(MEF)에, IRF8을 단독으로 코딩하는 유도성 렌티바이러스 벡터 풀을 형질도입하거나, 추가 pDC 유도 TF와 조합하여, Dox의 첨가 5일 후에 유세포 분석으로 분석했다. IRF8 단독 또는 개별 pDC 유도 후보 TF와의 조합에 의한 형질도입 후의 tdTomato+ 세포의 정량화. M2rtTA-형질도입된 세포를 대조군으로 포함시켰다.
도 7. 유도된 pDC는 세포 표면에서 항원 제시 분자를 발현한다. 8일차에 IRF8 및 SPIB의 과발현 후에 생성된 tdTomato+ 세포의 주요 조직적합성 복합체 클래스 II(MHC-II) 발현의 유세포 분석.
도 8. 추가 pDC 유도 TF와 IRF8 및 SPIB의 조합은 Clec9a 리포터 활성화의 효율성을 증가시킨다. IRF8 및 SPIB를 단독 또는 개별 pDC 유도 인자와의 조합에 의한 이중 유전자도입 Clec9a-tdTomato MEF의 형질도입 후의 tdTomato+ 세포의 정량화. 유세포 분석은 8일차에 수행했다. M2rtTa-형질도입된 세포를 대조군으로 포함시켰다.
도 9. 추가 pDC 유도 TF와 IRF8 및 SPIB의 조합은 세포 표면에서 MHC-II의 발현을 증가시킨다. 8일차에, M2rtTA, IRF8+SPIB 단독으로 또는 개별 pDC 유도 TF와의 조합에 의해 형질도입된 MEF의 MHC-II 발현에 대한 유세포 분석. MHC-II 수준의 정량화는 tdTomato 음성(tdT-) 및 양성(tdT+) 집단에 대해 제시된다.
도 10. 유도된 pDC는 TLR7 및 TLR9 자극시에 유형 I 인터페론을 분비한다. MEF는 M2rtTA, PIB(PU.1, IRF8 및 BATF3), IRF8 및 SPIB 단독으로 또는 ARID5A, BCL11A, CBFA2T3, ETS1, HOXA5, TCF4 및 TCF12와의 조합에 의해 형질도입하고, tdTomato+ 세포를 독시사이클린 첨가 후 9일차에 선별했다. 정제된 tdTomato+ 세포를 TLR7(R848) 및 TLR9(CpG ODN 1668)와 함께 밤새 인큐베이팅하고, IFN-α(A), IFN-β(B) 및 IL-10(C) 사이토카인 분비를 세포계측 비드 어레이를 사용하여 상청액에서 정량화했다.
도 11. pDC를 유도하기 위한 추가 TF 후보. Stat1(A) 및 Tsc22d1(B)은 cDC1 및 cDC2와 비교한 경우 pDC가 풍부하다. 이뮤놀로지컬 게놈 프로젝트에서 이용 가능한 데이터로부터 추출한 유전자 발현 프로파일.
도 12. 추가 pDC 유도 TF와 IRF8 및 SPIB와의 조합은 Clec9a 리포터 활성화 및 MHC-II 표면 발현의 효율성을 증가시킨다. (A) Clec9a 리포터 활성화 및 (B) M2rtTA(M2), IRF8+SPIB 단독으로 또는 STAT1 또는 TSC22D1과의 조합에 의해 형질도입된 MEF의 MHC-II 발현의 유세포 분석. 유세포 분석은 5일차에 수행했다. M2rtTa-형질도입된 세포를 대조군으로 포함시켰다.
도 13. 유도된 pDC는 TLR7 및 TLR9 자극시에 유형 I 인터페론을 분비한다. MEF는 M2rtTA, IRF8 및 SPIB 단독으로 또는 STAT1 및 TSC22D1과의 조합에 의해 형질도입되고, 독시사이클린의 첨가 후 9일차에 tdTomato+ 세포를 선별했다. 정제된 tdTomato+ 세포는 TLR7(R848) 및 TLR9(CpG ODN 1668)의 트리거와 함께 밤새 인큐베이팅하고, IFN-α(A), IFN-β(B) 및 IL-10(C) 사이토카인 분비가 세포계측 비드 어레이를 사용하여 상청액에서 정량화되었다.
도 14. 유도된 pDC는 세포 표면에서 CD45를 발현한다. 5일차에, M2rtTA, PIB(PU.1, IRF8 및 BATF3), IRF8+SPIB 단독 또는 개별 pDC-유도 TF와의 조합에 의해 형질도입된 MEF의 CD45 발현의 유세포 분석. M2rtTa(M2)-형질도입된 세포를 대조군으로 포함시켰다.
도 15. 유도된 pDC는 TLR7 및 TLR9 자극시에 프로-염증성 사이토카인과 케모카인을 분비한다. MEF는 M2rtTA, IRF8 및 SPIB 단독으로, 또는 ARID4A, BCL11A, CBFA2T3, ETS1, HOXA5, STAT1, TCF4, TCF12 및 TSC22D1과의 조합에 의해 형질도입하고, tdTomato+ 세포는 독시사이클린 첨가 후 9일차에 선별했다. 정제된 tdTomato+ 세포는 TLR7(R848) 및 TLR9(CpG ODN 1668)와 함께 밤새 인큐베이팅하고, IL-6(A), TNF-α(B), CCL5(C) 및 CXCL10(D) 사이토카인 분비는 세포계측 비드 어레이를 사용하여 상청액에서 정량화했다.
본 개시는, 세포를 pDC 또는 인터페론 유형 I-생산 세포로 재프로그래밍하기 위한 조성물, 핵산 작제물, 벡터, 방법 및 이의 키트에 관한 것이다. 목적은 단리된/합성 전사 인자를 도입 및 발현함으로써 분화된, 다분화능 또는 다능성 줄기 세포로부터 항바이러스 및 항종양 반응을 유도하는 능력을 갖는 pDC 및 인터페론 유형 I 생산 세포를 생산하는 것이다. 보다 구체적으로, 본 개시는 특정 전사 인자의 조합의 놀라운 사용을 수반하는 직접적 세포 재프로그래밍에 의해 pDC 또는 인터페론 유형 I-생산 세포를 수득하는 방법을 제공한다.
천연 DC는 모든 조직에 파종되는 골수 유래 세포이다. DC는 환경을 샘플링하고, 수집된 정보를 적응 면역 시스템의 세포(T 세포 및 B 세포)에 전달할 준비가 되어 있다. 항원이 삼켜지면, DC는 펩티드-주요 조직적합성 복합체(MHC) 분자 복합체의 형태로 처리된 항원을 림프 조직의 나이브(즉, 항원 미경험) T 세포에 제시함으로써 면역 반응을 개시한다. DC는, 형질세포양 DC(pDC), 및 cDC 유형 1(cDC1s) 및 유형 2(cDC2s)로 추가로 세분화될 수 있는 종래형 또는 고전적 DC(cDC)의 2개의 주요 서브세트로 분할할 수 있다(도 1). pDC는 통상 둥근 형태와, 활성화 후에 상향조절되는 낮은 수준의 MHC-II 발현을 특징으로 한다. 활성화 후, pDC는 통상 공자극 분자 및 MHC 분자를 과발현할 뿐만 아니라, 다수의 T 및 B 림프구 반응, 즉 종양 괴사 인자(TNF)-α, IFN-α, IFN-β, IL-12, IL-6, 및 CCL5 및 CXCL10 등의 케모카인의 개시 및/또는 증강에 관여하는 다양한 사이토카인 및 케모카인을 분비한다. pDC는 높은 수준의 핵산 감지 톨-유사 수용체(TLR) TLR7 및 TLR9를 발현한다. TLR7 또는 TLR9 자극은 pDC에 의한 병원체 유래의 핵산의 검출 및 대량의 유형 I 인터페론, 즉 IFN-α 및 IFN-β의 생성을 가능하게 한다. 활성화된 pDC는 사이토카인을 적극적으로 생성하고 항원 제시 및 교차 제시를 모두 수행할 수 있지만, 이러한 기능적 특징이 동일한 세포에 의해 수행되는지 또는 기능적으로 특화된 별개의 pDC 서브세트에 의해 수행되는지의 여부는 여전히 불분명하다. cDC는 일반적으로 주요 조직적합성 복합체 클래스 II 분자(MHC-II), 공-자극 분자(예: CD80/86 및 CD40), 인테그린 CD11c의 높은 발현 및 비림프계로부터 림프 기관으로 이동하고 나이브 T 세포를 자극하는 이들의 우수한 능력에 의해 식별된다. CLEC9A로도 공지된 DNGR-1은 마우스에서 사멸 세포-연관 항원에 대한 세포독성 T 림프구 반응(CTL)의 교차-프라이밍을 조장하는 괴사 세포에 대한 수용체이다. DNGR-1은 마우스 cDC1, cDC2 및 pDC에 의해 높은 수준으로 선택적으로 발현되고, 이는 세포 사멸 후에 노출된 세포내 리간드의 인식에 관여한다. 최근, Clec9a의 발현은, 림프 조직에서 종래의 또는 형질세포양 DC 계열 및 이들의 자손에 관여하는 DC 전구체(CDP)의 식별을 가능하게 하는 것으로 밝혀졌다[참조: Schraml et al., 2015].
본 명세서에 기재된 바와 같이, 분화된 세포를 유도된 pDC로 재프로그래밍할 수 있는 pDC 유도 인자의 성공적 동정은 다수의 방법으로 pDC 생물학에 대한 기본 이해를 발전시킬 수 있다. 이 작업은 pDC의 최소한 전사 네트워크에 대한 완전한 통찰을 제공한다. 또한, pDC 유도 인자의 동정은 pDC 상태가 어떻게 확립되고 주요 규제 기구가 어떻게 도입되는지를 이해할 수 있는 전례 없는 기회를 제공한다.
전사 인자(TF)는 발생 중의 모든 세포 유형의 사양에서 중요한 역할을 한다. TF 매개 재프로그래밍을 사용한 직접 재프로그래밍 전략의 성공은 만능성 ES/iPS 세포 또는 다분화능 줄기 세포의 분화를 이러한 인자를 사용하여 특정 운명으로 지시하는 것이 동등하게 타당하다는 것을 나타낸다. 따라서, 본 명세서에서 동정된 pDC-유도 인자를 사용하여, DC-풍부 TF의 발현에 의한 ES/iPS 세포의 결정적 DC 운명으로의 지시된 분화가 달성될 수 있다. 추가로, 본 명세서에서 동정된 pDC-유도 인자를 사용하여, DC-풍부 TF의 발현에 의한 결정적 DC 운명으로의 다분화능 조혈 줄기 세포 및 전구 세포의 지시된 분화가 달성될 수 있다.
전형적으로, pDC-유도 인자, 예를 들면, DNA 또는 RNA, 또는 이의 작제물을 코딩하는 핵산은, 바이러스 벡터를 사용하거나, 또는 바이러스 벡터 없이, 1회 또는 반복된 형질도입 또는 형질감염을 통해 세포 내로 도입되고, 유전자 산물의 발현 및/또는 RNA 분자의 번역은 본 명세서에 기재된 바와 같이 형태학적, 생화학적 및 기능적으로 pDC와 유사한 세포를 생성한다. 적절한 항원으로 프라이밍한 후에 이러한 유도된 pDC는 면역계의 효과기(effector) 세포(마크로파지, T 세포, B 세포, NK 세포)를 포획, 처리 및 제시하고, 유형 I IFN을 분비하여, 바이러스 감염 및 암에 대한 항원-특이적 면역 반응을 유도하는 능력을 갖는다(도 2).
본 개시의 한 양태는 암 세포(원위치 또는 생체외)에서 TF를 사용하거나, 또는 TF의 조합을 사용하여, 이들에게 유형 I IFN을 분비시켜, 이들 자신의 항원을 면역 세포에 제시하고, 종양 미소환경 내에서 다른 전염증성(pro-inflammatory) 사이토카인 및 화학유발물질을 분비시키게 하는 것이다. 이 방법은 암 회피 메커니즘을 우회하고, 종양 면역원성을 증가시키기 때문에, 항암 면역 요법의 임상 결과를 증가시키는 실행 가능한 전략을 나타낸다.
형질세포양 DC는, cDC1 및 cDC2 및 기타 관련 단핵 세포와 비교하는 경우, Tlr7 및 Tlr9를 특이적으로 발현한다(도 3). TLR7 및 TRL9 수용체는 pDC가 바이러스 DNA를 감지하고, 유형 I IFN을 분비함으로써 반응하도록 한다. 형질세포양 DC 및 cDC1은 Clec9a 및 Irf8을 발현한다.
일 실시형태에서, cDC1 및 cDC2와 비교하는 경우, 형질세포양 DC에서 이들의 특이적 농후화 유전자 발현으로 인해 22개의 후보 TF가 선택되었다(도 4). 22개의 후보 TF는 재프로그래밍이 증명된 독시사이클린(Dox) 유도성 렌티바이러스 벡터에서 개별적으로 클로닝되었다.
일 실시형태에서, 세포 재프로그래밍에 의한 pDC-유도 TF 및 pDC-유도 TF 조합의 효과를 스크리닝하기 위해, DC-특이적 리포터(Clec9a-Cre X R26-stop-tdTomato)를 보유하는 마우스 배아 섬유아세포(MEF)를 사용하여, DC 특이적 Clec9a-tomato 리포터를 활성화하는 pDC 유도 TF의 능력을 스크리닝했다(도 4). Clec9a-tomato 리포터 마우스에서, tdTomato 형광 단백질은 CDP, pre-DC, cDC 및 pDC에 의해 독점적으로 발현된다[참조: Schraml et al., 2015]. 배양 중의 마크로파지, 기타 면역 계통 또는 단핵구 유래 DC는 Clec9a를 발현하지 않기 때문에, 리포터 또는 tdTomato 단백질의 발현을 활성화하지 않는다(도 3). Clec9a 리포터 마우스로부터 단리된 비장 세포를 분석하고, 이는 pDC 세포(CD11clow BST2+ B220+ SiglecH+ 세포에 게이팅됨)의 92.4%가 tdTomato 형광 단백질을 발현하는 것을 확인했다(도 5).
이중 유전자도입 Clec9a-tdTomato 리포터 MEF는 E13.5 배아로부터 단리되었고, 형광 활성화 세포 선별(FACS)에 의해 조혈 계통에 이미 관여할 수 있는 오염된 tdTomato+ 또는 CD45+ 세포로부터 제외되었다.
일 실시형태에서, SPIB 및 IRF8은 Clec9a 활성화에 충분하다.
일 실시형태에서, Clec9a 리포터 MEF는, IRF8 단독 또는 2와 IRF8의 조합에 첨가하여 기타 21개의 후보 TF 중 하나로 형질도입시키고, tdTomato 발현에 대해 평가했다. 2개의 후보 TF 또는 IRF8 단독의 21개 조합으로 형질도입한 후, Dox를 첨가하고 나서 5일 후에 tdTomato+ 세포의 출현이 관찰되었다(도 6). IRF8과 SPIB의 조합은 tdTomato+ 세포의 5%를 생성했고, 이는 IRF8과 SPIB가 리포터 활성화를 유도하기 위해 필요한 인자의 최소 조합인 것을 시사한다. TdTomato+ 세포는 대조군 M2rtTA 벡터에 의한 형질도입 후에도, IRF8 단독에 의한 형질도입 후에도 검출되지 않았다.
일 실시형태에서, 항원 제시 세포 마커 MHC-II는 IRF8 및 SPIB로 형질도입된 MEF의 대략 60%에서 발현된다(도 7).
일 실시형태에서, 잔류 20개의 후보 TF를 IRF8 및 SPIB와 함께 발현시키는 것의 영향을 평가했다(도 8). 시험된 20개의 TF로부터, HHEX, ID3, MEF2C 및 RUNX2가 생성된 tdTomato+ 세포 수에 악영향을 미치는 것이 관찰되었다. ARID5A, HDAC5, HOXA5, IKZF1, IKZF2, IKZF3, IKZF5, IRF7, MYB 및 STAT3의 첨가는 생성된 tdTomato+ 세포의 수에 영향을 미치지 않았다. BCL11A, CBFA2T3, CREB3L2, ETS1, TCF12 및 TCF4의 첨가는 생성된 tdTomato+ 세포의 수에 긍정적 영향을 미치고, 이는 리포터 활성화의 효율을 증가시킨다.
일 실시형태에서, Clec9a-tdTomato 리포터의 활성화가 항원 제시 기구의 중요한 구성요소인 MHC-II의 표면 발현에 반영되는지를 평가했다. 주목할 만하게, 8일차의 tdTomato+ 세포가 표면에서 MHC-II를 발현하는 것이 관찰되었다(도 9).
일 실시형태에서, MHC-II 표면 분자에 첨가하여, pDC는 T-세포 반응의 발달에 중요한 프로-염증성 기능을 갖는 사이토카인을 분비한다. 이러한 반응은 적어도 11개의 상이한 Toll-유사 수용체(TLR)를 트리거함으로써 개시될 수 있고, 이는 명확하게 보존된 미생물 또는 바이러스 구조의 특정 인식을 가능하게 한다. DC 구획 내에서, pDC는 TLR7 및 TLR9 트리거에 특이적으로 반응한다(도 3). TLR7(Resiquimod 또는 R848 사용) 및 TLR9(ODN 1668 사용) 자극으로 챌린지될 때에, 유도된 pDC가 사이토카인을 배지로 분비하는지의 여부를 조사했다(도 10). 유도된 pDC의 TLR 챌린지시에, 각 TF 조합에 의해 생성된 비자극된 세포와 비교하는 경우, IRF8 및 SPIB(16.6배), IRF8, SPIB 및 ARID5A(3.9배); IRF8, SPIB 및 BCL11A(14.8배); IRF8, SPIB 및 CBFA2T3(3.5배); IRF8, SPIB 및 ETS1(3.7배); IRF8, SPIB 및 TCF4(3.6배); IRF8, SPIB 및 TCF12(8.3배); 및 IRF8, SPIB 및 HOXA5(7.7배)로 재프로그래밍된 tdTomato+ 세포에 의한 IFN-α 분비의 증가가 관찰되었다. 유도된 pDC의 TLR 챌린지는 또한, IRF8 및 SPIB(1.5배); IRF8, SPIB 및 ARID5A(2.3배); IRF8, SPIB 및 BCL11A(2.3배); IRF8, SPIB 및 CBFA2T3(1.9배); IRF8, SPIB 및 ETS1(1.6배); IRF8, SPIB 및 TCF4(1.3배); IRF8, SPIB 및 TCF12(1.9배); 및 IRF8, SPIB 및 HOXA5(2.6배)로 재프로그래밍된 tdTomato+ 세포에 의한 IFN-β의 분비를 증가시켰다. 유도된 pDC의 TLR 자극에 의해, 항염증성 사이토카인 IL-10의 분비의 증가는 관찰되지 않았다. 중요하게도, TF의 PU.1, IRF8 및 BATF3(PIB) 조합에 의한 형질도입으로 수득된 tdTomato+ 세포는 TLR7 및 TLR9에 반응하지 않았고, IFN-α 및 IFN-β를 분비하지 않았다. 종합하면, 이러한 데이터는 Clec9a 리포터 활성화와 인터페론 분비 능력을 조합함으로써 직접 세포 재프로그래밍에 의해 pDC 또는 인터페론 유형 I 분비 세포를 유도할 수 있는 TF의 조합을 성공적으로 동정했음을 시사한다.
일 실시형태에서, cDC1 및 cDC2: STAT1 및 TSC22D1과 비교하는 경우의 형질세포양 DC에서 이들의 특이적 농후화 유전자 발현으로 인해, 2개의 첨가 후보 TF가 선택되었다(도 11). 이 2개의 TF는 동일한 재프로그래밍으로 증명된 독시사이클린(Dox) 유도성 렌티바이러스 벡터에서 개별적으로 클로닝되었고, IRF8 및 SPIB와 조합하여 시험되어, Clec9a-tdTomato 리포터 활성화를 유도하는 능력에 접근했다(도 12). 흥미롭게도, IRF8 및 SPIB의 조합에 STAT1 또는 TSC22D1을 첨가하면, IRF8 및 SPIB 단독과 비교하여, Clec9a 리포터의 활성화가 증가했다(도 12a). IRF8, SPIB 및 STAT1, 및 IRF8, SPIB 및 TSC22D1에 의해 생성된 유도된 pDC는 또한 세포 표면에서 MHC-II 분자를 발현했고(도 12b), 이는 pDC 운명의 획득을 서포트한다.
일 실시형태에서, 유도된 pDC는 TLR7/9로 챌린지시키고, IRF8 및 SPIB(도 13a)에 의해 생성된 유도된 pDC와 비교하는 경우, IRF8, SPIB 및 STAT1(1.3배) 및 IRF8, SPIB 및 TSC22D1(4.8배)로 재프로그래밍된 tdTomato+ 세포에 의한 IFN-α의 분비의 증가가 관찰되었다. STAT1 또는 TSC22D1의 첨가는 또한, IRF8 및 SPIB 유도 세포와 비교하여, IRF8, SPIB 및 STAT1(1.3배) 및 IRF8, SPIB 및 TSC22D1(4.1배)로 재프로그래밍된 tdTomato+ 세포에 의한 IFN-β의 분비를 증가시켰다(도 13b). IRF8, SPIB 및 STAT1, 및 IRF8, SPIB 및 TSC22D1에 의해 생성된 유도 pDC는 항염증성 사이토카인 IL-10을 분비할 수 없었다. 이러한 데이터는 IRF8, SPIB 및 STAT1, 및 IRF8, SPIB 및 TSC22D1이 유도된 pDC 운명에 대한 재프로그래밍, 및 유형 I-인터페론을 분비하는 능력을 유도할 수 있음을 서포트한다.
일 실시형태에서, 조혈 마커 CD45의 표면 발현은 또한 pDC의 독특한 특징이다. pDC 유도 인자의 조합이 CD45의 표면 발현을 유도할 수 있는지의 여부를 조사했다. CD45는 IRF8 및 SPIB로 생성된 유도된 pDC의 1.79±0.33%로 발현된다. 놀랍게도, IKZF1이 IRF8 및 SPIB와 조합되면, CD45+의 집단은 최대 10.16±0.91% 증가한다(5.6배 증가).
일 실시형태에서, pDC에서 TLR7 및 TLR9에 의한 바이러스 또는 자가 핵산의 인식은 TLR7 및 TLR9가 이들의 리간드와 조우하는 구획의 유형에 의존하는 2개의 대체 경로를 유도한다. MYD88-IRF7 경로는 유형 I 인터페론 분비를 유발하는 반면, MYD88-NF-κB 경로는 프로-염증성 사이토카인과 케모카인을 생성한다. 이어서, TLR7/9 자극시에, 유도된 pDC가 추가 사이토카인을 분비하는지를 조사했다(도 15). 실제로, IRF8 및 SPIB의 과발현에 의해 생성된 정제된 tdTomato+ 세포는 프로=염증성 사이토카인 IL-6 및 TNF-α 및 케모카인 CCL5 및 CXCL10을 분비한다. 중요하게는, STAT1, TCF12 또는 TSC22D1을 IRF8 및 SPIB 조합에 첨가하면, TLR 의존적 방식으로 IL-6, TNF-α, CCL5 및 CXCL10의 분비가 증가한다. 유도된 pDC의 TLR 챌린지는 IRF8, SPIB 및 STAT1(5.6배), IRF8, SPIB 및 TCF12(7.5배) 및 IRF8, SPIB 및 TSC22D1(3.5배)로 재프로그래밍된 tdTomato+ 세포에 의한 IL-6의 분비를 증가시켰지만, 유사한 증가가 TNF-α에서도 관찰되었다(각각 1.8, 3.1, 1.3배). IRF8, SPIB 및 STAT1(2.5배), IRF8, SPIB 및 TCF12(3.1배) 및 IRF8, SPIB 및 TSC22D1(2.4배)로 재프로그래밍된 tdTomato+ 세포에 의한 케모카인 CCL5의 분비는 TLR 챌린지시에 증가했다. CXCL10에 관해서는, IRF8, SPIB 및 TCF12, IRF8, SPIB 및 TSC22D1의 과발현에 의해 생성된 유도된 pDC도 TLR 자극에 의한 분비를 각각 2.8배 및 1.7배 증가시켰다. 종합하면, 이 데이터는 2개의 세포내 경로를 통해 TLR7 및 9 자극에 반응하여, 유형 I 인터페론 분비 및 프로-염증성 사이토카인 및 케모카인을 유도하는 능력을 갖는 관련 없는 세포 유형에서 pDC를 유도하기에 충분한 TF 조합을 성공적으로 동정했음을 서포트한다.
일 실시형태에서, 각각의 후보 TF의 코딩 영역은 TF의 발현이 테트라사이클린 오퍼레이터 및 최소 CMV 프로모터의 조절하에 있는 유도성 렌티바이러스 pFUW-TetO 벡터 내로 개별적으로 클로닝되었다. 구성적으로 활성 인간 유비퀴틴 C 프로모터(FUW-M2rtTA)의 조절하에 역 테트라사이클린 트랜스활성화제 M2rtTA를 함유하는 전술한 렌티바이러스 벡터를 조합하여 사용했다. 인간 배아 신장(HEK) 293T 세포에 TF 코딩 플라스미드, 패키징 작제물 및 VSV-G 엔벨로프 단백질의 혼합물을 형질감염시켰다. 바이러스 상청액을 36, 48 및 60시간 후에 수거하고, 여과(0.45μm, Corning)하고, 아미콘(Amicon) 초원심분리 필터(Millipore)로 신선한 또는 40배 농축하여 사용했다.
일부 실시형태에서, 서열 목록에 제공된 서열에 의해 코딩된 참조 폴리펩티드와 동일 또는 유사한 활성을 갖는 폴리펩티드 변이체 또는 패밀리 구성원을 본 명세서에 기재된 조성물, 방법 및 키트에서 사용할 수 있다. 일반적으로, 본 명세서에 기재된 조성물, 방법 및 키트에 사용하기 위한 pDC-유도 인자를 코딩하는 특정 폴리펩티드의 변이체는, 본 명세서에 기재되고 당업자에게 공지된 서열 정렬 프로그램 및 파라미터에 의해 결정되는 바와 같이, 특정 참조 폴리뉴클레오티드 또는 폴리펩티드에 대해 적어도 약 95%, 적어도 약 96%, 적어도 약 97%, 적어도 약 98%, 적어도 약 99%의 서열 동일성을 갖는다.
일 실시형태에서, 호모 사피엔스 인터페론 조절 인자 8(IRF8), mRNA(서열번호 1), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈이 또한 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 Spi-B(SPIB), mRNA(서열번호 3), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈도 또한, 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 AT-풍부 상호작용 도메인 5A(ARID5A), mRNA(서열번호 5), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈도 당연히 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 고려된다.
일 실시형태에서, 호모 사피엔스 BAF 크로마틴 리모델링 복합체 서브세트(BCL11A), mRNA(서열번호 7), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈이 또한 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 CBFA2/RUNX1 파트너 전사 코-리프레서 3(CBFA2T3), mRNA(서열번호 9), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈도 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 CAMP 반응성 요소 결합 단백질 3 유사 2(CREB3L2), mRNA(서열번호 11), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈도 당연히 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 ETS 프로토-온코진 1(ETS1), mRNA(서열번호 13), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈이 또한 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 호메오박스 A5(HOXA5), mRNA(서열번호 19), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈도 당연히 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 IKAROS 패밀리 징크 핑거 1(IKZF1) mRNA(서열번호 23), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈이 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 신호 전달 및 전사 활성화제 1(STAT1), mRNA(서열번호 45), 및 동일한 아미노산을 코딩하는 코돈-최적화된 또는 상이한 코돈은 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 전사 인자 4(TCF4), mRNA(서열번호 41), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈도 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 전사 인자 12(TCF12), mRNA(서열번호 43), 및 동일한 아미노산을 코딩하는 코돈 최적화된 또는 상이한 코돈도 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
일 실시형태에서, 호모 사피엔스 TSC22 도메인 패밀리 단백질 1(TSC22D1), mRNA(서열번호 47), 및 동일한 아미노산을 코딩하는 코돈-최적화된 또는 상이한 코돈은 본 명세서에 기재된 핵산에 대한 참조에 의해 커버되는 것으로 당연히 고려된다.
본 명세서에 제공된 조성물, 벡터, 작제물, 방법 및 키트의 일부 실시형태에서, 섬유아세포 또는 조혈 계열 세포, 다분화능 줄기 세포, 유도 다능성 줄기 세포, 암 또는 종양 세포 등의 개시 체세포로부터 pDC를 생성하기 위해 사용 또는 선택되는 pDC 유도 인자의 수는 적어도 2개이다. 일부 실시형태에서, 사용 또는 선택된 pDC-유도 인자의 수는 적어도 3개, 적어도 4개, 적어도 5개, 적어도 6개, 적어도 7개, 적어도 8개, 적어도 9개, 적어도 10개, 적어도 11개, 적어도 12개, 적어도 13개, 적어도 14개, 적어도 15개, 적어도 16개, 적어도 17개, 적어도 18개, 적어도 19개, 적어도 20개, 적어도 30개, 적어도 33개, 적어도 35개, 적어도 40개 또는 그 이상이다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트의 일부 실시형태에서, IRF8, SPIB, ARID5A, BCL11A, CBFA2T3, CREB3L2, ETS1, HOXA5, IZKF1, TCF4, TCF12 및 TSC22D1 등의 pDC-유도 인자(들)를 코딩하는 핵산 서열 또는 작제물은, 표준 분자 생물학 기술을 사용하여 세포의 형질감염에 적합한 발현 벡터에 삽입 또는 작동 가능하게 연결된다. 본 명세서에 사용된 바와 같이, "벡터"는, 본 명세서에 기재된 핵산 작제물 또는 치환 카세트 등의 삽입된 뉴클레오티드 서열에 유용한 생물학적 또는 생화학적 특성을 제공하는 dsDNA 분자 등의 핵산 분자를 지칭한다. 예에는 플라스미드, 파지, 자가 복제 서열(ARS), 중심체 및 시험관내 또는 숙주 세포에서 복제 또는 복제될 수 있거나, 숙주 세포 내의 목적하는 위치로 목적하는 핵산 세그먼트를 운반할 수 있는 기타 서열이 포함된다. 벡터는 하나 이상의 제한 엔도뉴클레아제 인식 부위(유형 I, II, III 및 IV)를 가질 수 있고, 여기에는 벡터의 본질적 생물학적 기능의 손실 없이 결정 가능한 방식으로 서열을 절단될 수 있고, 핵산 단편은 이의 복제 및 클로닝을 초래하기 위해 스플라이싱되거나 삽입될 수 있다. 벡터는 또한 2개의 핵산 분자 사이에서 핵산 서열의 교환을 가능하게 하는 하나 이상의 재조합 부위를 포함할 수 있다. 벡터는 추가로, 예를 들면, PCR, 전사 및/또는 번역 개시 및/또는 조절 부위, 재조합 신호, 레플리콘, 추가의 선택가능한 마커 등을 위한 프라이머 부위를 제공할 수 있다. 벡터는, 벡터를 사용한 형질전환된 세포의 동정에 사용하기에 적합한 하나 이상의 선택가능한 마커를 추가로 포함할 수 있다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트의 일부 실시형태에서, 발현 벡터는 바이러스 벡터이다. 일부 바이러스 매개 발현 방법은 레트로바이러스, 아데노바이러스, 렌티바이러스, 파라믹소비리다에, 랍도바이러스, 알파바이러스, 플라바이러스, 헤르페스 바이러스, 폭스 바이러스 및 아데노-연관 바이러스(AAV) 벡터를 사용하고, 이러한 발현 방법은 유전자 전달에 사용되어 왔으며, 당해 기술분야에 공지되어 있다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트의 일부 실시형태에서, 바이러스 벡터는 레트로바이러스이다. 레트로바이러스는 유전자 전달을 위한 편리한 플랫폼을 제공한다. 선택된 유전자는 당해 기술분야에 공지된 기술을 사용하여 벡터에 삽입되고, 레트로바이러스 입자에 패키징될 수 있다. 이어서, 재조합 바이러스는 단리되어 생체내 또는 생체외에서 대상체의 표적 세포로 전달될 수 있다. 다수의 레트로바이러스 시스템이 기재되어 있다[참조: 예를 들면, U.S. Pat. No. 5,219,740; Miller and Rosman (1989) BioTechniques 7:980- 90; Miller, A. D. (1990) Human Gene Therapy 1:5-14; Scarpa et al. (1991) Virology 180:849- 52; Burns et al. (1993) Proc. Natl. Acad. Sci. USA 90:8033-37; Boris-Lawrie and Temin (1993) Curr. Opin. Genet. Develop. 3:102-09]. 본 명세서에 기재된 조성물, 벡터, 방법 및 키트의 일부 실시형태에서, 레트로바이러스는 복제 결핍되어 있다. 레트로바이러스 벡터 시스템은 5' 및 3' LTR 및 패키징 신호를 포함하는 최소 벡터가 벡터 패키징, 감염 및 표적 세포로의 통합을 가능하게 하기에 충분하다는 사실을 이용하고, 단, 바이러스 구조 단백질은 패키징 세포에서 트랜스로 공급된다. 유전자 전달을 위한 레트로바이러스 벡터의 기본적 이점에는 대부분의 세포 유형에서 효율적 감염 및 유전자 발현, 표적 세포 염색체 DNA로의 정확한 단일 카피 벡터의 통합 및 레트로바이러스 게놈 조작의 용이성이 포함된다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트의 일부 실시형태에서, 바이러스 벡터는 아데노바이러스 기반 발현 벡터이다. 숙주 게놈에 통합되는 레트로바이러스와는 달리, 아데노바이러스는 염색체외에 존속하고, 따라서 삽입 돌연변이유발과 관련된 위험을 최소화한다[참조: Haj-Ahmad and Graham (1986) J. Virol. 57:267-74; Bett et al. (1993) J. Virol. 67:5911-21; Mittereder et al. (1994) Human Gene Therapy 5:717- 29; Seth et al. (1994) J. Virol. 68:933-40; Barr et al. (1994) Gene Therapy 1:51-58; Berkner, K. L. (1988) BioTechniques 6:616-29; and Rich et al. (1993) Human Gene Therapy 4:461-76]. 아데노바이러스 벡터는 다양한 세포를 감염시키고, 광범위한 숙주 범위를 갖고, 높은 감염 효율을 나타내고, 이종 유전자를 높은 수준으로 직접 발현하고, 생체내에서 이러한 유전자의 장기간 발현을 실현한다. 바이러스는 무세포 비리온으로서 완전히 감염성이므로, 생산자 세포주의 주입은 필요하지 않다. 안전성과 관련하여, 아데노바이러스는 중증의 인간 병리와 관련이 없고, 바이러스로부터 유래하는 재조합 벡터는 바이러스 게놈의 초기 영역 1("E1")의 결실에 의해 복제 결함이 될 수 있다. 아데노바이러스는 또한 비교적 용이하게 대량으로 생산될 수 있다. 본 명세서에 기재된 조성물, 벡터, 방법 및 키트에 사용하기 위한 아데노바이러스 벡터는, 혈청형 2, 5, 12, 40 및 41 등의 아데노바이러스의 40개 초과의 혈청형 균주를 포함하지만 이들로 한정되지 않는 다양한 아데노바이러스 혈청형 중 임의의 것으로부터 유래할 수 있다. 본 명세서에서 사용된 아데노바이러스 벡터는 바람직하게는 복제-결핍이고, 적절한 프로모터에 작동 가능하게 연결된 목적 pDC-유도 인자를 함유한다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트의 일부 실시형태에서, IRF8, SPIB, ARID5A, BCL11A, CBFA2T3, ETS1, HOXA5, IKZF1, STAT1, TCF4, TCF12 및 TSC22D1 등의 pDC-유도 인자(들)를 코딩하는 핵산 서열은 하나 이상의 유도성 렌티바이러스 벡터를 사용하여 도입 또는 전달된다. 하나 이상의 유도성 렌티바이러스 벡터를 사용하여 전달되는 pDC-유도 인자의 발현 조절은, 일부 실시형태에서, 유도성 프로모터의 조절하에 또는 이에 작동적으로 연결된 발현 벡터 중에 적어도 하나의 pDC-유도 인자를 갖는 세포를 유도성 조절제(예: 독시사이클린) 또는 기타 유도제와 접촉시킴으로써 달성될 수 있다. 일부 유형의 유도성 렌티바이러스 벡터를 사용하는 경우, 이러한 세포를 유도제와 접촉시키면, pDC-유도 인자의 발현이 유도되는 반면, 조절제의 제거는 발현을 억제한다. 다른 유형의 유도성 렌티바이러스 벡터를 사용하는 경우, 조절제의 존재는 발현을 억제하는 반면, 조절제의 제거는 발현을 가능하게 한다. 본 명세서에 사용된 바와 같이, 용어 "발현의 유도"는, 예를 들면, 유도제의 존재하에, 또는 세포에서 유전자의 내인성 발현을 유발하는 또는 하나 이상의 약제 또는 인자의 존재하에 유도성 바이러스 벡터에 의해 코딩되는 pDC-유도 인자 등의 유전자의 발현을 지칭한다.
본 명세서에 기재된 양태의 일부 실시형태에서, 독시사이클린(Dox) 유도성 렌티바이러스 시스템이 사용된다. 레트로바이러스와는 달리, 렌티바이러스는 정지 세포를 형질도입할 수 있기 때문에, 다양한 조혈 세포 유형을 형질도입할 수 있다. 예를 들면, pFUW-tetO 렌티바이러스 시스템은 1차 조혈 전구 세포를 고효율로 형질도입하는 것으로 밝혀졌다.
본 명세서에 기재된 방법의 일부 실시형태에서, IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4), ARID5A(서열번호 5, 서열번호 6), BCL11A(서열번호 7, 서열번호 8), CBFA2T3(서열번호 9, 서열번호 10), CREB3L2(서열번호 11, 서열번호 12), ETS1(서열번호 13, 서열번호 14), HDAC5(서열번호 15, 서열번호 16), HHEX(서열번호 17, 서열번호 18), HOXA5(서열번호 19, 서열번호 20), ID3(서열번호 21, 서열번호 22), IKZF1(서열번호 23, 서열번호 24), IKZF2(서열번호 25, 서열번호 26), IKZF3(서열번호 27, 서열번호 28), IKZF5(서열번호 29, 서열번호 30), IRF7(서열번호 31, 서열번호 32), MEF2C(서열번호 33, 서열번호 34), MYB(서열번호 35, 서열번호 36), RUNX2(서열번호 37, 서열번호 38), STAT3(서열번호 39, 서열번호 40), TCF4(서열번호 41, 서열번호 42), TCF12(서열번호 43, 서열번호 44), STAT1(서열번호 45, 서열번호 46) 및 TSC22D1(서열번호 47, 서열번호 48) 등의 pDC-유도 인자(들)를 코딩하는 핵산 서열은 비통합 벡터(예: 아데노바이러스)를 사용하여 도입 또는 전달된다. 레트로바이러스 벡터 등의 통합 벡터는 숙주 세포 게놈에 도입되고, 정상 유전자 기능을 파괴할 가능성이 있지만, 비통합 벡터는 염색체외 전사에 의해 유전자 산물의 발현을 조절한다. 비통합 벡터는 숙주 게놈의 일부로 되지 않기 때문에, 비통합 벡터는 세포 집단에서 일시적으로 핵산을 발현하는 경향이 있다. 이것은 부분적으로 비통합 벡터가 종종 복제 결핍으로 된다는 사실에 기인한다. 따라서, 비통합 벡터는, (1) 숙주 게놈의 파괴 없음, 및 (2) 일시적 발현, 및 (3) 잔류하는 바이러스 통합 생성물 없음을 포함하지만 이들로 한정되지 않는, 레트로바이러스 벡터에 비해 몇몇 이점을 갖는다. 본 명세서에 기재된 방법에서 사용하기 위한 비통합 벡터의 일부 비제한적 예에는 아데노바이러스, 바큘로바이러스, 알파바이러스, 피코르나바이러스 및 백시니아 바이러스가 포함된다. 본 명세서에 기재된 방법의 일부 실시형태에서, 비-통합 바이러스 벡터는 아데노바이러스이다. 비통합 바이러스 벡터의 다른 이점에는 높은 역가로 이를 생성할 수 있는 능력, 생체내에서 이들의 안정성 및 숙주 세포의 효율적 감염이 포함된다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트에서 유도 pDC를 생성하는데 사용하기 위한 핵산 작제물 및 벡터는 일부 실시형태에서 세포의 양성 및 음성 선택을 위한 선택 마커를 코딩하는 하나 이상의 서열을 추가로 포함할 수 있다. 이러한 선택 마커 서열은 전형적으로 핵산 작제물의 도입이 없는 경우에 세포에서 통상 발견되지 않는 항생제에 대한 내성 또는 감수성의 특성을 제공할 수 있다. 선택가능한 마커를 항생제 등의 선택제와 조합 사용하여, 삽입된 핵산 작제물을 발현하는 세포를 배양에서 선택할 수 있다. 양성 선택 마커를 코딩하는 서열은 통상 항생제 내성을 제공하고, 즉, 양성 선택 마커 서열이 세포의 게놈에 존재하는 경우, 세포는 항생제 또는 작용제에 감수성이다. 음성 선택 마커를 코딩하는 서열은 통상 항생제 또는 작용제에 대한 감수성을 제공하고, 즉, 음성 선택 마커가 세포의 게놈에 존재하는 경우, 세포는 항생제 또는 작용제에 감수성이다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트에서 유도 pDC를 제조하는데 사용하기 위한 핵산 작제물 및 벡터는, 일부 실시형태에서, 작제물 또는 기타 벡터 유전자 요소의 조절, 발현, 안정화를 위한 다른 핵산 요소, 예를 들면, 프로모터, 인핸서, TATA-박스, 리보솜 결합 부위, IRES, 당업자에게 공지된 2A-유사 자가 절단 서열을 추가로 포함할 수 있다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트에서 유도 pDC를 제조하는데 사용하기 위한 핵산 작제물 및 벡터는 2A-유사 자가 절단 서열을 추가로 포함할 수 있다. 18-22개 아미노산 길이의 자가 절단 2A 펩티드는 프롤린과 글리신 잔기 사이의 '리보솜 스키핑'을 매개하고, 하류의 번역에 영향을 미치지 않으면서 펩티드 결합 형성을 억제한다. 이러한 펩티드는 복수의 단백질을 폴리단백질로서 코딩되도록 할 수 있고, 이는 번역시에 성분 단백질로 해리한다. 본 발명에 따라 사용될 수 있는 2A-유사 자가 절단 서열의 예에는, 구제역 바이러스(FMDV), 말과 비염 A 바이러스(ERAV), 토세아(Thosea) 아시그나 바이러스(TaV) 등의 아프토바이러스, 및 돼지과 테스코바이러스-1(PTV-1) 및 카디오바이러스, 예를 들면, 테일로바이러스(예: 테일러 뮤린 뇌척수염) 및 뇌심근염 바이러스를 포함하는 피코마비리다에 바이러스로부터의 것이 포함되지만, 이들로 한정되지 않는다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트의 일부 실시형태에서, IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4), ARID5A(서열번호 5, 서열번호 6), BCL11A(서열번호 7, 서열번호 8), CBFA2T3(서열번호 9, 서열번호 10), CREB3L2(서열번호 11, 서열번호 12), ETS1(서열번호 13, 서열번호 14), HOXA5(서열번호 19, 서열번호 20), IKZF1 (서열번호 23, 서열번호 24), TCF4(서열번호 41, 서열번호 42), TCF12(서열번호 43, 서열번호 44), STAT1(서열번호 45, 서열번호 46), 및 TSC22D1(서열번호 47, 서열번호 48) 등의 pDC-유도 인자(들)는 합성의 변형된 RNA로서 제공되거나, 또는 그 내용이 참조에 의해 그 전체가 본 명세서에 도입되는, 미국 특허 공개 제2012-0046346-A1호에 기재된 바와 같이 합성의 변형된 RNA로서 세포에 도입 또는 전달된다. 합성의 변형된 RNA를 사용하여 본 명세서에 기재된 방법에 따라 세포를 유도 pDC로 재프로그래밍하는 실시형태에서, 이 방법은 세포의 반복적 접촉을 포함하거나, 또는 예를 들면, 적어도 2, 적어도 3, 적어도 4, 적어도 5, 적어도 6, 적어도 7, 적어도 8, 적어도 9, 적어도 10, 적어도 11, 적어도 12, 적어도 13, 적어도 14, 적어도 15, 적어도 16, 적어도 17, 적어도 18, 적어도 19, 적어도 20, 적어도 25, 적어도 30, 또는 그 이상의 형질감염 등의 pDC-유도 인자를 코딩하는 합성의 변형된 RNA의 반복된 형질감염을 수반할 수 있다.
하나 이상의 변형된 뉴클레오시드에 추가하여, 본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트에 사용하기 위한 변형된 mRNA는 당업자에게 공지되어 있고 미국 특허 공개 제2012-0046346-A1호 및 제20120251618A1호 및 PCT 공개 WO 제2012/019168호에 기재된 임의의 추가 변형을 포함할 수 있다. 이러한 기타 성분에는, 예를 들면, 5' 캡(예: 5'-5'-트리포스페이트 구아닌-구아닌 결합을 함유하고, 이때 하나의 구아닌이 N7 메틸 그룹, 게다가 3'-O-메틸 그룹을 함유하는, 항-역 캡 유사체(Anti-Reverse Cap Analog; ARCA) 캡; 재조합 백시니아 바이러스 캡핑 효소 및 재조합 2'-O-메틸트랜스퍼라제 효소를 사용하여 생성된 캡, 이는 5'-최상위 뉴클레오티드와 구아닌 뉴클레오티드 사이에 표준 5'-5'-트리포스페이트 연결을 생성할 수 있고, 여기서 구아닌은 N7 메틸화를 함유하고, 최종적 5'-뉴클레오티드는 2'-O-메틸을 함유하여 Cap1 구조를 생성함); 폴리(A) 테일(예를 들면, 30개 초과의 뉴클레오티드 길이, 35개 초과의 뉴클레오티드 길이, 적어도 40개의 뉴클레오티드, 적어도 45개의 뉴클레오티드, 적어도 55개의 뉴클레오티드, 적어도 60개의 뉴클레오티드, 적어도 70개의 뉴클레오티드, 적어도 80개의 뉴클레오티드, 적어도 90개의 뉴클레오티드, 적어도 100개의 뉴클레오티드, 적어도 200개의 뉴클레오티드, 적어도 300개의 뉴클레오티드, 적어도 400개의 뉴클레오티드, 적어도 500개의 뉴클레오티드, 적어도 600개의 뉴클레오티드, 적어도 700개의 뉴클레오티드, 적어도 800개의 뉴클레오티드, 적어도 900개의 뉴클레오티드, 적어도 1000개의 뉴클레오티드, 또는 그 이상의 폴리-A 테일); 코작 서열; 3' 비번역 영역(3' UTR); 5' 비번역 영역(5' UTR); 핵산으로부터 절단될 수 있는 하나 이상의 인트론 뉴클레오티드 서열, 또는 이들의 임의의 조합이 포함된다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트에 사용하기 위한 변형된 mRNA는 내부 리보솜 진입 부위(IRES)를 추가로 포함할 수 있다. IRES는 유일한 리보솜 결합 부위로 작용하거나, mRNA의 복수의 리보솜 결합 부위 중 하나로서 기능할 수 있다. 하나 이상의 기능적 리보솜 결합 부위를 함유하는 mRNA는 리보솜에 의해 독립적으로 번역되는, 본 명세서에 기재된 pDC-유도 인자 등의 몇몇 펩티드 또는 폴리펩티드를 코딩할 수 있다("멀티시스트론 mRNA"). 핵산이 IRES와 함께 제공되는 경우, 추가로 임의로 제2 번역 가능한 영역이 제공된다. 본 발명에 따라 사용될 수 있는 IRES 서열의 예에는, 제한 없이, 피코르나바이러스(예: FMDV), 해충 바이러스(CFFV), 소아마비 바이러스(PV), 뇌근육염 바이러스(ECMV), 구제역 바이러스( FMDV), C형 간염 바이러스(HCV), 고전적 돼지과 열병 바이러스(CSFV), 뮤린 백혈병 바이러스(MLV), 시미안 면역 결핍 바이러스(SW) 또는 귀뚜라미 마비 바이러스(CrPV)가 포함되지만, 이들로 한정되지 않는다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트의 일부 실시형태에서, 합성의 변형된 RNA 분자는 적어도 하나의 변형된 뉴클레오시드를 포함한다. 본 명세서에 기재된 조성물, 벡터, 방법 및 키트의 일부 실시형태에서, 합성의 변형된 RNA 분자는 2개 이상의 변형된 뉴클레오시드를 포함한다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트의 일부 실시형태에서, 변형된 뉴클레오시드는 5-메틸시토신(5mC), N6-메틸아데노신(m6A), 3,2'-O-디메틸우리딘(m4U), 2-티오우리딘(s2U), 2' 플루오로우리딘, 슈도우리딘, 2'-O-메틸우리딘(Um), 2'데옥시우리딘(2'dU), 4-티오우리딘(s4U), 5-메틸우리딘(m5U), 2'-O-메틸아데노신(m6A), N6,2'-O-디메틸아데노신(m6Am), N6,N6,2'-O-트리메틸아데노신(m62Am), 2'-O-메틸시티딘(Cm), 7-메틸구아노신(m7G), 2'-O-메틸구아노신(Gm), N2,7-디메틸구아노신(m2,7G), N2,N2,7-트리메틸구아노신(m2,2,7G) 및 이노신(I)으로 이루어진 그룹으로부터 선택된다. 일부 실시형태에서, 변형된 뉴클레오시드는 5-메틸시토신(5mC), 슈도우라실, 또는 이들의 조합이다.
변형된 mRNA는 분자의 전체 길이를 따라 균일하게 변형될 필요는 없다. 상이한 뉴클레오티드 변형 및/또는 골격 구조는 핵산의 다양한 위치에 존재할 수 있다. 당업자는 핵산의 기능이 실질적으로 감소되지 않도록 뉴클레오티드 유사체 또는 기타 변형(들)을 핵산의 임의의 위치(들)에 배치할 수 있음을 이해할 것이다. 변형은 또한 5' 또는 3' 말단 변형일 수 있다. 핵산은 적어도 1개 및 최대 100% 변형 뉴클레오티드, 또는 적어도 50% 변형 뉴클레오티드, 적어도 80% 변형 뉴클레오티드, 또는 적어도 90% 변형 뉴클레오티드 등의 임의의 개재 퍼센티지를 함유할 수 있다.
본 개시의 일부 실시형태에서, 벡터 또는 작제물은, 파라믹소비리다에 벡터, 랍도바이러스 벡터, 알파바이러스 및/또는 플라비바이러스 입자, 또는 비-바이러스 벡터 또는 입자, 예를 들면, 네이키드 알파바이러스 또는 플라비바이러스 RNA 레플리콘 등의 복제 바이러스 벡터 또는 입자이다.
일부 실시형태에서, 분자 내의 소정의 뉴클레오시드의 각각의 출현이 변형되는 것이 바람직하지만, 절대적으로 필요한 것은 아니다(예를 들면, 각 시토신은 변형된 시토신, 예를 들면, 5-메틸시토신이고, 각각의 우라실은 변형된 우라실, 예를 들면, 슈도우라실 등이다). 예를 들면, 변형된 mRNA는 우라실 또는 시토신 등의 변형된 피리미딘을 포함할 수 있다. 일부 실시형태에서, 핵산 중의 우라실의 적어도 25%, 적어도 50%, 적어도 80%, 적어도 90% 또는 100%가 변형된 우라실로 치환된다. 동일한 뉴클레오시드의 상이한 발생은 소정 합성의 변형된 RNA 분자에서 상이한 방식으로 변형될 수 있다는 것이 또한 고려된다. 변형된 우라실은 단일의 고유한 구조를 갖는 화합물로 치환될 수 있거나, 또는 상이한 구조(예를 들면, 2, 3, 4 또는 그 이상의 고유한 구조)를 갖는 복수의 화합물로 치환될 수 있다. 일부 실시형태에서, 핵산 중의 시토신의 적어도 25%, 적어도 50%, 적어도 80%, 적어도 90% 또는 100%를 변형된 시토신으로 치환할 수 있다. 변형된 시토신은 단일의 고유한 구조를 갖는 화합물로 치환될 수 있거나, 또는 상이한 구조(예: 2, 3, 4 또는 그 이상의 고유한 구조)를 갖는 복수의 화합물로 치환될 수 있다(예: 5mC로서 변형된 일부 시토신, 2'-O-메틸시토신 또는 기타 시토신 유사체로 변형된 나머지). 이러한 다중-변형된 합성 RNA 분자는 모든 목적하는 변형된 뉴클레오시드를 포함하는 리보뉴클레오시드 블렌드 또는 혼합물을 사용함으로써 생성될 수 있고, 그 결과, RNA 분자가 합성될 때 목적하는 변형된 뉴클레오시드만이 pDC-유도 인자를 코딩하는 생성되는 RNA 분자에 도입된다.
특정 실시형태에서, 예를 들면, 단백질 생산의 정확한 타이밍이 요망되는 경우, 세포 내로 도입된 변형된 핵산을 세포내에서 분해하는 것이 바람직하다. 따라서, 본 명세서에 기재된 조성물, 벡터, 방법 및 키트의 일부 실시형태에서, 본 명세서에서 제공되는 것은 세포 내에서 지시된 방식으로 작용할 수 있는 분해 도메인을 포함하는 변형된 핵산이다.
유도된 pDC는 핵산(DNA 또는 RNA) 또는 아미노산 서열의 형태로 pDC-유도 인자의 전달에 의해 생성될 수 있는 것으로 이해되지만, 본 명세서에 기재된 조성물, 벡터, 방법 및 키트의 일부 실시형태에서, 유도된 pDC는, 예를 들면, 하나 이상의 pDC-유도 인자의 발현을 유도하는 소분자 또는 소분자 칵테일 등의 약제로 세포를 처리하는 것과 같은 기타 방법을 사용하여 유도될 수 있다.
본 명세서에 기재된 조성물, 벡터, 방법 및 키트를 사용하여 세포 내로 도입되거나, 또는 세포 집단에서 유도된 pDC-유도 인자의 발현의 검출은, 예를 들면, 웨스턴 블롯 분석, 면역세포화학 및 형광-매개 검출을 포함하는, 당업자에게 공지된 임의의 몇몇 기술에 의해 달성될 수 있다.
pDC-유도 인자의 소정 조합이 유도된 pDC를 생성했는지의 여부를 구별하기 위해, 일부 실시형태에서, 표면 항원의 차등적 발현 등의 하나 이상의 DC 활성 또는 파라미터를 측정할 수 있다. 본 명세서에 기재된 조성물, 벡터, 방법 및 키트를 사용한 유도된 DC의 생성은 바람직하게는, 예를 들면, CD45 및 MHC-II 등의 내인성 pDC에 특징적인 세포 표면 표현형의 출현을 야기한다.
DC는 기능적 거동에 의해 기타 면역 세포와 가장 확실하게 구별된다. DC 표현형의 기능적 측면, 또는 사이토카인을 분비하는 유도된 pDC의 능력 등의 DC 활성은 당해 기술분야에 공지된 일상적 방법을 사용하여 당업자에 의해 용이하게 결정될 수 있다. 본 명세서에 기재된 양태의 일부 실시형태에서, 재프로그래밍 인자를 동정하기 위한 기능적 검정을 사용할 수 있다. 예를 들면, 일부 실시형태에서, 사이토카인 분비는, 본 명세서에 기재된 조성물, 벡터, 방법 및 키트를 사용하여 생성된 유도된 pDC의 면역-조절 특성을 확인하기 위해 사용할 수 있다. 특히, TLR7 및 TLR9 경로를 통해 세포내 DNA에 반응하고, 유형 I 인터페론을 분비하는 능력은 pDC 기능을 특성화하는 데 특히 관련되어 있다.
본 명세서에 사용된 바와 같이, "세포 파라미터", "DC 파라미터" 또는 "사이토카인 분비"는 내인성 또는 천연 DC의 측정가능한 성분 또는 품질, 특히 정확하게 측정될 수 있는 성분을 지칭한다. 세포 파라미터는 세포의 표현형, 기능 또는 거동과 관련된 임의의 측정 가능한 파라미터일 수 있다. 이러한 세포 파라미터에는, 생존율, 세포 성장, 수용체, 이의 입체배좌 또는 번역후 변형을 포함하는 단백질, 지질, 탄수화물, 유기 또는 무기 분자, 핵산, 예를 들면, mRNA, DNA, 글로벌 유전자 발현 패턴 등의 세포 표면 결정인자 등의 마커의 하나 이상 또는 조합의 발현의 변화를 포함하지만 이들로 한정되지 않는 DC 또는 DC 집단의 특성 및 마커의 변화가 포함된다. 이러한 세포 파라미터는 당업자에게 공지된 다양한 검정 중 임의의 것을 사용하여 측정할 수 있다. 예를 들면, 생존율 및 세포 성장은 트리판 블루(Trypan blue) 배제, CFSE 희석 및 3H-티미딘 도입 등의 검정에 의해 측정할 수 있다. 단백질 또는 폴리펩티드 마커의 발현은, 예를 들면, 유세포 분석 검정, 웨스턴 블롯 기술 또는 현미경 검사법을 사용하여 측정할 수 있다. 유전자 발현 프로파일은, 예를 들면, RNA 서열분석 방법론 및 정량적 또는 반정량적 실시간 PCR 검정을 사용하여 분석할 수 있다. 세포 파라미터는 기능적 파라미터 또는 기능적 활성을 나타낼 수도 있다. 대부분의 세포 파라미터는 정량적 판독치를 제공하지만, 일부 경우에는 반정량적 또는 정성적 결과가 허용될 수 있다. 판독치는 단일 결정치를 포함하거나, 평균치, 중앙치 또는 분산 등을 포함할 수 있다. 특징적으로, 파라미터 판독치 범위는 동일한 검정의 다양성으로부터 각 파라미터에 대해 수득할 수 있다. 변동성이 예상되고, 시험 파라미터의 각 세트에 대한 값 범위는, 단일 값을 제공하기 위해 사용되는 일반적 통계 방법을 사용한 표준 통계 방법을 사용하여 수득할 수 있다.
본 명세서에 기재된 조성물, 벡터, 방법 및 키트의 일부 실시형태에서, 추가 인자 및 약제를 사용하여, 유도된 pDC 재프로그래밍을 증강시킬 수 있다. 예를 들면, 후성유전학적 경로를 변경하는 인자 및 약제는 유도된 pDC로의 재프로그래밍을 용이하게 하기 위해 사용될 수 있다.
본질적으로, 임의의 1차 체세포 유형을 사용하여, 현재 기재된 조성물, 벡터, 방법 및 키트에 따라, 유도된 pDC를 생성하거나, 또는 유도된 pDC로 체세포를 재프로그래밍할 수 있다. 이러한 1차 체세포 유형에는 또한 유도 다능성 줄기 세포(iPS 세포) 등의 다능성 줄기 세포; 기타 다분화능 줄기 세포; 올리고능(oligopotent) 줄기 세포; 및 단능성 줄기 세포를 포함하는 기타 줄기 세포 유형이 포함된다. 본 명세서에 기재된 방법의 다양한 양태 및 실시형태에서 유용한 1차 체세포의 일부 비제한적 예에는 섬유아세포, 상피, 내피, 뉴런, 지방, 심장, 골격근, 조혈 세포 또는 면역 세포, 간, 비장, 폐, 순환 혈액 세포, 위장관, 신장, 골수 및 췌장 세포, 뿐만 아니라 이러한 세포가 유래하는 줄기 세포가 포함되지만, 이들로 한정되지 않는다. 세포는, 비장, 골수, 혈액, 뇌, 간, 폐, 장, 위장, 창자, 지방, 근육, 자궁, 피부, 비장, 내분비 기관, 골 등을 포함하지만, 이들로 한정되지 않는 임의의 체세포 조직으로부터 단리된 1차 세포일 수 있다. 용어 "체세포"는 일부 실시형태에서, 체세포가 불멸화되지 않는 한, 배양물에서 성장한 1차 세포를 추가로 포함한다. 세포가 시험관내 조건하에 유지되는 경우, 종래의 조직 배양 조건 및 방법을 사용할 수 있고, 이는 당업자에게 공지되어 있다. 다양한 1차 체세포에 대한 단리 및 배양 방법은 당업자의 능력의 범위 내에 있다.
이러한 양태 및 본 명세서에 기재된 이러한 모든 양태의 일부 실시형태에서, 체세포는 섬유아세포이다.
이러한 양태 및 본 명세서에 기재된 이러한 모든 양태의 일부 실시형태에서, 체세포는 조혈 계통 세포일 수 있다.
이러한 양태 및 본 명세서에 기재된 이러한 모든 양태의 일부 실시형태에서, 체세포는 암 세포 또는 종양 세포일 수 있다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트의 일부 실시형태에서, 재프로그래밍되거나, 유도된 pDC 세포로 제조되는 체세포는 조혈 기원의 세포이다. 본 명세서에 사용된 바와 같이, 용어 "조혈 유래 세포", "조혈 유래 분화 세포", "조혈 계통 세포" 및 "조혈 기원 세포"는 다분화능 조혈 줄기 세포(HSC)로부터 유래 또는 분화된 세포를 지칭한다. 따라서, 본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트와 함께 사용하기 위한 조혈 계통 세포에는 다분화능, 올리고능 및 계통-제한 조혈 전구 세포, 과립구(예: 전골수구, 호중구, 호산구, 호염기구), 적혈구(예: 망상적혈구, 적혈구), 혈소판(예: 거핵모세포, 혈소판-생성 거핵구, 혈소판), 단핵구(예: 단핵구, 마크로파지), 수지상 세포 및 림프구(예: T-세포 수용체(TCR)를 운반하는 T-림프구, 면역글로불린을 발현하고 항체를 생산하는 B-림프구 또는 B 세포, NK 세포, NKT 세포 및 선천성 림프구)가 포함된다. 본 명세서에 사용된 바와 같이, 용어 "조혈 전구 세포"는 조혈계의 2개 이상의 세포 유형으로 분화할 수 있는 다분화능, 올기고능 및 계통-제한된 조혈 세포를 지칭하고, 이들에는 과립구, 단핵구, 적혈구, 거핵구 및 림프구 B-세포 및 T-세포가 포함된다. 조혈 전구 세포는 다분화능 전구 세포(MPP), 일반적 골수 전구 세포(CMP), 일반적 림프 전구 세포(CLP), 과립구-단핵구 전구 세포(GMP) 및 전거핵구-적혈구 전구 세포를 포함한다. 계통 제한 조혈 전구 세포에는 거핵구-적혈구 전구 세포(MEP), ProB 세포, PreB 세포, PreProB 세포, ProT 세포, 이중-음성 T 세포, pro-NK 세포, 전과립구/마크로파지 세포, 과립구/마크로파지 전구세포(GMP) 세포 및 프로-비만 세포(ProMC)가 포함된다.
본 명세서에 기재된 조성물, 벡터, 방법 및 키트에 사용하기 위한 조혈 기원의 세포는 이러한 세포를 포함하는 것으로 공지된 임의의 공급원, 예컨대, 태아 조직, 제대혈, 골수, 말초혈액, 동원된 말초혈액, 비장, 간, 흉선, 림프 등으로부터 수득될 수 있다. 이들 공급원으로부터 수득된 세포는, 본 명세서에 기재된 유도된 pDC를 제조하기 위한 조성물, 벡터, 작제물, 방법 및 키트와 함께 사용하기 전에, 당업자에게 허용되는 임의의 방법을 사용하여 생체외에서 확장될 수 있다. 예를 들면, 세포는, 선별, 분획화, 처리하여 특정 세포 유형을 제거하거나, 달리는 당업자에게 허용되는 임의의 절차를 사용하여, 본 명세서에 기재된 방법에서 사용하기 위한 세포의 집단을 수득하기 위해 조작될 수 있다. 단핵 림프구는, 예를 들면, 미국 특허 제4,690,915호에 기재된 바와 같이 연속 유동 세포 분리기를 사용하여 반복된 림프구성분채집에 의해 수집할 수 있거나, 또는 CLP 방법의 친화성 정제 단계, 예컨대, 사이토미터를 사용하는 유세포 분석, 자기 분리, 또는 항체 또는 단백질 코팅된 비드의 사용, 친화성 크로마토그래피, 또는 고체-지지체 친화성 분리(특정 단백질 또는 단백질 유형의 발현 또는 발현의 결여에 따라 세포가 기질 상에 유지되는 경우), 또는 목적하는 세포 유형에 의해 특이적으로 발현된 하나 이상의 표면 항원에 대한 하나 이상의 항체를 사용한 배치식 정제를 사용하여 단리할 수 있다. 조혈 기원의 세포는 말초 혈액으로부터도 수득할 수 있다. 말초 혈액으로부터 세포를 채취하기 전에, 대상체를, 예를 들면, 과립구-콜로니 자극 인자 등의 사이토카인으로 처리하여 골수로부터 혈액 구획으로부터의 세포 이동을 촉진하고/하거나, 목적하는 집단의 활성화 및/또는 증식을 촉진시킬 수 있다. 예를 들면, 표면 단백질을 동정하는 데 적합한 임의의 방법을 사용하여, 불균일 집단으로부터 조혈 기원의 세포를 단리할 수 있다. 일부 실시형태에서, 림프구 등의 조혈 기원 세포의 클론 집단이 수득된다. 일부 실시형태에서, 조혈 기원의 세포는 클론 집단이 아니다.
추가로, 본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트의 다양한 양태 및 실시형태와 관련하여, 체세포는 임의의 포유동물 종으로부터 수득될 수 있고, 비제한적 예에는 뮤린, 소과, 유인원, 돼지과, 말과, 양과 또는 인간 세포가 포함된다. 일부 실시형태에서, 체세포는 인간 세포이다. 일부 실시형태에서, 세포는 비-인간 포유동물 등의 비-인간 생물로부터 유래한다.
일반적으로, 본 명세서에 기재된 유도된 pDC를 제조하는 방법은, 이용 가능하고 당업자에게 공지되어 있는 임의의 배양 배지에서 조혈 기원의 세포 등의 체세포를 배양 또는 확장시키는 것을 포함한다. 이러한 배지에는 둘베코 변형 이글 배지(Dulbecco's Modified Eagle's Medium®(DMEM)), DMEM F12 배지®, 이글 최소 필수 배지(Eagle's Minimum Essential Medium®), F-12K 배지®, 이스코브 변형된 둘베코 배지(Iscove's Modified Dulbecco's Medium®), RPMI-1640 배지® 및 DC의 배양 및 확장을 위한 혈청-비함유 배지가 포함되지만, 이들로 한정되지 않는다. 다수의 배지는, 나트륨의 유무에 관계없이, 저글루코스 제형으로도 이용할 수 있다. 본 명세서에 기재된 방법에서 사용되는 배지는 일부 실시형태에서 하나 이상의 면역자극성 사이토카인을 보충할 수 있다. 일반적으로 사용되는 성장 인자에는 G-CSF, GM-CSF, TNF-α, IL-4, IL-3, Flt-3 리간드 및 키트 리간드가 포함되지만 이들로 한정되지 않는다. 또한, 바람직한 실시형태에서, 면역자극성 사이토카인은 인터류킨(예를 들면, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-8, IL-9, IL-10, IL-12, IL-18, IL-19, IL-20), 인터페론(예: IFN-α, IFN-β, IFN-γ), 종양 괴사 인자(TNF), 형질전환 성장 인자-β(TGF-β), 과립구 콜로니 자극 인자(G-CSF), 마크로파지 콜로니 자극 인자(M-CSF), 과립구-마크로파지 콜로니 자극 인자(GM-CSF), Flt-3 리간드 및 키트 리간드로 이루어진 그룹으로부터 선택된다.
배양 중의 세포는 현탁액으로 유지되거나, 예를 들면, 세포외 매트릭스 성분 등의 고체 지지체에 부착시키거나, 피더 세포에 플레이팅할 수 있다. 본 명세서에 기재된 방법에 사용되는 세포는 일부 실시형태에서 유형 I 및 유형 II 콜라겐, 콘드로이틴 설페이트, 피브로넥틴, "수퍼피브로넥틴" 및 피브로넥틴-유사 중합체, 젤라틴, 폴리-D 및 폴리-L-리신, 트롬보스폰딘 및 비트로넥틴 등의 고체 지지체에 대한 이들의 부착을 촉진하는 추가의 인자를 필요로 할 수 있다. 일부 실시형태에서, 세포는 현탁 배양물에서의 성장에 적합하다. 현탁-적격 숙주 세포는 일반적으로 단분산이거나, 실질적인 응집 없이 느슨한 응집체로 성장한다. 현탁-적격 숙주 세포에는 적응 또는 조작 없이 현탁 배양에 적합한 세포(예: 조혈 기원의 세포, 예를 들면, 림프계 세포) 및 부착-의존성 세포(예: 상피 세포, 섬유아세포)의 변형 또는 적응에 의해 현탁-적격으로 된 세포가 포함된다.
본 명세서에 기재된 이러한 양태 및 모든 이러한 양태의 일부 실시형태에서, 단리된 유도된 pDC는 이를 필요로 하는 대상체에 투여하기 위한 약제학적으로 허용되는 담체를 추가로 포함한다.
또한, 본 명세서에는, 일부 양태에서, pDC-유도 조성물 및 벡터를 사용하여 암 세포 또는 감염성 병원체를 제거하기 위해 항원-특이적 면역 반응을 유도하기 위한 치료를 필요로 하는 대상체를 치료하는 방법, 및 본 명세서에 기재된 유도된 pDC를 제조하는 방법, 또는 pDC-유도 인자, pDC-유도 조성물 및 벡터의 임의의 조합을 사용하여 생성된 단리된 유도 pDC 및 이의 세포 클론을 사용하는 방법, 또는 본 명세서에 기재된 유도 pDC를 제조하는 방법이 제공된다. 이러한 치료 방법에서, 섬유아세포 또는 조혈 계통 세포 등의 체세포를 먼저 대상체로부터 단리할 수 있고, 단리된 세포는 본 명세서에 기재된 바와 같이 각각 발현 벡터 또는 합성 mRNA를 포함하는 pDC-유도 조성물로 형질도입 또는 형질감염된다. 이어서, pDC 유도 인자, pDC 유도 조성물 및 벡터, 또는 본 명세서에 기재된 유도 pDC 제조 방법의 임의의 조합을 사용하여 생성된 단리된 유도 pDC는 대상체에 대한 유도된 pDC의 전신 주사 등을 통해 대상체에게 투여될 수 있다.
또한, 본 명세서에는, 일부 양태에서, pDC-유도 조성물 및 벡터 및 본 명세서에 기재된 pDC-유도 인자의 임의의 조합을 사용하여 암 세포 또는 감염성 병원체를 제거하기 위해 항원-특이적 면역 반응을 유도하기 위한 치료를 필요로 하는 대상체를 치료하는 방법이 제공된다. 이러한 치료 방법에서, 암 세포는 본 명세서에 기재된 바와 같이 발현 벡터를 포함하는 pDC-유도 조성물로 형질도입된다. 암 세포는 먼저 대상체로부터 단리되고, 발현 벡터를 포함하는 pDC-유도 조성물로 형질도입되고, 이어서 전신 주사 등을 통해 대상체에게 투여될 수 있다. 또는, 암 세포는 바이러스 발현 벡터를 포함하는 pDC-유도 조성물을 사용하여 원위치 또는 생체내에서 형질도입될 수 있다.
본 명세서에 기재된 조성물, 벡터, 작제물, 방법 및 키트를 사용하여 생성된 재프로그래밍된 유도된 pDC는 본 명세서에 기재된 치료 방법의 일부 실시형태에서 직접 사용되거나 면역요법을 필요로 하는 대상체에게 투여될 수 있다. 따라서, 본 명세서에 기재된 방법의 다양한 실시형태는, 본 명세서에 기재된 임의의 조성물, 벡터, 방법 및 키트를 사용하여 생성된 유효량의 유도된 pDC 또는 유도된 pDC의 집단을 세포 요법을 필요로 하는 개체 또는 대상체에게 투여하는 것을 포함한다. 투여되는 세포 또는 세포 집단은 자가 집단일 수 있거나, 또는 하나 이상의 이종 공급원으로부터 유래할 수 있다. 추가로, 이러한 유도된 pDC는 이들이 림프절로 이동하고, 효과기 T 세포를 활성화시키는 것을 가능하게 하는 방식으로 투여될 수 있다.
대상체에 세포를 투여하기 위한 다양한 수단이 당업자에게 공지되어 있다. 이러한 방법은 전신 주사, 예를 들면, i.v. 주사를 포함할 수 있거나, 대상체의 표적 부위에 대한 세포의 이식을 포함할 수 있다. 세포는 대상체에 대한 주사 또는 이식에 의한 도입을 용이하게 하는 전달 장치에 삽입될 수 있다. 이러한 전달 장치는 수용자 대상체의 체내에 세포 및 체액을 주입하기 위한 튜브, 예를 들면, 카테터를 포함할 수 있다. 바람직한 일 실시형태에서, 튜브는, 예를 들면, 이를 통해 세포가 목적하는 위치에서 대상체로 도입될 수 있는 니들(needle)을 추가로 갖는다. 세포는 다양한 상이한 형태로 전달을 위해 제조될 수 있다. 예를 들면, 세포는 이러한 전달 장치에 포함되는 경우 용액 또는 겔에 현탁되거나, 또는 지지체 매트릭스에 매립될 수 있다. 세포는 세포가 생존 가능한 상태로 유지되는 약제학적으로 허용되는 담체 또는 희석제와 혼합될 수 있다.
따라서, 본 명세서에 기재된 방법에 의해 생산된 세포는, 유방암(breast cancer), 전립선암(prostate cancer), 림프종(lymphoma), 피부암(skin cancer), 췌장암(pancreatic cancer), 결장암(colon cancer), 흑색종(melanoma), 악성 흑색종(malignant melanoma), 난소암(ovarian cancer), 뇌암(brain cancer), 원발성 뇌암(primary brain carcinoma), 두경부암(head-neck cancer), 신경교종(glioma), 교모세포종(glioblastoma), 간암(liver cancer), 방광암(bladder cancer), 비소세포 폐암(non-small cell lung cancer), 두경부암(head or neck carcinoma), 유방암(breast carcinoma), 난소암(ovarian carcinoma), 폐암(lung carcinoma), 소-세포 폐암(small-cell lung carcinoma), 윌름스 종양(Wilms' tumor), 자궁경부암(cervical carcinoma), 고환암(testicular carcinoma), 방광암(bladder carcinoma), 췌장암(pancreatic carcinoma), 위암(stomach carcinoma), 결장암(colon carcinoma), 전립선암(prostatic carcinoma), 비뇨생식기암(genitourinary carcinoma), 갑상선암(thyroid carcinoma), 식도암(esophageal carcinoma), 골수종(myeloma), 다발성 골수종(multiple myeloma), 부신암(adrenal carcinoma), 신장 세포암(renal cell carcinoma), 자궁내막 암종(endometrial carcinoma), 부신 피질 암종(adrenal cortex carcinoma), 악성 췌장 인슐린종(malignant pancreatic insulinoma), 악성 카르시노이드 암종(malignant carcinoid carcinoma), 융모막 암종(choriocarcinoma), 균상 식육종(mycosis fungoides), 악성 고칼슘혈증(malignant hypercalcemia), 자궁경부 증식증(cervical hyperplasia), 백혈병(leukemia), 급성 림프구성 백혈병(acute lymphocytic leukemia), 만성 림프구성 백혈병(chronic lymphocytic leukemia), 급성 골수성 백혈병(acute myelogenous leukemia), 만성 골수성 백혈병(chronic myelogenous leukemia), 만성 과립구 백혈병(chronic granulocytic leukemia), 급성 과립구 백혈병(acute granulocytic leukemia), 모발 세포 백혈병(hairy cell leukemia), 신경모세포종(neuroblastoma), 횡문근염(rhabdomyosarcoma), 카포시 육종(Kaposi's sarcoma), 진성 다혈증(polycythemia vera), 본질적 혈소판감소증(essential thrombocytosis), 호지킨 질환(Hodgkin's disease), 비호지킨 림프종(non- Hodgkin's lymphoma), 연조직 육종(soft-tissue sarcoma), 골형성 육종(osteogenic sarcoma), 원발성 거대글로불린혈증(primary macroglobulinemia), 및 망막모세포종(retinoblastoma) 등을 포함하지만 이들로 한정되지 않는 몇몇 암 및 종양을 치료 또는 경감시키기 위한 세포의 제조에 사용될 수 있다.
상기에 추가하여, 본 발명의 방법을 사용하여, 특정 암의 소인으로 되는 것이 공지되어 있는 병원체에 의한 감염을 예방 또는 제거할 수 있다. 본 명세서에서 제공되는 암 백신에 사용하기 위한 특히 관심 있는 병원체는 B형 간염 바이러스(간세포 암종), C형 간염 바이러스(간세포암), 엡스타인 바르 바이러스(EBV)(버킷 림프종, 비인두암(nasopharynx cancer), 면역억제된 개체의 PTLD), HTLVL(성인 T 세포 백혈병), 발암성 인간 유두종 바이러스 유형 16, 18, 33, 45(성인 자궁경부암) 및 세균 헬리코박터 파일로리(B 세포 위 림프종)을 포함한다. 포유동물, 특히 인간에서 항원으로 작용할 수 있는 기타 의학적으로 관련된 미생물은 문헌[참조: 예를 들면 C. G. A Thomas, Medical Microbiology, Bailliere Tindall, (1983)]에 광범위하게 기재되어 있다.
상기에 추가하여, 본 발명의 방법은 바이러스 감염에 사용될 수 있다. 예시적 바이러스 병원체에는 포유동물, 특히 인간을 감염시키는 감염성 바이러스가 포함되지만 이들로 한정되지 않는다. 감염성 바이러스의 예에는 레트로비리다에(Retroviridae)(예: HIV-I 등의 인간 면역결핍 바이러스(HTLV-III, LAV 또는 HTLV-III/LAV 또는 HIV-III으로도 지칭됨); 및 HIV-LP 등의 기타 단리물; 피코르나비리다에(Picornaviridae)(예: 폴리오 바이러스, A형 간염 바이러스, 엔테로바이러스, 인간 콕사키에(Coxsackie) 바이러스, 리노바이러스, 에코바이러스); 칼시비리다에(Calciviridae)(예: 위장염을 유발하는 균주); 토가비리다에(Togaviridae)(예: 말과 뇌염 바이러스, 풍진 바이러스); 플라비리다에(Flaviridae)(예: 뎅기열 바이러스, 뇌염 바이러스, 황열병 바이러스); 코로노비리다에(Coronoviridae)(예: SARS 코로나바이러스 등의 코로나바이러스); 랍도비리다에(Rhabdoviradae)(예: 수포성 구내염 바이러스, 광견병 바이러스); 필로비리다에(Filoviridae)(예: 에볼라 바이러스); 파라믹소비리다에(Paramyxoviridae)(예: 파라인플루엔자 바이러스, 볼거리 바이러스, 홍역 바이러스, 호흡기 합포체 바이러스); 오르토믹소비리다에(Orthomyxoviridae)(예: 인플루엔자 바이러스); 붕가비리다에(Bungaviridae)(예: 한탄 바이러스, 붕가 바이러스, 플레보바이러스 및 나이로 바이러스); 아레나 비리다에(Arena viridae)(출혈열 바이러스); 레오비리다에(Reoviridae)(예: 레오바이러스, 오르비바이러스 및 로타바이러스); 비르-나비리다에(Bir-naviridae); 헤파드나비리다에(Hepadnaviridae)(B형 간염 바이러스); 파르보비리다(Parvovirida)(파르보바이러스); 파포바비리다에(Papovaviridae)(유두종 바이러스, 폴리오마 바이러스); 아데노비리다에(Adenoviridae)(대부분의 아데노바이러스); 헤르페스비리다에(Herpesviridae) 단순 포진 바이러스(HSV) 1 및 2, 수두 대상포진 바이러스, 사이토메갈로바이러스(CMV), 헤르페스 바이러스; 피. 옥시이디다에(P.oxyiridae)(바리올라 바이러스, 백시니아 바이러스, 수두 바이러스); 및 이리도비리다에(Iridoviridae)(예: 아프리카 돼지 열병 바이러스); 및 미분류 바이러스(예: 해면상 뇌병증의 병인 인자, 델타 간염의 병원체(B형 간염 바이러스의 결함 위성으로 생각됨), 비-A형, 비-B형 간염의 병원체(클래스 l=내부 전염, 클래스 2=비경구로 전염(즉, C형 간염), 노르워크(Norwalk) 및 관련 바이러스, 아스트로(astro) 바이러스)가 포함된다.
상기에 추가하여, 본 발명의 방법을 사용하여, 척추동물에서 그람 음성 및 그람 양성 세균을 표적화할 수 있다. 이러한 그람 양성 세균은 파스테우렐라 종(Pasteurella sp.), 스타필로콕시 종(Staphylococci sp.) 및 스트렙토콕쿠스 종(Streptococcus sp.)이 포함되지만, 이들로 한정되지 않는다. 그람 음성 세균에는 에스케리키아 콜라이(Escherichia coli), 슈도모나스 종(Pseudomonas sp.) 및 살모넬라 종(Salmonella sp.)이 포함되지만, 이들로 한정되지 않는다. 감염성 세균의 특정 예에는 헬리코박터 파일로리스(Helicobacter pyloris), 보렐라 부르도르페리(Borella burgdorferi), 레지오넬라 뉴모필리아(Legionella pneumophilia), 마이코박테리아 종(Mycobacteria sp.)(예: 엠. 투베르쿨로시스(M. tuberculosis), 엠. 아비움(M. avium), 엠. 인트라셀룰라레(M. intracellulare), 엠. 칸사이(M. kansaii), 엠. 고르도나에(M. gordonae)), 스타필로콕쿠스 아우레우스(Staphylococcus aureus), 네이세리아 고노르호에아에(Neisseria gonorrhoeae), 네이세리아 메닝기티디스(Neisseria meningitidis), 리스테리아 모노사이토게네스(Listeria monocytogenes), 스트렙토콕쿠스 피오게네스(Streptococcus pyogenes)(그룹 A 스트렙토콕쿠스(Streptococcus)), 스트렙토콕쿠스 아갈락티아에(Streptococcus agalactiae)(그룹 B 스트렙토콕쿠스), 스트렙토콕쿠스(Streptococcus)(비리단스 그룹), 스트렙토코커스 파에칼리스(Streptococcus faecalis), 스트렙토콕쿠스 보비스(Streptococcus bovis), 스트렙토콕쿠스(혐기성 종), 스트렙토콕쿠스 뉴모니아에(Streptococcus pneumoniae), 병원성 캄필로박터 종(Campylobacter sp.), 엔테로콕쿠스 종(Enterococcus sp.), 헤모필루스 인플루엔자(Haemophilus infuenzae), 바실루스 안트라시스(Bacillus antracis), 코리네박테리움 디프테리아에(Corynebacterium diphtheriae), 코리네박테리움 종(Corynebacterium sp.), 에리시펠로트릭스 루시오파티아에(Erysipelothrix rhusiopathiae), 클로스트리디움 퍼레프린거스(Clostridium perfringers), 클로스트리디움 테타니(Clostridium tetani), 엔테로박터 아에로게네스(Enterobacter aerogenes), 클렙시엘라 뉴모니아에(Klebsiella pneumoniae), 파스누렐라 물토시다(Pasturella multocida), 박테로이데스 종(Bacteroides sp.), 푸소박테리움 누클레아툼(Fusobacterium nucleatum), 스트렙토바실루스 모니리포르미스(Streptobacillus moniliformis), 트레포네마 팔리디움(Treponema pallidium), 트레포네마 페르테누에(Treponema pertenue), 레프토스피라(Leptospira), 릭케트시아(Rickettsia) 및 악티노마이시스 이스라엘이(Actinomyces israelii)가 포함되지만, 이들로 한정되지 않는다.
상기에 추가하여, 본 발명의 방법을 사용하여, 포유동물, 보다 특히 인간을 감염시키는 감염성 진균 및 기생충을 포함하지만 이들로 한정되지 않는 병원체를 표적화할 수 있다. 감염성 진균의 예에는 크립토콕쿠스 네오포르만스(Cryptococcus neoformans), 히스토플라스마 캡슐라툼(Histoplasma capsulatum), 콕시디오이데스 이미티스(Coccidioides immitis), 블라스토마이세스 더마티디스(Blastomyces dermatitidis), 클라미디아 트라코마티스(Chlamydia trachomatis) 및 칸디다 알비칸스(Candida albicans)가 포함되지만 이들로 한정되지 않는다.
상기에 추가하여, 본 발명의 방법을 사용하여, 세포내 기생충 및 절대 세포내 기생충 등의 기생충을 표적화할 수 있다. 기생충의 예에는 플라스모디움 팔시파룸(Plesmodium falciparum), 플라스모디움 오발레(Plasmodium ovale), 플라스모디움 말라리아에(Plasmodium malariae), 플라스모디움 비박스(Plasmdodium vivax), 플라스모디움 노울레시(Plasmodium Knowlesi), 바베시아 마이크로티(Babesia microti), 바베시아 디베르겐스(Babesia divergens), 트리파노소마 크루지(Trypanosoma cruzi), 톡소플라스마 곤디이(Toxoplasma gondii), 트리키넬라 스피랄리스(Trichinella spiralis), 레이쉬마니아 메이저(Leishmania major), 레이쉬마니아 도노바니(Leishmania donovani), 레이쉬마니아 브라질리엔시스(Leishmania braziliensis), 레이쉬마니아 트로피카(Leishmania tropica), 트리파노소마 감비엔세(Trypanosoma gambiense), 트리파노소마 로데시엔세(Trypanosoma rhodesiense), 우체레리아 반크로프티(Wuchereria bancrofti), 브루기아 말라이(Brugia malayi), 브루기아 티모리(Brugia timori), 아스카리스 룸브리코이데스(Ascaris lumbricoides), 온코세르카 볼부루스(Onchocerca volvulus) 및 쉬스토소마 만소니(Schistosoma mansoni)가 포함되지만, 이들로 한정되지 않는다.
변형된 유도된 pDC를 사용하여, 하나 이상의 표적 항원에 대한 장래 또는 기존의 면역 반응의 억제를 포함하는 관용 반응을 유도할 수 있다. 따라서, 유도된 pDC는, 예를 들면, 이식편 거부, 이식편 대 숙주 질환, 알레르기, 기생충 질환, 염증 질환 및 자가면역 질환을 포함하는 바람직하지 않은 면역 반응을 치료 또는 예방하는 데 유용하다. 본 발명에 따라 치료 또는 예방할 수 있는 이식편 거부의 예에는 골수 및 심장, 간, 췌장, 신장, 폐, 눈, 피부 등의 장기의 이식과 관련된 거부반응이 포함된다. 알레르기의 예에는 계절성 호흡기 알레르기; 꽃가루 알레르기 등의 공기 알레르겐에 대한 알레르기; 혈청 IgE 및 호산구 증가증을 감소시킴으로써 치료 가능한 알레르기; 천식; 습진; 동물 알레르기, 식품 알레르기; 라텍스 알레르기; 피부염; 또는 알레르기성 탈감작에 의해 치료 가능한 알레르기가 포함된다. 본 발명에 의해 치료 또는 예방될 수 있는 자가면역 질환에는, 예를 들면, 건선(psoriasis), 전신성 홍반성 루푸스(systemic lupus erythematosus), 중증 근무력증(myasthenia gravis), 강직성 증후군(stiff-man syndrome), 갑상선염(thyroiditis), 시드넘 무도병(Sydenham chorea), 류마티스 관절염(rheumatoid arthritis), 당뇨병(diabetes) 및 다발성 경화증(multiple sclerosis)이 포함된다. 염증성 질환의 예에는 크론병(Crohn's disease), 만성 염증성 안 질환(chronic inflammatory eye diseases), 만성 염증성 폐 질환(chronic inflammatory lung diseases) 및 만성 염증성 간 질환(chronic inflammatory liver diseases), 자가면역 용혈성 빈혈(autoimmune hemolytic anemia), 특발성 백혈구감소증(idiopathic leucopoenia), 궤양성 대장염(ulcerative colitis), 피부근염(dermatomyositis), 경피증(scleroderma), 혼합 결합 조직 질환(mixed connective tissue disease), 과민성 대장 증후군(irritable bowel syndrome), 전신성 홍반성 루푸스(systemic lupus erythromatosus; SLE), 다발성 경화증(multiple sclerosis), 중증 근무력증(myasthenia gravis), 길란-바레 증후군(Guillan-Barre syndrome)(항인지질 증후군(antiphospholipid syndrome)), 원발성 점액종(primary myxoedema), 갑상선 중독증(thyrotoxicosis), 악성 빈혈(pernicious anemia), 자가면역 위축성 위염(autoimmune atrophic gastritis), 애디슨병(Addison's disease), 인슐린 의존성 당뇨병(insulin-dependent diabetes mellitus; IDDM), 굿파스퇴르 증후군(Goodpasture's syndrome), 베체트 증후군(Behcet's syndrome), 쇼그렌 증후군(Sjogren's syndrome), 류마티스 관절염(rheumatoid arthritis), 교감성 안염(sympathetic ophthalmia), 하시모토병/갑상선기능저하염(Hashimoto's disease/hypothyroiditis), 체강병/포진성 피부염(celiac disease/dermatitis herpetiformis), 탈수초성 질환 원발성 담즙성 간경변증(demyelinating disease primary biliary cirrhosis), 혼합 결합 조직 질환, 만성 활동성 간염(chronic active hepatitis), 그레이브스병/갑상선 기능항진염(Graves' disease/hyperthyroiditis), 경피증(scleroderma), 만성 특발성 자반세포증(chronic idiopathic thrombocytopenic purpura), 당뇨병성 신경병증(diabetic neuropathy) 및 패혈성 쇼크(septic shock)가 포함된다.
약제학적으로 허용되는 담체 및 희석제에는 생리식염수, 수성 완충 용액, 용매 및/또는 분산 매질이 포함된다. 이러한 담체 및 희석제의 사용은 당해 기술분야에 공지되어 있다. 용액은 바람직하게는 멸균 및 유체이다. 바람직하게는, 세포 도입 전에, 용액은 제조 및 저장 조건하에서 안정하고, 예를 들면, 파라벤, 클로로부탄올, 페놀, 아스코르브산, 티메로살 등을 사용함으로써 세균 및 진균 등의 미생물의 오염 작용으로부터 보호된다.
세포 투여의 방식은, 예를 들면, 정맥내 주사, 흡입을 통한 폐 전달, 국소 투여 또는 비강내 투여에 의한 비교적 비침습적인 것이 바람직하다. 그러나, 세포 투여의 경로는 치료되는 조직에 의존하고, 이식을 포함할 수 있다. 세포 전달의 방법은 당업자에게 공지되어 있고, 본 명세서에 기재된 방법 및 조성물에서 사용하기 위해 의학 분야의 숙련자에 의해 외삽될 수 있다.
또한, 일부 양태에서, 본 명세서에 제공되는 것은, 유도된 pDC를 제조하기 위한 키트이고, 이 키트는 본 명세서에 기재된 하나 이상의 발현 벡터 성분을 포함하는 임의의 pDC-유도 조성물을 포함한다.
또한, 일부 양태에서, 본 명세서에 기재된 유도된 pDC를 제조하는 방법을 위한 성분으로서 본 명세서에 기재된 pDC-유도 인자 중 하나 이상을 포함하는 키트가 본 명세서에 제공된다.
따라서, 일부 양태에서, 본 명세서에 제공된 것은 하기 성분을 포함하는 유도 수지상 세포를 제조하기 위한 키트이다: (a) IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4), ARID5A(서열번호 5, 서열번호 6), BCL11A(서열번호 7, 서열번호 8), CBFA2T3(서열번호 9, 서열번호 10), CREB3L2(서열번호 11, 서열번호 12), ETS1(서열번호 13, 서열번호 14), HDAC5(서열번호 15, 서열번호 16), HHEX(서열번호 17, 서열번호 18), HOXA5(서열번호 19, 서열번호 20), ID3(서열번호 21, 서열번호 22), IKZF1(서열번호 23, 서열번호 24), IKZF2(서열번호 25, 서열번호 26), IKZF3(서열번호 27, 서열번호 28), IKZF5(서열번호 29, 서열번호 30), IRF7(서열번호 31, 서열번호 32), MEF2C(서열번호 33, 서열번호 34), MYB(서열번호 35, 서열번호 36), RUNX2(서열번호 37, 서열번호 38), STAT3(서열번호 39, 서열번호 40), TCF4(서열번호 41, 서열번호 42), TCF12(서열번호 43, 서열번호 44), STAT1(서열번호 45, 서열번호 46), TSC22D1(서열번호 47, 서열번호 48)로부터 선택된 적어도 1, 2, 3, 4, 5, 6, 7, 8 또는 그 이상의 pDC-유도 인자를 코딩하는 하나 이상의 발현 벡터, 및 (b) 이에 대한 패키징 및 설명서.
본 명세서에 기재된 키트는, 일부 실시형태에서, 혼합물에서 또는 개별 분취물로서 합성 mRNA 또는 pDC-유도 인자를 코딩하는 하나 이상의 발현 벡터를 추가로 제공할 수 있다.
일부 실시형태에서, 키트는 재프로그래밍의 효율성을 증강시키기 위한 약제를 추가로 포함할 수 있다. 일부 실시형태에서, 키트는 pDC 상태로 유도된 세포를 동정하기 위해 세포-유형 특이적 마커를 검출하기 위한 하나 이상의 항체 또는 프라이머 시약을 추가로 포함할 수 있다.
일부 실시형태에서, 키트는 완충액을 추가로 포함할 수 있다. 이러한 일부 실시형태에서, 완충액은 pH 7.0의 RNase-비함유 TE 완충액이다. 일부 실시형태에서, 키트는 세포 배양 배지를 갖는 용기를 추가로 포함한다.
본 명세서에 기재된 모든 키트는 완충액, 세포 배양 배지, 형질도입 또는 형질감염 배지 및/또는 배지 보충물을 추가로 포함할 수 있다. 바람직한 실시형태에서, 완충액, 세포 배양 배지, 형질감염 배지 및/또는 배지 보충물은 DNAse 및 RNase가 없다. 일부 실시형태에서, 키트에 제공된 합성의 변형된 RNA는, 최종 사용자가 적절한 양의 완충액 또는 배지를 첨가하여 성분을 목적하는 농도(예: 100ng/μl)로 되게 하도록, 특정 양 또는 질량(예: 20㎍)의 비-용액 형태, 예를 들면, 동결건조 분말 형태로 할 수 있다.
본 명세서에 기재된 모든 키트는, 본 명세서에 기재된 키트 성분을 사용하여 생성된 세포의 단일-투여 또는 반복 또는 빈번한 주입을 용이하게 하기 위한 디바이스, 비-이식가능한 전달 디바이스, 예를 들면, 니들, 시린지, 펜 디바이스 또는 이식가능한 전달 디바이스, 예를 들면, 펌프, 반-영구적 스텐트(예: 정맥내, 복강내, 대조내 또는 피막내) 또는 저장소를 추가로 포함할 수 있다. 이러한 일부 실시형태에서, 전달 디바이스는 유도된 pDC를 포함하는 약제학적 조성물의 단위 용량을 분배하기 위한 메커니즘을 포함할 수 있다. 일부 실시형태에서, 디바이스는, 예를 들면, 확산에 의해, 조성물을 연속적으로 방출한다. 일부 실시형태에서, 디바이스는 대상체 내의 파라미터를 모니터링하는 센서를 포함할 수 있다. 예를 들면, 디바이스는, 예를 들면, 펌프, 및 임의로 관련 전자 장치를 포함할 수 있다.
일 실시형태에서, 유도된 pDC는, 예를 들면, 체세포, 다능성 세포, 전구 세포 또는 줄기 세포의 본 명세서에 개시된 인자 중 적어도 하나의 유전자 발현을 변형시키거나, 또는 이들 세포 유형 중 임의의 하나를, 본 명세서에 개시된 적어도 하나의 단백질을 생성하는 적어도 하나의 단백질 또는 RNA에 노출시킴으로써 인간의 손에 의해 제조된다. 세포는 본 명세서에 개시된 인자 중 적어도 하나를 작용시키는 소분자에 이를 노출시킴으로써 추가로 제조될 수 있다. 일부 양태에서, 적어도 2, 3, 4, 5, 6, 7, 또는 8개의 인자가 유도된 pDC를 제조하기 위해 사용된다.
일 실시형태에서, DC 서브세트 및 기타 골수 세포(단핵구, 마크로파지 및 미세아교세포)에서 Clec9a, Tlr7, Tlr9 및 후보 TF에 대한 발현 데이터는 임젠(Immgen) 데이터베이스(www.immgen.org)로부터 수득되었다. 발현 데이터는 클러스터 3.0(로그 변환 데이터, 중심 유전자, 중심, 클러스터 및 정규화된 세포 유형)에 의해 분석되었고, 트리뷰( Treeview)에 의해 표시되었다. 또는, GraphPad Prism을 사용하여 발현 값을 표시했다.
일 실시형태에서, 마우스 배아 섬유아세포(MEF)는 하기 방식으로 단리 및 정제했다: Clec9aCre/Cre 동물(10마리)을 Rosa26-stopflox-tdTomato 리포터 마우스(The Jackson Laboratory)와 교배하여, 이중 호모접합성 Clec9aCre/Cre RosatdTomato/tdTomato(Clec9A-tdTomato) 마우스를 생성했다. 모든 동물은 제어된 온도(23 ± 2℃)에서 사육되었고, 12시간 명암 사이클이 고정되고, 음식과 물에 자유롭게 접근할 수 있게 했다.
일 실시형태에서, MEF의 1차 배양물은 Clec9A-tdTomato 또는 C57BL/6 마우스의 E13.5 배아로부터 단리했다(6, 10). 두부, 태아 간 및 모든 내부 장기를 제거하고, 나머지 조직을 기계적으로 분리했다. 절개된 조직을, 0.12% 트립신/0.1mM 에틸렌디아민테트라아세트산(EDTA) 용액(배아당 3mL)을 사용하여 효소 소화하고, 37℃에서 15분 동안 인큐베이팅했다. 배아당 동일한 용액 3mL를 추가로 첨가한 후, 15분의 배양 기간을 추가로 수행했다. 단일 세포 현탁액을 수득하고, 성장 배지에서 0.1% 젤라틴 코팅된 10cm 조직 배양 접시에 플레이팅했다. 세포를 컨플루언스(confluence)로 될 때까지 2 내지 3일 동안 성장시키고, 트리플 익스프레스(Tryple Express)로 해리하고, 소 태아 혈청(FBS) 10% 디메틸 설폭사이드(DMSO)에서 동결시켰다. 렌티바이러스 형질도입을 위해 플레이팅하기 전에, MEF를 선별하여, 조혈 능력을 갖는 세포를 나타낼 수 있는 잔류 CD45+ 및 tdTomato+ 세포를 제거했다.
일 실시형태에서, HEK293T 세포 및 MEF는, 성장 배지[10%(v/v) FBS, 2mM L-글루타민 및 항생제(10㎍/ml 페니실린 및 스트렙토마이신)을 보충한 둘베코 변형된 이글 배지(DMEM)]에서 유지되었다. 모든 세포는 37℃ 및 5%(v/v) CO2에서 유지되었다. 달리 명시되지 않는 한, 모든 조직 배양 시약은 써모 피셔 사이언티픽(Thermo Fisher Scientific)에서 입수했다.
일 실시형태에서, 바이러스 형질도입 및 재프로그래밍 실험은 하기 방식으로 수행했다: Clec9A-tdTomato MEF는 0.1% 젤라틴 코팅된 6-웰 플레이트 상에 웰당 40,000개 세포의 밀도로 파종했다. 세포를, 8μg/mL 폴리브렌을 보충한 성장 배지에서 1:1 FUW-TetO-TF 및 FUW-M2rtTA 렌티바이러스 입자의 비율로 밤새 인큐베이팅했다. TF의 조합을 시험하는 경우, 각 개별 바이러스 입자의 동일한 MOI가 적용되었다. 세포를 연속하여 2회 형질도입하고, 밤새 인큐베이팅한 후, 배지를 신선한 성장 배지로 교환했다. 2회차 형질도입 후, 성장 배지에 독시사이클린(1μg/mL)을 보충했다(0일차). 배지는 배양 기간 동안 2 내지 3일마다 교환했다. 출현 tdTomato+ 세포는 형질도입 5 내지 8일 후에 분석했다.
일 실시형태에서, 유세포 분석은 다음과 같은 방식으로 수행했다: 형질도입된 Clec9A-tdTomato MEF를 TrypLE Express로 해리시키고, 200μL PBS 5% FBS에 재현탁시키고, BD FACS LSR II(BD Biosciences)에서 분석 전에 4℃로 유지했다. MHC-II 세포 표면 마커 발현의 분석을 위해, 해리된 세포를, PBS 5% FBS에서 희석된 APC-접합된 랫트 항-마우스 I-A/I-E 항체(Biolegend) 또는 APC-Cy7-접합된 항-CD45 항체(Biolegend)와 함께, 비특이적 결합을 차단하기 위해 랫트 혈청(1/100, GeneTex)의 존재하에 4℃에서 30분 동안 인큐베이팅했다. 세포를 PBS 5% FBS로 세척하고, PBS 5% FBS에 재현탁하고, BD FACS LSR II에서 분석했다. 유세포 분석 데이터는 FlowJo 소프트웨어(FLOWJO, LLC, 버전 7.6)를 사용하여 분석했다.
일 실시형태에서, 형광 활성화된 세포 선별(FACS)은 하기 방식으로 수행했다: Clec9A-tdTomato MEF를 정제하기 위해, 세포를 PBS 5% FBS에서 희석된 APC-Cy7-접합된 항-CD45 항체(Biolegend)와 함께 4℃에서 30분 동안 인큐베이팅했다. 이어서, MEF를 PBS 5% FBS로 세척하고, PBS 5% FBS에 재현탁하고, tdTomato-CD45-MEF를 BD FACSAria III에서 정제했다. 기재된 경우, tdTomato+ 세포는 BD FACSAria III를 사용하여 정제했다. FACS 데이터는 FlowJo 소프트웨어에서 처리했다.
일 실시형태에서, Clec9a-tdTomato 마우스로부터 새롭게 단리된 비장을 2개의 멸균 슬라이드의 프로스트 말단을 사용하여 균질화했다. 5% FBS가 보충된 PBS에서 세포를 수확하고, 70μm 세포 여과기(BD Biosciences)를 통해 여과했다. 적혈구를 BD Pharm Lyse(BD Biosciences)로 실온에서 8분 동안 용해시켰다. 5배 용적 이상의 PBS 5% FBS를 첨가하여 용해를 중단시켰다. 비장세포를 1회 세척하여 단일 세포 현탁액을 수득하고, 이는, 랫트 혈청의 존재하에 PBS 5% FBS에서 희석시킨 FITC-접합된 항-CD11c 항체(Biolegend), APC-접합된 항-Bst2 항체(Biolegend), APC-Cy7-접합된 항-B220 항체(Biolegend) 및 BV605-접합된 항-Siglec-H 항체(Biolegend)의 혼합물과 함께 4℃에서 30분 동안 인큐베이팅했다. 적절한 보상 및 게이팅(gating)을 위해, 단일 염색 및 형광 마이너스 1 대조군이 포함되었다. 4℃에서 30분 후, 세포를 세척하고, PBS 3% FBS로 재현탁하고, BD FACSAria III(BDiosciences)에서 분석했다. 이 분석으로부터 수득된 데이터는 FlowJo 소프트웨어를 사용하여 처리되었다. 비장 pDC는 살아있는 단일 세포 CD11clow Bst2+ B220+ Siglec-H+로 식별된다.
일 실시형태에서, 염증성 사이토카인 검정은 하기 방식으로 수행했다: tdTomato+ 세포를 9일차에 FACS 선별하고, TLR7 및 TLR9의 밤새 자극을 위해 각각 1μg/mL의 R848(Invivogen) 및 0.5μM CpG ODN 1668(Invivogen)과 함께 밤새 배양했다. 사이토카인 인터페론-α(IFN-α), 인터페론-β(IFN-β), 인터류킨-10(IL-10), 인터류킨-6(IL-6), 종양 괴사 인자-α(TNF-α) C-C 모티프 케모카인 리간드 5(CCL5) 및 C-X-C 모티프 케모카인 리간드 10(CXCL10)의 수준은 10일차에 평가되었다. 96웰 플레이트 웰로부터 50μL의 배양 상청액을 수집하고, 제조업체의 지시에 따라 V 플레이트(Biolegend)를 갖는 LEGENDplex™ 마우스 항바이러스 반응 패널(13-plex)에 의해 분석했다. 획득은 BD FACS LSR II로 수행하고, 데이터는 LEGENDplex™ 데이터 분석, 버전 8.0(Biolegend)을 사용하여 분석했다.
당업자는 본 명세서에 기재된 본 발명의 특정 실시형태에 상당하는 다수의 등가물을 인식하거나, 또는 일상적 실험만을 사용하여 확인할 수 있을 것이다. 본 발명의 범위는 상기 설명으로 한정되는 것을 의도하는 것은 아니고, 오히려 첨부된 특허청구범위에 기재된 바와 같다.
단수 형태의 요소 또는 특징이 특허청구범위의 명세서에 사용되는 경우, 복수의 형태도 또한 포함되고, 특별히 배제되지 않는 한, 그 반대의 경우도 마찬가지이다. 예를 들면, 용어 "전사 인자" 또는 "전사 인자"는 또한 복수 형태의 "전사 인자" 또는 "전사 인자"를 포함하고, 그 반대의 경우도 마찬가지이다. 특허청구범위에서, "a", "an" 및 "the" 등의 관사는, 상반되게 표시되거나, 또는 문맥에서 달리 명백하지 않는 한, 하나 또는 하나 이상을 의미할 수 있다. 그룹의 하나 이상의 구성원 사이에 "또는"을 포함하는 청구항 또는 설명은, 상반되게 표시되거나, 또는 문맥에서 달리 명백하지 않는 한, 그룹 구성원 중 하나, 하나 이상 또는 모두가 소정 제품 또는 프로세스에 존재하거나, 이용되거나, 또는 달리는 관련되는 경우에 충족된 것으로 간주된다. 본 발명은, 그룹의 정확히 하나의 구성원이 소정 제품 또는 프로세스에 존재하거나, 이용되거나, 또는 달리는 관련되는 실시형태를 포함한다. 본 발명은 또한, 그룹 구성원 중 하나 이상 또는 모두가 소정 제품 또는 프로세스에 존재하거나, 또는 이용되거나, 또는 달리는 관련되는 실시형태를 포함한다.
추가로, 본 발명은, 하나 이상의 특허청구범위 또는 설명의 관련 부분으로부터 하나 이상의 제한, 요소, 절, 설명 용어 등이 또 다른 청구항에 도입되어 있는 모든 변형, 조합 및 순열을 포함하는 것으로 이해되어야 한다. 예를 들면, 또 다른 청구항에 종속하는 임의의 청구항은, 동일한 기본 청구항에 종속하는 또 다른 청구항에서 발견되는 하나 이상의 제한을 포함하도록 변경될 수 있다.
추가로, 청구항이 조성물을 언급하는 경우, 달리 지시가 없는 한, 또는 당업자에게 모순 또는 모순이 발생하는 것이 명백하지 않는 한, 본 명세서에 개시된 임의의 목적을 위해 조성물을 사용하는 방법이 포함되고, 본 명세서에 개시된 임의의 제조 방법 또는 공지된 기타 방법에 따라 조성물을 제조하는 방법이 포함되는 것으로 이해되어야 한다.
범위가 지정되는 경우, 종점이 포함된다. 추가로, 문맥 및/또는 당업자의 이해로부터 달리 지시 또는 달리는 명백하지 않는 한, 범위로 표현되는 값은, 문맥이 명확하게 달리 지시하지 않는 한, 본 발명의 상이한 실시형태에서 기재된 범위 내의 임의의 특정 값을 범위의 하한 단위의 10분의 1까지 가정하는 것으로 이해된다. 또한, 문맥 및/또는 당업자의 이해로부터 달리 지시 또는 달리는 명백하지 않는 한, 범위로 표현되는 값은, 소정 범위 내의 임의의 하위 범위를 상정할 수 있고, 여기서 하위 범위의 종점은 범위의 하한 단위의 10분의 1과 동일한 정확도로 표현된다.
본 개시는 어떤 방식으로든 기재된 실시형태로 한정되는 것으로 보여서는 안 되고, 당업자는 이의 변경에 대한 다수의 가능성을 예견할 것이다.
상술한 실시형태는 조합 가능하다.
하기 표는 본 개시에 포함된 서열의 개요를 제공한다.
| 서열번호 |
서열 설명
(폴리뉴클레오티드) |
서열번호. |
서열 설명
(폴리펩티드) |
| 1 | 인간 IRF8 | 49 | 인간 IRF8 |
| 2 | 마우스 IRF8 | 50 | 마우스 IRF8 |
| 3 | 인간 SPIB | 51 | 인간 SPIB |
| 4 | 마우스 SPIB | 52 | 마우스 SPIB |
| 5 | 인간 ARID5A | 53 | 인간 ARID5A |
| 6 | 마우스 ARID5A | 54 | 마우스 ARID5A |
| 7 | 인간 BCL11A | 55 | 인간 BCL11A |
| 8 | 마우스 BCL11A | 56 | 마우스 BCL11A |
| 9 | 인간 CBFA2T3 | 57 | 인간 CBFA2T3 |
| 10 | 마우스 CBFA2T3 | 58 | 마우스 CBFA2T3 |
| 11 | 인간 CREB3L2 | 59 | 인간 CREB3L2 |
| 12 | 마우스 CREB3L2 | 60 | 마우스 CREB3L2 |
| 13 | 인간 ETS1 | 61 | 인간 ETS1 |
| 14 | 마우스 ETS1 | 62 | 마우스 ETS1 |
| 15 | 인간 HDAC5 | 63 | 인간 HDAC5 |
| 16 | 마우스 HDAC5 | 64 | 마우스 HDAC5 |
| 17 | 인간 HHEX | 65 | 인간 HHEX |
| 18 | 마우스 HHEX | 66 | 마우스 HHEX |
| 19 | 인간 HOXA5 | 67 | 인간 HOXA5 |
| 20 | 마우스 HOXA5 | 68 | 마우스 HOXA5 |
| 21 | 인간 ID3 | 69 | 인간 ID3 |
| 22 | 마우스 ID3 | 70 | 마우스 ID3 |
| 23 | 인간 IKZF1 | 71 | 인간 IKZF1 |
| 24 | 마우스 IKZF1 | 72 | 마우스 IKZF1 |
| 25 | 인간 IKZF2 | 73 | 인간 IKZF2 |
| 26 | 마우스 IKZF2 | 74 | 마우스 IKZF2 |
| 27 | 인간 IKZF3 | 75 | 인간 IKZF3 |
| 28 | 마우스 IKZF3 | 76 | 마우스 IKZF3 |
| 29 | 인간 IKZF5 | 77 | 인간 IKZF5 |
| 30 | 마우스 IKZF5 | 78 | 마우스 IKZF5 |
| 31 | 인간 IRF7 | 79 | 인간 IRF7 |
| 32 | 마우스 IRF7 | 80 | 마우스 IRF7 |
| 33 | 인간 MEF2C | 81 | 인간 MEF2C |
| 34 | 마우스 MEF2C | 82 | 마우스 MEF2C |
| 35 | 인간 MYB | 83 | 인간 MYB |
| 36 | 마우스 MYB | 84 | 마우스 MYB |
| 37 | 인간 RUNX2 | 85 | 인간 RUNX2 |
| 38 | 마우스 RUNX2 | 86 | 마우스 RUNX2 |
| 39 | 인간 STAT3 | 87 | 인간 STAT3 |
| 40 | 마우스 STAT3 | 88 | 마우스 STAT3 |
| 41 | 인간 TCF4 | 89 | 인간 TCF4 |
| 42 | 마우스 TCF4 | 90 | 마우스 TCF4 |
| 43 | 인간 TCF12 | 91 | 인간 TCF12 |
| 44 | 마우스 TCF12 | 92 | 마우스 TCF12 |
| 45 | 인간 STAT1 | 93 | 인간 STAT1 |
| 46 | 마우스 STAT1 | 94 | 마우스 STAT1 |
| 47 | 인간 TSC22D1 | 95 | 인간 TSC22D1 |
| 48 | 마우스 TSC22D1 | 96 | 마우스 TSC22D1 |
하기 청구범위는 본 개시의 특정 실시형태를 추가로 설명한다.
SEQUENCE LISTING
<110> Asgard Therapeutics AB
<120> Composition for reprogramming cells into plasmacytoid dendritic
cells or interferon type I-producing cells, methods and uses
thereof
<130> P5666PC00
<160> 96
<170> PatentIn version 3.5
<210> 1
<211> 2669
<212> DNA
<213> Homo sapiens
<400> 1
gtgaggtcat ggaggccagc attgccttct catggcaggt gtcccggagt ccctgaatct 60
gatgtgtgac cggaatggtg gtcggcggct tcgacagtgg ctgatcgagc agattgacag 120
tagcatgtat ccaggactga tttgggagaa tgaggagaag agcatgttcc ggatcccttg 180
gaaacacgct ggcaagcaag attataatca ggaagtggat gcctccattt ttaaggcctg 240
ggcagttttt aaagggaagt ttaaagaagg ggacaaagct gaaccagcca cttggaagac 300
gaggttacgc tgtgctttga ataagagccc agattttgag gaagtgacgg accggtccca 360
actggacatt tccgagccat acaaagttta ccgaattgtt cctgaggaag agcaaaaatg 420
caaactaggc gtggcaactg ctggctgcgt gaatgaagtt acagagatgg agtgcggtcg 480
ctctgaaatc gacgagctga tcaaggagcc ttctgtggac gattacatgg ggatgatcaa 540
aaggagccct tccccgccgg aggcctgtcg gagtcagctc cttccagact ggtgggcgca 600
gcagcccagc acaggcgtgc cgctggtgac ggggtacacc acctacgacg cgcaccattc 660
agcattctcc cagatggtga tcagcttcta ctatgggggc aagctggtgg gccaggccac 720
caccacctgc cccgagggct gccgcctgtc cctgagccag cctgggctgc ccggcaccaa 780
gctgtatggg cccgagggcc tggagctggt gcgcttcccg ccggccgacg ccatccccag 840
cgagcgacag aggcaggtga cgcggaagct gttcgggcac ctggagcgcg gggtgctgct 900
gcacagcagc cggcagggcg tgttcgtcaa gcggctgtgc cagggccgcg tgttctgcag 960
cggcaacgcc gtggtgtgca aaggcaggcc caacaagctg gagcgtgatg aggtggtcca 1020
ggtcttcgac accagccagt tcttccgaga gctgcagcag ttctataaca gccagggccg 1080
gcttcctgac ggcagggtgg tgctgtgctt tggggaagag tttccggata tggccccctt 1140
gcgctccaaa ctcattctcg tgcagattga gcagctgtat gtccggcaac tggcagaaga 1200
ggctgggaag agctgtggag ccggctctgt gatgcaggcc cccgaggagc cgccgccaga 1260
ccaggtcttc cggatgtttc cagatatttg tgcctcacac cagagatcat ttttcagaga 1320
aaaccaacag atcaccgtct aagtgcgtcg cttgggcgcc ccaccccgtc tgcgtcctgc 1380
atccatctcc ctgttacagt ggcccgcatc atgattaaag aatgtggatc cctctgtctg 1440
gggtgggatg ccttactttg cacttaattt aataagggca ttctcggagg agtagacgtt 1500
taatacgaag tggcggcata gccctgccga gatgtcggtg atggcctgga tgctgtaacc 1560
acaacctgtg gctaaaaatt ttattttcta tcctttaccc gtcattatca ttagttgcta 1620
tgattctttc tgcattttcg gttaactatc atttccaaag acttgtcatt cagtaatatt 1680
agcagatagc tgcttcgata aaggaatttg gagtttaaaa atcaacttgt gaaaacaagg 1740
ttgtttttgt ctttatcgtt tgttagagtt atagatttat gatttcatag gcttgattct 1800
atgtgaaata tctttttact tttatgcatt ttaataagat ttaaaaatat ttagattaaa 1860
gcccccttta atgagtacaa gaaaaactct tggcttgtta gaagaaagta tattctttct 1920
agaatttggt gcaggaatat gtgttcatat ccaggcaaac gggtgtgttt ttatcttcag 1980
acaatgaaac cttctcctct ggggctttgt tgccaggaag attagaacta aatttatttt 2040
tttcatttct gtcatgaaat cattccagat acctcttttc ttctttccaa atggttttca 2100
catgtgtttg aaatatttgt acttcgaatt gtcggatttt ccatgtcctc ctttctcctt 2160
tgtgcccagc ctgagtcagc accaatcccg cattcagaac ctcccagtga aagggcagcc 2220
ttcattttga gaaggtggaa ggtgttaggg tttgggagac agctcatcca atctcccaag 2280
tctcatggtg gatttgtgac tgtgagagtt tccggtttaa aatctgaaaa gccagatatg 2340
cctgtttcct tttcccagca ccatgcctgt ggaggggaca gtcagaccca gaggtccttt 2400
acgtgtggat ggagttcaca ggcgaataga ggagaggacc aggggacgtg gcttgtccct 2460
tttgtccaac aaagcattat atttttaaga atggcagacc tgtttgctga agtgttcata 2520
agataacaat aggcttgaat ctccaattca aatgaatgtc aaagcacata tctttaatat 2580
gctgaatgaa tatttatttt tgtatccatt aaaacagtat attgatctct tttattcttt 2640
attaaaataa aatgctcttt tttaaagct 2669
<210> 2
<211> 3391
<212> DNA
<213> Mus musculus
<400> 2
ttccaagccc actggtggca gttagggctg ctgtgtggct aaaaccagcc ctggagagac 60
ctcatctccc tcctctcagg ctgctgccgt ctttcctggc cccactacca cctgcaagcg 120
gcctggagtt tctgaccctc aggcctcttt ccagcaatcc tgactttgtg ggacatgctg 180
gctctggatg tgactatgtt cttggggata tcttgacttc tcactgatga taacttcttt 240
tttttttttt tttccctacc ccaagaggtc attttagttg gaagactaga agtgctgtgt 300
tctggttttc agggtgggcg tctgtccaac tgctttgggg atttccaggc tgttctagta 360
aatgctggct gcaagtccct gtgcacaaat gccctctctc cccacgctgt aggaaaagca 420
gacccgagag tgtccaagtg tgccattagg tgtctgggga tggcgggcct ggatatggag 480
tccctgagct ggctttgtac tgtccctttg ttctcactga gggctgattg taagagggac 540
tccctgtgtt gttggaggag tcctctagga tacaggctct gattgcagga tgtgtgaccg 600
gaacggcggg cggcggctgc ggcagtggct gatcgaacag atcgacagca gcatgtaccc 660
ggggctgatc tgggaaaatg atgagaagac catgttccgt atcccctgga agcatgccgg 720
caagcaggat tacaatcagg aggtggatgc ttccatcttc aaggcctggg cagtttttaa 780
agggaagttt aaagagggag acaaagctga accagccacg tggaagacga ggttacgctg 840
tgctctgaac aagagcccag attttgaaga agtgactgac cggtcccagc tggacatttc 900
tgagccatat aaagtttacc gaattgtccc cgaggaagaa caaaaatgca agctgggcgt 960
ggcacctgca ggctgcatga gcgaagttcc tgagatggag tgtggccgct cagagattga 1020
ggagctgatc aaggaacctt ctgtggatga gtacatgggt atgaccaaga ggagcccatc 1080
cccaccagag gcctgcagga gccagatcct ccctgactgg tgggtccagc agcccagtgc 1140
aggcctgcca ctggtgaccg gatatgccgc ctatgacaca caccattcag ctttctccca 1200
gatggtcatc agcttctact acgggggcaa gctggtgggc caggccacca ccacctgcct 1260
tgaaggctgc cgtctctccc tgagccagcc ggggctgcct aagttgtatg ggccggatgg 1320
cctggaaccc gtgtgctttc cgacggccga caccatcccc agtgagcggc agaggcaggt 1380
gacccggaag ctgtttgggc acctggaacg tggcgtgcta ctgcacagca accgcaaggg 1440
cgtgttcgtg aagcggctgt gccagggccg cgtgttctgc agcggcaacg cggtggtgtg 1500
caagggcagg cccaacaagc tggagcggga cgaggtggtg caggtctttg acaccaacca 1560
gttcatccga gagctgcagc aattctacgc cacccagagc cgcctacctg acagcagggt 1620
ggtcctgtgc ttcggggagg agtttccgga cactgtgccc ttgcgctcca aactcattct 1680
ggtgcaggta gagcagctgt atgccaggca gctggtggag gaagcgggca agagctgcgg 1740
tgctggctcc ctgatgccag ccctggagga gccccagccg gaccaggctt tccgcatgtt 1800
tccggatatc tgtacctcac accagagacc cttttttaga gaaaatcaac agatcaccgt 1860
ctaagcctca gtccgggcac cccacctcgc ctgagctcaa gcttcaagag tctgtgacta 1920
agagaattcc gaaaggatgt ggagccctct gactggggtg ggcgggtgtc ctccaagggg 1980
cctccggaag cccacagagg gatgcgctcc tgctcaggca ggtgtcagaa gcttgcaggg 2040
gctgtggccg caacctgtga ttaaagcatt cctttcctgc gtttccccct tcaccactaa 2100
tggctggcct ttctgtgtgc tgaggtcttt cgacagttca aatcatctgg tggcagcaga 2160
ctcgcctttg cccttctgcg gccgagggcg gagatttatg actttctctg cttggttgga 2220
gaagaagaat ctttactatt cagcttcttt tctttttggc cagaactctg aaaaaaaaaa 2280
aaactctttt taagacaata tttgtattct cacaggctca gctgtcaatc acttgagacc 2340
ttccctgtaa agtggggcag attttaaata tgggtgtaga tactgcttgc agccttcgca 2400
ggaattttgg ttgtggttca ttgattcaca cagactctgt gtcagctgac agggctgtgt 2460
ggggcatcaa aggaggacca ggcactgtgg agaagaccca ttcactggca tctcaccctt 2520
ccttgtccag ctccataccc agtcctaaga cccagtgaaa agccacgtcc aaactgtgct 2580
ctgggctcat cagtgcccac ccacgtacca gggaaaggca cacaccctac ccagtgggca 2640
cagagcggaa tgtcccccta ccgcaccatt tgcgccccca atctggctgt ccaacctagt 2700
ttgtaagtaa tctaaatcag tgactatagc cccgcctaag ggacacttcc cggaggaggg 2760
agccgctgaa aaggagttag tttgagggtc agtacacaac aggggcagaa agccaagcag 2820
atgtgggggc agggagagtc atcatctgct tttgtctgag agaaggagag cttctccgtt 2880
tgttcaactt tgtaacaagc tgggttacat gctccacgca gctagagaag cctaggtgct 2940
ctgcattccc tggggaactg caggaaagcc ttacctgctg actgttgctc tggggaaaag 3000
cctgagggtc cagagcagct acaagctaca ggccatacct tacaacctga aaagctaagg 3060
accacggtga ccttcccggc tactgtgtga aggtgctggg tggggcctgc tcaacagaca 3120
gggtcgacag agtgtgtgat acatgcaaac agaatccttg gagtgtgtga tacatgcaaa 3180
cagaatcctg ggcccctgct tctccccctc agtcaaagca ggagtgtccc ttccgaagcc 3240
aggacaacct gttcacaagg ccccttgtca catgtcacct tccacctgcc tcaaggagtg 3300
ctagtgtcca aatatttatt tttgtattct cttaagaagt attgatttca tcctttatta 3360
aaaaaagttg ctctttcaca aaaaaaaaaa a 3391
<210> 3
<211> 3792
<212> DNA
<213> Homo sapiens
<400> 3
ggcaaacagc ccgcccggca ccaccatgct cgccctggag gctgcacagc tcgacgggcc 60
acacttcagc tgtctgtacc cagatggcgt cttctatgac ctggacagct gcaagcattc 120
cagctaccct gattcagagg gggctcctga ctccctgtgg gactggactg tggccccacc 180
tgtcccagcc accccctatg aagccttcga cccggcagca gccgctttta gccaccccca 240
ggctgcccag ctctgctacg aaccccccac ctacagccct gcagggaacc tcgaactggc 300
ccccagcctg gaggccccgg ggcctggcct ccctgcatac cccacggaga acttcgctag 360
ccagaccctg gttcccccgg catatgcccc gtaccccagc cctgtgctat cagaggagga 420
agacttaccg ttggacagcc ctgccctgga ggtctcggac agcgagtcgg atgaggccct 480
cgtggctggc cccgagggga agggatccga ggcagggact cgcaagaagc tgcgcctgta 540
ccagttcctg ctggggctac tgacgcgcgg ggacatgcgt gagtgcgtgt ggtgggtgga 600
gccaggcgcc ggcgtcttcc agttctcctc caagcacaag gaactcctgg cgcgccgctg 660
gggccagcag aaggggaacc gcaagcgcat gacctaccag aagctggcgc gcgccctccg 720
aaactacgcc aagaccggcg agatccgcaa ggtcaagcgc aagctcacct accagttcga 780
cagcgcgctg ctgcctgcag tccgccgggc ctgagcacac ccgaggctcc cacctgcgga 840
gccgctgggg gacctcacgt cccagccagg atccccctgg aagaaaaagg gcgtccccac 900
actctaggtg ataggactta cgcatcccca ccttttgggg taaggggagt gctgccctgc 960
cataatcccc aagcccagcc cgggcctgtc tgggattccc cacttgtgcc tggggtcctc 1020
tgggatttct ttgtcatgta cagactccct gggatcctca tgttttgggt gacaggacct 1080
atggaccact atactcgggg aggcagggta gcagttcttc cagaatccca agagcttctc 1140
tgggattttc ttgtgatatc tgattcccca gtgaggcctg ggacgttttt aagatcgctg 1200
tgtgtctgta aaccctgaat ctcatctggg gtgggggccc tgctggcaac cctgagccct 1260
gtccaaggtt ccctcttgtc agatctgaga tttcctagtt atgtctgggg ccctctggga 1320
gctgttatca tctcagatct cttcgcccat ctatggctgt gttgtcacat ctgtcccctc 1380
atttttgaga tcccccaatt ctctggaact attctgctgc ccctttttat gtgtctggag 1440
ttccccaatc acatctaggg ctcctccaag atccttttgt catgtctgaa atcactcttg 1500
agaggtctgg ggtggaggat ggggagtcag tgaaatgtgt catgtctggg ccctgtcagg 1560
gacacccttg ttatatctgg gatcctccaa tcacatctga gacctcctag gctctccatc 1620
tgatatgccc tttcagggac cccacaaaga ctgagttctc atggggatcc tacccttcct 1680
agtgccactc cctatggcca tgctgaagac cactctggcc acgcgactga ttttgggtga 1740
tcatggcagc tccccaccca tgtcatttct aaccagaagt ctcaaggtcg tcacccccct 1800
gccccccaac cgaggccccg gtcgctggtg gtggtctctt tagtgcactg tagcacttgg 1860
tggtggaggt gtgagggatc cacattaaca gcaggccatc agctgggcaa tggctcacac 1920
ctgtaatccc agcactttgg gaggcgaggc agggggaatg gcttgaaccc aggcattcaa 1980
gaccagcctg ggcaacataa tgagacctcg tctctacaaa acataacaaa aacaattagc 2040
cgagcgtggg ggtgaacacc tgtggtccca gctgctcagg aggctgaggt gggaggatct 2100
cttgagccca ggaagtagga ggctgtagtg agctgtaatc gtgccactgc actccagcct 2160
gggcgacaga gtgagacacc gtcttaaaaa caaaaacaag gccgggcacg gtggctcatg 2220
cctgttgtcc cagcactttg ggaggccgag gcaggcggat cacgaggtcg agagatcgag 2280
accatcctgg ccaacatggt gaaaccctgt ctctactaaa aatacagaaa ttagctgggc 2340
gtggtggcac gtgcctgtag tcccagctac tcgggaggct gaggcaagag aatcgcttga 2400
acgtgggagg cagaggttgc agtgagccta gattgtgcca ctgcactcca gcctggggga 2460
cagagcgaga ctccgtctga aaataaaaac aacaaaaaca gcagaccatt caaaataggg 2520
agactttgca taatccagat ttctgccttc acttaaaact ttggacggtc tggagagagt 2580
cggccagttt tcggtggggg gtggggagct ggaacaggac agtagccttt cctaatgagg 2640
catttgttct ccaatctgcc ccagtcgctg ccatccctgg ctatctcacc ctagcagctt 2700
ctcaagcctg ttggctttag accactgtat aaacccagct ggaactgaag cctgggtgga 2760
ctatggagcc ctggttggga cccccaggga gtcaaaggct gcgggccaag aggccagagg 2820
tccttgagcc tgggtgggca ggtggatcta gggtgcatga cttgctgctt cccaacctta 2880
gtttgtccct tctgtgaaaa agggagagaa ggaggaggaa gatctcaaaa agactttcca 2940
gcccagtgcg gtggctcacg cctgtaatcc cagcactttg ggaggccgat gcaggtggat 3000
cacctgaggt aggagttcaa gaccagcctg accaacatag tgaagcccct tctctactaa 3060
aaatacaaaa ttagctgggc gtggtggcat gtgcctgtac tcccagctac ttgggaggct 3120
gaggcaggag aatcgcttga acctgggagg cggaggttgt agtgagctga gatcacacca 3180
ctgcacacca gcctgggcga caagagcgaa actccgtctc aaaaaaaaaa aactgttgca 3240
gccccgttga gcctttgaca ccgcctgaaa tccaccccac tcccaggagg aggaggagga 3300
aggaatgcca atgacctaga gacacgagaa gtccatgtgg aggcacacag cagctgatgg 3360
cagagcccag gctgggacct gcccttaaga gaatgagtgg gaagggggag ggaggaaggg 3420
caggtaaaac gtcctcccca gggccccctg caacggggaa ggtacttttt acaaaagcta 3480
tcattgtcac cctaaatgtg gaataaaata agatgcatcg acgtagacaa acctcctggg 3540
accttttgtc agggactgca atcctgcccc tccactgagg ccgctggctc tcagagacac 3600
cgtgacatca cgggtgatga tgagaggagt tcaaagagag aattatatgc tggcgcggtg 3660
gctctgtaat cccaacactt tggggggcca aggcaggagg atcgcttgag tacaggagtt 3720
tgaaaccagc ctgggcaaga tagtgagatc cccttcccac ccgtctacaa aaaaaataaa 3780
aaattagcgg gg 3792
<210> 4
<211> 2786
<212> DNA
<213> Mus musculus
<400> 4
agcctgctct gaaccaccat gcttgctctg gaggctgcac agctggatgg cccacactta 60
agctgtttgt acccagaagg agtcttctac gacctggaca gctgcaagcc cttcagttac 120
ccagattcag atgggggcct tgactctaca tggggctgga cagaggcccc gcctgctcct 180
gccatcgctc cctatgaagc cttcgatcct gctactgctg cctttagcca ctcccaaact 240
gttcagctct gttatagcca tggtcctaac ccctccacct atagccccat ggggaccctc 300
gacccagccc ccagcttgga ggccccaggg cctggcctcc aggtgtaccc cccagaggac 360
ttcaccagcc agaccctggg ctccttggct tatgctccgt accccagccc tgtgctatca 420
gaggaagaag acattatgct ggacagcccc gccctggagg tctcggacag tgagtcagac 480
gaggccctct tggctggctc cgaggggagg ggatctgagg caggtgcacg caagaagctg 540
cgcctgtacc agttcttgct ggggttgctc ctacgcgggg acatgcgcga gtgcgtgtgg 600
tgggtggagc caggtgccgg cgtcttccag ttctcctcca agcacaagga gttgttggct 660
cgccgctggg gccagcagaa gggcaaccgc aagcgcatga cgtatcagaa gctggcccga 720
gcgctgcgca actatgccaa gacaggcgaa atccgcaagg tcaaacgcaa actcacctac 780
cagtttgaca gcgcgctgct gccagcctcc cggcatgtct gagcactccg ctaaggaccc 840
ctttctggcc cctaagtccc atggagcccc atatgagggc agtcagggtt ctcagctctc 900
cctagagcct ccccagagtt tcctgtgccg tgtataggat tccaatctag gatggtcgtg 960
tttgagggag cactggccat tctacacggt ttcagaatgg caggtttctc gggggggggg 1020
gggatggggg agccctgatg tcgtctacgg ttccagaaac cgcagttctt gcgagtcctg 1080
tgagctcaca tgacatctca ccagcaggtg gcgctgtcta cagccccccc caaacccttg 1140
ttttgttggc cagataggtc ggtccctctg tactccccct gaagcccttg ttagatctga 1200
ggtctagtta tgtttggagc tctctgagaa ccctgtgcca cctgtgtgtg acttttctct 1260
gcgtccgttt atgacttttg tttgtttgag acagggtctc attatgtagc tcaggctggc 1320
cccccaactt ttaacaatcg tcctgcctcg gcctcctgag tgctgggatg acaagggtgc 1380
accatcacac caggtttttt ccttttttga gagattttac tatgtaaccc gggctgggct 1440
attctcaagc tagtggcagt cctcttgcct caggctcctc ttgcctcagg caccccttgg 1500
gaccctctgg gacctatgtc cgagatgaat ggctgggtaa ggtagggtgg gaggttcagt 1560
gaaccttata ggttgggccc ttccttctgg gatcccttga tcatatggga agttctctag 1620
gctctcagca gccctgcatt cacacactga ctgaggcgcg acctgtatgt tgtgtttgag 1680
ggggatgtgt ggcagaggta tggctgtggc aaggccggtg ccttttattc ttgagattga 1740
gtcttatgta gctcaggctg gtcttgaact cactctcact gtgtagctag ggaagacctt 1800
gagcccttgc ctcagccaga atgctcagat gtcaggcagc gcaccacgtg actgtttctt 1860
tccattgtct tgtctttttg ttgttgttgt tttcgagaca gggtttctct gtgtagccct 1920
ggccgttctg gaactcactc tgtagaccag gctggcctta aactcagaaa tccacctgcc 1980
tctgcctctc aaatgctggg attaaaggcg tgcaccacca cgcccttttt cctttttctt 2040
aagtcaaggt ctatttgtgt agcccaggct ggcttcaagc tcatgacact cttcctgcct 2100
ctgcgtctgg aactatgaac ataccttact actctgtgct tacccacgcc atgggtagac 2160
agacttctag acttggtcaa cccccaccca caaggcaggc aaattaagtc cctgcaggtg 2220
ctttctttgg aggaaagccc gctttcatag tgatctgtca agctagaaag cactcccgcc 2280
acccagatat ctaagtgtga atctttggac aactggtgac ttctggccag cttttctggg 2340
gccggcctct gtccaggtgt ctgcccagga ccctgctcag tgcctgtctg tctcacacca 2400
gtgacttcct cacacccgcc tgttcaggcc cagtcttttc cgttcaagtg ctacaggcca 2460
agtaggctca aactgtgggt ttgtcttggg catccacagc agaatcagaa cccagagctt 2520
tgaagcctga gtgaggggag gggggcactc aggcttccgt ctctctgaga aacagacgat 2580
gaagaggccc ttaaaactct ttgcaacccc atgagcctcc ccaatgagcc tgtgacacac 2640
cggaactcac ctctgtgggt ggccgggagg gggaacaggg tcatggaaga tccagatgtc 2700
catgtggtca aggctaaact gtactaaata aaattatttc tcatcaccac tatacatgca 2760
taataaataa agtgtacatc aaaatt 2786
<210> 5
<211> 2343
<212> DNA
<213> Homo sapiens
<400> 5
atctcagaga gcgcggggtc cggacagccg cgcgctgagg gtctcggggc gggcgccgcg 60
ggacctctcc gggccatggc agcccctgtc aaagggaaca ggaagcagtc cacggagggt 120
gacgccctag acccacctgc atcccccaaa cctgctggca agcagaacgg aatccagaac 180
cccatctcgc tggaggactc ccccgaggca ggcggggagc gggaggagga gcaggagcgg 240
gaggaggagc aggccttcct ggtcagcctc tacaagttca tgaaggagcg acacacgccc 300
atcgagaggg tgccccatct cggcttcaag cagattaacc tgtggaagat ctacaaagca 360
gtggagaagc tgggggccta tgagctgcag tccatggccc taggagagag aatcggctgg 420
ccgctgctgg agccgcagag cagctgccaa actgcagtcc ttcgagtccc tgcgagggcg 480
gccggagctg caaggacccc gccgccaggg ggcgcccgcc ggccgcgccc tcacgaggtg 540
cccttgcagg tgaccgggcg ccgcctctgg aagaacgtgt acgacgagct ggggggcagc 600
ccaggcagca ccagcgcggc cacgtgcacg cgccgccact acgagaggct ggtcctgcca 660
tacgtgcggc acctgaaggg ggaggatgac aagccgctgc ccacctccaa gcccaggaaa 720
cagtacaaga tggctaagga gaacaggggg gatgatgggg ccaccgagag gccgaagaag 780
gccaaggagg agcggcgcat ggaccagatg atgccaggaa agaccaaagc agatgctgct 840
gacccagcac cacttcccag ccaggagccc cccaggaaca gcacagaaca gcagggcctg 900
gcctctgggt cttctgtgtc ctttgtgggt gccagcggct gtcctgaggc ctacaagcgg 960
ctcctatcca gcttctactg caaggggaca cacggcatca tgtcaccact ggccaaaaag 1020
aagctcctgg cccaggtgag caaggtggag gccttgcagt gccaggagga gggctgccgc 1080
catggggcag agccccaggc gtccccagct gttcacctcc cagagagtcc ccagagcccc 1140
aaagggctga ctgagaactc caggcaccgg ctgacccctc aggagggatt gcaggcccca 1200
ggtggcagcc tcagagagga ggcgcaggca ggcccctgcc cggcagcccc catcttcaag 1260
ggctgcttct acacccaccc caccgaggtg ctgaagcctg tcagccagca ccccagggac 1320
ttcttctcta gacttaaaga tggggtgcta ttggggcctc ctggcaaaga ggggctgtca 1380
gtgaaagagc cccagctggt gtggggcgga gacgctaacc gcccttctgc gttccataaa 1440
ggtggctcca gaaagggcat cctctacccc aagcccaaag cctgctgggt gtcccccatg 1500
gccaaggtcc cagccgagag ccccacgctc ccgcccacct tccccagtag cccaggcctg 1560
ggcagcaagc gcagcctgga ggaagagggt gctgcccaca gtgggaagag actgcgggcc 1620
gtgtctccct ttcttaagga ggcggatgcc aagaagtgtg gggccaaacc tgcagggtcc 1680
ggcctggtct cctgccttct gggcccagcc ctggggcctg tgcccccaga ggcctacagg 1740
ggcaccatgc tgcactgccc gctgaacttc actggcaccc cgggcccctt gaagggccag 1800
gctgcactcc ccttcagccc cctggtcatc ccggccttcc cggcccactt cctggccacc 1860
gcaggcccct cgcccatggc cgctggcctg atgcacttcc ccccaacgtc cttcgacagt 1920
gccctccgcc acagactttg cccggcctca tctgcctggc acgcaccacc agtcacaacc 1980
tatgcagcgc cccacttctt ccacctcaac accaagctgt aggccagccc atggtgttgt 2040
gtacactgtg gagtcgacag gggcctacaa caggcaggta ctgctgccag ggggctctga 2100
actagtgcct gctacccagg acacccgggc catgcccctg gctgggcagc ctggcacaag 2160
tgaagaagaa ggcagtggga aaactgggtt tatctcaagg cagcagcctg agcccaggag 2220
cagaggaccc agttgttata aggcgctggg agaggatggg cagctcccac tgccccagag 2280
cggagctcga agcacccagg ttgcccacgg aaaatccaat aaaaagacac cagtgtgaat 2340
cca 2343
<210> 6
<211> 5699
<212> DNA
<213> Mus musculus
<400> 6
agtcgagcgg cgccggtagt cagtcgcgcc gagagcgctg ggacaggacg gctgtgcgtg 60
tagagggtct ctgcatagcg acgcgcgctc tcgctgggcc atggcagcac ctccggccaa 120
agggaacaca gagcagtcag aagaaggtga cctcccgcag cttcctgtat cccccaagcc 180
agatgatgag cagagcagga gccagagccc cacccagctc caggactccc ctgaggcagg 240
tggggagcag gaggaggaac aggccttcct ggtcagcctc tacaagttca tgaaggagcg 300
acacacgccc atcgagaggg tgccccatct tggcttcaag cagattaacc tgtggaagat 360
ctacaaggca gtggagaagc tgggggccta tgagctggtg acaggccgcc gcctctggaa 420
gaacgtgtat gatgaacttg gcggtagccc aggcagcacc agtgcggcca catgcacacg 480
ccgccactat gagaggctgg tcctcccata tgtgcggcat ctgaaggggg aggacgacaa 540
gccactgcct cctaccaagc ccaggaagca atacaagatg gccaaggagc tgaggggaga 600
cgatgggacc actgagaagc tgaagaaggc caaggactca gaggagaggc gggtggagca 660
gaccacgcca ggaaagacca aatcagatgc cactggccag acacagcttc cctgccaggg 720
atcctcgagg gacagcacag aacagctggg cccagtatct ggaccctctc caccactcac 780
gggtgctagt agctgccctg aggcctacaa gcggctcttg tcaagctttt actgcaaagg 840
ggcgcatggc atcatgtcac cactggccaa aaagaaactc ctggcccagg tcagcaaggc 900
agaggccttg cagtgccaag aagagggctg tcgccatgga gcaaggagcc ccaacaagga 960
cattcaagac agtccccaga acctaagagg gccggctgag aactctgaac accagctaac 1020
cccccgggaa ggattgcagg cccctggtgg gagcaccagg atggaggccc aagtgggccc 1080
ctgccctaca gcccccatgt tctcaggctg ttttcatgcg taccccaccg aggtgctgaa 1140
acctgtcagc cagcacccta gggacttctt ctccggcctt aaagacaggg tgctgttggg 1200
accacctggt aaagaagaag gtccgacaac caaagagtcc catctggtgt ggggtgggga 1260
tgccaaccac ccctctgcat tccataaagg cagcacaaga aaaagaagtt tctaccccaa 1320
acccaaagcc tgctgggtgt ctcccatggc caaggtccct actgagaggc ctggagcccc 1380
atcccctcat cccagtagcc caggtcttgg cagtaagcgc ggcttggaag aagagggatt 1440
cgctcatggt ggcaagaaac tgagggcagt gtctcccttt ctgaaggagg tggattccaa 1500
ggagactggg ggcaagcctg cagcccctgg cttggctgta tcctgtctac tgggcccaac 1560
cccggggccc actcctccag aggcctacag gggcaccatg ctgcggtgtc ctctaaactt 1620
caccggtagc gcagaccctc tgaagggcca ggcctcactc cccttcagcc ccctggtcat 1680
ccctgctttc ccagcccacc ttctggctac aacaggctcc tcacctatgg ctgccagcct 1740
gatgcatttc cctcccacgc cctatgacgc tgtcctacgc aacagactgg gtccagcttc 1800
gtctgcctgg cacatgccac ccgtcacaac ctatgcggca cctcacttct tccacctcaa 1860
caccaaactg taggccagag cctatcctgc tatgctgtgg aggatttgat gggcagctgc 1920
cgccattatc tcaggcctga gccgactacc cagattccca ggccagtgag gctccccgag 1980
tctgtgtctc tctggtacag acagcaggga ggcagtgggg cttgtctgaa tgaagcagcc 2040
cgggcccaaa gccaggggac caagttgtgg taagatcatg aaagtacctg agctggtatt 2100
ttctctccac tgagaggccg gggagctagt tggcagctca aggcatccag gttggccatg 2160
aaagacccaa taaaaagaca ctggtgtgat tgcactcagc cctggggtgt acagcactgg 2220
atgtttgcaa ggggaggtga ggcaggagca agtgtgtagg tgtggtgacc aatgtgcgag 2280
caaagatgaa aggaggccac tctggcctgg ctgccatcac cccactggaa gggtggcagg 2340
gccagagcca aactcagcct ctggtgcaca gatgaacagc tgtgattcct ttcgctccag 2400
ctccagcctc ggggcacctg actgttgagg ttgccacggt gccaaagccc agagcacact 2460
ggtgacctgt gagacaagat ggaggggctg tgtcactgca accctctgag ctgagccaca 2520
cgcccccatc ccagaaggcc tcgggtcttt cagtgaacgg catcacttgc tctgagaggt 2580
tcttgctgtg ttgctcaggt tagtctcgga ctcccgacct aaagaattcc tgctgcggcc 2640
ttctcagtag ctggaactac tggtgtgaac ctgtgaagag gggatttgtg ggagctcaca 2700
taaaacccaa gtgaatctgt cctggtagtg ggcagacctg tgagcccagc tgcctagtgt 2760
tcccagtgag cgacctgtca cattcacacc tactttcctg ttctacatac tgggtgaagg 2820
gtagagggga cccatctcta cctgtgaatc tgttgccaag tcacagtgat atttacctgt 2880
ggttgctcca ggtgcccaca cagaaatccc atggcttggc acccattcct accttggaca 2940
tggcttgctc tgccagtccc aaggagactg tcagtacagc ttcacactgt tcctggaaag 3000
gcagtgccac tgtggaccag agatgccagg atgccagtga gccaagtcaa cagatggtta 3060
ctgacctaca tcatgggaac tcaccctgtt cctgacctca ggccatgggt aggagggcaa 3120
gtttttatgg cccccttagt tcacaggcgg aatggccaag gccagagaca gcaggtgtca 3180
ttgaggatgt ctggctctgg gaaacgggtg gccagggaaa gcagctgcct gtggaaaaga 3240
gctgggacac aggtgtcctc caagaccagg tagctagagg gtaagggtcc cactgatgca 3300
tcttgcaact ccccaccttc cttctggaga taccaggatg ccagcctgag tattcagatg 3360
acaagccctg agctcctggc taccccactg cacccatgtg ctacctgtct gggagctttt 3420
acagccccgt gaggagggat tctaggctag caaatgccct ggctgttggg ctgtacactg 3480
tggggtcagg tcccaggata gacagagggt accttcgtgc gtgcgtggaa ggatcccctt 3540
catctacaaa gtaacactag tctcaacctg ctcaaaggtg gcgtatgaca gacagcctga 3600
taatggtagc ttgttccaag ctgcaggaac ggagccctct gcaggttcat ctggagaata 3660
cacagctggg agggtagggt gtgtggcttt ctgggttgta ctccactctg cttcagcaaa 3720
aactctagaa atgaatgcac atcaggcttc ctgggaaatc ttgggacttt gcacccatgc 3780
gctagcccca catgattctc cttccttctg tgaatgagag aactcagctc agaggtgact 3840
ccaaacactg tggtacacac accttcctat gttcacttgt gtccctaaca ggttccccca 3900
gaggacccac aggccagcaa agctcttggc gtctgtgtcc agggcataac ttgtggtctg 3960
agcctacttc caaatcattc gtgacatttg agctaataat ggtgggagga ggcagaggcc 4020
actctggtat ttgtgctgac cccacccctg tccgtggtcc tggctcattt ccctggaaac 4080
agcttaagtg tgatgagttg ggcattcagt gggaaatacc tttgtttgcc ttgggtgtca 4140
aagcatgctg cccctgtaac tgtcttaggt ggcattggtt agcattacat gtgcatctcc 4200
cacacgaggc aagtatcacc accgccatag ttgtttggtt ggttggtttt cttggcttct 4260
ttttaagaca ggatttctct gtgtagccct ggctgacctg gaacttactc tgtagaccag 4320
gctggtctct aatagaggtc caccctctgc ctctacttgg attaaagata tgcaccacca 4380
tgcccagcaa ccacctcgcc cagcaaccat cagagtttta aaccgaatgg ctgggaattt 4440
tcctttgaag accttgcgaa tggctacagg aggtgatgga gaaacagcag caagtccccg 4500
agggagtggc gagagagtgg ggccaggagc caggggggct gttgggcagg gacggaggaa 4560
gccagagatg acttaggctg catttagaac cttctagtcc aggaggcagt tgggctttta 4620
tgtgaaataa agaaagatgg aagagagtcc tggctcccag atttggttgt ttgctttatg 4680
gtgctaggga tggaaccctg gacatttttt atgctcagca agctctgatc acttgctgca 4740
tcccagccct ggactctggc aagtggtagg tgtggacact ggagactaga acagagtagg 4800
gaacgtatcc ttggagatgg cagagtcaac atctggacac aggtctggag atgctgcgga 4860
cacatctggc cagcgtgtct gtttatactg tgagcagagt gagtgtgggg gctgggcttg 4920
gagaagggaa gcgagctagg cagtgatcac agtagagcaa agccgtccaa gggcacagcc 4980
agggcacaag agctcgggtt tccacttgac cttagcagcg tgagtatcat tgcacctagg 5040
aggccggctg gacacaatct caaggcaagg gacaactaag caccactcca gtgggagccg 5100
aagtggctgc atgaagggca tcaacagaga accagggaat gaagtgggga tggggggagg 5160
gagttgggaa cagtgggtaa gatctctaga ctgcagatct tggtgtgctg tggggacttg 5220
atggggtggg tgcacatgag aggcttggct gaatcagcag ctattggttg ctggatgagc 5280
tagagcaaga aggggtcaac agagctcagg catgggggac tttgaaacaa gggcagcggg 5340
catgctgggt gggcacagcc gccagggtaa ggtgtgtagg cacaggaaag gaggtgatgg 5400
ggcctcagca aaaaacacag cacaggaggc aagaagcaaa ggttaccttc cacatgaagt 5460
tgctgggctg gccagagcct tagactggca gaatagacat tagagaaggc cagaggcaat 5520
gaaaaacttc atggctttaa aggaatttta aatcaagagc agaggctgcc tggcatgttt 5580
agatgtgttt gttttctagt gtgctggatg gaacccagag ccttgggtat gctgggcaag 5640
tatccaacac tgagctatat catttggtgt tttttaaaaa aaagaattaa caatatttg 5699
<210> 7
<211> 6102
<212> DNA
<213> Homo sapiens
<400> 7
gtctctgtcc atccagactc ctgacgttca agttcgcagg gacgtcacgt ccgcacttga 60
acttgcagct caggggggct tttgccattt ttttcatctc tctctctctc tctccctcta 120
tctctcttct ctctctctcc ctcttttttt tttttttttt tttttttttt ttgcttaaaa 180
aaaagccatg acggctctcc cacaattcat cttccctgcg ccatctttgt attatttcta 240
atttattttg gatgtcaaaa ggcactgatg aagatatttt ctctggagtc tccttctttc 300
taacccggct ctcccgatgt gaaccgagcc gtcgtccgcc cgccgccgcc gccgccgccg 360
ccgccgcccg ccccgcagcc caccatgtct cgccgcaagc aaggcaaacc ccagcactta 420
agcaaacggg aattctcgcc cgagcctctt gaagccattc ttacagatga tgaaccagac 480
cacggcccgt tgggagctcc agaaggggat catgacctcc tcacctgtgg gcagtgccag 540
atgaacttcc cattggggga cattcttatt tttatcgagc acaaacggaa acaatgcaat 600
ggcagcctct gcttagaaaa agctgtggat aagccacctt ccccttcacc aatcgagatg 660
aaaaaagcat ccaatcccgt ggaggttggc atccaggtca cgccagagga tgacgattgt 720
ttatcaacgt catctagagg aatttgcccc aaacaggaac acatagcaga taaacttctg 780
cactggaggg gcctctcctc ccctcgttct gcacatggag ctctaatccc cacgcctggg 840
atgagtgcag aatatgcccc gcagggtatt tgtaaagatg agcccagcag ctacacatgt 900
acaacttgca aacagccatt caccagtgca tggtttctct tgcaacacgc acagaacact 960
catggattaa gaatctactt agaaagcgaa cacggaagtc ccctgacccc gcgggttggt 1020
atcccttcag gactaggtgc agaatgtcct tcccagccac ctctccatgg gattcatatt 1080
gcagacaata acccctttaa cctgctaaga ataccaggat cagtatcgag agaggcttcc 1140
ggcctggcag aagggcgctt tccacccact ccccccctgt ttagtccacc accgagacat 1200
cacttggacc cccaccgcat agagcgcctg ggggcggaag agatggccct ggccacccat 1260
cacccgagtg cctttgacag ggtgctgcgg ttgaatccaa tggctatgga gcctcccgcc 1320
atggatttct ctaggagact tagagagctg gcagggaaca cgtctagccc accgctgtcc 1380
ccaggccggc ccagccctat gcaaaggtta ctgcaaccat tccagccagg tagcaagccg 1440
cccttcctgg cgacgccccc cctccctcct ctgcaatccg cccctcctcc ctcccagccc 1500
ccggtcaagt ccaagtcatg cgagttctgc ggcaagacgt tcaaatttca gagcaacctg 1560
gtggtgcacc ggcgcagcca cacgggcgag aagccctaca agtgcaacct gtgcgaccac 1620
gcgtgcaccc aggccagcaa gctgaagcgc cacatgaaga cgcacatgca caaatcgtcc 1680
cccatgacgg tcaagtccga cgacggtctc tccaccgcca gctccccgga acccggcacc 1740
agcgacttgg tgggcagcgc cagcagcgcg ctcaagtccg tggtggccaa gttcaagagc 1800
gagaacgacc ccaacctgat cccggagaac ggggacgagg aggaagagga ggacgacgag 1860
gaagaggaag aagaggagga agaggaggag gaggagctga cggagagcga gagggtggac 1920
tacggcttcg ggctgagcct ggaggcggcg cgccaccacg agaacagctc gcggggcgcg 1980
gtcgtgggcg tgggcgacga gagccgcgcc ctgcccgacg tcatgcaggg catggtgctc 2040
agctccatgc agcacttcag cgaggccttc caccaggtcc tgggcgagaa gcataagcgc 2100
ggccacctgg ccgaggccga gggccacagg gacacttgcg acgaagactc ggtggccggc 2160
gagtcggacc gcatagacga tggcactgtt aatggccgcg gctgctcccc gggcgagtcg 2220
gcctcggggg gcctgtccaa aaagctgctg ctgggcagcc ccagctcgct gagccccttc 2280
tctaagcgca tcaagctcga gaaggagttc gacctgcccc cggccgcgat gcccaacacg 2340
gagaacgtgt actcgcagtg gctcgccggc tacgcggcct ccaggcagct caaagatccc 2400
ttccttagct tcggagactc cagacaatcg ccttttgcct cctcgtcgga gcactcctcg 2460
gagaacggga gtttgcgctt ctccacaccg cccggggagc tggacggagg gatctcgggg 2520
cgcagcggca cgggaagtgg agggagcacg ccccatatta gtggtccggg cccgggcagg 2580
cccagctcaa aagagggcag acgcagcgac acttgtgagt actgtgggaa agtcttcaag 2640
aactgtagca atctcactgt ccacaggaga agccacacgg gcgaaaggcc ttataaatgc 2700
gagctgtgca actatgcctg tgcccagagt agcaagctca ccaggcacat gaaaacgcat 2760
ggccaggtgg ggaaggacgt ttacaaatgt gaaatttgta agatgccttt tagcgtgtac 2820
agtaccctgg agaaacacat gaaaaaatgg cacagtgatc gagtgttgaa taatgatata 2880
aaaactgaat agaggtatat taatacccct ccctcactcc cacctgacac cccctttttc 2940
accactcccc ttccccatcg ccctccagcc ccactccctg taggattttt ttctagtccc 3000
atgtgattta aacaaacaaa caaacaaaca gaagtaacga agctaagaat atgagagtgc 3060
ttgtcaccag cacacctgtt ttttttcttt ttctttttct tttttctttt tccttttttt 3120
tttttttcct ttatgttctc accgtttgaa tgcatgatct gtatggggca atactattgc 3180
attttacgca aactttgagc ctttctcttg tgcaataatt tacatgttgt gtatgttttt 3240
ttttaaactt agacagcatg tatggtatgt tatggctatt ttaaattgtc cctaattcgt 3300
tgctgagcaa acatgttgct gtttccagtt ccgttctgag agaaaaagag agagagagag 3360
aaaaagacca tgctgcatac attctgtaat acatatcatg tacagtttta ttttataacg 3420
tgaggaggaa aaacagtctt tggattaacc ctctatagac agaatagata gcactgaaaa 3480
aaaatctcta tgagctaaat gtctgtctct aaagggttaa atgtatcaat tggaaaggaa 3540
gaaaaaaggc cttgaattga caaattaaca gaaaaacaga acaagtttat tctatcattt 3600
ggttttaaaa tatgagtgcc ttggatctat taaaaccaca tcgatggttc tttctacttg 3660
ttataaactt gtagcttaat tcagcattgg gtgaggtaat aaaccttagg aactagcata 3720
taattctata ttgtatttct cacaacaatg gctacctaaa aagatgaccc attatgtcct 3780
agttaatcat catttttcct ttagtttaat tttataaaca aaactgatta taccagtata 3840
aaagctactt tgctcctggt gagagcttaa aagaaatggg ctgttttgcc caaagtttta 3900
ttttttttaa acaatgatta aattgaatgt gtaatgtgca aaagccctgg aacgcaatta 3960
aatacactag taaggagttc attttatgaa gatatttgct ttaataatgt ctttttaaaa 4020
atactggcac caaaagaaat agatccagat ctacttggtt gtcaagtgga caatcaaatg 4080
ataaacttta agaccttgta taccatattg aaaggaagag gctgacaata aggtttgaca 4140
gaggggaaca gaagaaaata atatgattta ttagcacaac gtggtactat ttgccattta 4200
aaactagaac aggtatataa gctaatattg atacaatgat gattaactat gaattcttaa 4260
gacttgcatt taaatgtgac attcttaaaa aaagaagaga aagaatttta agagtagcag 4320
tatatatgtc tgtgctccct aaaagttgta cttcatttct tttccataca ctgtgtgcta 4380
tttgtgttaa catggaagag gattcattgt ttttattttt atttttttaa ttttttcttt 4440
tttattaagc tagcatctgc cccagttggt gttcaaatag cacttgactc tgcctgtgat 4500
atctgtatct tttctctaat cagagataca gaggttgagt ataaaataaa cctgctcaga 4560
taggacaatt aagtgcactg tacaattttc ccagtttaca ggtctatact taagggaaaa 4620
gttgcaagaa tgctgaaaaa aaattgaaca caatctcatt gaggagcatt ttttaaaaac 4680
taaaaaaaaa aaaactttgc cagccattta cttgactatt gagcttactt acttggacgc 4740
aacattgcaa gcgctgtgaa tggaaacaga atacacttaa catagaaatg aatgattgct 4800
ttcgcttcta cagtgcaagg atttttttgt acaaaacttt tttaaatata aatgttaaga 4860
aaaatttttt ttaaaaaaca cttcattatg tttagggggg aactgcattt tagggttcca 4920
ttgtcttggt ggtgttacaa gacttgttat ccatttaaaa atggtagtgg aaattctatg 4980
ccttggatac acaccgctct tcaggttgta aaaaaaaaaa acatacattg gggaaaggtt 5040
taagattata tagtacttaa atataggaaa atgcacactc atgttgattc ctatgctaaa 5100
atacatttat ggtctttttt ctgtatttct agaatggtat ttgaattaaa tgttcatcta 5160
gtgttaggca ctatagtatt tatattgaag cttgtatttt taactgttgc ttgttctctt 5220
aaaaggtatc aatgtacctt ttttggtagt ggaaaaaaaa aagacaggct gccacagtat 5280
atttttttaa tttggcagga taatatagtg caaattattt gtatgcttca aaaaaaaaaa 5340
aaagagagaa acaaaaaagt gtgacattac agatgagaag ccatataatg gcggtttggg 5400
ggagcctgct agaatgtcac atggatggct gtcatagggg ttgtacatat ccttttttgt 5460
tcctttttcc tgctgccata ctgtatgcag tactgcaagc taataacgtt ggtttgttat 5520
gtagtgtgct ttttgtccct ttccttctat caccctacat tccagcatct taccttcata 5580
tgcagtaaaa gaaagaaaga aaaaaaaagg aaaaaaaaaa aaaaaccaat gttttgcagt 5640
ttttttcatt gccaaaaact aaatggtgct ttatatttag attggaaaga atttcatatg 5700
caaagcatat taaagagaaa gcccgcttta gtcaatactt ttttgtaaat ggcaatgcag 5760
aatattttgt tattggcctt ttctattcct gtaatgaaag ctgtttgtcg taacttgaaa 5820
ttttatcttt tactatggga gtcactattt attattgctt atgtgccctg ttcaaaacag 5880
aggcacttaa tttgatcttt tatttttctt tgtttttatt ttttttttta tttagatgac 5940
caaaggtcat tacaacctgg ctttttattg tatttgtttc tggtctttgt taagttctat 6000
tggaaaaacc actgtctgtg tttttttggc agttgtctgc attaacctgt tcatacaccc 6060
attttgtccc tttattgaaa aaataaaaaa aattaaagta ca 6102
<210> 8
<211> 6122
<212> DNA
<213> Mus musculus
<400> 8
gacgttcaag ttcgcaggga cgtcacgtcc gcacttgaac ttgcagctca ggggggcttt 60
tgccattttt ttcatctctc tctctccctc tatccctctt ctctcttcct ctctctcttt 120
tttttcctta aaaaaaaaaa agccatgacg gctctcccac aattcatctt ccctgcgcca 180
tctttgtatt atttctaatt tattttggat gtcaaaaggc actgatgaag atattttctc 240
tggagtctcc ttctttctaa cccggctctc ccgatgtgaa ccgagccgtc gtccgcacgc 300
cgccgccgcc gccgccgccc gccccgcagc ccaccatgtc tcgccgcaag caaggcaaac 360
cccagcactt aagcaaacgg gaattctcgc ccgaacctct tgaagccatt cttacagatg 420
atgaaccaga ccatggcccg ttgggagctc cagaagggga ccacgacctt ctcacctgtg 480
ggcagtgcca gatgaatttc ccactggggg acattcttat ttttatcgag cacaaacgga 540
aacaatgcaa tggcagcctc tgcttagaaa aaggtgtgga taagccgcct tccccttctc 600
ccatcgagat gaaaaaggca tccaatcctg tggaggttgg catccaggtc acgccagagg 660
atgacgattg tttatcaacg tcatctagag gaatttgccc caaacaggaa cacatagcag 720
ataaacttct gcactggagg ggcctgtcct ctcctcggtc tgcacacgga gctctaatcc 780
ccacgcccgg gatgagtgca gaatatgccc cgcagggtat ttgtaaagat gagcccagca 840
gctacacatg tacaacttgc aaacagccat tcaccagtgc atggtttctc ttgcaacacg 900
cacagaacac tcatggatta agaatctact tagaaagtga acacggaagt cccctgaccc 960
cgcgggttgg tatcccttca ggactaggtg cagaatgtcc ttcccagcca cctctccatg 1020
ggattcatat tgcagacaat aaccccttta acctgctaag aataccagga tcagtatcga 1080
gagaggcttc cggcctggca gaagggcgct ttccacccac tccccccctg tttagtccac 1140
caccgagaca tcacttggac ccccaccgca tagagcgcct gggggcggaa gagatggccc 1200
tggccaccca tcacccgagt gcctttgaca gggtgctgcg gttgaatcca atggctatgg 1260
agcctcccgc catggatttc tctaggagac ttagagagct ggcagggaac acgtctagtc 1320
caccgctgtc cccaggccgg cccagtccta tgcaaaggtt actgcaacca ttccagccag 1380
gtagcaagcc acccttcctg gcgacgcccc ccctccctcc tctgcaatcc gcccctcctc 1440
cctcccaacc cccggtcaag tccaagtcat gcgagttctg cggcaagacg ttcaaatttc 1500
agagcaactt ggtggttcac cgacgcagcc atactggtga gaagccctat aagtgcaacc 1560
tgtgcgacca cgcgtgcaca caggccagca agctgaagcg tcacatgaag acacacatgc 1620
acaaatcgtc ccccatgaca gtcaagtccg acgatggcct ctccacagcc agctccccgg 1680
aacctggtac cagcgacctg gtgggcagcg ccagcagtgc gctcaagtca gtggtggcca 1740
agttcaagag tgagaacgac cccaacttga tcccagagaa cggggatgag gaggaagagg 1800
aggacgacga ggaagaagaa gaagaggagg aagaggagga ggaggagctg acggagagcg 1860
agagggtgga ctacggcttc gggctgagcc tggaggctgc acgccaccat gagaacagct 1920
ctcggggcgc agtggtgggc gtgggcgacg agggccgcgc cctgcccgat gtcatgcagg 1980
gcatggtgct cagctccatg cagcacttca gcgaggcctt ccaccaggtc ctgggcgaaa 2040
agcataagcg tagccacctg gccgaggccg agggccatag ggacacttgt gatgaagact 2100
cggtggccgg tgagtcagac cgcatagacg atggcactgt taatggtcgt ggctgctccc 2160
ccggcgaatc ggcttcgggg ggtctgtcca aaaagctgct gctgggtagc cccagctcgc 2220
tgagcccctt ctccaagcgc atcaagctgg agaaggagtt tgacctgccc ccggccgcga 2280
tgcctaacac ggagaacgtg tattcgcagt ggctcgctgg ctatgcggcc tccaggcagc 2340
tcaaagatcc cttccttact ttcggagact ccagacaatc gccttttgcc tcctcatcag 2400
agcactcctc ggagaacggg agcttgcgct tctccacacc gcccggggag ctggacggag 2460
ggatctcagg gcgcagcggc acaggaagtg gagggagcac gccccatatt agtggtccgg 2520
gcccgggcag gcccagctca aaagagggca gacgcagcga cacttgtgag tactgtggga 2580
aagtcttcaa gaactgtagc aatctcactg tccacaggag aagccacacg ggcgaaaggc 2640
cttataaatg cgagctgtgc aactatgcct gtgcccagag tagcaagctc accaggcaca 2700
tgaaaacgca tggccaggtg gggaaggacg tttacaaatg tgaaatttgt aagatgcctt 2760
ttagcgtgta cagtaccctg gagaaacaca tgaaaaaatg gcacagtgat cgagtgttga 2820
ataatgatat aaaaactgaa tagaggtata ttaataccct ccctcactcc cacttgatgc 2880
cccccttcca ccccttcccc attgtccttc cagccctact ccctgtagga tttttctagt 2940
cccatgtgat caaacaaaca aacaaacaaa caacagaggt aatggaagct aagaatatga 3000
atgagtgctt gtcaccagca cacctggttt tttgttttgt ttttcctttt ttttttcttt 3060
ttcttcttct tttttttaaa ttttaaattc tttatgttct caccgtttga atgcatgttt 3120
ggggcaatac tattgcattt tacgcaaact ttgagccttt ctcttgtgca ataatttaca 3180
tgttgtgtat gtttttcccc ccttaactta gacagcatgt atggtatgtt acggctattt 3240
taaattgtcc ctaattcatt atgagcaaac atgttgttgc tgtttccagt tccattctga 3300
gagtgtgagg gagggagggt agaaaacaac gcatgctgca tacataattc tgtaatacag 3360
atcatgtgca gctttatttt ataacacgag gagggaaacg gtgtctgggt tgactaaccc 3420
tctgcagaca gagcagatag cagtgaaaaa aaggtgctaa atgtctgtct ctaaagggtt 3480
acatgtatta attggagagg gaaaaaaggc cttgaattga caaattaaca gaagaacaag 3540
tttattctat catttggctt ttaaaatgag tgccttggat ctattcaaac catgttgatg 3600
gttttttttc tgcttgttat aaacttgtag tttaatctag cattgggtga ggtaataaac 3660
tttaggacct agcatgtaat tctgtgttgt atttctcaca acaatggcta cctaaaaata 3720
tgacccatta tgtcctagtt aatcattgat ttttgccttt aactttgtga acaaaactga 3780
ttataccagt ataaaagcta ctttgctcct tgtgagagca taaaagaaat gggctgtttc 3840
gcctaaagtt ttattttatt ttatttttaa atggttatca aattgaatgt gaaatgtgca 3900
aaggccctgg aatgtgatga aatacattag caagaagttc atcttgtgac aatacttgtt 3960
taaaatgatg catttaatga aattctggcg ccaaaagaag tagatccggc tctagttggt 4020
tgttgagtgg acaataaaat gataaagccc tttagaggac atttgaaaga acaggctgat 4080
atgatgagag agagagagag agacagaaaa cggtagtgat tggttagcac gatgtagtac 4140
tgtttgccat ttgaaactag aacaggtgta taaggggcca gcgatacaat gatgattaac 4200
tctgaagctc taagacttgc atttaatgtg acagtcttca aaaagaagag gaagaccttt 4260
aagagcagca gtatctatgt ctgtgctccc tggaagttgt acttcatttc ttttccatac 4320
actgtgtgct atttgtgtta acattgaaga ggatttgttt ttattttgtt ttattctttc 4380
tttctttctt ttttcttcct tctttgtttt aagctagcat ctgccccagt tggtgttcaa 4440
atagcacttg actctgccta tgatacctgt atcttttctc taatcagaga tacagaggtt 4500
gagtataaaa taaacctgct cagataggac aattaagtgc actgtacagt tttcccagtt 4560
tacaggtctt tattaaggga aacgttgcaa gaatgctgaa aacaattgaa cacaatctca 4620
atgatgagca ttaaaaaata ataaaaaaaa acaagcaaac ctaaaaaaaa ctaagacaga 4680
cgttgccagc cattgacttg actattgagc ttcctcactt ggatgcaaca ttgcaagcgc 4740
tgtggatgga aacaacacac ttaacataga aacgaatgac tcctttgctt ctacagtgca 4800
aggatttttg tacaaaactt ttttaagtat aaatgttaag aaaagaattt ttaaaaagac 4860
acttcattat gtttaggggg gaacagcatt ttagggttcc attgtcttgg tggtgttaca 4920
agacctgtta tccatttaaa aatggtagtg gaaattctat gccttggatc acacaccgct 4980
cttcaggttg taaaaaaaaa tgaaaacaaa acaaaacaaa aaaaaaacat acatggggaa 5040
aggtttaaga ttatatagta cttaaaaata ggaaaacgca cactcatgtt gattcctatg 5100
ctaaaacaca gttatggtct tctttctgta tttctagaat ggtatttgaa ttaaatgttc 5160
atctagtgtt aggcactata gtatttatat tgaagcttgt atttttaact gttgcttgtt 5220
cactcaaaag gtatcaatgt acctttttgt tagtagaaaa aaaaagacag gctgccacag 5280
tatatttttt taatttggca ggataatata gtgcaaatta tttgtatgct gagagagaga 5340
gagagagaga gagagagaga gagagaggtg tgacattgta cagagaagcc atataatggc 5400
ggtttgggga gcctgctaga atgtcacatg gatggctgtc ataggggttg tacatatcct 5460
tttccccctt tcctgctgcc atgctgtacg cagcactgca agctaatagc gttggtttgt 5520
tatgtagtgt gctttggccc ctcctccccg ctcacccgac attccagcat cttaccttca 5580
tatgcagtaa aagaaagaaa gaaaaaaaaa aaggaaaaaa aaaacaacaa caatgttttg 5640
cagttttttt cattgccaaa aactaaatgg tgctttatat ttagattgga gagaatttct 5700
tatgcaaagc atattaaaga gaaagcccgc tttagtcaat acttttttgt aaatggcaat 5760
gcagaatatt ttgttattgg ccttttctat tcctgtaatg aaagctgttt gtcgtaactt 5820
gaaattttat cttttactat gggagtcact atttattatt gcttatatgc cctgttcaaa 5880
acagaggcac ttaatttgat cttttatttt tctctgtttt tattattatt ttttttaatt 5940
tggatgacca aaggtcattg caacctggct ttttactgta tttgtttctg gtctttgtta 6000
agttctattg gaaaaaccac tgtctgtgtt tttttggcag ttgtctgcat taacctgttc 6060
atacacccat tttgtccctt tattgaaaaa aaataaaaaa attaaagtac taaaaaaaaa 6120
aa 6122
<210> 9
<211> 4480
<212> DNA
<213> Homo sapiens
<400> 9
aaaccggaat ggcccgaggg aaggccgcgc agggcagggc cccagatggt tcctgtcagg 60
gaagtggcgg gcgcagctgc aggcctccgg ccccggcatt atcacgggga cacagctggc 120
tgcctcaccc gcaggctgca gggagacctt ccccagcctg cagccccagg cccgccccgc 180
gtcacatgag ccccagggct cccaccccct ccccagggca gaggacaccc agttggtggc 240
cgggagggcc tcggctttcc agggacagag gcccaactcc aggacgcccc agctggccca 300
gcccctcctc tttccctcaa ggctgcagga ggtcgggaaa ggcagtcctg gtagaggcct 360
gtcctgggct ccaggttggc ccctgagggt ggccctcctc atgccggctt caagactgag 420
ggacagggca gccagttcag cctcgggatc cacctgtggc tccatgtccc agacgcaccc 480
tgtgctggag agcggcctcc tggcatctgc cggctgctcc gcaccccggg gtcccaggaa 540
gggcggccca gccccagtgg acaggaaagc taaggcctca gcgatgccgg actccccagc 600
ggaggtgaag acgcagcccc ggtccacacc ccccagcatg ccgcccccac cgcctgccgc 660
atcccagggg gccacacgcc ccccctcctt cacgccacac acacatcgag aggacgggcc 720
tgcgacgctg ccccacggcc gttttcatgg ctgcttaaaa tggtctatgg tctgtctctt 780
gatgaacggc agcagccact caccaacagc catcaatggt gcaccgtgca cacccaacgg 840
cttcagcaat ggcccggcca cctcgtccac agcctccttg tccacacagc acctgccccc 900
agcctgcggg gcccggcagc tcagcaagct caagcgcttc ctcaccacac tgcagcagtt 960
tggcagcgac atctccccag agattgggga gcgcgtgcgc acactggtgc tgggcctggt 1020
gaactcgaca ttgacgatcg aggagtttca ttccaagctt caggaggcca ccaacttccc 1080
tctgcggccg tttgtcattc ccttcctgaa ggcaaacctg cccttgctgc agcgggagct 1140
cctgcactgt gcacgcctgg ccaagcagac gcccgcccag tacttggccc agcatgagca 1200
gctcctgctg gacgccagcg cctcctcccc catcgactcc tcagagctgc tactggaagt 1260
caacgagaac ggcaagagga ggacgcccga caggaccaaa gagaacgggt cagaccgcga 1320
cccgctgcac cccgagcacc tcagcaaacg gccatgcacc ctgaaccctg cccagcgcta 1380
cagccccagc aacgggccac cgcagcccac accgccgccg cactaccgcc tggaggacat 1440
agccatggcc caccacttcc gagatgccta ccgccaccca gacccccggg agctacgaga 1500
gcgccatcgg ccgcttgtgg tgcctgggtc ccggcaggaa gaagtgatcg accacaagct 1560
cacagagcgt gagtgggcag aagagtggaa gcacctcaac aacctcctga actgcatcat 1620
ggacatggtg gagaagacgc ggcgctcgct cacggtgctg cgcaggtgcc aggaggccga 1680
ccgcgaggag ctcaaccact gggcgcggcg ctacagcgac gccgaggaca caaagaaggg 1740
ccccgctccc gccgcggccc ggccccgcag cagctccgcc ggtcccgaag ggcctcagct 1800
agacgtgcct cgcgagttcc tgccgaggac cctcaccggc tacgtgcctg aggacatctg 1860
gaggaaggct gaagaggccg tgaatgaggt gaagcggcag gccatgtcgg agctgcagaa 1920
agccgtgtcg gacgcggagc gcaaagcgca cgagctcatc accacggagc gtgccaagat 1980
ggagcgggcc ctggccgagg cgaagcggca ggcctccgag gacgccctga cggtcatcaa 2040
ccagcaggag gactccagcg agagctgctg gaactgcggg cggaaagcca gtgagacgtg 2100
cagcggctgc aacgcggcac gctactgcgg gtccttctgc cagcatcggg actgggagaa 2160
gcatcaccac gtgtgtggcc agagcctgca gggccccaca gccgtggtgg ccgacccggt 2220
gcctggaccg cccgaagccg cccacagcct gggcccctcc ctgcctgtgg gtgctgccag 2280
ccccagcgaa gccggctctg cggggccttc tcgccccggc tcccccagcc cacctggccc 2340
actggacacc gtgccccgct gaccccactg gcccctggcc tgccggacac agcaccgtgc 2400
caaccccacc cagctccagg cccaccggat gctgtgcctg gcctccgatg cctggcctgc 2460
cagacactgc gccccgcctg acctggggga gccgaccaat tagtcactgc tgctactgcc 2520
cctctccgaa agaagacaca gaaccaacaa aaccgcattc agtgcacctg cctcagctac 2580
ctaatgattc cgcgcggaga cctcctgaca acgtctcttc aagcatcctc agaagcctcg 2640
actgagcttt agacagcaga gcagatgccg caggcgcggc ggctctgccc acctctcttt 2700
tcctctctgt ctgtctctcc ccctctgtct tctctatcct ctctctctct atgactatca 2760
cacactttct cttcaatgaa aaaatcgaat tggtggctta tattttcagc aaagaatttt 2820
ggggggtttt gtgtgttggc aaaagagcta ctcagaaatg gacaaagaaa acgggggggt 2880
tctccccctc ctgattaaaa agggagaaag aaaactgcga ttttatagct ggagatctga 2940
acccagctgt gcccctcccc caggggcgtg aggctgatca gcgaagacgg gaggaaagat 3000
ttcgatttct gactcaagat gcatttttgg tttcagattt ttttttcctg taatgttaaa 3060
ctctttggct ttaagtaaaa atccaaaaag tttttttaaa aaagcaaagg aagcatactt 3120
gtgaactacc ttgctagcta gccagccaag gataccggac acacctctgc tccaaaggaa 3180
atccaaaaaa gcaaacacaa gaaatcaaaa tccaaaattt gtttgtcact gccaaagtat 3240
ttttttcact gtttcacttg ctcttgggtt tgtttggatg tgggtctttt tctcttctgt 3300
tctgattttg tttgtgggtg tcgggatatt tgggtgcaga gggtttgtgc ccagttagaa 3360
gcgacttttg ttctcttctg cgtaggcgtt ggtgcgtccg ccgcgtgtgc gtggtccgtg 3420
tgccgttgct ccggcctgcg tctccatatg tgtaggaaag gacacgccgt ctgtcctcac 3480
gccccctgtg acttttcata tttccgtttt ccacttgtgg aaaaaaagtg ctaaagtttt 3540
cttcccagag agagcataat tccgaaacaa aactgtgaca atcttttggg ttgattctcg 3600
actgcttttc gagcatgcgg agccagcagg cctccctgaa acactgcttc tcggccagcc 3660
cgtcctcctc tacctctctc ctctccgcgc cctccgacct ctctcggccc cctcacccca 3720
gctccgacct ctctcagccc catcgcccca actccaacct ctcggcccca tcgccccacc 3780
gcagctactc ccctttcttc caaacttttg cagaaaaaac aaaaaaacta caaacaaaag 3840
cagccctctg cctcctcccc agggaagacc ctgaccgtgt acatagccct ggtgctcctg 3900
cccagccacc cctcagatgc gttcgcctct ggccctgggg tgtgtctcgg tgacgttttc 3960
tatcagacgt gctccctccc atcctccagc cctgcccacc ctccctccac tcctctcaac 4020
tgcctcagcg atttcaagaa ggaaataaag ggataaagaa attcatgctt gcaccgagta 4080
caaggacaga cagcaggcac ggcccgcagc ctggcatctg tgcgtgtggc gtggcccgtg 4140
gcttggcatc tgtgtgcgtg gtgtggcccg tggcctggca tctgtgtgcg tggcgtggcc 4200
cgtggcctgg catctgtgtg tgtggcgtgg cccgtggcct ggcatctgtg cgcgtggcgt 4260
ggcccgtggc ctggcatctg tgtgcgtggc tatcaggagt tctaggaact cagtgcaata 4320
cgggagtgac ccagctactg aaccagccac gaacagcccg ccagaggcct gaagctgagc 4380
gtgtacgtta atgtgaatgt atatagtctt tgcagaggtc caaatgatat tcatgatggt 4440
aataaacgag atgtttgcca aataaaaaac agaaaccgca 4480
<210> 10
<211> 7659
<212> DNA
<213> Mus musculus
<400> 10
agggccacaa cccagctctg ccggctgtag tgactagaaa ggcctggagc ctccaaggaa 60
cagaggcacg ggctccgaga cgccaaagct cctccagccc tcctgttctc tccagacccc 120
acgaaatcag aaaaggtgct tcagggtggg ctctggaggc cggccagctc cctccagccc 180
caggtaccat caatctccgg ctccatctgc agctccatgt cccaggcatc caccaccact 240
ctggagagtg gggcactcct ctcgggaccc cggggtcttc agaatggaag cccagctcac 300
aggaaggaga aggctgcagc aatgccagac tccccggctg aagtgaagac gcagccccgg 360
tccacacccc ccagcatgcc gcccccacct cccacctcat cccagggagc cacacgacca 420
ccctccttca cacctcacac acatggcgag gatggacctg cgacgtctct tccccatggc 480
cgtttccacg gctgcttaaa gtggtccatg gtctgtctct tgatgaacgg cagcagccac 540
tcacccacgg ccatccacgg tgccccatct acacccaatg gcttcagcaa cggcccagcc 600
acctcatcca cggcctcgct ctccacacag cacctgcccc cggcgtgcgg ggcacggcag 660
ctcagcaagc ttaagcgttt cctcaccacc ctacagcagt ttggcagtga catctcacct 720
gagatcgggg agcgcgtgcg cacactggtg ctgggcctgg tgaactcaac tctgacgatc 780
gaagagtttc atgccaagct ccaggaagcc accaactttc cactgaggcc gtttgttatc 840
ccttttctga aggctaatct tccactgctg cagcgtgagc tcctgcactg tgcccgcctg 900
gccaaacaga cacctgccca gtacctggcc cagcacgaac agctgctgct ggacgccagc 960
gccacctccc ctgtcgactc gtctgagctc ctgctggaag tcaacgagaa cggcaaaagg 1020
agaacacctg acaggaccaa agagaatgga tcagaccggg accctctgca ccccgaccac 1080
ctcagtaagc ggtcctgcac cctgagcccc gcccagcgct gcagccccag caatgggctg 1140
ccccacccga cgccaccccc acccccgcac tatcgcctgg aggacatggc catggcccac 1200
catttccggg actcctaccg ccatcctgat ccccgagagc tacgggaacg ccaccggccc 1260
ctggccatac ctgggtctcg acaagaagaa gtgattgatc acaggctcac agaacgcgag 1320
tgggcagaag aatggaagca cctcaacagt cttctgaact gcatcatgga catggtggag 1380
aagacccggc gatccctcac cgtcctgcgc cggtgtcagg aggccgaccg tgaggaactc 1440
aaccactgga tccggtgcta cagtgactct gaggagggga agaagggccc tacccccatc 1500
tctgcccggt ccctcaacag ctgcagtggc cctgaggggt ctcagctaga tgttcaccgg 1560
gacttcacgc ccaggaccct gtctggctac atgcctgaag agatctggag gaaggctgaa 1620
gaagctgtga atgaggtgaa gcgccaggcc atgtcagaac tacagaaagc tgtgtctgat 1680
gcggagcgca aagcccatga actcatcacc acagagcgtg ccaagatgga acgagccctg 1740
gcggaggcca agcgacaggc ctcggaggat gccctgactg tcatcaacca gcaagaggac 1800
tccagcgaga gctgctggaa ctgcgggcgc aaggccagcg agacgtgcag tggctgtaac 1860
gccgcccgct actgcgggtc cttctgtcag cacaaagact gggagaaaca ccatcacgtg 1920
tgcggccaga gtctgcaggg ccccgcggct gcagtggctg acccactacc tggacagcct 1980
gacgccactg ccagccccag cgaagccggc tcggcagggc cctctcgtcc ctgctctccg 2040
gggccgccag gcccgctgga cgctgctgtg ccccgctgac ctccagatct gacacccagc 2100
ccatggacgc catgccctgc caacctcctg gccccaccgt ggcccaccag ttgcctggag 2160
ccattgctgc tactgcttct ctccaaaaga aaacacagat ccaacagaac tgcatccgtg 2220
cagccccagc tacctgacaa ggtctgccgg gacctctaca gcctctcgtc catcgcaagc 2280
accctcagaa agcatcgcag agcgtcagac agtggcacca gcaggagtgt ggccagctcc 2340
gccgctgtct gtcccctctg tgtccgtctc tctgtgtccg tctgtctttc tgcgtctgcc 2400
tctctctgtg tgtctctccg tgtctttgtc tcctgccgtt tccctgactc tccggcgtct 2460
ctgtctttgt aaagtccaca tgatctctct gtcatcagag aaacctagtt ggtagctttt 2520
cttttccatg aagaactttt ggagattttg ttttgttttg ttggcaaaca agctacttag 2580
aaatggacaa agaagactgt ggggttctcc ccattcctca tgagtaaggg aagaaactgt 2640
gatttttcta tccagagttg ctgtatcgcc cagccagccc caggggcatc agcgagcaca 2700
cagcagagat aatgagagca actgcaattt ccaacttaag aagcagcttt tgtttcaggt 2760
tttactcctt taatgtcaaa ctctttggct ttaagtgaaa aaaaaaaaaa ggaaaaaaaa 2820
atccaaaaag tttttttttt ttttaagcaa aagaaacaca cctgtaaact accttgccag 2880
ctagccagcc aaggatgcca gacacacctc gctccaaagg aagcccaaaa aagcaaactc 2940
aagaaattga aatccaaaat ttatttttat cactgccaaa gtattttctt catggtctct 3000
ccgccctggg ttggtttgca tgtcagtctt tgatttgggt tttgattttg ttcagggggt 3060
gttgggatgc tgggatttgg tgggtggggc caagaagaaa ccttttgttc ctttttgact 3120
agtaggcagc atccttgctg ggcagagcca tcggcagcaa ggccacgtga ccctcagcac 3180
cgcatccaga agccccagtc agcgtgagcc tgagcgttgt gtgccctagg gctccgtcca 3240
tgcgttccct acatgcaagg gaggcacctc cttccatcgg tccccacacc ttcctgggac 3300
ttctcataag tcatttccac ttgtgaaaaa aaaaaaagtg ctaaagtgct cttcccagag 3360
agagcacact tcctaaacga aactgtgaca atctttttgg ttgattcttg actgcttttg 3420
agagcataag gagacagcaa atcacgcttt ctcagttttc cctcctctac ctctctgctc 3480
ttccatccca ccctacctcc atctcggccc catcaccctg cccccagtgt cttgctgtgg 3540
ctaccctcat ttctttcaaa cttttacaga aaaaaaggaa aaagaaaaaa aaaaaacacg 3600
aaagccagca gccacccgca cctcacccgg aagactccag cccggctgta catatccctg 3660
tgttgtatcc ccaatgttgg tctccagtcc tgggggtgac ggtgatgctt gcccatctac 3720
actctagccc ctgcccaccc tgcccttcgc ccgctcgact ccctcaagga ttcaaggagg 3780
aaatgaagga agaaggctca tgcctgtacc aaacaaaaag agacagcaga ctcagtccag 3840
gtctgcacct ctgttgtggc tgcagcaagc cgcaggccta gcgtgcaata tgggggattg 3900
ctcctgaacc ctgggcccgg gggggccctg cccagagcaa ggtgtgcagc gtgtgttaat 3960
gtgaatgtac atagtctcca cagaggtccc aaaccgtggc atcagtaccg aggagatgtt 4020
tgccaaataa aaagaaatta agacaaacca cggaagtctg tgaggtttag gaaacgcttt 4080
ggaaggagtc tgagtcctat aggcttcttt ggtggctggt gtttcttcac agctgtatga 4140
ccattgttta acagaacgtt ctatggattc tgttgggtag cccggaatgg agcctgacag 4200
caacccttgc tcggaaggct ggggtagatc tcattccctg gaaggttccc gcggccgcag 4260
ccctccaagg ccgcagagat gtattcttgt gggtttcaga gaagccagga cacaaggcgg 4320
cctcctgcct gcccgccctt ctctagtgga ccagtcctcc tgagcgtctg cctgcaaaca 4380
ctgagtctgt gtgctggtag agcgagacct gcctcccgtc gcaaggagca tcactggatt 4440
ccattcccaa ctgtacccca tgcggtactt cttgtctctg ctactccact gcatgcagca 4500
accttggccc ttccagaagg gcaggccagt gaccactggt aggaaagagc tctgggtgat 4560
ggggtggtga gcaccatgtt gggggggggg gggaacaaag ctaagcccct caggttgtgc 4620
ttaagagctg tagtctctag aagtccgggc caggagtcct gaggtggcat tcctgatgac 4680
ctacgtccct ggtgtcagga cttcggagca cctgctccta tgtggtccag atattctgag 4740
gtaggtccca aagggtcacc agtttgcttt agttcaaata cctcctttct tacccttacc 4800
agccttaccc accttttagg aacagagggc ccaccacaga caacaaaatg ctgcccagcc 4860
aaattcatct ccatgagcca ggttacatat ttagggttta gcagagacac caccccccca 4920
tctatactct agccgttggg agcgacagcc cctcaaggcg gctgtcagat ggcattggac 4980
cacagtgagt ctcctgtgca tgggatttga ctagcaattg tagacatcga gggtgagatg 5040
ccatgtctgc taggcagagc tcaggagtca aggcaagtgc agaatcaggg tggcagggag 5100
atggggctgg aaagggttag gtgtcgcctg aggcaaggag gctggaggat aaggtggggt 5160
tgctaagccg ggcaccgagg ccctggctaa gctgtgagtt gtgctttgac cccagctacc 5220
cagagacctc acagcacaac cagacaacct cacagctttg aagggacagg gaccatgggt 5280
gttctttatt gggaggtata ccctgggtgg ccataaccgc agcctaccct tggtttcaac 5340
ctacagtctg cctggggctc tccacagagc tgggggcggg gcatggtact ccatccccat 5400
ccctgctacc tttctctggt tcacacacca tggacccagg ccctgcctcc tgggaaccac 5460
agccaagcat gaaccaaacc ccctaggcga tgtggctctc acagagcctt gctcccccag 5520
agcctccaac tcagaatacc actttacttc ctgttctgtg gccaaagcta aaccaggaag 5580
gctgagtagg gagggcaggt agcaggcaga gctctccaac ccccaaggcc cagcccagat 5640
cccatctcat gaccttatgg cttcttggca caagtcctgt gtgtcccagc cctgcctcag 5700
acccagactg gcctttccgt gaggactacc caagagacta ctttccagct cagtcctaag 5760
ctctgctcag gagcggaggc cagtgtttct cctcccaggt gtggtcacag ctggatagga 5820
actggctgaa tgacaccaca gctcaggtcc cacccactgc ctgacaagtg agaggagcca 5880
gcccccaggg gagcacccag aaggattcag ttaacaggga catctgtcag aagacctgag 5940
agggttagct ggggatggag aaggccaaga atgggaggcg gggcctctgt gggcagtgtc 6000
accttaaggc cacagtgggc agggatcagg atgggaccca aagtttagtt tctccaaata 6060
aatcattagg ctgacaccaa agtatcatcc cggcacccat ctgtcctggc atccatctgt 6120
ccactcttgt actcctcagc ctaacggaca gatcaacgct ttcctgagct cctccttctg 6180
acacgtgcag ccatcttccc atgaacccgt ttgcctctga ccattcatca tcctctgcct 6240
cccttccagc caactacccc catctatcta tcttgaccca ttggcaaatc catctttcca 6300
cctgtccatt gctccatcca aactgtctct ccaccccacc atcccagcat actataccta 6360
cgcccttaca ccttccagcc ccatgcacac aaccatgttc cctatcatct ctctattcac 6420
tgtactcaga gttctgtcag ctccatcagt gtaccaaaga caccaggtcc tcctacgccc 6480
tctactctgc ttggcctaaa ctgtccaggg ctgctctagg aatatctacc catgaggcaa 6540
caggcgtctc ccacccctgg cactctgccc caccatggtg ttcagatacc tccagaaata 6600
tgagttctta ccgtaggcat cgtgggcagg ttggatacat tcttgtggca gctgtgacac 6660
atctggagct gcttggggag agaagggaac aagaattgtg ctgtggggtg ggtctgtacg 6720
cctgctcacg agctctggaa gcctgggtta ggcagccacg ttccctgaaa ttagggcaaa 6780
gtccttgttt ccaggagtct gtccagaaga gagcaagcca gggctggcct cccttgacac 6840
cggggtgctc ttagtcccct gtgcccctgg acttttgtgc accattccca tcttctctgt 6900
taggatcccg aggagctcag agttggacct gtccggtctg cccctcctca atccacggat 6960
ggaaaggagt atttgctggg tgtttgggac cattcacaag tccccctggg aactccttgc 7020
tcatcctgaa gctcctacta tgtagggaag cttctgaaat gaggctgggc agagacccct 7080
gggtacccat catgctggca agaggaagag aagataggga gagaagcctg aggcgagctg 7140
ggctcagggg gactgtctat tcctggagac agctcacaga taaagcccag gacagtcaac 7200
caacaactcg cacaagtccc caaatcctag aaacctctgt cttgtgttct gttccttttc 7260
cttccgttca gctggccctt agggtaccaa gccagactgg gagacaggaa tgcagcatct 7320
gagtcaaagc atggcctgct cagcacatcc tcctgctccc aacccagaca agaggcccag 7380
gagccctcag ctcacaccat acctggggtg agcatagcat cacacagcct gcctggggag 7440
ccactgcttc tccccctaca ggagctggga ggagagtact ggatgttttg ttcatgaaaa 7500
gctgtgttcc atgccctaca catctatctg ggtgctgggt cccgccaccc acctctatct 7560
actgctgtcc tatatgtttg ccctgtgggc cacggatgtg gcgatcaggt taattacatc 7620
tgtgtaataa agtaagcatt tgctacgacg aaaaaaaaa 7659
<210> 11
<211> 7441
<212> DNA
<213> Homo sapiens
<400> 11
agagccgagg agccctgggg tccctcaaag tttgtgtctg gagccgtagc ggcaagtggg 60
cttgcggcta agggattttc ctgggatgag agcgggtctt ctgccttcat tttggatgca 120
catcccgctt tagccccggc agcctttggt ccggctcgtg tccctgggga ttctcggatc 180
tccgaggaca ccggacggga gcgcttggcc atcctctctc cggcagagga gcagacgttt 240
gctttccaag tgcaaaacta cagacacgcg cgcgcacaca cgcaagcaca cgcggagaga 300
gaggaacctt gccggtccga ggcagctctg cgcgtcccct cctgcgctta gcatcctcgg 360
cccagcgcgg cccgcaccgc catggaggtg ctggagagcg gggagcaggg cgtgctgcag 420
tgggaccgca agctgagcga gctgtcagag cccggggacg gcgaggccct catgtaccac 480
acgcacttct cagaacttct ggatgagttt tcccagaacg tcttgggtca gctcctgaat 540
gatcctttcc tctcagagaa gagtgtgtca atggaggtgg aaccttcccc gacgtccccg 600
gcgcctctca tccaggctga gcacagctac tccctgtgcg aggagcctcg ggcccagtcg 660
cccttcaccc acattaccac cagtgacagc ttcaatgacg atgaggtgga aagtgagaaa 720
tggtacctgt ctacagactt cccttcaaca tccatcaaga cagagccagt tacagacgaa 780
ccacccccag gactcgttcc gtctgtcact ctgaccatca cagccatctc caccccgttg 840
gaaaaggagg aacctcctct ggaaatgaac actggggttg attcctcgtg ccagaccatt 900
attcctaaaa ttaagctgga gcctcatgaa gtggatcagt ttctaaactt ctctcctaaa 960
gaagccccag tggaccacct gcatttgccg cccacccctc cgagcagtca cggcagtgac 1020
tcagagggca gcctgagtcc caacccacgc ctgcacccct tcagcctgcc tcagacccac 1080
agcccctcca gagctgcacc ccgggccccc tccgccctct ccagctcccc tctcctcacg 1140
gctcctcata aactgcaggg atcaggccct ctggtcctga cagaggagga gaagaggacc 1200
ctgatcgctg agggctatcc catccccacc aaattgcccc tgtcaaaatc agaggagaag 1260
gccctgaaga aaattcggag gaagatcaag aataagattt ctgctcagga aagtaggaga 1320
aagaagaaag aatacatgga cagcctggag aaaaaagtgg agtcttgttc aactgagaac 1380
ttggagcttc ggaagaaggt agaggttcta gagaacacta ataggactct ccttcagcaa 1440
ctccagaagc ttcagacttt ggtgatgggc aaggtttctc gaacctgcaa gttagctggc 1500
acgcagactg gcacctgcct catggttgtg gtgctgtgct ttgccgttgc attcggcagc 1560
ttctttcaag gctacgggcc ctatccttct gccaccaaga tggctctgcc cagccagcat 1620
tccctgcagg agccctacac agcctccgtg gtgagatcca gaaacctgct gatctacgag 1680
gaacattctc ccccagagga gtcatccagc ccgggctcgg ctggggagct ggggggctgg 1740
gatagaggtt cctccctgct cagggtgtca gggctggagt ccaggccgga tgtggatctt 1800
ccccatttca ttatctcgaa tgagaccagc ctggagaagt cagtgctttt ggagctgcag 1860
cagcacctgg tcagcgccaa actggagggg aatgaaacac taaaagttgt agaactcgac 1920
agaagagtga acaccacttt ctaaagaggc tgcctgcacc ccctcccttt cccttaactc 1980
tacttttaca tccccaaacc acctttgtca tcagcttttc ctctttgcca ctggatcttc 2040
atggagacat gggcaagcat tagtggcttc agattggaga ccagcctggg acttccctgc 2100
agtgagagag catctccccc tggtccatgc ccctcctgtg cagaagggag cctgcatccc 2160
tcccttcctt tctcttactg ccataggaaa ttattttagg ggttggaggt gggacaagca 2220
ggcttgtttc caccaatagt gccaaaaaga tattgcctaa tgtgcacctg tgaggtgtaa 2280
ccccccgctt tggagacgag atggctcttg ttcagtcaag accccagact ctggccacaa 2340
aaatgccata atgcctgttg gtatttggca aagcactgac ccgtgtcctc cgttgctcgc 2400
actggggtct ctggtgtgaa cacccccgac agcagccctc cgcccactct gccccctggg 2460
agccctcgct ggatcgtctc gtctcctgca gcagcactgg caggcgaggg ctctcgttca 2520
tattctcagg ccgcaagtgc aatgcctgag gggatcaggc ttttctactc caggcaaacc 2580
tgccccatct tgtcgctttt aggacctccc acaacctggt tccccacaca tccatagttc 2640
tgcctcccca gcttctcctc cccagttgta aatagtattt attagcttgc cgaggcttcc 2700
tgctagcaac cacactgaag agatcgatgc ctcctttcaa gctagccaag ttttctgcga 2760
gccttcagag ctaggagggc accctaggct ctgggatccc gtgtctttcc agacaatgtt 2820
ttgtttcctt tcctttgttt tttcttttaa ctggaataat taccattgaa aaagaagttc 2880
ctttgagcat gtatgtgtct gcctctagga tgagctcaga gcgagagatg acacaatgcc 2940
tcactcaggc cccgggctcc ctggccacaa gctttttcta tcctgttttc atgacagaga 3000
aggggaagcc ctgttctgac aacagacatt tcagacaacc ttgctggctt tccacacctg 3060
cctggccccc tcctccctcc acacttccac tttgtcctcc tcgtccccta cctcaacaaa 3120
gcagggtggg gtaggtgaca tttgtgtatc cacattctta cctttggtag tcaggtttgg 3180
ctactttgca gctcgcccaa agagatacaa cctaatcccc aacctacttt tagttttttt 3240
gttttttttt tatggttaaa agtaactttt gtagtttaaa aaaatctttc ctctttcata 3300
taaataagaa gtggaaattg cctttttatt gtgtaatgta gaaaaccctc aagtgttttt 3360
tccgagcttg ggaaagattt tgtgtaggaa atgtgcatag agtttgtatt ttatttttat 3420
tagcagctga aatgcctttg gttttggctt ctctctctcc ctctctctct ctgtctctcc 3480
ttctctctct ccccccacca cccaccccca cacacgtcat ctgcattgtt attggagcct 3540
gtacttagag ggattaagcc cacaccctgg cttccattcc atatcaggta caggatttga 3600
tgttattaac atttgtcgtc atacctcata agtcggtccc tgccttgtct gtctaggccc 3660
atttggggct ccctgtgagt gattcccctc tctctgctat gctggagacg gttccagcct 3720
ggaaagcggc caagttcatc ttctcactgt gagtggaagc tggatcgggc ccccgtagtc 3780
ctggcagccc tgttgtctgg agggttcttg ttgtccctcc cattagccag ggcggagact 3840
gtctgagctg tgcaggagga gggttgctag taggttctgc ttctgcttct ctctgctcca 3900
ctgtctgcag cccagatcct gttgggcctg gctggtgtct ggtaaccatg ggcctccact 3960
gacccatccc tctcttttaa actgtcaggt cattatcagg cataggcagc ctatagggcc 4020
caaagaaggc aaaaagataa gatttactca agtagcattt gggcaatgag gaaggaaagg 4080
tttcaaattt aggggcagaa gtgagagaat gagccaaccc atgtacctgc tgcaactgaa 4140
ccagactggg ttttcaaggc tcccagacgt agagtaggaa acgtgctctt ctaaatgagg 4200
agggagaaga taaaggaaac ttctagcccc tgtccttagt gctttgagga ttttattttc 4260
tcccttacta cgcttgcttg acgtcactct ctctcgacct ccaaacagca ggactctttc 4320
tctgggaaac catccttcca aaacggaatc tatgtagaca atgggacgtt aggcagagag 4380
ctcagatggc ccttttaagg gggctccaag aaccaacatc actgctcttt tagataaacc 4440
tctgccctcc actccttgct tgagtgggtt aaaggaacta acagttgtcc ctttaggagg 4500
acaaaatggg gtcaagagga cacagaagag ttgtatagca ccagattggt tccaaatagt 4560
taatggatgt gtgcacattt tctgttcagg gattaagacc agaatatcag tggatttgtt 4620
ttccccacca agtggcctct tagactagtc attaacttat gattagctct aaagatttca 4680
aatagtggca gacagtgtct tctgaatgta agttttgaga aatacgagtc tgtcagagcg 4740
gccataagcc ataaagagtc aatctcttaa ttatattttt catcatgtaa acaagtttcc 4800
catttccctt tcttagattg caccagtgaa ggagatgttt tgcaaagatt cagagaacta 4860
atttttcact ggataagacc tgagtaaccc agacccccca ccgtggttct tttcacagcc 4920
ctcgactttg cacttaaaaa gggatattgt aaatgaaagg ctgcagtgcc agttttaaga 4980
aagaatttct gtgaagtgtg aggactctgg agtctagctc acataaagag agtgttatat 5040
aaaaatccga cagctgaact aggttgctct tttttggcag ggagtgggga tgagatttga 5100
caccaatatg ggcaaaatta gataaccttt tggttaatat aaatgatttt gatttggagg 5160
cctaatttgt agattgtgaa agcagctttt agtttaactt attcacagac cccttataat 5220
taccatgttt ttttttttct tcctaaatct cttggttcag cttgtgaatc ttacgtgccc 5280
gtaaagttgg gatgttgaat tggctcttct ttgttctggc agtgagtcaa gtgtccagca 5340
ttttttcata agtgtttttt aaaattgttc tccagcattt tatggctcct ccctcccatg 5400
tcctcagacc cagcaaaagc gtagaggcag aattagaggc ctctccaggc cagctcctct 5460
gcccacatgt catacaaggt gtgaatttga gcacagtcca gaaatggaga catcccaccc 5520
ccagttgaat aatggcccat tcatgccaac cttgccaaca cggagagggc agagatgcac 5580
tagaagacct tcatcctccc cttcctctgc cccaagtcac tacagttggt tctattgaag 5640
ccagtcttta agaaacctgg gttaaagaca ccagcacttc tgcttgctgg gctggctgga 5700
cctgtgaagc catgggcagg tagtgccctc ttgagagtca ttttatttgg ccaccttcag 5760
gtgagactat ccatagacac atgctaggat aggccccgct gggagggcag ttacaggaga 5820
gagtaggtgg tggtgacgtg agggctgtga aggatccaga gacaagactt agatgtttcg 5880
ttcattcact cactcattca gttactccta agacttttca gtttcataag gaagagtgtt 5940
gcctgaggcc ctagggaata ttggggaata gaagggattg aggaaacatt aataatagtt 6000
attcaaaaga cccaaatgct tatacttctc tctcccttct tctctctctg acacacacac 6060
acacacacac acacacacac acacacacgt gcacattcct cccttacatg ctcatttgtg 6120
ccttaaatgt gccttatagg taaatccagg atgactgagg aatccctcgt cactgggaga 6180
ttttgtatat attcttttat tattagattg agttgggtgt ggggaaaaat ttttttctga 6240
aggctcaaaa gtggtttcct aaaagtgagc cactatcaga tttgcacatc aggagaaaag 6300
aaatagggtt acgtccatta ggaaaatccc agtttgcagg agtgcaatca catcaaaaaa 6360
acaaccagcc aggattaaag gtattataaa tcctcatagc ggaacatttc tcagggcaaa 6420
ggaacctggc tcatttgaag attaatgttc catgcctttg tggtcaaagg gtcagcactt 6480
aacacaggaa aaaactaggt gttgttttgt tttgttattt tggacaacat aaaattcagg 6540
aatgttttat ttagccttgg tttctagaag gaagggaaat aatatttctt gagcatttac 6600
tagggtgttg cgtgctgtgc taagtaaatt ttaagtcttt cagttttata gatacggaaa 6660
acaagggtga ctctttacca caggatgaat aaagaactaa gtaatatggg aaatgcagca 6720
atttctggac tagctgagcc gattccttcc tgtgagcaca ctgtaagctt tcaagttctc 6780
tgggcaggaa ttacagcacc tgtcccctgc aatggccctg ctgtgtgatg ctcatcgctt 6840
cccttcgtgc tggagcagtc ccccaggtgt ccatctccta tctttttgtt ccaatcttct 6900
gtgagttcca gctagcaggc tttacatctg gggaaaggaa aaccaggggt tttagctctg 6960
ttctctgctc ccatccttcg ctcaccagct gagtgagaac atgaactttt tgcaccatgt 7020
acccatggct tacactactt agaaaatcac cttttcagat aaaacagttt atgagttcat 7080
agagaacacc agcactcttt gacaaaactg tgagtgaccc tttttaaaca atgctgagca 7140
ggccctgagc tataatcaac ggtgagcttt aatgtctatg ctgacagtta ggttttgctc 7200
tcttttgtaa caggttacgt agaccagcag tgtttaaatc taaatacgtt gtgagtctgt 7260
tatctgtcct atcgcgtttt ttaaatgact ttttattctt tatcatagct aagtaaatac 7320
caaaaaaaaa aaaaagcttt gtaggacact tgtacttagt ttgggaaaaa aaaataaatt 7380
gaaattgtta tgcttttgta tttccatttc ttgcaaataa atattttttc ttaaatagta 7440
a 7441
<210> 12
<211> 3318
<212> DNA
<213> Mus musculus
<400> 12
gggagtctca aagtttgtct ggagccctag tggggagtgg gcttgttgcg cgaggacttt 60
cttgggatga gcgctgcctt tttgccttcc ttttggatgc acagcccgat ttaacccctg 120
caccttccgc ccgatcccag caggcttgtc ctccccgggg agtcacagat ttccgaggac 180
aagggtcgcg tagccttcgg cagggctctc ccgagttcct gctccagtgc ataagttcca 240
cgcgcgcaca cgccaagtac acggggagaa gcgtctcacc ggcccgcggc ggctctgcgc 300
ggtcccctcc tgcctcagca tcctcggccc tgcgcggcgc ccaccgccat ggaggtgctg 360
gagagcgggg agcagagcgt cctgcagtgg gaccgcaagc tgagcgagct gtcagagccc 420
ggagagactg aggccctcat gtaccacacg cacttctcgg agctcctaga cgagttttcc 480
cagaacgtcc tgggtcagct cctgagtgac cctttcctct cagagaagag cgagtcaatg 540
gaggtggagc catctccaac atcaccagcg cctctcatcc aggctgaaca cagctactct 600
ctgagcgagg agccccggac tcagtcacca tttacccatg cggctaccag cgacagcttc 660
aatgacgagg aggtggagag tgaaaaatgg tacctgtcta cagagtttcc ttcagctacc 720
atcaagacag agccaatcac agaggagcag cccccgggac ttgtcccttc tgtcactctg 780
accatcacag ccatttccac tccttttgaa aaagaagagt cccctctgga tatgaatgct 840
gggggggact cctcatgcca gacgcttatt cctaagatta agctggagcc gcacgaagtg 900
gatcagttct taaacttctc cccgaaagaa gcctccgtgg atcaactgca cttaccacca 960
acaccaccca gtagtcacag cagtgactct gagggcagct tgagccccaa cccacgcctg 1020
catcccttca gcctgtctca ggcccacagc cctgccagag ccatgccccg gggcccctct 1080
gccttgtcca catctcctct cctcacagct ccacataagc tgcagggatc gggccccctg 1140
gtcctgacag aagaggagaa gaggaccctg gttgccgagg gctatcccat tcccaccaag 1200
ctgcctctga caaaatctga ggagaaggcc ctgaagaaaa tccggagaaa gatcaagaat 1260
aagatttctg cccaagaaag caggagaaag aagaaagaat acatggacag cctggagaaa 1320
aaagtggagt cttgttcaac tgagaacttg gagcttcgga agaaggtgga ggtgctggag 1380
aacaccaata ggactctcct tcagcaactt cagaagcttc agactttggt gatggggaag 1440
gtctctcgaa cctgcaagtt agctggcaca cagactggca cctgcctcat ggtcgttgtg 1500
ctttgctttg ctgttgcatt tggaagcttc tttcaaggct atgggcctta tccttctgcc 1560
accaagatgg ctctgcccag ccagcatcct ctgtcagagc catacacagc ctccgtggtg 1620
agatccagga acctgctaat ctatgaggaa cacgctcccc tggaagagtc gtcgagccca 1680
gcctcagccg gggagctggg gggctgggac agaggctcct ctctgctcag ggcatcgtcg 1740
gggcttgagg ccctgccaga ggtggatctt ccccatttcc ttatctccaa tgagacgagc 1800
ttggagaagt cagtactgtt ggagcttcag cagcacctgg tcagcagcaa actggaaggg 1860
aacgaaacac tcaaggttgt agagctggag aggagagtga acgccacctt ctgaggagag 1920
ctccaccctc ctcttctcct aactccatct gatcgtcctt tcagtttccc cttcaccact 1980
ggatctcgag gaggagatgg cctagtgtta cggctcgaga caggaggcca gcccaggggg 2040
ttctgcttat gtgtccccgt ggctctccac aaaagggagc tagcacctct ccatcccttt 2100
ctcttactgc cattggaaat tattttaggg ctgagatagg ggtggaacga gcaggcttgt 2160
ttccaccaat agtgccaaga agacactgcc tgattcttcc ccgggaggag tgactcctct 2220
gaagaagaca tgactcatgt tcagttgaga ccccagactc tagccacaca catgccacag 2280
acatgccagg gagtggcaaa gcactgactc ctgagctccc ttcctcacta ggactccagt 2340
gtgaccctgc actgagagga ccaaagcgtc attgcagtct tctctccacc ctgtaccccg 2400
gagtcctgat tggatgtctg cagaggcaga tggggctccc accatatttt caggccgcaa 2460
gtgcaattcc tgaaggcatc aggctcttct ctcccaggct ctcctgccca ctgtgttgtt 2520
tgtaggacac ccccacaccc actcatacac agcctgcatc tccacaggac aatagctctg 2580
tctccctggc ctcccctccc catttgtaaa tagtatttat tagcttgctc aagctcccag 2640
ctggccatag tgaaaagatt tcccctttca accagcaaag tcttctgttg gcctttggaa 2700
caggagagtc cccggaatct aggaccctag tctttgtact tgatgccttg tttcccccct 2760
tttcttcttt aaaattgggg acctataaca tcatcgctgt tgcggaatcc acttaggcat 2820
gtgtcccctg atggatgaat acatgggaat ggtggatact gtcttctgac tcaggctcta 2880
ggctccatgg cttcctctct ctggtcctgc cacacagaag gaaagccctg tccaggataa 2940
tgagcgttgc tgacaccctt gctagcttgt cctgcctacc tgcttacccc actccctcac 3000
cttcctcctt cccttctgcc ctccatccac ctgccttaac taattggggc tggagttggt 3060
catttttgta cacccacagt ggtacctttt acagtcaggt ttggatactt tgcagctcat 3120
ccaaagagac ataactaaac cctaaactct ttttttgttg ttgttgttgt tgtttttttt 3180
ttttatgatt aaaaagtaaa aattgtagtt taaaaaatcc tttcctcttt catacaaata 3240
agaaatggaa attgctcgtt tattgtataa gatagaagat tcgtttaaag tgtttcccca 3300
cccccacccc cagcttgt 3318
<210> 13
<211> 5139
<212> DNA
<213> Homo sapiens
<400> 13
agttggaaag agaccacaga ctttgaggga agctcactca ggatctgctc tccggcaaag 60
tagtaagtga ggtgctgaga gcagaatgag ctactttgtg gattctgctg ggagcagccc 120
cgtcccttac tcagcgcctc gtcctgcagt ggtgaggcaa ggacctagca acacttatga 180
agatcctcga atgaactgtg gtttccagtc caattatcac cagcaaagac cttgctaccc 240
cttttgggat gagatggcaa ctcaggaagt tcctactggt cttgaacact gtgtctcaga 300
tatggaatgt gcagatgtcc cactattaac tccaagcagc aaagaaatga tgtctcaagc 360
attaaaagct actttcagtg gtttcactaa agaacagcaa cgactgggga tcccaaaaga 420
cccccggcag tggacagaaa cccatgttcg ggactgggtg atgtgggctg tgaatgaatt 480
cagcctgaaa ggtgtagact tccagaagtt ctgtatgaat ggagcagccc tctgcgccct 540
gggtaaagac tgctttctcg agctggcccc agactttgtt ggggacatct tatgggaaca 600
tctagagatc ctgcagaaag aggatgtgaa accatatcaa gttaatggag tcaacccagc 660
ctatccagaa tcccgctata cctcggatta cttcattagc tatggtattg agcatgccca 720
gtgtgttcca ccatcggagt tctcagagcc cagcttcatc acagagtcct atcagacgct 780
ccatcccatc agctcggaag agctcctctc cctcaagtat gagaatgact acccctcggt 840
cattctccga gaccctctcc agacagacac cttgcagaat gactactttg ctatcaaaca 900
agaagtcgtc accccagaca acatgtgcat ggggaggacc agtcgtggta aactcggggg 960
ccaggactct tttgaaagca tagagagcta cgatagttgt gatcgcctca cccagtcctg 1020
gagcagccag tcatctttca acagcctgca gcgtgttccc tcctatgaca gcttcgactc 1080
agaggactat ccggctgccc tgcccaacca caagcccaag ggcaccttca aggactatgt 1140
gcgggaccgt gctgacctca ataaggacaa gcctgtcatt cctgctgctg ccctagctgg 1200
ctacacaggc agtggaccaa tccagctatg gcagtttctt ctggaattac tcactgataa 1260
atcctgtcag tcttttatca gctggacagg agatggctgg gaattcaaac tttctgaccc 1320
agatgaggtg gccaggagat ggggaaagag gaaaaacaaa cctaagatga attatgagaa 1380
actgagccgt ggcctacgct actattacga caaaaacatc atccacaaga cagcggggaa 1440
acgctacgtg taccgctttg tgtgtgacct gcagagcctg ctggggtaca cccctgagga 1500
gctgcacgcc atgctggacg tcaagccaga tgccgacgag tgatggcact gaaggggctg 1560
gggaaaccct gctgagacct tccaaggaca gccgtgttgg ttggactctg aattttgaat 1620
tgttattcta ttttttattt tccagaactc attttttacc ttcaggggtg ggagctaagt 1680
cagttgcagc tgtaatcaat tgtgcgcagt tgggaaagga aagccaggac ttgtggggtg 1740
ggtgggacca gaaattcttg agcaaatttt caggagaggg agaagggcct tctcagaagc 1800
ttgaaggctc tggcttaaca gagaaagaga ctaatgtgtc caatcatttt taaaaatcat 1860
ccatgaaaaa gtgtcttgag ttgtggaccc attagcaagt gacattgtca catcagaact 1920
catgaaactg atgtaaggca attaatttgc ttctgttttt aggtctggga gggcaaaaaa 1980
gaggtgggtg ggatgaaaca tgttttgggg ggggatgcac tgaaaatctg agaactattt 2040
acctatcact ctagttttga agcaaagatg gacttcagtg gggaggggcc aaaaccgttg 2100
ttgtgttaaa atttatttta ttaaattttg tgccagtatt ttttttctta aaaatcgtct 2160
taagctctaa ggtggtctca gtattgcaat atcatgtaag tttgttttta tttgccggct 2220
gaggattctg tcacaatgaa agaaaactgt ttatatagac cccattggaa aagcaaaacg 2280
ctctcactga gatcagggat cccaaattca tgggacttat ataagaagga caattaatgc 2340
tgatttgggt acaggggaat tatgtgtgtg aatgtcatct acaattaaaa aaaattagca 2400
catcccttta cttacttgtt atcagtggat tctcggggtt tggacttaat gttgagctaa 2460
gaagcattaa gtctttgaac tgaatgtatt ttgcatccct ggttttggac gacagtaaac 2520
gtaggagcac tgttgaagtc ctggaaggga gatcgaagga ggaagattga cttggttctt 2580
tcttagtcct atatctgtag catagatgac ttggaataaa agctgtatgc atgggcatta 2640
cccctcaggt cctaagaaat aagtcctgaa tgcatgtcgt tccaaactaa cactctgtaa 2700
tttttctttt atgtcttatt ttccaagagt cctccatttt ttgcaccccc tcaccgccaa 2760
ctctgttatt cagtagagag aagtgtacgg ctttctgatt ggtgagtgaa aaagtaactt 2820
gagacacgac ctaagttgaa gagtttagac ttgctgagtt ttagaagtga tggaaattaa 2880
gagagcattt caataaaatg tgacttggct gtctttggaa gagaagtgca aggctttcct 2940
ttgaagaatt taaattagtc cggtaggatg tcaggtgaga ctgtgtatgc aaaatgaatg 3000
gcacaggtga tgccagggcc tcttgcttgg gtctgatgtc ttggcacagg gtaagtgaag 3060
gttaattcca gaagagagga atgacttgaa ggcaaaggaa actaaggaag gaggttcagt 3120
gaggaaaata aggttgtcca tgagatttga atagattttt agttccccca aggtttaaat 3180
acaaacatag tcaagcaagg tagtcatctt tctgctggtt gtgaggggga atctgaaaat 3240
ggagttttag aggaaaagtc aacatctaac tagtgaggaa aagtgcctaa tacaattaga 3300
atctccctca ctctatagtt gcccagttga aaggataagg aggaggggtg gcttttatgg 3360
acttccatga gagaaggaaa gaaatatttc aggtaagctt ctcagggctg gccctttttg 3420
ggatttggat gagaaattgg aagtactaac tactttctag catatcttta agaaaattga 3480
ttgttattta ctcccagatc ctcttgcaga cccagaatta tcaggaacat agctctgtga 3540
ttcatgagtg tccccatact gatgaattgg agcatccata tggaaagcaa aggcagaatt 3600
atcccagctg tattattttg atcttttgga tgcaggtgcc ttaatgaagc tctcaaaata 3660
ttttaggagc tgctcaggga gtgttgggtg gaactgtttg gactacattg ttttctctta 3720
gattatgtga tttttgttgg gcactggcaa aaggtgtgtg tgtgaatgtg tgcatgtgtg 3780
tgaatgttgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtttgcagac 3840
atgcaaaact gcagctgaaa taatacctta gatttctagg taagtctttc cacatttcaa 3900
taatgggtaa gagtagaacc agggccgggt atcaattatt gcttgctgtt tgcaaccagg 3960
cataaaatca ctttctcaaa tcatccaccg ttcctattaa atttatgccg gaaactctcc 4020
ttctgtgagt ataactcctg cagttcctat agcagataag atataagaaa gtgcctccta 4080
gtgctcctcc gcccgcttgt ttgctaaaat tccctttctc tctaagtcca ccattttcaa 4140
gatttgtaga tagtgtatta gttaagacag ctttgtcgat ctggccagat gttttttctc 4200
ctttgtccaa aggccagaga ccatcccagg aagagtggtg ggtggtttat acactggaaa 4260
tgttgcgttt atgcttttta aaaacacacg ttaacttcag aggaaggatg ggcaaatctg 4320
gtctagctgg gtgaaaccct tattttccca gagatgcctt aacctttgtt ggttttggct 4380
ttagggttca gagtcacttt tgttcccttc tccattctgg agagggactt cccctacata 4440
gagccctgat ttttgtggct gtggggattg gaggtagcat tcaaagatca gatgtgcttt 4500
tcctcacttt ggagatgaac actctgggtt ttacagcatt aacctgccta accttcatgg 4560
tgagaaatac accatctctc ttctagtcat gctgtgcatg ccgcttactc tgttggggtc 4620
tatataaatt tgttgaactc ttacctacat tccaaagaag tttcaaggaa ccataaatat 4680
atgtatacat atacatatat aaaatatata tattaaaata aaattatcag gaatactgcc 4740
tcagttattg aacttttttt tttaagaata cttttttttt aagctgagaa gtatagggat 4800
gaaaaagatg ttatattgtg tttgactatt ttccaacttg tattttcata taatttatat 4860
tttttaaaag ctgaaaattt agaagcaaga tgaaaaaaag gaaaagcagg tgctttttaa 4920
aaatcagaac tgaggtagct tagagatgta gcgatgtaag tgtcgatgtt tttttaaaaa 4980
aaaatgcaaa aaaattctta tggcggagtt ttttgtttgt ttattttagt agctgatgct 5040
ggcacatcat tttgctggag agttttttat atactgtagc ctgatttcat attgtatttt 5100
aaactgtgtg aaattaaaaa caaagaattt cattcataa 5139
<210> 14
<211> 5065
<212> DNA
<213> Mus musculus
<400> 14
taaagcggag gcgagctgca ctgcgccagc gccggccagc cgtgcgagcg agcaagggag 60
cgagcgcccc ggacggagga gggagcgagc gcccgggaca gaggagcgag cgggcgggcg 120
aggcgcgggc gaggctggga cctaagcgcg ctctctgctc cgccaagtgc caacttcgcg 180
cggactggct gggcgcgcac cttcccgcgg ggcggtcagc gggaatttga gattttaggg 240
ttgcgctctg tccccttcca ctgggttcaa aaatccccat taaaaagcaa aacaacagtt 300
acagcaaact tactctcatc ccgccggccc cctcaactcc gggcaccatg aaggcggccg 360
tcgatctcaa gccgactctc accatcatca agacagaaaa agtggatctc gagcttttcc 420
cttccccgga catggaatgt gcagatgtcc cgctgttaac tccgagcagc aaagaaatga 480
tgtcccaagc cttgaaagct actttcagtg gtttcacaaa agaacagcag cgactgggaa 540
tccccaaaga cccccggcag tggacagaaa cccacgtccg ggactgggtg atgtgggctg 600
tgaatgagtt cagcctgaaa ggtgtggact tccagaagtt ctgtatgagt ggagcagcac 660
tgtgtgccct gggtaaagaa tgcttcctcg agctggctcc agactttgtt ggggatatcc 720
tgtgggagca tctagagatc ctgcagaaag aggatgtgaa accatatcag gttaatggag 780
ccaaccctac ctacccagaa tcctgttaca cctcggatta cttcatcagc tacggtatcg 840
agcatgctca gtgtgttcct ccctcagagt tctcagagcc cagcttcatc acagagtcct 900
atcagacgct gcatcctatc agctcggaag aactcctgtc cctcaagtat gagaacgact 960
acccttctgt cattctccag gaccctctcc agacagacac cttgcagaca gactactttg 1020
ccatcaagca agaggtgtta actccagaca acatgtgcct ggggagagcc agtcgtggta 1080
aactcggggg ccaggactct tttgagagcg tagagagcta cgatagttgt gaccgcctca 1140
cccagtcctg gagcagccag tcatccttca acagcctgca gcgggtcccc tcctatgaca 1200
gcttcgacta cgaggattat cccgctgccc tgcccaacca caagcccaag ggcaccttca 1260
aggactatgt gcgtgaccgt gctgacctca acaaggacaa gcctgtcatt cctgctgctg 1320
ccctggctgg ctacacagga agtgggccga tccagctgtg gcagtttctt ctggaattac 1380
tcactgataa gtcttgtcag tcctttatca gctggacagg agatggctgg gaattcaagc 1440
tttctgaccc agatgaggtg gccaggagat ggggaaagag gaaaaacaaa cctaagatga 1500
attatgagaa actgagccgt ggccttcgct actattatga caaaaatatc atccacaaga 1560
cggcgggcaa gcgctacgta taccgctttg tgtgcgacct gcagagcctg ctgggataca 1620
cccctgaaga gctgcacgcc atgctggatg taaagccgga tgctgactag tcatggacag 1680
acgcgcagaa ggaaggggct gggggaaccc tgctgagacc tttcaaagag caaccctgtt 1740
ggttggactc ttcattttta attgttattc aatgttttat tttccagaac tcatttttca 1800
cattcagggg tgggagctga gggagcgccg ctgtattcca ttggccattg gtgggccgga 1860
aagaggaggt caggacctgc ggggtgggcg gggcaatagc tcctgagcag actttcagaa 1920
gggagaggtc ttctcagaag cctgttggac ctggcttgca gaggaaaaaa aaacttaagt 1980
gtccgttttt tttttttttt tttttaaatc aaagaaaaaa aaattcatct tgagttgtgg 2040
atctactagt gggaggaatg atcacattga gatgaaagag attgatgaaa gccagtcagt 2100
tttgtgggtg ggctgaaaac agtttcttca ggggattact aaactcaaga attattaacc 2160
tttctacttt ttgaaacaat gatggacttt gattgaaggg gtccaaaact gtttttatgt 2220
tgaagtttat tttattaaat tttgtgccag tatttttttt tccttaaaaa aatatcgtct 2280
taagctctaa ggtggtctca gtattgcagt attgtgagtt tgttgttatt tgctggctga 2340
ggactcttgt cacagtgaaa gacaactgtt tatatagacc ccattggaaa aatcccagtt 2400
ctgtactgag atcagagacc ccaaactctt acagctaaag gaaacgaatg ctgatctggg 2460
gacaggggga ctgtgcgtgt gacttccacc tgcggtttgt aaaaactgtt ttcctttgat 2520
tcactgtcag gctttggact tagtgttagt tacggggcgt taagtctctg cactgaatgt 2580
attctgcagc tcttctatgg aatcgtcggc atcatagcac agttcaagtc ttggaaacga 2640
aatccaagga gcaggattaa cctgggtttt ggttaaaccg ctacccgaaa catggaagac 2700
tcagaataaa agccgtttgc atgggcatta ccccgagggt cttaaggcct caatgcatgc 2760
cattccaaac taacattctc agttctcctc tactttgtct tatgttcccc ccggcatccc 2820
tcattgctgc ccctccctca tcactgatca gtgaaagtgg agtgtaatgc atcctgacac 2880
gtgactgaaa gtgtagtttc agccatcaca acacaaatcc aagagtccag acttgctagg 2940
gctcggaggc cacggcagtg gagagggtat ttcagtagca tgtgactcgg cctcctttga 3000
agacttggtg ctcgtcaggt aggatttcag gtgagactgc ttgccgggaa gtggcaggga 3060
gcactggcac ttgacctgtt accacctcag cagagggcaa gcccaggtca actgcggtga 3120
gagggagacg gagaaaatac aagggaaggc gcttaggtaa ggaaaataag gtggcccgag 3180
acagttagat agatgtttag tttcctccaa gtttaaactc agacttaatt gaggcagcca 3240
tcatcctgcc tgatgggaga ggagacctga aaataagcca ttgtgggtta aaaaaaaaag 3300
taaggagaca tgcctgggat cattagaatc ccttccactg tatagctgcc tagttaagac 3360
agtgacagtg acatccctga gagaagagag gcaattggct gaggtgggcc tctccaggct 3420
cacccttcgg ggtttgtagc tccctggtat catcttccag gagagttgat ggctgactcc 3480
cacattccct tgaagactct gaattactaa gactataact cttgtccgtg ggtgttctgt 3540
actgactgag tggagcatcc ccacaaggaa gcaaaggcca aacattccag ctatatattt 3600
tgatcttaca aatgcaggtg ccttaatgaa gctctcaaaa tatttaggag ctgctcaggg 3660
agtgttaggt gggatcattt ggattatgct gttttctctt atgttatgtg atctttgttg 3720
ggcactgaca gtgtgagtgt gtgtgtgtgt gtgtgtgtac atttgtataa agttgcagct 3780
gaaatagtac tgaattttct acttagagtc tgttcacatt tccataatgg tgaatgaaag 3840
agtacagccg gggctggtat tgttgtttgc tctttgcaac agggcttaaa aaaatcactt 3900
ccccaagtct tcacccttct ccatattggg ttcctgctgg gaatgcccct cctgagagcc 3960
taccacctgc agtcccctag cagagaagac ataagaaagt gtctcccaca ctcctcagcg 4020
tgctgacttg cctgccttga tgccctttct ccctaggtcc accacttttc aggatttgta 4080
gatagtatat tagtcagaca gctttgttgt ccatctggcc agatgctttc ccccatctcc 4140
tccgaaggcc agagaccatc ccaggaagag tggcgggtgg tttatacact ggaaatgtag 4200
cagcattgct gcattgatgc tcttttaaaa cacgttcact tcacaggaag gatgaacaga 4260
tctgacctag ctgggcgact ccatcatttt cccagagaaa tgctttaacc tgtgtggctg 4320
gctttgggct cagaggcggg gctaaggatg ctccctgcgg agagctctga tggtgtggcc 4380
atggagacct tgtaagcatt caggatcaga gatgctcttc ctcactttgg agaccagcac 4440
tctgggtttt aaagcattaa ccttcatggt gaaatcacac cttctctctc ctagccatgc 4500
tgtgcatgcg gccttctctg ttggggtcta tataaacctg ttgaactctt acgtacattc 4560
caaagacgtt tcaaggaacc acaagtatat gtatacaaat acatatatga agtatatatg 4620
ttaaagtgaa tttatctcta tcaggaatac tgcctcagtt attgaatttt ttttaaggat 4680
actttttttt ttaaagctga gaattattga ggtgaaaaag atgttatatt gtgtttgact 4740
ttttccaact tgtattttca tataatttat attttttaaa tgctgaaaat ttaaaagcaa 4800
gatttaaaaa ggaaaagcag gtgcttttta aaaatcagaa ctgaggtagc ttagagatgt 4860
agcgatgtaa gtgtcttaaa tgttttttgt ttttttttta aaaacaaatg caaaaaattc 4920
ttatggggga gtttttggtt tgtttcattt aagtagctga tgctggcaca tcattttgct 4980
ggaaaatttt ttatatactg taggctgatt tcatattgta ttttaaactg tgtgaaatta 5040
aagaaacaaa gaaattcatt cataa 5065
<210> 15
<211> 5322
<212> DNA
<213> Homo sapiens
<400> 15
gttgttgttg gtggcggcgg cgagcggagc cggaggagcc gccgcaaaga tggaggagcc 60
gtcgaggagg tgctgccgcc gctgccgccg ccgctgctgc cgccgccgcc cgcgaagccg 120
gagctcgagc cgcagcgggg atgccgttct gagtgcctga ctgcctcgcc ccgaaggatg 180
gcctcggatg ggcattagag gcacggcggc cccgggctcc cgtcccgtcc gtctgtctgt 240
tatcgtctgt ctctcttgac atcaccgcag ctccaccccc tcccgtccca gcccccaacg 300
ccagcttcct gcaggcccag agccggcatg aactctccca acgagtcggc agatgggatg 360
tcaggtcggg aaccatcctt ggaaatcctg ccgcggactt ctctgcacag catccctgtg 420
acagtggagg tgaagccggt gctgccaaga gccatgccca gttccatggg gggtgggggt 480
ggaggcagcc ccagccctgt ggagctacgg ggggctctgg tgggctctgt ggaccccaca 540
ctgcgggagc agcaactgca gcaggagctc ctggcgctca agcagcagca gcagctgcag 600
aagcagctcc tgttcgctga gttccagaaa cagcatgacc acctgacaag gcagcatgag 660
gtccagctgc agaagcacct caagcagcag caggagatgc tggcagccaa gcagcagcag 720
gagatgctgg cagccaagcg gcagcaggag ctggagcagc agcggcagcg ggagcagcag 780
cggcaggaag agctggagaa gcagcggctg gagcagcagc tgctcatcct gcggaacaag 840
gagaagagca aagagagtgc cattgccagc actgaggtaa agctgaggct ccaggaattc 900
ctcttgtcga agtcaaagga gcccacacca ggcggcctca accattccct cccacagcac 960
cccaaatgct ggggagccca ccatgcttct ttggaccaga gttcccctcc ccagagcggc 1020
ccccctggga cgcctccctc ctacaaactg cctttgcctg ggccctacga cagtcgagac 1080
gacttccccc tccgcaaaac agcctctgaa cccaacttga aagtgcgttc aaggctaaaa 1140
cagaaggtgg ctgagcggag aagcagtccc ctcctgcgtc gcaaggatgg gactgttatt 1200
agcaccttta agaagagagc tgttgagatc acaggtgccg ggcctggggc gtcgtccgtg 1260
tgtaacagcg cacccggctc cggccccagc tctcccaaca gctcccacag caccatcgct 1320
gagaatggct ttactggctc agtccccaac atccccactg agatgctccc tcagcaccga 1380
gccctccctc tggacagctc ccccaaccag ttcagcctct acacgtctcc ttctctgccc 1440
aacatctccc tagggctgca ggccacggtc actgtcacca actcacacct cactgcctcc 1500
ccgaagctgt cgacacagca ggaggccgag aggcaggccc tccagtccct gcggcagggt 1560
ggcacgctga ccggcaagtt catgagcaca tcctctattc ctggctgcct gctgggcgtg 1620
gcactggagg gcgacgggag cccccacggg catgcctccc tgctgcagca tgtgctgttg 1680
ctggagcagg cccggcagca gagcaccctc attgctgtgc cactccacgg gcagtcccca 1740
ctagtgacgg gtgaacgtgt ggccaccagc atgcggacgg taggcaagct cccgcggcat 1800
cggcccctga gccgcactca gtcctcaccg ctgccgcaga gtccccaggc cctgcagcag 1860
ctggtcatgc aacaacagca ccagcagttc ctggagaagc agaagcagca gcagctacag 1920
ctgggcaaga tcctcaccaa gacaggggag ctgcccaggc agcccaccac ccaccctgag 1980
gagacagagg aggagctgac ggagcagcag gaggtcttgc tgggggaggg agccctgacc 2040
atgccccggg agggctccac agagagtgag agcacacagg aagacctgga ggaggaggac 2100
gaggaagacg atggggagga ggaggaggat tgcatccagg ttaaggacga ggagggcgag 2160
agtggtgctg aggaggggcc cgacttggag gagcctggtg ctggatacaa aaaactgttc 2220
tcagatgccc agccgctgca gcctttgcag gtgtaccagg cgcccctcag cctggccact 2280
gtgccccacc aggccctggg ccgtacccag tcctcccctg ctgcccctgg gggcatgaag 2340
agccccccag accagcccgt caagcacctc ttcaccacag gtgtggtcta cgacacgttc 2400
atgctaaagc accagtgcat gtgcgggaac acacacgtgc accctgagca tgctggccgg 2460
atccagagca tctggtcccg gctgcaggag acaggcctgc ttagcaagtg cgagcggatc 2520
cgaggtcgca aagccacgct agatgagatc cagacagtgc actctgaata ccacaccctg 2580
ctctatggga ccagtcccct caaccggcag aagctagaca gcaagaagtt gctcggcccc 2640
atcagccaga agatgtatgc tgtgctgcct tgtgggggca tcggggtgga cagtgacacc 2700
gtgtggaatg agatgcactc ctccagtgct gtgcgcatgg cagtgggctg cctgctggag 2760
ctggccttca aggtggctgc aggagagctc aagaatggat ttgccatcat ccggccccca 2820
ggacaccacg ccgaggaatc cacagccatg ggattctgct tcttcaactc tgtagccatc 2880
accgcaaaac tcctacagca gaagttgaac gtgggcaagg tcctcatcgt ggactgggac 2940
attcaccatg gcaatggcac ccagcaggcg ttctacaatg acccctctgt gctctacatc 3000
tctctgcatc gctatgacaa cgggaacttc tttccaggct ctggggctcc tgaagaggtt 3060
ggtggaggac caggcgtggg gtacaatgtg aacgtggcat ggacaggagg tgtggacccc 3120
cccattggag acgtggagta ccttacagcc ttcaggacag tggtgatgcc cattgcccac 3180
gagttctcac ctgatgtggt cctagtctcc gccgggtttg atgctgttga aggacatctg 3240
tctcctctgg gtggctactc tgtcaccgcc agatgttttg gccacttgac caggcagctg 3300
atgaccctgg cagggggccg ggtggtgctg gccctggagg gaggccatga cttgaccgcc 3360
atctgtgatg cctctgaggc ttgtgtctcg gctctgctca gtgtagagct gcagcccttg 3420
gatgaggcag tcttgcagca aaagcccaac atcaacgcag tggccacgct agagaaagtc 3480
atcgagatcc agagcaaaca ctggagctgt gtgcagaagt tcgccgctgg tctgggccgg 3540
tccctgcgag aggcccaagc aggtgagacc gaggaggccg agactgtgag cgccatggcc 3600
ttgctgtcgg tgggggccga gcaggcccag gctgcggcag cccgggaaca cagccccagg 3660
ccggcagagg agcccatgga gcaggagcct gccctgtgac gccccggccc ccatccctct 3720
gggcttcacc attgtgattt tgtttatttt ttctattaaa aacaaaaagt cacacattca 3780
acaaggtgtg ccgtgtgggt ctctcagcct tgcccctcct gctcctctac gctgcctcag 3840
gcccccagcc ctgtggcttc cacctcagct ctagaagcct gctccctctg cagggggtgg 3900
tggtgtcttc ccagccctgt cccatgtgtc cctcccccca ttttcctgca ttctgtctgt 3960
ccttttcctc cttggagcct gggccagctc aaggtgggca cgggggccca gacagtactc 4020
tccagttctg gggccccccg agtgaggagg gaacgggaag tcggtgcctt ggtttcagct 4080
gatttggggg gaaatgcctt aatttcactc tcctcccttc tccagcctca ggggaggatc 4140
tggaggatcc actactgtct ttaagatgca gagtggaggg gaggtgggca cccaccctgc 4200
gattctccac cctttcccct tctttcgtcc tcaccatctc tgcagacccc tctcctcctc 4260
cttcctcttg gtctcagcac tgatgggagg ctggtgccca agctgtggcc tgcagtctgt 4320
gaggagggct gtcttgcctc acactcctca cagcctactt ccccttcccc ggggctgaga 4380
gggtgaaagt gtgtggggaa ggagaggact ggtttcctgg gttctcaggg gccaggagga 4440
gtaacagaac caggtctgct ccccacctta ctcggatggc ctccctgccc ctctgctggc 4500
acagcctggg caaggggaga aggtggtccc tgcagagggg ctccaggctg gtgagagccc 4560
ccctgctgtc aggaccagat tttcccagcc atccagcatg ctgcggggag aaggggcaga 4620
ggctcacctc cctcctgggg ccttttgttt tggatcctgg ggatggtgag aatggaggtt 4680
ctagaagggg taaggccaga acccagggat ccaggagtcg gctctcagct ggagcttcca 4740
taccttctgg gctccctttg ctgaccacca gcccaaggga gctaagacca ggagggggct 4800
gggcgctgtc ccttctcttt cccaggagcc ctgccagggg ctgtgggcct acaaggcttc 4860
caggggatgc catccagcct gtaggaaacc aaagatggga agtggctcct agggggctga 4920
ctcttccttc ctcctcctcc ccagtaccac atatactttc tctccttcta tctccagggc 4980
cccaccaatc tgtttacata tttattatcc tatgggggcc tgagcaggat tgagggagcc 5040
aggggagggg caggagtccc agcaccatcg gttcatagtg tgcttgtgtg tttgttttag 5100
atcctcctgg gggatgggga tggggccagg ctcagtgtac taggcctctc tgtgctgagc 5160
cccaggctcc cggcccctta cccactctct ccctgtggct ggtctggttc tcatgtaaac 5220
ccactccttg ctttgtctcc ctggatatgg atttcagtta agtattttgt aacccgttac 5280
actgtgtgtc cttgtgtaaa taaacttgtt tctggcagtg cc 5322
<210> 16
<211> 4332
<212> DNA
<213> Mus musculus
<400> 16
ggtcacgtga cgagagtgac gtctccgaat gttgttgttg gtggcggcgg cgagcggagc 60
cggaggagcc gccgcaaaga tggaggagcc gtcgaggagg cgctgccgct gctgttgccg 120
ccgctgctgc cgccgccgcc cgcgaagccg gagctcgagc cgcagcgggg atgccgttct 180
gagtgcctga ctgcctcgcc ccgccccgaa ggatggcctt ggatgggcat tagaggcact 240
gcggccctgg gctcgggctc ctgtcccgtc cgtctgtctg ttatcgtctg tctctcttga 300
catcacagca gctccgcccc ctcccgtccc agcccccaac gtcagcttcc tgcaggccca 360
gagccggcat gaactctccc aacgagtcgg cttccttcca gagggattgg aggctcagga 420
ctggctggtg aggagaggca gtatcaaccc agagaggaag tagaagatga caaaaaaggg 480
ggaagagaga agatccaggc tggctgcttg gtgtccagtc cgttgtttgc ccccagcagt 540
ggccaaagct gaccccagat gcatgggtcc tctgcctgca cccttctcta gtccagccac 600
tggccaccca gactttggtc cacgctcctg gagcggagag caggcccttc agcctcatta 660
gcctccctgc gtctgctgcc tccggagcgc gcccaggccg gatgaggtgc ctccttgcct 720
cgtgggtccc agcggcagtg gcctgaggga gtccttgagc agccagctgg ccccgctgac 780
caccttttcc ctcaccggct tccgcctcgg gcggcccctc cctggcatgc tgctggtgcc 840
caaggcacag gggcttgtgg agatgctgca gaccatctat gagaccgagt cctgtttctc 900
agcagatggc atgtcaggcc gggaaccatc cttggaaatc ctgccacgga ctcctctgca 960
cagcatccct gtggcagtgg aggtgaagcc ggtgctgcca ggagccatgc ccagctccat 1020
ggggggtgga ggtggaggta gccccagccc cgtggagctt cggggggctc tggcgggccc 1080
catggaccct gcgctacggg agcagcaact gcagcaggag ctcctggtcc tcaagcagca 1140
gcagcagctc cagaagcagc tcctgttcgc cgagttccag aagcagcacg accacttgac 1200
gcggcagcac gaggtccagc tgcagaagca cctcaagcag cagcaggaga tgctggcggc 1260
taagaggcag caggagctgg agcagcagcg gcagcgggag cagcagcggc aggaggagct 1320
ggagaaacag cggctggagc agcagctgct catcctgcgc aacaaggaga agagcaaaga 1380
gagtgccatc gccagcaccg aggtaaagct gaggctccag gaattcctgt tgtccaagtc 1440
aaaggagccc acgccaggcg gcctcaacca ttccctccca cagcacccca aatgctgggg 1500
agcccaccac gcttctttgg accagagttc ccctccccag agcggccctc ctgggacgcc 1560
tccctcctac aaattgcctt tgcttgggcc ctatgacagc cgtgatgact ttcccctccg 1620
taaaacggcc tcggaaccca acttaaaagt acgttcgagg ctaaaacaga aggtagccga 1680
gaggagaagc agtcccctcc tgcgtcgaaa ggatggcact gttattagta cttttaagaa 1740
gagagcagtt gagatcaccg gcacggggcc tggggtgtcg tccgtgtgta acagtgcgcc 1800
cggctctggc cccagctctc ccaacagttc ccacagcacc atcgctgaga acggctttac 1860
tggctcagtc cccaacatcc ccactgagat gatcccccag caccgggccc tccctctgga 1920
cagttcccca aaccagttca gcctctatac gtctccttct ctgcccaaca tctccctagg 1980
gctgcaggcc actgtcactg tcaccaactc gcacctcacc gcctccccga agctgtcaac 2040
acagcaggag gctgagaggc aggcccttca gtccctgcgg cagggcggca cactgaccgg 2100
caagttcatg agcacatcct ccatccctgg ctgcctgttg ggagtggcac tggagggtga 2160
cacaagcccc cacgggcacg cttccctgct gcagcacgtt ttgctcctgg agcaggcccg 2220
gcaacagagc acgctcatag cagtgccgct ccatgggcag tccccactgg tgacgggtga 2280
acgtgtggcc accagcatga ggacggtggg taagctcccg aggcaccgac ctctgagccg 2340
cactcagtcc tccccgctgc cgcagagtcc ccaggccctg cagcagctgg tcatgcagca 2400
gcagcaccag cagttcctgg agaagcagaa gcagcagcag atgcagctgg gcaagatcct 2460
taccaaaact ggggagctgt caaggcagcc caccactcac ccggaggaga cagaagagga 2520
gctgacggag cagcaggagg ccttgctggg agagggggcc ctgaccattc cccgggaagg 2580
ctctacagaa agtgagagca cccaggaaga cctagaagag gaggaggagg aggaggagga 2640
ggaagaggag gactgcattc aggtcaagga tgaggatggc gagagtggtc ctgatgaagg 2700
ccctgactta gaagagtcca gtgctggtta caaaaagttg ttcgcagatg cccagcagtt 2760
acagcccctc caggtgtacc aggcacccct cagcctggcc actgtgcctc atcaggccct 2820
gggccgcacc cagtcctcac ctgctgctcc tgggagcatg aagagcccca cagaccaacc 2880
cactgtggtg aagcacctct tcaccacagg tgtggtctat gacacgttca tgctgaagca 2940
ccagtgtatg tgcggaaaca cacacgtgca cccagagcac gccggccgca tccagagcat 3000
ctggtcccgg ctgcaggaaa ctggtctgct cggcaagtgt gagcggatcc ggggtcgtaa 3060
agccacactg gatgaaatcc agaccgtgca ctctgagtac cacaccctgc tctatgggac 3120
cagccccctt aaccggcaga agctggacag caagaagctg cttggcccca tcagccagaa 3180
gatgtacgcc atgctgccct gtgggggcat tggggtggac agtgacacgg tgtggaatga 3240
gatgcactcc tcaagtgccg tgcgaatggc agtgggctgc ctggtggagc tggccttcaa 3300
ggtggctgca ggagagctca agaatggatt tgctatcatc cggcccccag gacaccatgc 3360
tgaggagtcc acagccatgg gattctgctt cttcaactcc gtagccatca cagctaaact 3420
cctgcagcag aagctgagcg tgggcaaggt cctcatcgtg gactgggata ttcaccatgg 3480
caacggcacc cagcaagcat tctacaacga tccctctgtg ctctacatct ccctgcatcg 3540
ctacgacaac gggaacttct ttccaggctc tggggctcct gaagaggttg gtggagggcc 3600
aggtgtgggg tacaacgtaa atgtggcgtg gacaggaggt gtggatcccc ccattggaga 3660
tgtggaatac ctgacagcct tcaggacagt ggtgatgccc attgcccagg agttctcacc 3720
tgacgtcgtc ctagtctccg ctgggtttga tgctgttgaa ggacatctgt ctccactggg 3780
tggctattct gtcaccgcca gatgttttgg ccacttgacc aggcagctca tgacactggc 3840
tgggggccgg gtggtgctgg ccctggaggg aggccatgac ttgaccgcca tctgtgatgc 3900
ctctgaggcc tgtgtctcgg ctctgctcag cgtggagctg cagcccttgg atgaagcagt 3960
cttgcagcaa aagcccagcg tcaatgcggt tgccacacta gagaaagtca tcgagatcca 4020
gagcaaacac tggagctgtg tacagaggtt tgccgctggt ctgggctgct cgctgcggga 4080
ggctcagaca ggtgagaaag aggaggccga gactgtgagc gccatggccc tgctttccgt 4140
gggggctgag caggcccagg ctgttgccac tcaagagcac agccccaggt aagccagcag 4200
aggagcccat ggagcaggag cctgccctgt gacaccctgg cccccatccc tctgggcttc 4260
atcattgtga ttttgtttat tttttctatt aaaaacaaaa agtcacacat tcaaaaaaaa 4320
aaaaaaaaaa aa 4332
<210> 17
<211> 1724
<212> DNA
<213> Homo sapiens
<400> 17
agctctgcga ggggccggag cgcggcggag ccatgcagta cccgcacccc gggccggcgg 60
cgggcgccgt gggggtgccg ctgtacgcgc ccacgccgct gctgcaaccc gcacacccga 120
cgccctttta catcgaggac atcctgggcc gcgggcccgc cgcgcccacg cccgccccca 180
cgctgccgtc ccccaactcc tccttcacca gcctcgtgtc cccctaccgg accccggtgt 240
acgagcccac gccgatccat ccagccttct cgcaccactc cgccgccgcg ctggccgctg 300
cctacggacc cggcggcttc gggggccctc tgtacccctt cccgcggacg gtgaacgact 360
acacgcacgc cctgctccgc cacgaccccc tgggcaaacc tctactctgg agccccttct 420
tgcagaggcc tctgcataaa aggaaaggcg gccaggtgag attctccaac gaccagacca 480
tcgagctgga gaagaaattc gagacgcaga aatatctctc tccgcccgag aggaagcgtc 540
tggccaagat gctgcagctc agcgagagac aggtcaaaac ctggtttcag aatcgacgcg 600
ctaaatggag gagactaaaa caggagaacc ctcaaagcaa taaaaaagaa gaactggaaa 660
gtttggacag ttcctgtgat cagaggcaag atttgcccag tgaacagaat aaaggtgctt 720
ctttggatag ctctcaatgt tcgccctccc ctgcctccca ggaagacctt gaatcagaga 780
tttcagagga ttctgatcag gaagtggaca ttgagggcga taaaagctat tttaatgctg 840
gatgatgacc actggcattg gcatgttcag aaaactggat ttaggaataa tgttttgcta 900
cagaaaatct tcatagaaga actggaaggc tatataagaa agggaatcaa ttctctggta 960
ttctggaaac ctaaaaatat ttggtgcact gctcaattaa caaacctaca tggagacctt 1020
aattttgact taacaaatag tttatgtact gctcttaggt tgttttgata aagtgacatt 1080
atagtgatta aattcttccc cctttaaaaa aacagttagt ggttttcact atttataaaa 1140
aattaatttt gaactttttg ttaaattttt aagttatagc tttaaaggtt ttaataggac 1200
cttcttgaac gacttttctg taatctgttt atctcccact taatggaaag gcaaaggggt 1260
accccaaatc cagaggtgcc tacatttcag gcagccttgg agtattttaa aaggaaaaca 1320
ttctttactt ttatatgaca ttcttatact gctgtctcaa atccaaaaac atttcagagc 1380
tcttgtctca gagatgtgtg ttctttttgt cagagatatg gttgatgaga atcttaaatg 1440
cttgttttgc actatcactt agtacctgtt tgaccaaggt gttaagggga tagtacctcc 1500
caattcaagc agagaaactg acctgactaa agttaatcgc agatgaacta gaagtcacag 1560
gttaattaaa tgtaagtaga ttgtagatac tgttttatat caaacaatgt ttataatgtg 1620
tatatagaat tgttcactgt aaaaaaaatg gccaaaatgt gttttttttt taataagtaa 1680
cttgactata aaataaagcc gtccgtggga cgactgacct cgtt 1724
<210> 18
<211> 1771
<212> DNA
<213> Mus musculus
<400> 18
agctctctgc gaggggctgc ggagcggcca tgcagttccc gcacccgggg cccgcggctg 60
cgcccgccgt gggagtcccg ctgtatgcgc ccacgccgct gctgcagccc gctcacccga 120
cgcccttcta catcgacgac atcttgggtc gcgggcccgc cgcccccacg cccactccca 180
cgctgccgtc ccccaactcc tccttcacca gcctcgtgtc ctcctaccgg accccggtgt 240
acgagcccac gccggtccac cccgccttct cgcaccaccc ggccgccgcg ctggccgccg 300
cctacggccc cagtggcttc ggaggccctc tgtacccgtt cccgcggacg gtgaacgact 360
acacgcacgc cctactccgc cacgaccccc tgggcaagcc cttgctctgg agccccttcc 420
tccagcgacc tctgcacaaa aggaaaggcg gtcaagtgag gttctccaac gaccagaccg 480
tcgagctgga gaagaagttc gagactcaga aatacctctc cccacccgag agaaagcgtc 540
tggccaagat gttacagctc agtgagagac aggtcaaaac ctggtttcag aatcgccgag 600
ctaaatggag aagactgaaa caggagaatc ctcaaagcaa caaaaaggat gcgttggaca 660
gtttggacac ttcctgtgag cagggtcaag acttgcccag tgaacagaat aaaggtgcct 720
ctttggatcg ttcgcagtgt tcaccctccc cagcctctca ggaagacccc gactcggaga 780
tctcagagga ttccgaccag gaggtggaca tcgaggggga taaaggctac tttaatgctg 840
gatgacagtc atcggccatg tttagagacc ggactttaga ataatgtttt gctacagacc 900
aactggaaaa ttcgggggga gagagagaga gagaaagaga gagagagaga gagagagaga 960
gagagataac aattcttgta gagttttgaa aatgtttggt gcactggcta attaacaaac 1020
atgcattgcg ttgagacctt aactttggtt taacatacgg tatctatacc agtttttaag 1080
ttgttttgat aaagtgacta aatgtgacct cattttttaa aaagtgaatt tatttctatt 1140
tatgagaggt aatttgaact tttgtctaaa gcttaaatta tgactttaaa ggttttaagt 1200
tttaggaggc tgatcttgac tgactttcct aagtctgtag ctattccctc gactttagag 1260
gtgcacttag gtgggggcaa catttgggga atccatggaa cactttgaaa gggtataccc 1320
aacttttaca tggcatctta cattgctgcc ttaactccaa agccatttca gagcacttgg 1380
ctcccggtgt ctgttcttac aagcaagata gttgataaga ttctaaaaat cttgttttgc 1440
tcagccagtg cctctgaccc tggtgttaag ggatgacgca gtccctacag gcagggaaac 1500
tgactcattt gagactgatc tcacacgaac tagaaatagc aggacaattc aatgtaagta 1560
gattgtagat agtgtgtttt atagaaactg tgtctataac atgtatatag cattacttct 1620
tgtaaaaact ctgccaaaat gatgtttgtt tgtttggttg gttttttgta atttaatgaa 1680
ttaactttca tatacattca tcatcagatg aacgaccctg tttgaattct cattctttgg 1740
ttaaaatacc taaacatgac acctaaagag c 1771
<210> 19
<211> 1670
<212> DNA
<213> Homo sapiens
<400> 19
ataaattgtg caagggtgct atagacgcac aaacgaccgc gagccacaaa tcaagcacac 60
atatcaaaaa acaaatgagc tcttattttg taaactcatt ttgcggtcgc tatccaaatg 120
gcccggacta ccagttgcat aattatggag atcatagttc cgtgagcgag caattcaggg 180
actcggcgag catgcactcc ggcaggtacg gctacggcta caatggcatg gatctcagcg 240
tcggccgctc gggctccggc cactttggct ccggagagcg cgcccgcagc tacgctgcca 300
gcgccagcgc ggcgcccgcc gagcccaggt acagccagcc ggccacgtcc acgcactctc 360
ctcagcccga tccgctgccc tgctccgccg tggccccctc gcccggcagc gacagccacc 420
acggcgggaa aaactcccta agcaactcca gcggcgcctc ggccgacgcc ggcagcaccc 480
acatcagcag cagagagggg gttggcacgg cgtccggagc cgaggaggac gcccctgcca 540
gcagcgagca ggcgagtgcg cagagcgagc cgagcccggc gccgcccgcc caaccccaga 600
tctacccctg gatgcgcaag ctgcacataa gtcatgacaa cataggcggc ccggaaggca 660
aaagggcccg gacggcctac acgcgctacc agaccctgga gctggagaag gagttccact 720
tcaaccgtta cctgacccgc agaaggagga ttgaaatagc acatgctctt tgcctctccg 780
agagacaaat taaaatctgg ttccaaaacc ggagaatgaa gtggaaaaaa gataataagc 840
tgaaaagcat gagcatggcc gcggcaggag gggccttccg tccctgagta tctgagcgtt 900
taaagtactg agcagtatta gcggatcccg cgtagtgtca gtactaaggt gactttctga 960
aactcccttg tgttccttct gtgaagaagc cctgttctcg ttgccctaat tcatctttta 1020
atcatgagcc tgtttattgc cattatagcg cctgtataag tagatctgct ttctgttcat 1080
ctctttgtcc tgaatggctt tgtcttgaaa aaaaatagat gttttaactt atttatatga 1140
agcaagctgt gttacttgaa gtaactataa caaaaaaaga aaagagaaaa aaaaacacac 1200
aaaaagtccc ccttcaatct cgtttagtgc caatgttgtg tgttgcactc aagttgttta 1260
actgtgcatg tgcgtggaag tgttcctgtc tcaatagctc caagctgtta aagatatttt 1320
tattcaaact acctatattc cttgtgtaat taatgctgtt gtagaggtga cttgatgaga 1380
cacaacttgt tcgacgtgta gtgactagtg actctgtgat gaaaactgtg actccaagcg 1440
gtgtgtccct gcgtgccttt ataggaccct ttgcacgaac tctggaagtg gctcttataa 1500
gcgcagcttc agtgatgtat gtttttgtga acaaagttac aaatattgtc caagtctggc 1560
tgttttaagc aaactgtgat cagctttttt tttttttttt ttttttttgt atttgttttt 1620
aaggaaaaaa tactgactgg aacaaaaaat aaactttcta ttgtaagttc 1670
<210> 20
<211> 1877
<212> DNA
<213> Mus musculus
<400> 20
ctccacccaa ctcccccatt agtgcacgag tttacctcta gaggtcatca ggcaggattt 60
acgactggac aacaaaagca cgtgattcga agtcgtaccc catatttggg tgcctacgta 120
ggagggaacc gagtacatgt cccagtcatt tccataattc atcataaatt gtgcaagggt 180
gctatagacg cacaaacgac cgcgagccac aaatcaagca cacatatcaa aaaacaaatg 240
agctcttatt ttgtaaactc attttgcggt cgctatccaa atggcccgga ctaccagttg 300
cataattatg gagatcatag ttccgtgagc gaacaattca gggactcggc gagcatgcac 360
tccggcaggt acggctacgg ctacaatggc atggatctca gcgtcggccg ttcgggttcc 420
ggccactttg gctccggcga gcgcgcccgc agctacgcgg ctggggccag tgcggcgccc 480
gccgagccca ggtacagcca gccggccacg tccacgcact cgccaccgcc cgacccgctg 540
ccctgctcag cggtggcccc ctcgcccggc agcgacagcc accacggcgg gaaaaactcc 600
ctgggcaact ccagcggcgc ctcggccaac gccggcagca cccacatcag cagcagagag 660
ggggttggca cggcgtccgc agccgaggag gacgcccctg ccagcagcga gcaggcgggc 720
gcccagagcg agccgagccc ggcgccgccc gctcagcccc agatctaccc ctggatgcgc 780
aagctgcaca ttagtcacga caatataggt ggcccagaag gcaaaagggc ccggacggcc 840
tacactcgct accagaccct ggagctggag aaagaattcc acttcaaccg ctacctgacc 900
cgccgaagaa ggatcgaaat agctcatgcc ctttgcctct ccgagagaca aattaaaatc 960
tggttccaaa acaggaggat gaagtggaaa aaagataata agctgaaaag catgagtatg 1020
gccgcggcag ggggggcttt ccgcccctga gcatctgagc ggccaaagta ctgagcagta 1080
gtagccgggc agctctctgt agtgtcagta ctaaggtgac tttctgaaac tccccttgtg 1140
ttccttctgt gaagaagccc tgttctcgtt gccctaattc atcttttaat catgagcctg 1200
tttattgcca ttatagcgcc tgtataagta gatctgcttc tgttcatctc tttgtcctga 1260
atggctttgt cttgaaaaaa aaatagatgt tttaacttat ttatatgaag caagctgtgt 1320
tacttgaagt aactaaaaca aaaaaaaaaa aaaaagaaaa gagaaaaaaa aactacacac 1380
acaaaaagcc cccccacctc gtttagtgcc aatgttgtgt gttgcacttg agttctttaa 1440
tgtgcatgta cgtggaagtg ttcctgtctc aatagctcca agctgttaaa gatattttta 1500
ttcaaactac ctatattcct tgtgtaatta atgctgttgt agaggtgact tgataagaca 1560
caaattaact tgttcaacgt gtagtggcta gtggctctgt gacgaaaact gtgactccaa 1620
gcggtgtgtc cctgcgtgcc tttgtaggac cctttgcacg aactctggaa gtggctctta 1680
taagcgcagc ttcagtgatg tatgtttttg tgaaaaagtt acaaatattg tccaagtctg 1740
gctgtttaag caaactgtga tcagcttttt tttttttttg tatttgtttt taaggaaaaa 1800
aaacactgac tggaaacaaa acaaaataaa ctttctattg taagttctct tggtctgatt 1860
tatgccaaat agcaagc 1877
<210> 21
<211> 950
<212> DNA
<213> Homo sapiens
<400> 21
gcgttgcagg tcactgtagc gggacttctt ttggttttct ttctctttgg ggcacctctg 60
gactcactcc ccagcatgaa ggcgctgagc ccggtgcgcg gctgctacga ggcggtgtgc 120
tgcctgtcgg aacgcagtct ggccatcgcc cggggccgag ggaagggccc ggcagctgag 180
gagccgctga gcttgctgga cgacatgaac cactgctact cccgcctgcg ggaactggta 240
cccggagtcc cgagaggcac tcagcttagc caggtggaaa tcctacagcg cgtcatcgac 300
tacattctcg acctgcaggt agtcctggcc gagccagccc ctggaccccc tgatggcccc 360
caccttccca tccagacagc cgagctcact ccggaacttg tcatctccaa cgacaaaagg 420
agcttttgcc actgactcgg ccgtgtcctg acacctccag aacgcaggtg ctggcgcccg 480
ttctgcctgg gaccccggga acctctcctg ccggaagccg gacggcaggg atgggcccca 540
acttcgccct gcccacttga cttcaccaaa tcccttcctg gagactaaac ctggtgctca 600
ggagcgaagg actgtgaact tgtggcctga agagccagag ctagctctgg ccaccagctg 660
ggcgacgtca ccctgctccc accccacccc caagttctaa ggtctcttca gagcgtggag 720
gtgtggaagg agtggctgct ctccaaacta tgccaaggcg gcggcagagc tggtcttctg 780
gtctccttgg agaaaggttc tgttgccctg atttatgaac tctataatag agtatatagg 840
ttttgtacct tttttacagg aaggtgactt tctgtaacaa tgcgatgtat attaaacttt 900
ttataaaagt taacattttg cataataaac gatttttaaa cacttgtgta 950
<210> 22
<211> 964
<212> DNA
<213> Mus musculus
<400> 22
gcactgtttg ctgctttagg tgtctctttt cctccctctc tatctctact ctccaacatg 60
aaggcgctga gcccggtgcg cggctgctac gaggcggtgt gctgcctgtc ggaacgtagc 120
ctggccattg cgcgaggccg cggtaagagc ccgtcgaccg aggagcctct tagcctcttg 180
gacgacatga accactgcta ctcgcgcctg cgggaactgg tgccgggagt cccgcgaggc 240
actcagctta gccaggtgga aatcctgcag cgtgtcatag actacatcct cgaccttcag 300
gtggtcctgg cagagccggc gcctggaccc ccggacggtc cgcatctccc gatccagaca 360
gctgagctca ctccggaact tgtgatctcc aaggacaaga ggagcttttg ccactgaccc 420
ggtcgtcctg gcacctcccg aacgcaggtg ctggcgcccg ttccgcttgg gaccctggga 480
ctctgggacc ctctctccag ccggaagcct gagggcatgg atgagcttcg atcttaaccc 540
agccctcttc acttaccctg aactcaacgc ctcgaggctg gacctggagc ccgagagaag 600
gactgaactt gggtggcctg aagagctagc acacgctggt cagcagctgg gcaacgtcac 660
tctgtcccca ccctgactca agtctaaaag actggctttt ccgagaatgg ggtgtcgaga 720
gggtgtgggg ggatgcgagt ggctgccctg cgcactctgc caaggcagca taagagctgt 780
tcttctggtt tccttggaga aaagctctgc tgccctgatt atgaactcta taatagagta 840
tatagctttt gtaccttttt tacaggaagg tgactttctg taatcatgtg atgtatatta 900
aactttttat aaaagttaac attttgcata ataaaccatt tttgaacact ttgaaaaaaa 960
aaaa 964
<210> 23
<211> 6255
<212> DNA
<213> Homo sapiens
<400> 23
actctaacaa gtgactgcgc ggcccgcgcc cggggcggtg actgcggcaa gccccctggg 60
tccccgcgcg gcgcatccca gcctgggcgg gacgctcggc cgcggcgagg cgggcaagcc 120
tggcagggca gagggagccc cggctccgag gttgctcttc gcacccgagg atcagtcttg 180
gccccaaagc gcgacgcaca aatccacata acctgaggac catggatgct gatgagggtc 240
aagacatgtc ccaagtttca gggaaggaaa gcccccctgt aagcgatact ccagatgagg 300
gcgatgagcc catgccgatc cccgaggacc tctccaccac ctcgggagga cagcaaagct 360
ccaagagtga cagagtcgtg gccagtaatg ttaaagtaga gactcagagt gatgaagaga 420
atgggcgtgc ctgtgaaatg aatggggaag aatgtgcgga ggatttacga atgcttgatg 480
cctcgggaga gaaaatgaat ggctcccaca gggaccaagg cagctcggct ttgtcgggag 540
ttggaggcat tcgacttcct aacggaaaac taaagtgtga tatctgtggg atcatttgca 600
tcgggcccaa tgtgctcatg gttcacaaaa gaagccacac tggagaacgg cccttccagt 660
gcaatcagtg cggggcctca ttcacccaga agggcaacct gctccggcac atcaagctgc 720
attccgggga gaagcccttc aaatgccacc tctgcaacta cgcctgccgc cggagggacg 780
ccctcactgg ccacctgagg acgcactccg ttggtaaacc tcacaaatgt ggatattgtg 840
gccgaagcta taaacagcga agctctttag aggaacataa agagcgctgc cacaactact 900
tggaaagcat gggccttccg ggcacactgt acccagtcat taaagaagaa actaatcaca 960
gtgaaatggc agaagacctg tgcaagatag gatcagagag atctctcgtg ctggacagac 1020
tagcaagtaa cgtcgccaaa cgtaagagct ctatgcctca gaaatttctt ggggacaagg 1080
gcctgtccga cacgccctac gacagcagcg ccagctacga gaaggagaac gaaatgatga 1140
agtcccacgt gatggaccaa gccatcaaca acgccatcaa ctacctgggg gccgagtccc 1200
tgcgcccgct ggtgcagacg cccccgggcg gttccgaggt ggtcccggtc atcagcccga 1260
tgtaccagct gcacaagccg ctcgcggagg gcaccccgcg ctccaaccac tcggcccagg 1320
acagcgccgt ggagaacctg ctgctgctct ccaaggccaa gttggtgccc tcggagcgcg 1380
aggcgtcccc gagcaacagc tgccaagact ccacggacac cgagagcaac aacgaggagc 1440
agcgcagcgg tctcatctac ctgaccaacc acatcgcccc gcacgcgcgc aacgggctgt 1500
cgctcaagga ggagcaccgc gcctacgacc tgctgcgcgc cgcctccgag aactcgcagg 1560
acgcgctccg cgtggtcagc accagcgggg agcagatgaa ggtgtacaag tgcgaacact 1620
gccgggtgct cttcctggat cacgtcatgt acaccatcca catgggctgc cacggcttcc 1680
gtgatccttt tgagtgcaac atgtgcggct accacagcca ggaccggtac gagttctcgt 1740
cgcacataac gcgaggggag caccgcttcc acatgagcta aagccctccc gcgcccccac 1800
cccagacccc gagccacccc aggaaaagca caaggactgc cgccttctcg ctcccgccag 1860
cagcatagac tggactggac cagacaatgt tgtgtttgga tttgtaactg ttttttgttt 1920
tttgtttgag ttggttgatt ggggtttgat ttgcttttga aaagattttt atttttagag 1980
gcagggctgc attgggagca tccagaactg ctaccttcct agatgtttcc ccagaccgct 2040
ggctgagatt ccctcacctg tcgcttccta gaatcccctt ctccaaacga ttagtctaaa 2100
ttttcagaga gaaatagata aaacacgcca cagcctggga aggagcgtgc tctaccctgt 2160
gctaagcacg gggttcgcgc accaggtgtc tttttccagt ccccagaagc agagagcaca 2220
gcccctgctg tgtgggtctg caggtgagca gacaggacag gtgtgccgcc acccaagtgc 2280
caagacacag cagggccaac aacctgtgcc caggccagct tcgagctaca tgcatctagg 2340
gcggagaggc tgcacttgtg agagaaaata ctatttcaag tcatattctg cgtaggaaaa 2400
tgaattggtt ggggaaagtc gtgtctgtca gactgccctg ggtggaggga gacgccgggc 2460
tagagccttt gggatcgtcc tggattcact ggctttgcgg aggctgctca gatggcctga 2520
gcctcccgag gcttgctgcc ccgtaggagg agactgtctt cccgtgggca tatctgggga 2580
gccctgttcc ccgctttttc actcccatac ctttaatggc ccccaaaatc tgtcactaca 2640
atttaaacac cagtcccgaa atttggatct tctttctttt tgaatctctc aaacggcaac 2700
attcctcaga aaccaaagct ttatttcaaa tctcttcctt ccctggctgg ttccatctag 2760
taccagaggc ctcttttcct gaagaaatcc aatcctagcc ctcattttaa ttatgtacat 2820
ctgtttgtag ccacaagcct gaatttctca gtgttggtaa gtttctttac ctaccctcac 2880
tatatattat tctcgtttta aaacccataa aggagtgatt tagaacagtc attaattttc 2940
aactcaatga aatatgtgaa gcccagcatc tctgttgcta acacacagag ctcacctgtt 3000
tgaaaccaag ctttcaaaca tgttgaagct ctttactgta aaggcaagcc agcatgtgtg 3060
tccacacata cataggatgg ctggctctgc acctgtagga tattggaatg cacagggcaa 3120
ttgagggact gagccagacc ttcggagagt aatgccacca gatcccctag gaaagaggag 3180
gcaaatggca ctgcaggtga gaaccccgcc catccgtgct atgacatgga ggcactgaag 3240
cccgaggaag gtgtgtggag attctaatcc caacaagcaa gggtctcctt caagattaat 3300
gctatcaatc attaaggtca ttactctcaa ccacctaggc aatgaagaat ataccatttc 3360
aaatatttac agtacttgtc ttcaccaaca ctgtcccaag gtgaaatgaa gcaacagaga 3420
ggaaattgta cataagtacc tcagcattta atccaaacag gggttcttag tctcagcact 3480
atgacatttt gggctgacta cttatttgtt aggcgggagc tctcctgtgc attgtaggat 3540
aattagcagt atccctggtg gctacccaat agacgccagt agcaccccga attgacaacc 3600
caaactctcc agacatcacc aactgtcccc tgcgaggaga aatcactcct gggggagaac 3660
cactgaccca aatgaattct aaaccaatca aatgtctggg aagccctcca agaaaaaaaa 3720
tagaaaagca cttgaagaat attcccaata ttcccggtca gcagtatcaa ggctgacttg 3780
tgttcatgtg gagtcattat aaattctata aatcaattat tccccttcgg tcttaaaaat 3840
atatttcctc ataaacattt gagttttgtt gaaaagatgg agtttacaaa gataccattc 3900
ttgagtcatg gatttctctg ctcacagaag ggtgtggcat ttggaaacgg gaataaacaa 3960
aattgctgca ccaatgcact gagtgaagga agagagacag aggatcaagg gctttagaca 4020
gcactccttc aatatgcaat cacagagaaa gatgcgcctt atccaagtta atatctctaa 4080
ggtgagagcc ttcttagagt cagtttgttg caaatttcac ctactctgtt cttttccatc 4140
catccccctg agtcagttgg ttgaagggag ttattttttc aagtggaatt caaacaaagc 4200
tcaaaccaga actgtaaata gtgattgcag gaattctttt ctaaactgct ttgccctttc 4260
ctctcactgc cttttatagc caatataaat gtctctttgc acaccttttg ttgtggtttt 4320
atattgtaac accatttttc tttgaaacta ttgtatttaa agtaaggttt catattatgt 4380
cagcaagtaa ttaacttatg tttaaaaggt ggccatatca tgtaccaaaa gttgctgaag 4440
tttctcttct agctggtaaa gtaggagttt gcatgacttc acactttttt tgcgtagttt 4500
cttctgttgt atgatggcgt gagtgtgtgt cttgggtacc gctgtgtact actgtgtgcc 4560
tagattccat gcactctcgt tgtgtttgaa gtaaatattg gagaccggag ggtaacaggt 4620
tggcctgttg attacagcta gtaatcgctg tgtcttgttc cgccccctcc ctgacacccc 4680
agcttcccag gatgtggaaa gcctggatct cagctccttg ccccatatcc cttctgtaat 4740
ttgtacctaa agagtgtgat tatcctaatt caagagtcac taaaactcat cacattatca 4800
ttgcatatca gcaaagggta aagtcctagc accaattgct tcacatacca gcatgttcca 4860
tttccaattt agaattagcc acataataaa atcttagaat cttccttgag aaagagctgc 4920
ctgagatgta gttttgttat atggttcccc accgaccatt tttgtgcttt tttcttgttt 4980
tgttttgttt tgactgcact gtgagttttg tagtgtcctc ttcttgccaa aacaaacgcg 5040
agatgaactg gacttatgta gacaaatcgt gatgccagtg tatccttcct ttcttcagtt 5100
ccagcaataa tgaatggtca acttttttaa aatctagatc tctctcattc atttcaatgt 5160
atttttactt taagatgaac caaaattatt agacttattt aagatgtaca ggcatcagaa 5220
aaaagaagca cataatgctt ttggtgcgat ggcactcact gtgaacatgt gtaaccacat 5280
attaatatgc aatattgttt ccaatacttt ctaatacagt tttttataat gttgtgtgtg 5340
gtgattgttc aggtcgaatc tgttgtatcc agtacagctt taggtcttca gctgcccttc 5400
tggcgagtac atgcacagga ttgtaaatga gaaatgcagt catatttcca gtctgcctct 5460
atgatgatgt taaattattg ctgtttagct gtgaacaagg gatgtaccac tggaggaata 5520
gagtatcctt ttgtacacat tttgaaatgc ttcttctgta gtgatagaac aaataaatgc 5580
aacgaatact ctgtctgccc tatcccgtga agtccacact ggcgtaagag aaggcccagc 5640
agagcaggaa tctgcctaga ctttctccca atgagatccc aatatgagag ggagaagaga 5700
tgggcctcag gacagctgca ataccacttg ggaacacatg tggtgtcttg atgtggccag 5760
cgcagcagtt cagcacaacg tacctcccat ctacaacagt gctggacgtg ggaattctaa 5820
gtcccagtct tgagggtggg tggagatgga gggcaacaag agatacattt ccagttctcc 5880
actgcagcat gcttcagtca ttctgtgagt ggccgggccc agggccctca caatttcact 5940
accttgtctt ttacatagtc ataagaatta tcctcaacat agccttttga cgctgtaaat 6000
cttgagtatt catttaccct tttctgatct cctggaaaca gctgcctgcc tgcattgcac 6060
ttctcttccc gaggagtggg gtaaatttaa aagtcaagtt atagtttgga tgttagtata 6120
gaattttgaa attgggaatt aaaaatcagg actggggact gggagaccaa aaatttctga 6180
tcccatttct gatggatgtg tcacaccttt tctgtcaaaa taaaatgtct tggaggttat 6240
gactccttgg tgaaa 6255
<210> 24
<211> 5451
<212> DNA
<213> Mus musculus
<400> 24
gtcagggtcc cgaagccgcg tgccgtgcgc gcaggccggg tgggctgtgg gacaagccga 60
gcgggaggcg agtcgcaagc gccaacccaa agtttgcacg gtgcggggcg aggggcgcgc 120
gctccgggct gccgcaggtg gcggcgcggt gagcccgggc caggtgcccc ggcagcgggg 180
cggcgctgtc gtgcgggaca gccgggctgc caggggctcg gagccgggtc ggagcccgcg 240
gggggcgggg agtgtggcga gaaatgggga acaatgcgag tgagcaactt gaggaagtca 300
ttgtgaaaga aagctgggaa ttgctccgca gccaacttag cagggcactc taacaagtgc 360
ctgcgcggcc gcgcccgggc cggggacagg ggcagcccgg cgcagtacag cccatcccgg 420
gacgctcggc cgcggctgcc ggagacccgg taggtcccgc ggggtgcagg agcccccaga 480
tccccggctg ctcttcgcgc cccaggatca ttcttggccc ccaaagcgcg gcgcacaaat 540
ccacataacc tgaagacaat ggatgtcgat gagggtcaag acatgtccca agtttcagga 600
aaggagagcc ccccagtcag tgacactcca gatgaagggg atgagcccat gcctgtccct 660
gaggacctgt ccactacctc tggagcacag cagaactcca agagtgatcg aggcatggcc 720
agtaatgtta aagtagagac tcagagtgat gaagagaatg ggcgtgcctg tgaaatgaat 780
ggggaagaat gtgcagagga tttacgaatg cttgatgcct cgggagagaa aatgaatggc 840
tcccacaggg accaaggcag ctcggctttg tcaggagttg gaggcattcg acttcctaac 900
ggaaaactaa agtgtgatat ctgtgggatc gtttgcatcg ggcccaatgt gctcatggtt 960
cacaaaagaa gtcatactgg tgaacggcct ttccagtgca accagtgtgg ggcctccttt 1020
acccagaaag gcaacctcct gcggcacatc aagctgcact cgggtgagaa gcccttcaaa 1080
tgccatcttt gcaactatgc ctgccgccgg agggacgccc tcaccggcca cctgaggacg 1140
cactccgttg gtaagcctca caaatgtgga tattgtggcc ggagctataa acagcgaagc 1200
tctttagagg agcataaaga gcgatgccac aactacttgg aaagcatggg ccttccgggc 1260
atgtacccag tcattaagga agaaactaac cacaacgaga tggcagaaga cctgtgcaag 1320
ataggagcag agaggtccct tgtcctggac aggctggcaa gcaatgtcgc caaacgtaag 1380
agctctatgc ctcagaaatt tcttggagac aagtgcctgt cagacatgcc ctatgacagt 1440
gccaactatg agaaggagga tatgatgaca tcccacgtga tggaccaggc catcaacaat 1500
gccatcaact acctgggggc tgagtccctg cgcccattgg tgcagacacc ccccggtagc 1560
tccgaggtgg tgccagtcat cagctccatg taccagctgc acaagccccc ctcagatggc 1620
cccccacggt ccaaccattc agcacaggac gccgtggata acttgctgct gctgtccaag 1680
gccaagtctg tgtcatcgga gcgagaggcc tccccgagca acagctgcca agactccaca 1740
gatacagaga gcaacgcgga ggaacagcgc agcggcctta tctacctaac caaccacatc 1800
aacccgcatg cacgcaatgg gctggctctc aaggaggagc agcgcgccta cgaggtgctg 1860
agggcggcct cagagaactc gcaggatgcc ttccgtgtgg tcagcacgag tggcgagcag 1920
ctgaaggtgt acaagtgcga acactgccgc gtgctcttcc tggatcacgt catgtatacc 1980
attcacatgg gctgccatgg ctttcgggat ccctttgagt gtaacatgtg tggttatcac 2040
agccaggaca ggtacgagtt ctcatcccat atcacgcggg gggagcatcg ttaccacctg 2100
agctaaaccc agccaggccc cactgaagca caaagatagc tggttatgcc tccttcccgg 2160
cagctggacc cacagcggac aatgttggga gtggatttgc aggcagcatt tgttctttta 2220
tgttggttgt ttggcgtttg atttgcgttg gaagataagt ttttaatgtt agtgacagga 2280
ttgcattgca tcaggaacat tcacaacatc catccttcta gccagttttg ttcactggta 2340
gctgaggttt cccggatatg tggcttccta acactctccc cacccacccc accccccaaa 2400
acagagcctg aatcttcatg aagtgaataa aacaattatc caagaaggag taaggtggat 2460
cttgccctaa gcagagttta tgccacaaag attctccaaa tcccccaaga cagcacagcc 2520
actggggttg agccatctca gggagctctg caggtgagcc agaggaccag atataaggca 2580
gctggggagg agcagggaca tcagcctgtg cagagaccaa ggccaaaggt tgaactttga 2640
aagactatta agtcatatat tgtatggcaa tatggtgtct ggacaagttg tgcaatgtgc 2700
tgaagggaag ggattggaga gccttgaaga ctcttcttca tttgcctgat caacccgacc 2760
tccagagggt ttgttgccca gtaagacgag ctcagtgctc ttgtgatcat ttttctctta 2820
tcgtttccat gccgttgatg gccctgaagc tcatcactgc attttagaac ccaatcctga 2880
aattgggacc ttttttttaa acttctgata ctgtaaaact tcttggaagc caaagctttc 2940
ttccaagccc catcctcagt tatcctggtt cctgttcttc cccgagctga tagtaccagg 3000
acctgttatt ccacaaaagc acaggcatcc gtcacttcaa ttcaatccct gttcagatta 3060
tagatatgga ctttgctatc ttgataaatg tcttctctat gttattttgt ctgaaaaacc 3120
tataaaacca ttattaagaa tgaccatttt tagatggaag aaatgagccc agcatctcag 3180
tggctaaaac acaaaatatc catgctttta aacaaaattg ttaaatattc cgaagctctc 3240
tagtataaac accaagtagc atgtgttttc acataaagaa gacaggggcc atgcaacctt 3300
tatcaagtgg aggtattaga atgttgtaat gtttggagac acagtgtgac cagtacaggt 3360
tcccagagag gaatgcccac catatcacag aaaggtagag gtgggatctg gtatagccag 3420
accaagacag ggatgtcacg ctgaagccaa gtcagttagc tgaagattct caacaggaag 3480
gcctctctta agagtcagta atagggttgt taccatccac cacctcaaca aaacaaaaag 3540
cttataattg taaatgttta cagcactgtc ttcgcagaaa ctttctgagg tgattccaaa 3600
gaactagagg ggagatggtc tataacagct cttgaagtaa acgaggttct tagtctcagc 3660
tctcctgaca tatagggctt gatcattact ggtagggatt gttctgtgaa ttgcttacta 3720
ctacccctgg tctctcccca gtagatgcca ggaacattct agctgatacc taactgtctt 3780
cccaggtgtt cgagggagca aaccactgat ctaaactcta aacgctgaag tacgcaggtt 3840
ttctaaaaat gacaagccct tgaaaccttt cccagtaggc agcctcgagc tggacttgtg 3900
tctttggaat gctgatgaat tctatagatc agcattgcaa atacacttca aatacgtctg 3960
agttcaagtg cagggactga gttcaccaag gtgtgaaatg tgctcaaaaa gttcaaaagt 4020
gtgtgtttct ttgtttctaa aacattgtgg catctttttc atttgtttct aaaacttttt 4080
ttttagaaac aaatgaagca cttggaaagt gaaagtaaaa ttacaaatat aaggatttac 4140
actgaagaga gaaaaatttt aggaactata gctgtgaaaa gattttgttc aaaaggcagg 4200
ctagccttac ccaaattcat atatggcagg tgtcaacctc ccaagcttac agttagcagg 4260
cagcttttgc tcactcatcc ttagccatga gagccattaa gtgtggtcca agaaagatgg 4320
ctccaaaccc tacccccgac ccaccagtgg tattcagaga ttaaagcaga attgtaaata 4380
gtggcttcag gagctctttt ttagaatgct ttgccccttc ctctcactgc cttttttagc 4440
caatataaat gtcaatttgc acaccttttg ttgtggtttt atattgtaac agcatttttt 4500
tgaaactatt gtatttaaga taaggtttca tattatgtcc acaagtaatt aaattatgtt 4560
tgaaggtggc tatatgctgt atcagaagtt gatgatgttt ttctttagct ggtaaaggag 4620
ggttttgcat gacctcactg tttgttctgt ggtttgttct gttgtatgat gtgtgtcttg 4680
agttttgctg tgtgatgaag tgcgctgaga ttccagtgcc ctcaagttgt gttttaagta 4740
gctatcagag gcaagagggt tcctaagagc aggttgacct gttggcgaca gatggcaatc 4800
accatttctc attccttctt ctccctgtta ccccagcttc ctgtcccagg tcccttctgt 4860
gattcttacc ttagtgtgca tgtgtgtctg tcctggtgag agtcaggagc atcgatatgt 4920
tatcattgca ttatcaccaa gggcacgcac agcctagcac ctgttgcttc agataccgtc 4980
acactctgtt tccaatttag atacaaccac ataataaaat gttagagtct tcaatgggaa 5040
gcagaggtgc ttgttataaa gatgggggct tatgcttgtg tcacattttg tgttcttttc 5100
ttcttttgtt tggttttaac ttaattgtga cccttgtaac atcatcttgc caaaaaaaaa 5160
aaaaaagttg aactggattt atgtagacat gtcaagacgt actatctatt tctttgtcag 5220
ttatagcaat aagagtggat aaactctaaa atccagatct cccacaatga acatccgtgt 5280
tctttctatg atttttcttt ctttatggtg agccacaatt aaacttgaga tgtacagcca 5340
cccaaaccca ggaagctcat gtgcatctgg tgctatggca ctcactgtga ataagtgtga 5400
ccagatatta atatgcaata ttgtttccaa tcctttctaa tacatttttt c 5451
<210> 25
<211> 9515
<212> DNA
<213> Homo sapiens
<400> 25
atttcttggt tttgtttatc agccgatctg tttgctggat ttgggcttgg aatgacccac 60
ctgtaaagtg cttttccttc ctcctcccct tgaactctgc agggggcttg gcttggaggg 120
ggcaagggag ggaaagagag aagggggaaa cacaaaaaac ttctttcttt ctccctccgt 180
ttatcttcag cccgacattg tcacctcctc tttgaggggt tagaagaagc tgagatctcc 240
cgacagagct ggaaatgcat tgcactttga ctatggaaac agaggctatt gatggctata 300
taacgtgtga caatgagctt tcacccgaaa gggagcactc caatatggca attgacctca 360
cctcaagcac acccaatgga cagcatgcct caccaagtca catgacaagc acaaattcag 420
taaagctaga aatgcagagt gatgaagagt gtgacaggaa acccctgagc cgtgaagatg 480
agatcagggg ccatgatgag ggtagcagcc tagaagaacc cctaattgag agcagcgagg 540
tggctgacaa caggaaagtc caggagcttc aaggcgaggg aggaatccgg cttccgaatg 600
gtaaactgaa atgtgacgtc tgtggcatgg tttgcattgg gcccaatgtg cttatggtac 660
ataaaaggag tcacactggt gaacgcccct tccactgtaa ccagtgtgga gcttctttta 720
ctcagaaggg caaccttctg agacacataa agttacactc tggagagaag ccgttcaaat 780
gtcctttctg tagctacgcc tgtagaagaa gggacgccct cacaggacac ctcaggaccc 840
attctgtggg taaacctcac aagtgcaact actgtggacg aagctacaag cagcgcagtt 900
cactggagga gcacaaggaa cgctgccaca actatctcca gaatgtcagc atggaggctg 960
ctgggcaggt catgagtcac catgtacctc ctatggaaga ttgtaaggaa caagagccta 1020
ttatggacaa caatatttct ctggtgcctt ttgagagacc tgctgtcata gagaagctca 1080
cggggaatat gggaaaacgt aaaagctcca ctccacaaaa gtttgtgggg gaaaagctca 1140
tgcgattcag ctacccagat attcactttg atatgaactt aacatatgag aaggaggctg 1200
agctgatgca gtctcatatg atggaccaag ccatcaacaa tgcaatcacc taccttggag 1260
ctgaggccct tcaccctctg atgcagcacc cgccaagcac aatcgctgaa gtggccccag 1320
ttataagctc agcttattct caggtctatc atccaaatag gatagaaaga cccattagca 1380
gggaaactgc tgatagtcat gaaaacaaca tggatggccc catctctctc atcagaccaa 1440
agagtcgacc ccaggaaaga gaggcctctc ccagcaatag ctgcctggat tccactgact 1500
cagaaagcag ccatgatgac caccagtcct accaaggaca ccctgcctta aatcccaaga 1560
ggaaacaaag cccagcttac atgaaggagg atgtcaaagc tttggatact accaaggctc 1620
ctaagggctc tctgaaggac atctacaagg tcttcaatgg agaaggagaa cagattaggg 1680
ccttcaagtg tgagcactgc cgagtccttt tcctagacca tgtcatgtac accattcaca 1740
tgggttgcca tggctaccgg gacccactgg aatgcaacat ctgtggctac agaagccagg 1800
accgttatga gttttcatca cacattgttc gaggggagca cacattccac taggcctttt 1860
cattccaaag gggaccccta tgaagtaaag aactgcacat gaagaaatac tgcacttaca 1920
atcccacctt tcctcaaatg ttgacatacc ttttattttt tttaatatta ttactgttga 1980
taattcttat tttgtggagg cagtgtcatt tgctctgcct aattacgata aggaagaaac 2040
agaagagaga aggggcggga atattgtttc tttatcacct ggcttgttta ttttgtggga 2100
atttaagagc agtccatttc taccaaggca tatcatgctt tgaaaaatca cttgattcat 2160
aaagattcac ctaagagatt ctgatttgcc actgatattc agaattatga tggaagacag 2220
gaaagttcag agttttctgg gtaggacttt ggtggtttaa aaatggtata agtaacttta 2280
ttcttgaaag aagaatgtgt ttcaaactgt aaaccaattt tttgttcttc agagatcatg 2340
gaacacaaac acattgttat tttcagtgat aactcctaag aggagctgag ttgttgtggg 2400
ttctatgttt acttccccta tggaatttat aattcagtat gttttacact gtaccatata 2460
gcaaaacttt taaactacag gtagttaagg gccacctaca atacatctga ggtcctgtga 2520
tcttattttt ctaaacgtaa gcactgtttt tccatagttt tgatgactgg cattttatag 2580
acaccctggc agccttactt ttaacacctt taaggaatag tatttttatg tagttttcag 2640
aataacatat ggtctaagag tggataaaag gcagtcaata atttctggga gggacttcta 2700
ctttcataaa tttgtttgag aggttttctt ttaaagttgt aatgtgatgg cagcatagta 2760
tatgtatttg tttctaaaag tatgcttacg attgtcactt tatcagcatt taatcagtgt 2820
taaccagtca gcagaaaaat ataattatgc taacagtagg gggagaaaac ccacttagaa 2880
atcccttttc tggtatttct cttttcacta gtttttttca agatgtgacc tcccggtgtt 2940
ctgtccatag ttcattcatc ctttactctt cgagtagaag gtcttaaaag tcttcctgtc 3000
ggctgtttct ttcaaaatct cctcagagca attgctaatt tggcctgaat ctggtaactt 3060
gaaccctgta aggttacaga actagggcta tttattttag catttcttca gtagtattta 3120
ctactcttgt tgcaaagaaa agggaatggg acttctttgt aacctgtacc ttggacaaca 3180
gataaaagaa acaaaaaaat aagaaagttt acttttaccc ttcttggagt ctagaatgtg 3240
acagaacccc caaaggaaag tcctgcacat ttttctgttt ccaaaacatt taattgtgta 3300
agtccttgtc agaaatgaat ctcaatccct tagtatagaa ttccccttac atggtatagg 3360
ttgccatatt tcatgtgcag attttaattt catttatgtg ggcgctctgt tttttctttg 3420
cagtccagcc acattagagg ggaggaaccg agtgatattg attcaagtca ttttaggggg 3480
acatacttgg aaggcagaac ttgctgcttc tgtttgggga ggacagacct gactgtgact 3540
ggattatctg ataaccattt gtgaatactg aaattctgtt aggcagtaac tgataactgc 3600
tctaaaggat cattaaatag gatgctgaaa ttatgtatct taatacagtg tggtatgaga 3660
attaccaagt caagagaatt gtggacataa gcaagtttgg ccccaatact gctcttaact 3720
cattttccag cttactattt gctatttaaa tggtaggcac cagctaagca cttctaagca 3780
ctaacacagc tagaactagg caaaaatggt tagaactcag ctctcttcta ctagtccctg 3840
tcataattat ttttgggaaa atgtccaaac tgcccccttt aaatctaagg gaatgcacca 3900
aaacagagat atatagaatg tcaaccattt catttttttt tttctgcatg ccttggtaca 3960
tagtgaacat acaacctatt taaagataaa gcatgttttt gagactcgct cacccccccc 4020
cacccaacca ctcccaaata ataattggga tgccattttt tttccttttg gatgaggtaa 4080
ataattttaa ggttcacaat tttgtctttt actgcaattt aaggaaacat ttggatgtca 4140
gtcaatatgt tcataatttt ggctgtgtgc gaatttctgc tggcattatc tatgaatttt 4200
cttcctactt attttttttt cagtatatga acaatcatgt atctacctgc cccaggatga 4260
aactaaattt aggtggaccc taaaccttat gaagacagtg ctgaggcact ttccttttct 4320
gatttcatct ttttgggaat ctgttttatt gaaggtagtt agtagttgag agtgcatttg 4380
ctacaagcat atacttgtat cttcctagct tcatgaggaa cagaaagagg tggatatggc 4440
tcagggtgtg gcagggacaa ttgaggacaa agtcaattca aatttgtggg tcagaaagaa 4500
tttttgtgga cgtagtgttt ttggagaaac tctggatggt tatatgtgca tgccttttct 4560
tcaaaaggaa atacgcaagg ttgtagcatc taaaaataaa cataagagtc agacaccaaa 4620
taaatcaagt tttacataac agttgtatgc ccagtttgtt taggtgagat ttcacattac 4680
agaaagtatt tgaggagcat gaaaatgggt tatcttctgt attttccagt ttggcaaaag 4740
ttcagaattt catcacattg ctttgcccta attttgccca gaattttatc ttagcctctc 4800
tctgacagtg atgaatcatg ctcaaaagcc attctaattg gaccttttta agacagggaa 4860
agggatcagt aggcggattg gaagaaattt caagtcattg aaatattcca ttgagatttc 4920
ctaaagggac aaaattggga aaataagaaa ctacgactta gatttggcta cgtagtagaa 4980
agtatctccc ctacatacat acaggcaatt gtatgtatga atcatagggt atatgtgtgt 5040
gtatactaca cacacattct tttaaagaga attcatggaa aaaaaagcag ttggagtgat 5100
cagatgtatt gcaaaaacat acagagaatt taaatgacag ttaataccaa gaaattagtt 5160
gggtttactt tatcaggtcg taataggaat cactaaagaa gttactagtg tgtctttagg 5220
accagtggca actcttaaac taaaactttg ggtccttatt atctacttac agaacaaagt 5280
gaaacaaaca atgattaagc tgattggata tacattcaaa gatatttaat gtaaagtttt 5340
ttggaatacg aagaaaattc agaaaataaa tattatcaac agttacttat tggcaaatag 5400
agaaagacaa gaatagttta gtgagcccgg tattttgttt ttatagtttt tatctcagtt 5460
gtacaactca caaaaccatg aagtctttgg tattttataa atgtttaaca aaatttacat 5520
cagattaagg catttagatg aaaattatta tgttctcact atcttccaaa ttttatttca 5580
tcctatctcc aaaatgattt cttagggtac aaaaagagca gacggggctg taaaaataca 5640
agcaaaaaac tgtgtgcccc tagtttcagg cagaacttaa actgtcagag gtactagcta 5700
catgatttgt tttttaactt tggattgttc acgtccaaaa atggataaat tacatttgtg 5760
tttatcatca gttgcatttt atgtattatt ttaataaata ctatctgaat gaagactatt 5820
ctaaaccaga aaattcccca aatccaaaag aaaaaaaaag tgggaagagg tgaaattgaa 5880
gtttgtgtat atgaaagtta tcttagacat atttttaatt ctccagtttc tgcaaaataa 5940
ttaaaatata cagtaactgg tctcctaaat cctgaattta atgtattaaa tacttatgtt 6000
ctttatattg gtgccttttt aaaatgcatt gagagtgttg gttagctgtt gcagctgtac 6060
aacactttta atatgcattt ttaaaaatca cttaaaattg agtactatat aattcatctc 6120
tgcattttta gtgcaaatct ttagagcaat ttctaataga gaaattttca gctcagctgt 6180
taaaaggaaa aggaaacttt gaaactagac tttactacct ttttagtttc atagtatttc 6240
tgaatatgat tacaagatta tgcaggtaaa atatagagtg aaactttacc tgtgaattga 6300
attataattt gtgtttttgt tttgttttta aggaagaata agttctgtat caaacaagaa 6360
tttattagat aattttttgg tcaataaaat acagtattca tttggatttt catctccaga 6420
ctagtattgt tctagtcttg gaatctgtat tttctaatct gttagaaaat agagattgaa 6480
aattgatgga ataatgtgaa aaagcaggta attaattctc cttgaacaaa gcaaaactga 6540
acagtcatat cacattgcta ttctccaaag cataatctca aatggtttca tatcatggtt 6600
gtgtattact tgcaatgggt gtgttaggat atgacagctt tttaaaaaaa tgagctgctg 6660
gttatacaaa gcaaatggca tatgaccaag aagctgtgat atgctagtgt ttctttttat 6720
catagtgtat tactaggcca aataatgaca ccttgaatat ttttacattt attgcagaaa 6780
ccttaaactt tggaatttcc ataaggtttt tatgtaatat tctatttcta gctttttagt 6840
tttatcttgc tgtactgtaa gtttgaggat atttttcacc tgcactctta ggaataagtt 6900
cataattctg tttatggggc tttcctccca taacactgca tttgtatatt ttctgtataa 6960
aatatgtgtt gtgtattaac ctttatccca tacagagagt ggtacatgaa tgactagttt 7020
tctaagatgt cctttttatt gtgaataaaa tataaaagtt aaaggccctc tgctaagtca 7080
cataaagtac agcatataag ttcatatagg tacaaataaa tgagtttgca gtgaattggg 7140
ccttcaaatt acctcaagtg acagatagta agaaaagctt cttgagcagg tggaggtcac 7200
tgaatcccct actatgcact taccaagatt ttacttactt taatttactg gaaattgatt 7260
ttttaaaaaa tgactacact gtaacaaggg aagggatctg ggtttttttg ttgttttatt 7320
cttgtttttt ttaagtagtt caaattctga aactgtgatt taaaaatttt ttacagtcaa 7380
gcattctgat tttgaacata actcccttcc ctttctgtgt aacaaaggtc tctctgttat 7440
ctcttaaatt ttgttacatc tccctcagcc tctttctttg tccgtctccc ttctgtcatt 7500
gtctatggat gtttacctct ctgttctcct aaaagtttga agattaggtc aactcttatt 7560
tctagttcat tggtaattta atcttaattt ttttttcgtg atttttgttg gttgtataat 7620
ctgctgacgt atttttatac tcaagtgtag ttttctatta aaaagaaaag tggttggatt 7680
aaaaatagta agctatgtaa ccctcatgtt actttcactt tcaaatattg ggtacctaaa 7740
acattacttc agagattatg taatcctatt atagtatgtt tgctttcctt tattgttgga 7800
ttttacattc tgatttggct ttcctccaaa aaatgtatat catgaaagac tagacagtta 7860
tttgcaagtg tttagaaagg tgttaaaaat gtaaagcaaa gagtcttaac tttctcctaa 7920
ttgggagaaa aatgctttaa cattactata ataatattcc aggtttggag ggggtctcca 7980
ggccccatat ttgctgttaa tagttggacc ttttagacca tgtgttattt gcaatcccag 8040
aatgattgct tctgctatta gttaaaaaga tactattctt ttctttctgt acaagtgcaa 8100
tactcccctt gaagtcttaa aaactatggt gatttttttt tcttttctga cctattcttc 8160
ctttagctaa tgacaaaaag aaactcataa aagtcatagt atgttaaagg acacaacaag 8220
caaagagaaa aacactccac aatcaaaaga ttacagaatg tggaaaccac tagtctgatc 8280
tcatggtatc tttatttaag ctaaatttcc atggaaatta gtaatctttt gcttgaaaaa 8340
tgtgtcctaa agttgaactt tttacagatt gaatcttctt agaccctcgc ccaatgctct 8400
aaattaagaa cctaatactt aatattttta ttttacttct ccccttttag aaataaactt 8460
ttaaataaaa gcaaagcact tagctgagtt ttaaacactt acatatcacc tattggagaa 8520
atttttttta aaaatatttg gagcagtcct gttttcatac aaatttaagt aagaggtatt 8580
tttcttatac atatttatat gtagtgtgct aattttcttt ttttatacct gtgtccctgt 8640
agtaaaactg ctgtaatata aatacatgtt ttgttaaaag ataacatttc tttggcattt 8700
cttttaaagg cagttactgc atttctgcat ttgtacagta tgtgtcttgg ccattttaga 8760
tattctttct ttaacaatac caaaggtaat tagactattt taaagactaa ttgcttgaca 8820
gtttctaggg tattttgtgt tttagaagca aaaaaagaaa aaaaaatagg tcaaaccagt 8880
aaacctcatt ttttttcaaa ctaataattt ggggaaataa aaactattgt ttaaaaaaga 8940
aatatatata tatatatata aatatatatg taaagttaaa attccatacc ttgtatgtca 9000
ggtttgctaa gtgtaatgta gtttttttaa ggctcaaata ccatacctca gaaaatgagg 9060
tttactatgg aaatactgaa acagtctttg cagctgtgtg acaagtcact ctactacata 9120
ctgatttgga gacctccgct aaatagtttt atcactgcag actaaaatgt gggacttgta 9180
tcttctttgt ttttaatgca cacacataca tgttctgtgc atgtatgtgg ttactgtgta 9240
tatgtgtatg agtgttgtat atgcatgtgt gagtgtgtgt ctgtatgtgt gtacaactaa 9300
agaagctgca gaaactttgt aatactttgt gaaaaggatt atattataaa ggtttgtact 9360
gtctgagtgc acagctactg gaataaattt agggaatctc aggaacaagc atataatttg 9420
tccaagattt atttcttctc agaagtgtaa gtgcagtttt taattctgta tattatttaa 9480
tattttacca ataaaataaa cttctgacat aaaaa 9515
<210> 26
<211> 9457
<212> DNA
<213> Mus musculus
<400> 26
tgtttgctgg attcggtctt ggaatgaccc acctgtaaag tgctttccct cctcctcggc 60
ttcaactctg cagggggctt tgcctggagg gggcagggag ggaagggggg ggggacacaa 120
aaaacttctt tctttctttc tttctttctc cgtttctctt cagcccgaca ttgtcacctc 180
ctccttgagg ggttagaaga agctgggagc tcccgacaga gctggaaatg gtgatgactg 240
ttttttaatc agaggacaat ttcttttcac tgcactttga ctatggaaac agacgcaatt 300
gatggctata taacatgtga caatgagctt tcacccgaag gggaacacgc caatatggcc 360
attgacctca cctcaagcac acccaatgga cagcacgcct cgccaagtca catgacaagc 420
acaaattctg taaagctgga aatgcagagt gatgaagagt gtgacaggca gcccctgagc 480
cgtgaggatg agatcagggg ccacgatgag gggagcagcc tagaagaacc cctaattgag 540
agcagcgagg tggccgacaa caggaaagtc caggaccttc aaggcgaggg aggaatccgg 600
cttccgaatg gtaaactgaa atgtgacgtc tgtggcatgg tttgcattgg gcccaatgtg 660
cttatggtac ataaaaggag tcacactggt gagcggccct tccactgtaa ccagtgcgga 720
gcttctttta cccagaaggg caaccttctg agacacataa agttacactc tggagagaag 780
cccttcaaat gtcctttctg tagctatgct tgtagaagaa gggacgctct cacaggacac 840
ctcaggaccc attctgtggg taaacctcac aagtgtaact actgtggccg aagctacaag 900
cagcgcagct cactggagga acacaaggaa cgctgtcaca actatctcca gaatgtcagc 960
atggaggctg ccgggcaggt catgagtcac catgtaccgc ctatggaaga ttgtaaggaa 1020
caagagccta tcatggacaa caatatttct ctggtgcctt ttgagagacc tgctgtcata 1080
gagaagctca cggcaaatat gggaaagcgc aaaagctcca ctcctcagaa gtttgtgggg 1140
gaaaagctta tgcgattcag ctacccagat attcattttg atatgaactt aacatatgag 1200
aaggaggctg agctgatgca gtctcatatg atggaccaag ccatcaacaa tgcaatcacc 1260
taccttggag ctgaggccct tcaccctctg atgcagcatg caccaagcac aatcgctgag 1320
gtggccccag ttataagctc agcttattct caggtctatc atccaaacag gatagaaaga 1380
cccattagca gggaaacatc tgatagtcac gaaaacaaca tggatggccc catctctctc 1440
atcagaccaa agagtcgacc ccaggaaaga gaggcctcgc ccagcaatag ctgcctcgat 1500
tctactgact cagaaagtag ccatgatgac cgccagtcct accaaggaaa ccctgcctta 1560
aatcccaaga ggaaacaaag cccagcttac atgaaggagg atgtcaaggc tttggatgct 1620
accaaggccc ccaagggctc tctgaaggac atctataagg ttttcaatgg agaaggagaa 1680
cagataaggg ccttcaagtg tgagcactgc cgagtccttt ttctagacca tgtcatgtac 1740
accattcaca tgggttgcca tggctaccgg gacccactgg aatgcaacat ctgtggctac 1800
agaagccagg accgctacga attttcatca cacattgttc gaggggagca cacattccac 1860
taggcctttt cattccaaag gggaccccta tgaagaactg cacatgaaga aatactgcac 1920
ttacagtccc accttccctc ggatggcgac atgctgtctt ctggatgctg tcactgtcta 1980
taattcttat tttgtggaca aaatgtcatt tgctctgcct aactacaatg aggaagaaac 2040
aaaagaaaag ggatgggatg ttcaatgata acttggcttg tttatttcgt gagcatttaa 2100
agcagttcat tgcagccatg catccttgtt aaggcctatc ataatttagg agatcattca 2160
gttcatagag gttcatccaa gagattctga tctgccattc atattcagga ttgtgataga 2220
aggcaggaaa gttgagagtt ttctgggtag gatgcttggc aatttaaaat ggtctaagtc 2280
attttactct caaagaagtt tcaaaatgta aaccgatttt attttctgtt cgttagagat 2340
catggaacac aaaaacaatg ttattttcca taactactag gatgagttga attgttgtgg 2400
gttctgtgtt tacctcccct acggaattta taattgagta tgttttacac tgtatcatat 2460
agcaaaaatt ttaaactaca ggtagtcaag ggccgctacg atacatctga ggtcctttga 2520
tcttattttt ctaaacttgg cgcactgttt ttccatagtt ttgatgactg gcattttata 2580
gacaccctgg cagccttact tttaacacct gtaacaaata gtatttttta tgtagttttc 2640
agaataacat atggtctcaa gagtgggtaa gaggcagtca gtaatttcca ggaagaattc 2700
tgcttttcac aatttgagat ttttttttaa gctgtaatat gatggcagct tagtatacat 2760
gtttgcttct aaaggtgtgt ttacgatcgt cactttatca gcattcaatc agtgttaaca 2820
agtcagcaga aaagtgtaat taggcgaaca gtagggggaa ttcccactct aagaaccctt 2880
ttctggtatt tctcttcaag ctgtgaccac tcagtgttct gtccacagtc cattcctctt 2940
tgactcttgg aatagaaggt cttaaaaagc cttgctagca gttgcttctt ttaaaatctt 3000
ggagcaactg ttaattggac ctgaaagtgg taacttgaac cctggaaggt cttttattta 3060
ctagggctat ttattccact atttcttcag taataagagt tactaccttt gctggagaca 3120
aaagggaact tctttgttac ctgaataaca tagtgcaggt caaacaaaca agcaaaaagt 3180
tttctttcag ccttcccgga gttgagaatg tgaccatctt taggagaagg tcccgcactt 3240
taaaaataaa aacaaaaaat ccaactctag agttccttat cagaaatgaa tctcaacccc 3300
ttagtcaaga attttctgtc gtctcttaat ttgcacgtga gaaatacttc catatctcat 3360
gctcaggttt taatctgatc tttgtgagtt ctcaattgtt tttttttttt tttttctttt 3420
tcttttctga acttgacttg catttgtggg taggattgga gcacactgtt atcaaggcat 3480
tcgggggaat caacttggca gacataactt gctgcttgtg tttgaggaaa acaaacctga 3540
ccataactgg attatttgac agtcatttgt aaatgctgag aggtctgctg tgtggtaaca 3600
catcgctgct ccaacagtcc cttgagtgac atgcccaaac catgtcactg cactttgcct 3660
tgggaagtac cacgactgga gaagtaccca cggatgagca gtgtgctccg aactcgcttt 3720
gcaggtttct gtctgatcat ttaaggaact tcttagctct tccatagcca gagcgaggta 3780
gttctgactt gcctctttta ctaatcctta tcttagttct ttctggagaa atatccaact 3840
ggttccttaa catgtaagag aatgcaccaa accagagcta tatcaaatgc caattgttgg 3900
ttttgttttt ttttttttgg cggggggggg ggggggggtt gtatcccttg gtacatttta 3960
aaaacatagc ttcctcgggg atgaaacatc tcatcatgcc ttccctatcc ccacttaccc 4020
tacacactct ggaatcacag tgaaaaggat atttatttct gaatgaggta aataagttta 4080
aggctcctga cttctttgtt ttaactgcaa cttgaggaag catctggatg tctgtcagtg 4140
tgtccctttc ggctctttgt gaacacctgc aggcatctgc tatctcttcc ttctctctgc 4200
tagcacctgc tctattaaca atcatgtacc tacctgccct gggatgacac tgaatttagg 4260
tgtactggaa gagttgtgtc cttcccctac gaaggtggta ccgatgtgct ctgcctttct 4320
gatcccattt tattggaaaa cctgatgtac tcaaaggcgt gaactataag ggtagattgg 4380
ctgtacatat gcacttagcc ttttctttct ttttcagctg catggcacaa gatacagaaa 4440
aaaaagtaga tagctctgct gtgacaggga caaatgggga caagctgaat tcaagatttg 4500
tgggttacga taaactttgt ggacatagtg ctgtctgagg gaccctcaat gactgtattt 4560
gcctcttttt caccaaagag aataggagac atggtagcac ctaaaaatag gtatgaaggc 4620
cagataccaa ataaatcaaa tttacataac cgttacaaga ccagtttatt taggtgacat 4680
tttacagttg agagagaatt tgaggggcac gaaaatgggt tatcctctgt gttttccagt 4740
ttgtcaggaa tttatcagat ggctctgccc taattttgcc cagatttttt tttttttatc 4800
accagttcct tctggagaaa catgctgcgt ctctatagta gtgattgatt gcttgttata 4860
aaggcttttt agaacagtga gagccgccag cccaatgagc ggtagaggga agtgtgaaac 4920
actgtcattc aaacattccg ttaataattc tctggataaa atggggatgt gagggccaac 4980
cattaagatt tagaatgaag ttggctgcct ggctggcata catacaggtc agtgtttgaa 5040
tgcagtacag tttgcatgca catgcatatt gcacattctt ttaatgaaaa ttcacagaaa 5100
agaagcaatt agcattgcca gttgtattac aaaagcttag agttagaagt acagtacagt 5160
tactacgcca gcagttgggt ctaattcagc aggttgtatt aagaaagccc catgttgtca 5220
gtgtgtcttt aaggctaatg gcaatttaaa tcacaaatct ccattgtctg catccagaaa 5280
aacaaacaaa gcaaggcaaa aaacaatgaa acaatgaaaa gatattgagt tgactggaga 5340
atatttgaag aaatatagat tttttttgtg agaggaagaa gttgcaggaa gtaatttagc 5400
aaccttggct tgtgtttgtg cttctctgac ccagttgcac acctcacaag tttggtcttt 5460
ccaaaccttc atcttctctc ctaaatgaca agttagggta gaaagattca tggaagaggc 5520
tggagaggac aaggagagct gtctgcccct agattcagga ctgcgcctta cactgtccaa 5580
gtcacctgcc acatactgtc ttagccttga aattgtagat tggtggtgat cgtcagttgt 5640
acttcatgtt attttaataa ctactgtctg tataattatt ctacagcaaa agctccccca 5700
aatccaaaag gggaaaaaag tgagggatga attgaaactt tgtatatata aaagttattt 5760
tataaatgtt ttagtcttcc agtttctgca aaataattaa aatatacagt aactggtctc 5820
ttaaaccctg aacttaatgt attaaatact tataaaattt tatattggtg ccttttaaaa 5880
atgcattgag agtgttggtt agctctttag ctctaccaca cttttactgt gtatttttta 5940
agaaaaaaaa aaatcacata aaatctaagt actctctaat tcacctttgt gttcttagaa 6000
gaagaagaaa aaaactgcta aaagaatttc cagactttta gctgagctgg caaaagtgac 6060
aaaaaaaaaa aaaaaaaaaa caaactttga aaccagattt taatcttttt agcttgatga 6120
tatttctgga cattattcta tggtagaggc aaaatagaag gtagactcac atatcagcaa 6180
tgaattggat tatgctatat gttttgattt cttcttgagg aagaatatgt tttgcatcac 6240
acaggggttt ctttgtataa tttggagtca gtaattacag tattgctttg ctttgtttta 6300
aatacccgac tgatgttact ctagtcttgg gtcttctgtc tcttctgtct tctaacctgt 6360
ggttgttttg tgaaatggcg tgggaatgca gatcattgtc tcctcttgaa caagacaaag 6420
ctcagcacac tagtcccgtg actggtctcc aaaatgtcat ctcagatgtg tagtctgggg 6480
tcgtctgtca cttctaaggg gtgtcttcaa ctatgacagc tttttaaaaa cgagctgctg 6540
gctgggtaaa gcagacatca tatgaccaag aagctgtgat acgctagtgt ttccttctgt 6600
catcgtgttg tactcttagg ccaaataatg acaccttgac tgtttttaca tttactacag 6660
aaacctaaac ttttggaatt ttcaaaggtt tttatgtaat gttctatttc acagcggttt 6720
ccttttctct tgctgtactg agtctgtgag tatttttttt ttcagatgca ctcttggaaa 6780
taagttctga attctgttta tggcgtttct ctcgcttgac actccgtgta tagatgttct 6840
gtataagttt gttatgaatc cacctttctc atgtatggac agtgagaagt acatgaacaa 6900
ctagtttcct aagatgactt ttatattatg aattaatatg aaatttacag gtcatgtgca 6960
ccttaagtgc agaatcaaaa cttcctatag gtccacataa gcagttctca gtgaaccggg 7020
ccttcagttt acctcaagtg acatgtagta aggaaagccc gggaacatgg aggtcactct 7080
ctgcagcaca gtgcacttag tagcatgttg ctgaatctca gttacagaaa atggatattt 7140
aaaggaacac actggaagga tgcaagggat tgagggactg ctgatatttt cgttgttgct 7200
gttgctttgt gcttttcaaa aagttgttca aattatggaa ctgtgatcta aaaacggttt 7260
gacagtggag caccagagag gatgtccacc actcacttgc ccttcggtac gactaagctc 7320
tgagtttgcg tcttcaactc taccttcctc tcccctcctc atccctactc tgtctgtggc 7380
cctcctctcg gtgtcatttc ctcttggtgg ctctcttgac actcctacta gttaggaggt 7440
caactctgaa cttctgactc attaaatctt aatttttgtc tcagtggttt tagttagctg 7500
tgtagtctgc tggcgtattt ttatacccac gtgtagtttt atatttttaa agcgtggttg 7560
agttgacatg gtgcactccg tagtccttat tttgcttcac tctcaagtag gaggcaccta 7620
acgtgactcc agaaattctg taatcagagt atccgtctgg ctcctttgtg cttggatttt 7680
gatttgtttg gctttcttct taaatacaaa tcatacaaga gtagactttc cccccaccat 7740
agaggataaa aatgtaaagc aaagagtctt aactttctcc caaccggggg gcggggcgag 7800
tgctgtccca cttctgcagt gatgttccag gctcagaggg gtctccagac cccaggcttg 7860
cctgtcatcg ggtctcttcg accctgttat ttgcagcttt gggatggttt cttttgctat 7920
ggagtttaac agctcttctt ttttccataa aagtgcaata cccctcttga agtcttaaaa 7980
actatggtaa ttttcttctt ttctttctct gacatttgtc tcattagcca atgatgaaaa 8040
gaaatctttg gaaattctaa catgtcatag gacataggca aatatggaaa ccactctgct 8100
atgaaaagtt gaaaaaaaaa acgtattaac aaacgactcc tctgactttc tagaaacttc 8160
gtttagacta aattttcttt gaaatcatga atgaaagttt atcctgaggc tgaaatataa 8220
tttttctccc actcttgtct aatgctctta agttaaataa ctaatattta atgttttcat 8280
ttctctcatt ttggaaaata aatatcaaag cacttaggtc aggtttaaat caatattacc 8340
tgttggaaaa aaattttttt acatatttaa agcagacctg tttcaatgca gatggagaag 8400
tatcttttgt attattcata tttatatgta gtgtgttctt ttcttttttt aatacctgtg 8460
tttctgtagt aagactgctg taatgtaaat acacgtttta ttaaaaagta acatttcttt 8520
ggcatttctt ttgatggcac atactgtatt tttacagtat atgtcttggc tacttaactt 8580
ttttttcttt aataatacca aaggtaatta gactatttta aggactaatt gcttgacagt 8640
ttctagacta ctttgatttt tttagaagaa aaaagaaaaa aggataaaaa aaagtcaaac 8700
cagtgaacct cattttttca aactaataat ttggggaaat aaaaactatt gtttaaaaag 8760
aaatatatat aaatatatat ataaatatct gtaaaattaa aatcccagac cttgtatgtc 8820
aggtttgctc agtgtaatgt agggtttttt tttgttttgt ttttgttttt gtttttaaag 8880
gctcaaatac ctcagaaaat ggggtttact atggaaatac tgcgacagtc tctgcagctg 8940
tgtgagctgt cattctgctg catactgatt gggagacctc cactaaacag ttttatcact 9000
gcagactaaa atgtgggact tgtattttct ttgtttttaa tgcacacacg tgcatgctct 9060
gtgcgtgtat gtgggtaccg tgtatatgtg tgtgagtgtt gtatatgcat gtgtgaatgt 9120
gtgtgtgtgt gcgtgcttgt gtgtgtgtgt gcgtgcttgt gtgtgtgtgt gtgtgtgtgt 9180
gtgtgtgtac aactgaagaa gctgcaaaaa ctttgtaata ctttgtgaaa gggttatatt 9240
ataaaggttt gtactgtctg agtgcacagc tactggaata aacttagcca atctcaggaa 9300
caagcatata atttgtccaa gatttatttc ttctcagaag tgtaagtgca gtttttaatt 9360
ctgtatatta tttaatattt taccaataaa ataaacttct gacagaaatt atttggtaca 9420
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaa 9457
<210> 27
<211> 9788
<212> DNA
<213> Homo sapiens
<400> 27
aaccccgcgc accggcaggt cgccggctcc tgcccttttc agtctgcgcc gacgcggctg 60
ccggatcccg gggactcccc gcgccgggaa tctcccgcca gctgcgcgct gagtccaggc 120
gacggcagga gcacgtggag aggccgagta gccacagcgg cagctccagc ccggcccggc 180
agcgacatgg aagatataca aacaaatgcg gaactgaaaa gcactcagga gcagtctgtg 240
cccgcagaaa gtgcagcggt tttgaatgac tacagtttaa ccaaatctca tgaaatggaa 300
aatgtggaca gtggagaagg cccagccaat gaagatgaag acataggaga tgattcaatg 360
aaagtgaaag atgaatacag tgaaagagat gagaatgttt taaagtcaga acccatggga 420
aatgcagaag agcctgaaat cccttacagc tattcaagag aatataatga atatgaaaac 480
attaagttgg agagacatgt tgtctcattc gatagtagca ggccaaccag tggaaagatg 540
aactgcgatg tgtgtggatt atcctgcatc agcttcaatg tcttaatggt tcataagcga 600
agccatactg gtgaacgccc attccagtgt aatcagtgtg gggcatcttt tactcagaaa 660
ggtaacctcc tccgccacat taaactgcac acaggggaaa aaccttttaa gtgtcacctc 720
tgcaactatg catgccaaag aagagatgcg ctcacggggc atcttaggac acattctgtg 780
gagaaaccct acaaatgtga gttttgtgga aggagttaca agcagagaag ttcccttgag 840
gagcacaagg agcgctgccg tacatttctt cagagcactg acccagggga cactgcaagt 900
gcggaggcaa gacacatcaa agcagagatg ggaagtgaaa gagctctcgt actggacaga 960
ttagcaagca atgtggcaaa acgaaaaagc tcaatgcctc agaaattcat tggtgagaag 1020
cgccactgct ttgatgtcaa ctataattca agttacatgt atgagaaaga gagtgagctc 1080
atacagaccc gcatgatgga ccaagccatc aataacgcca tcagctatct tggcgccgaa 1140
gccctgcgcc ccttggtcca gacaccgcct gctcccacct cggagatggt tccagttatc 1200
agcagcatgt atcccatagc cctcacccgg gctgagatgt caaacggtgc ccctcaagag 1260
ctggaaaaga aaagcatcca ccttccagag aagagcgtgc cttctgagag aggcctctct 1320
cccaacaata gtggccacga ctccacggac actgacagca accatgaaga acgccagaat 1380
cacatctatc agcaaaatca catggtcctg tctcgggccc gcaatgggat gccacttctg 1440
aaggaggttc cccgctctta cgaactcctc aagcccccgc ccatctgccc aagagactcc 1500
gtcaaagtga tcaacaagga aggggaggtg atggatgtgt atcggtgtga ccactgccgc 1560
gtcctcttcc tggactatgt gatgttcacg attcacatgg gctgccacgg cttccgtgac 1620
cctttcgagt gtaacatgtg tggatatcga agccatgatc ggtatgagtt ctcgtctcac 1680
atagccagag gagaacacag agccctgctg aagtgaatat ctggtctcag ggattgctcc 1740
tatgtattca gcatcgtttc taaaaaccaa tgacctcgcc taacagattg ctctcaaaac 1800
atactcagtt ccaaacttct tttcatacca tttttagctg tgttcacagg ggtagccagg 1860
gaaacactgt cttccttcag aaattattcg caggtctagc atattattac ttttgtgaaa 1920
cctttgtttt cccatcaggg acttgaattt tatggaattt aaaagccaaa aaggtatttg 1980
gtcattatct tctacagcag tggaatgagt ggtcccggag atgtgctata tgaaacattc 2040
tttctgagat atatcaacca cacgtggaaa agcctttcag tcatacatgc aaatccacaa 2100
agaggaagag ctgaccagct gaccttgctg ggaagcctca cccttctgcc cttcacaggc 2160
tgaagggtta agatctaatc tccctaatct aaatgacagt ctaagagtaa gtaaaagaac 2220
agccataaaa taagtatctg ttacgagtaa ctgaagaccc cattctccaa gcatcagatc 2280
catttcctat cacaacattt ttaaaaaatg tcatctgatg gcacttctgc ttctgtcctt 2340
taccttccca tctccagtga aaagctgagc tgctttgggc taaaccagtt gtctatagaa 2400
gaaaatctat gccagaagaa ctcatggttt taaatataga ccatcatcga aactccagaa 2460
atttatccac tgtggatgat gacatcgctt tcctttggtc aaggttggca gagcaagggt 2520
ataaaggggg aaattgtttg gcagcaccaa cagaaaacaa acaaacaaaa aacagctacc 2580
taaaacttct tgaaagagtt catggagaat tggtgataca gacccaaagc aaatttgcca 2640
atgatatttt ccacaaaaaa agtccaaaaa gtatggctca gcctccccct ccccacagga 2700
gaggaattgg agatagatgg catgtgtgtt tagatcggag ttgagctccg gaatggggtg 2760
aggagggaca cctctattga gaggttctcc ttgatcaggc aggcttcggc cctttttttc 2820
ccatttaaat ggaactgctg tattccatga aaattcctga aagtctgatc acggttctgc 2880
agatgtataa gtcatccttg tcactcataa tatgtacata ctatcaggag gagtgctgtt 2940
atcatggtaa aattagcact ggaataggag gtcacaaaat gctggctaat tagctatgtg 3000
actttgagaa atcgtttaac tttttttttt tttttttttt tgagacagga tctcactctg 3060
ttgcccaggc tggagtgcag tggtgcaatc atggctcagt gcagcctcga cctccccagg 3120
ctcaggtgat cctcccacct cagcctcttg agtactggga caacaagtgc acaccaccat 3180
gtctggctac attttgttct ttttgtagag ataggggtct cactatgttg cccatgctgg 3240
tcttgaactc ctgggctcaa gcaatcagcc cgcctcagcc tcctaaagtg ctgggattac 3300
aggtgtgagc caccacaccc agccttattt aactcttaaa actcagtttc cggccaggct 3360
cggtggctca cacctgtaat cccaacactt tgggaagccg aggcaggcgc atcatttgag 3420
gtcaggagtt cgagaccagc ctgacccaca tggtgaaacc ctgtctctac taaaaataca 3480
aaaattagct gggcagtagt ggcacatgcc tgtaatccca gctactccgg aggctgaggc 3540
agaaaaatcg cttaagcctg ggaggttgag gttgcggtga gtggagatca cactactgca 3600
ctccagtctg ggcgacagag tgagaccctg tctcaaacaa aacaaaacaa aaacaaacaa 3660
acaaaaacaa aaaaaactca gtttcctcat ccataaaata ggaattagat ttcaatgttc 3720
tcttaggtcc cttctagctt taattcatat gtgattatgc agtaaccaca aggtattttt 3780
taaacctcct aatgtatgga tattaagcag aagagtattt atatgaatac atgtttcaca 3840
ttcctttggt atgaaaatgg tgtgttaagt ttttccttta accactgagt tgtgaatgtg 3900
aagaaggtgg tggagaggaa caaaaaacag aaaggtattt tgatcttgcc acaaagcata 3960
cacacaaatt ggcacatgca gctgtttgcc aaagccttct tttttttttt actttttaag 4020
aaattatgtt agggaaaata aattctgctt ccagggacaa cttcatggag cctatttaca 4080
aattaagagt cagcttaatt tgtaacattt ctaccagagc caagaatccc aaattcctgg 4140
tagattagtg ttttatttct aaggggctta tgcattcggc tccaactcaa ctcgtctatg 4200
tgctgccagt aattaaaatg ttccacctca gactgcacaa atggcttatc cttctttgtg 4260
gcatggcgtc tgtctcagga aaaaaggttt tatgaaattc catggcaaca gtcccaacat 4320
gtttgagact tcagctaaag gaatggatgt attttggtgt gtagtcttca gtatatcact 4380
gtatttccgt aatactagac tccaagctat gccagattgc ttattccctt tgtgaaagag 4440
gagttgctca ttacgttctt gaaatatcgc acatcctgtt ggttcttcaa gggacaagag 4500
aaagagaatt tggaagcagg gattagtaga agagaaaacg agggaaagga agcctttcca 4560
ccagattagt gttcaagtct ttgcagagga gaccaacttt ttttgttttc ttttgttttg 4620
agacagtctc tcgctctgtt gcccaggctg gagtgcagtg gcgcgatctc ggctcacggc 4680
aacctccgcc tcccgggttc aagcaattct cctgcctcag cctcccaagt agctgggatt 4740
acaggtgctc accaccaagc ccggctaatt tttgtatttt tagtagagac aaggtttcac 4800
catgttggcc aggccagtct caaactcctg acctcaggtg atctgcccgc cttggcctcc 4860
cacagtgctg ggattacagg catgagctac cgcacccagc ctgagaccac cttttgcatc 4920
tcaagattgt gaaaccaagg cccattccac cagcctgggg actcttttta tagatatgat 4980
cctccttttt cctgtgacta atgaatttgc tgcatgattt ctattcttct gaggttagtt 5040
ttctgagtaa ggtgaccact cacaaaggca ctttctttgt ggcattctga gcctagattg 5100
gggcccatca attccagaaa aaatttatgt gtggaaactc tgcatcctta agtcttgaag 5160
ttgaaccaga tatgcagtgg ttaccatcac acagataaac gctgccttct gtacataccc 5220
cttatgctgt actaattaac aaaccccttg ccagggctgg ggaggtgagg gtgaaggaga 5280
atcttagcag aagggcagag tcaggacttg catctgccac tgctgggcac tgaagccctg 5340
gagcagcttc agatagtacc tgtactttct catgcagact ccctctgaac aagagccttg 5400
taggcccctc tccttcattt cccaccagcc tcttatcagg cgggctttcc accatacacc 5460
caggaggcca cggtctgagg aacaaccaaa cccatgcaaa gggccgggcg cgatagctca 5520
cgcctgtaat gccagcactt tgggaggctg gggcaggcag atcacctgag gttgggagtt 5580
cgagacctgc ctgaccaaca tggagaaacc cccatctcta ctaaaaatac aaaattagcc 5640
gggcgtgatg gcacatgcct gtaatcccag ctactcagga ggctgaggca ggagaatcgc 5700
ttgaacccgg gaggcggagg ttgcggtgag ccgagatggc accactgcac tccagcctcg 5760
gcaacaagag cgaaactctg tctaaaacaa aaacaaacaa acaaacaaaa aaacccaggc 5820
aaagtttcct tgcagccaag gtgacagaac tgggctgagg gtggaaaaga aacagaacca 5880
gtgctccagg tgttttttaa ttttttaatt tatttttatt ttttttgtat atgtatatat 5940
atgtatgtat attttagagg accagggtct cactatgttg cctaggccag actcaaactc 6000
ctgtgctcaa gcaatcctgc ctcagcctcc caagtagctg ggattacagg catgcacaaa 6060
caatgcccag ctctccaaat gttttctgtc actacctgaa gtgttgcatc ggtacttcct 6120
acggaaagaa aactaaatag aagtgtctct cccgtgagcc cccaccacta ccaccagaaa 6180
aaaaaaagag agaaaatgaa ctcatcagtc tttagtttcc tcaagttatt ctcccaaaaa 6240
gacattcgcc ttggcacaga taagccagct aatcttatgc tttatgaccc actgtgagct 6300
gttcctgaca cagcttctga ctttgtcagt gacaaaattt ctcacctttt aaatgcagtg 6360
cttaacattt tgttaggccc atactcaaaa tcggccagat ataaaatgac ctcagatttt 6420
gatctcctag gctcaaacaa tcctcctacc tcagcctccc aagtagctgg gactataggc 6480
acaccaccat gcacagctaa ttttttttgt atttttctgc agagatggcg tttcgccata 6540
ctgcccaggc tagtctcaaa atcctgggct caagcaatct gcccacctca gcctcccaaa 6600
gtgctggaac tacaggcaag agccactgcg cccagccaca acctcagatt tctttggcaa 6660
acagaaatgt ttaaaaacac aaaattttgc tcaggtgaaa cactgtgtta ctatcaaatc 6720
tcacatccac ataaagtttt tcttttcggc tttgtttcgt gaggaacaga cagaacaaag 6780
tttttccagg tagcatctgt atcactatta ttctcctatt tcctgtacca cccccacctc 6840
cccaagccct actgaatgtg aggtttagaa tgttttaagg agggtcaggt gcggtggctc 6900
acgcctgtaa tcccagcact ttgggaggcc aaggcgggcg gatcacctga gtttgggagt 6960
tcgagaccag cctgaccaac atggagaaac cctgtctcta ctaaaaatac aaaattagcc 7020
aggcgtggtg gcacatgcct gtaatcccag ctacttagga ggctgaggca ggagaatcgc 7080
ttgaacccag gaggaggagg ttgtggtgag ccgagatcgt gccattgcac tccagcctgg 7140
gtgacagagt gagactccat ctcgaaaaaa aaaatacaaa aattagctgg gtgtggtggt 7200
gcacacctgt aatcccagct actcgggagg ctgacgcagg agaattgctt gaacctggga 7260
ggtggaggtt gcagtgagcc gagatcgcgc cattgcaatc cagcctggac aacagagtga 7320
gactccatct caaaaaaaaa aaaaaaaaga atgttttaag gaaaaaaata gtactgttac 7380
atataatccc aggtgataag accacaatgg aaatgtttaa gtcctcactt taaagagtac 7440
cccactgaga agaggtatgt tggactctag cagagatttg gaaactctgg gacactcaag 7500
atgtgaaaga gcctggctat ctgaggactc aaagagtcag catcgggact tgtgagctca 7560
agaagagaaa agggagtggt gaaactttgt cctaaaagtt agcaccagga acagaagaaa 7620
aaaacccgat atatagtgat acctcatctt ttagagaatg ggaagctatt tttgtgttca 7680
cacagaaagt atagttcaaa aaacctctat atccagagtt cagacaagga gaatgatttg 7740
agatataagt gccgatgaag gaggtcaatt ttgatctgaa accagcagct ggacctgggc 7800
cacctcagga aaaggactct gttctccaag gcagcacgac tgaatggttc tgagaataag 7860
ccagggttca ggactcctga ccctttagga ccatggactc agaagagcct gaaggacaat 7920
tgtgggcttt aaacttctga gagcttgtaa agtaacacaa gactgtgcct ctcccttgcc 7980
ccagctgtag atagtctttg ccccaccatt gttatgaaga tacacagggt tttgcagttt 8040
gaataaattg gatacaagtt tcctcttttt ttttttcttt ttgagacaaa gtctcgctct 8100
gtttccccag gctgagtgca gtggcacaat caaggcttac ttgccgcctc aacctcctgg 8160
gctcaagcaa cgagccatcc tcccgtctta gcctcccaac tagctgagac tacaggcgtg 8220
ggtcaccaca cccagctaat ttttgtactt tttgtagaga cagggtctca ccatgttgcc 8280
caggctggtc ctgaactcct gggctcaagt aatctgccca cctcagcctc ccaaagtgtt 8340
ggggttacag gcgtgaggca ccgcggctgg cctgagtttc ttcttaatac tgtatcacaa 8400
ttgtgggctg tcttatgtgt tgatatcgat tgagctattt gaaataggaa tgttaatggg 8460
tgtattaaat ttttgtaagg atataacaat atctaccttc caaggatgtt gtgaggtttt 8520
ccatgatttt gtatatgagc taatgttacc tttgaggggt ggtgtgcatt atgttggatg 8580
attgtaaatt ttcagtggaa aatgtaccgt gtcctaaatt taaagacatg aaaaatatcc 8640
caagatcata ctagatcata atagcaattc ctttacaaat gaattatgga ggtaactgat 8700
ctctaacagt ttccttcatg ttgttttaat gcacaagggc agaggatctg ctgacccttg 8760
gaaccagcgt gagctaacca cgtgctatag acacttcatg gtgtcgcacc cagggaagtc 8820
aaagcgcttt gctccctcac tgtctgtgag tcctcagcca ttagtacccc accccccgct 8880
gctccaaaac ttgagttatt tcaaatgttt ctcactgttc atctctccac tgaccccact 8940
ccagaaagcc tggagagagt cccaagatgc cacccacctt ccccaatccc tcgccacaga 9000
tctgtgtcta tctcacactc tgtaagtgcc gctttgcttc ttcctctctt gaaaagactg 9060
agaacacaca ttttaacatg ttaggaaaat ggggcagcct aaaaaatgac tgatcccacc 9120
gccagtgact catgtatact ccaggctagc agacaaggcc ctttttggtg ggcctgcttc 9180
tgtgggttca cagaaaccaa attactgtgg gttgcaaaga attagcaggt catttacaaa 9240
gcagacatcc cttcacccag actgtggttt tgcatgctca ggttctcagt ctatgagctt 9300
tggtgcagga tcattttggc tactggaaaa accatagctt attttaaatt tctggttgcc 9360
aaagccacca cacgtgtggt ctgtggatga ccattgtctg cagaatgacg aggaaggaac 9420
agaatgtggt ttggggctca gggtggcctt cccactggga gggaaggcgg gagggagccc 9480
ttgccctggg ttttgacaca gcctgtgctc acagcctctc ctctcatctg catttctcag 9540
aaatgccctc cctgcccagt ggtgactttc cctcgtcact cctatggagt tctacctgga 9600
gcccagccat gtgtggaact gtgaagttta ctcctctgta aagatggttt aaagaaagtc 9660
agcttctgaa atgtaacaat gctaaccctt gctggaaccc tgtaagaaat agccctgctg 9720
atagttttct aggtttatca tgtttgattt ttacactgaa aaataaaaaa atcctggtat 9780
gtttgaaa 9788
<210> 28
<211> 4098
<212> DNA
<213> Mus musculus
<400> 28
ttccacgcga tcagggttcc tcaggcttga cattcaaaag tgggtgcgga acccgcggca 60
ctcggagcgt gctttaaagc ggccgccagc cagcgccgct ctaacctcgc gccccggctg 120
ccggcggctc ccgccctgca tctgcgccga cgcgaccgag cgatcccggg gcctccctgc 180
gcccggaatc tcccgccagc cgcgcgggtc cccacggcag cagcacgtgg agcggccgcg 240
gagcctgagc gacagctgca gcccgcgcgg cccgcggcga catggaagat atacaaccga 300
ctgtggagct gaaaagcacg gaggagcagc ctctgcccac agagagccca gacgctctga 360
atgactacag cttgcccaaa cctcatgaga tagaaaacgt ggacagtaga gaagccccag 420
ccaatgaaga cgaagatgca ggagaagatt cgatgaaagt gaaagatgaa tacagcgaca 480
gagatgagaa cattatgaag ccggagccca tgggagatgc agaagagagt gaaatgcctt 540
acagctatgc aagagaatac agcgactatg aaagcattaa gctggagaga cacgtgccct 600
atgacaacag cagaccaacc ggtgggaaga tgaactgcga cgtgtgcggg ttatcctgca 660
ttagcttcaa cgtcttgatg gttcataagc gaagccatac cggcgaacgc ccgttccagt 720
gtaatcagtg cggggcatct tttactcaga aaggtaacct cctccgtcat attaaactgc 780
acacggggga aaaacctttt aagtgtcacc tctgcaacta cgcatgccaa aggagagatg 840
cgctcacggg acaccttagg acacattctg tggagaagcc gtacaagtgt gagttctgcg 900
gaagaagcta caagcagaga agctccctgg aggagcacaa ggaacgctgc cgagcttttc 960
ttcagaaccc tgacctgggg gacgctgcaa gtgtggaggc aagacacatc aaagccgaga 1020
tgggaagtga gagagctctc gtcctggaca gattagcaag caatgtggct aagcgaaaaa 1080
gctcgatgcc tcagaaattc atcggtgaga agcggcactg cttcgatgcc aactacaatc 1140
ccggctacat gtacgagaag gagaacgaga tgatgcagac ccggatgatg gaccaagcca 1200
tcaataacgc catcagctat ctaggggctg aagcccttcg ccccttagtc cagactccgc 1260
ctgctcccac ctctgagatg gtcccagtca tcagcagtgt gtaccccata gcacttactc 1320
gggccgatat gcccaatggg gccccgcagg agatggaaaa gaaacggatc ctcctgccag 1380
agaagatctt gccttctgaa cgaggtctgt cccccaataa cagtgcccag gactccacag 1440
acaccgacag caaccacgag gatcgccaac atctctacca gcaaagccac gtggtcctcc 1500
cccaggcccg caatgggatg cctcttctga aggaggtccc tcgctctttt gaactcctca 1560
agccccctcc catctgcctg agggactcca tcaaagtgat caacaaagaa ggggaggtga 1620
tggatgtgtt tcgatgtgac cactgccacg tcctcttcct agattatgtg atgttcacca 1680
tccacatggg gtgccatggt ttccgtgatc cctttgagtg taacatgtgt ggctatcgaa 1740
gccacgatcg ctatgagttc tcctctcaca tcgccagagg agagcacaga gccatgttga 1800
agtgagcatc tgtcctcaat gcgagggtca acattgtttt ttaaagctga tggtagcctt 1860
atccagtaga ctgaactcaa acccacagtc ccacccagtt ctgttagctc tcaatcatgt 1920
ccacatgaac agtcagggaa ataactgtct tcattcagaa actgtttgca gagctatcat 1980
gttactctgt gaaacctccc ttcccatcag ttgagtttga tgggatttaa aagccaaaga 2040
agtatctggt tcattatctt ttgtagcaat agacagccat ctactggagc tcccggccaa 2100
ttggaacagt cctccgtggg ccgcaggagt cattcactgg aatacagcag ccatatgtgg 2160
aaaagccctt tgatcctatg cccagatcca cacagcggaa gagccgccca gctgcccttg 2220
ctcttgggca ccaacacaag gcagaagcct tagcgtgtag tccccctccc ttcacgttct 2280
aacagcaagg aagaggtggc cgtacagtaa ggacctgctg atagtaatgg aagaccctat 2340
tcttggagca tcaacccact tcctatcaaa caaaactgaa gccacctgag caaggaccct 2400
tctcctttac ctacggtcac aagggtgaac ctcagatgat ttggcctgag ccagaccctg 2460
atcctcctgc ctccgtctgg aggaaaattc tactccagaa gaactgatgc gtttaaatat 2520
tgggtatcat tgaaaccgca gagtcatgca ccgaggggtg gtatttgtct cctttgattg 2580
ggattggtag agcaagtggt ggggacatag tttaagggta cagtgcctgc caggtacaac 2640
caccacacca gggggcaaag agggaagaaa gaaaatggag ggaagagagg ttggctgagt 2700
agagcgtgta aggttgactg gttggcaacc cttgtcacct tggtggagta ctggctgaaa 2760
ccccaaagaa catttgaaaa gtgatttttg gcaaaggagc caaaatgtgc tgcttagttc 2820
cccaccacct cccaccccac aggcgtgaga tcagggacag aaccacagat gttctctcag 2880
gacggtgtga catcacactc tcctgggtta gaaatgcatg gtttttatta tattactcta 2940
ttttcaaaac agggtctcct ggtgccccgg caagcctcaa actcattgct ggctgaagct 3000
gcccagcact ctgagcctcc tgcctcagcc tacagagtgc tgggttgaga gggttatcag 3060
caccgtggtg ttgggcttct gctgtcctaa agaggagctg ccacatccca ctgagagtct 3120
gggaaggctg atcttgttct gtagatagac caggtagtca cctttgtcac acaggcacca 3180
agacatcaag attcttggaa aaatgctcca taaacaagca ctggaatcga ggccaccaac 3240
cgtgcttgcc aagctcatat ttgcaactaa ttggttaact ctaaaagaca aatggcctca 3300
accataaaat aagagtagca tccaaaccct cttgatggtc acttctggct ttgatacatg 3360
attattcaat agccacaggt tttttgcttt tgtttttgtt tttttaactt cttgatgtgt 3420
gggcattaag cagacaagtc tgcgtgtgag aatgtgtttc atatgtcttt gatgtgaaaa 3480
tatagttgtg ttaagttttt ccttcagcta ctgagtcatg accatgaagg aggcgatgag 3540
gggggactaa ggacaggaag ggttttgatc atgcagtcgt gtatacacga gctggcatct 3600
gcagcagccg tgtacacacg agctggcatc tacagcttct tgccggagcc cttttcttcc 3660
tttcctttta aaagaacttg tgttagggaa aaataagttc tgcttacagg gacggcttca 3720
tggagcctat ttacaaatta agagcttagc ttttatgaac atttctgcca gagccaggaa 3780
tcccaaattc ccggtatgtt agcattttcc ttctaagggg cttatggatt cggctcttac 3840
tcattcatgt atacgatgcc agtaattaaa acattcctcc tcaaacacac aaatagctta 3900
gcctgccttg tagcatggtg tctgtctcag ggtaaggggg gtgggttatg agattccgtg 3960
gcaacaattc tgtggcaaca atcccgtgtc agcttaaggg ctaggtgtct tcagcacatc 4020
tctgcatctc agcagaatcg gatgtgagct gcaccacatt gttcatgccc actgtgaaag 4080
aggacctgcc tagtctag 4098
<210> 29
<211> 4553
<212> DNA
<213> Homo sapiens
<400> 29
agcaggctgc cggctcggac ggcggcgacg cggcaggaca gggcggataa gaaggagcgg 60
ccggagactg gagctgggtt cgtggcgggc cggctgatcc ggacggagac tcaacctctg 120
tatggctttt caattttagt tgaaattctc tctccatggc cttttggagt cccttgctgt 180
atctccgaag taaatttcaa ttactctaca tttcatcaat gttggagtgg caagaaaaag 240
gaggaacaga tttggggtga aaagttttgt tttctaggtc taacaaactg taaatgttaa 300
aaaagcaaag atgggtgaaa aaaaaccaga gcctttggac ttcgtgaaag attttcagga 360
atacctgact cagcagaccc atcacgtgaa catgatttct ggatcagtta gtggggacaa 420
agaagcagag gctcttcagg gagctggaac agatggtgat caaaatggac ttgatcaccc 480
atctgttgaa gtttccttgg atgaaaactc aggaatgtta gtagacgggt ttgaaaggac 540
ctttgatggg aagcttaagt gtcggtactg caactatgcc agcaaaggaa cagcccggct 600
tattgaacac atcagaatcc acacaggtga aaaacctcat cgatgtcatc tttgtccatt 660
tgcatctgct tatgagcgtc atctggaagc ccatatgcgt tctcatactg gagaaaaacc 720
atacaaatgt gaattatgtt ccttccgctg cagtgatcga agtaacttgt cccatcatcg 780
aaggcgcaag cataaaatgg taccaattaa aggtactagg tcttccttaa gcagcaagaa 840
aatgtggggg gttttacaga agaaaacaag caatctgggc tatagcagaa gagcactaat 900
caacttaagt ccaccttcca tggtggttca gaaaccagac taccttaacg attttaccca 960
cgaaatccca aatatccaga ctgactccta tgaaagtatg gcaaaaacca caccaactgg 1020
tggccttcca agggaccccc aagaactcat ggttgataac cctttgaatc agctctcgac 1080
tctagcaggg cagttgtcca gtctgccacc cgaaaaccaa aaccctgcat cccctgatgt 1140
agttccctgc cctgatgaaa agcctttcat gattcagcag ccctctaccc aagcagtagt 1200
ttctgccgta tcagcaagta ttcctcagag ctcctctccc acaagcccag aacctcggcc 1260
atcccatagt caaaggaact atagtccagt ggcaggtcca agcagtgagc caagtgccca 1320
cacgagcact cccagcatag gaaacagcca gccaagcacc ccagccccag ccctgccggt 1380
ccaggaccct cagcttctgc accactgcca gcactgtgat atgtactttg cagacaacat 1440
cctttacact attcatatgg gatgtcatgg gtatgaaaat ccttttcagt gtaatatatg 1500
tggatgcaaa tgtaaaaaca agtatgattt tgcctgtcat tttgcaagag ggcaacataa 1560
ccaacattga ttgaaaatag tcatatttta cttagttttg ctgtttttgt ggtttggttt 1620
tttttgtttt ttgttttggt catccctaat aaagtgtctg ctaattcaag gcttatacat 1680
tatatttata gaatataaat ttgtcagtgg aataaaattt cccctttttt tcataaaaat 1740
ctggtcaggg tcatttatat attagaacag ttagacacat tggtgtctct tttttccttt 1800
cctttcgaca ttggagaatt ggagtgcagt cataatctta caagatgttc atttgaattt 1860
ctcacattta tggtccataa aaacttcaag gcttatccat acttttgatg tttcaatatg 1920
cattgaactg gatgttattt ctgccatatt tcaaaatggt agaataaatt acagaattta 1980
ttactactca tttcagtgtt tagtacagaa attgccttaa aaattgctat taattgaaat 2040
atcatttagt tcacattcct taagttgaat cggtagtttc atttcaactg ataatagtaa 2100
agctatttca gtttagtaaa aattttcttt tttccacaag aggaaatgta aaacagttaa 2160
gacttgaaat tgaaaattct tttaatattt aaaataactt gtttattcaa tgtctaaaca 2220
catgtcagtt ttccactgga tttttatttt cacaggtaaa tacactagag tgctagatgc 2280
ctttttcccc tgtcagtttg actttcattt aaatccttca ttctgatatc attactgtta 2340
ggtgaggtgg ataactataa tgagaatctc ttattcttcc tattcctttg atgaccaaag 2400
agataaagtg aagtcatcct tattattaaa atgcagcctc caaacaaatt tctcaagatt 2460
ccttttcctt ccttctatcc attttctgcc cataatttcc aagaaaaggt gggtatggaa 2520
acacatgaga gaatgtgata gtgaagtcat atttacaaaa ctgagaacat gtccaaaatg 2580
gattcttgtc tcctcttcag aattagccat ttaaaatatt ttctgtgact tcaaattgta 2640
attcttattt gcagttttac cagtcttcat gtacagtgac gaaactgtgt agaaactaaa 2700
tcatcgcttt agtaagaaag gataaaaagg tgtggaagtg aatataaaat gcatctaaac 2760
atgacattta atttgtttat aaaaataaga cttactaaat atagagtaat tcattttgaa 2820
taggaggcta ttgtttttat attgtgtaat aactcacgta ctctgaagag agcttggtca 2880
aacaataaaa tacattgtta ctaacttggt ttcttttctg tgtactttgc aaaaattcta 2940
tttttaattt tgttcatatg ttgaatgtgc ccctaattgg catcttaaag agaatagtaa 3000
gcatctatta accaaaaaag aactctaata gtaaaggaaa gggaaatatt ggtggtatgt 3060
acccacaaaa cccccaagtg ccaagttaat ggaatctctg ctttcccttt cagatgctag 3120
aaagccactg taatgagttc ttgcagttta gcatccagtc taagctactg cattgtttaa 3180
agagcagcat caaggacact ttctccaaac tggaactctc ttctttgtca aatcttgtac 3240
tttaaaattc tacaattctg ttacattgtt gtttaaatca cagactgctc agatccattt 3300
tactgcagta gtttccaagt gtgtaacttg gctttagtat ttatcagttg ccagaaagaa 3360
acaggttgtc atttggaagt ttttgtggtt attttttccc atttttattc ttcagataaa 3420
agcagtaccc caaaatagaa aatgaaaatt ttcatgaaac aaagagaact cccttgttaa 3480
aaccagctta ttaactctgt attctgtcaa atgcattttt ttctaacaac tgaccatgga 3540
tgttgtgaag gtgcatttta atttaaacat ggaaaagatt tttttcataa ttacatacta 3600
gaatgtaaaa ttataatttt gccatgactt aaagagcaca gttgatatcc caaaggtttt 3660
gatgctaaga agctacagtt attctaaatg cactaaaatg tttgaggcaa atctacctta 3720
gaggcttttt tggtatggta ttttttaaaa tatttagatt ttatttaaat ttcctgtgag 3780
ttattctgta tttgaaaaga tgttcgtgtc ttcccctctg tattgaatgt ttcactcatt 3840
ttatttttaa tcaaatattt tatagaaatg agttgttggg aagagtttaa catgcactat 3900
ttatagtact ttgccgttaa caggcaatgt tctgaaacta aatttatttt tgttcagtga 3960
acataagttt agatttttaa agttggtaga taatttatct ccactaatat ttttttaaga 4020
aactgtgaag agattaactg ggaataattt tatttcagat tttactaatg tagtatgtag 4080
ctacaacttc ttgaacttca agttaaggct agacatttac tttgaaaaaa ttccactggg 4140
tgtttccagg gctatttcat tttagaaata agtgtttgcc attcttctgc aaaaactgga 4200
caaggggaat actacaaaaa atactcagag ataaaatcct catttcaagt tctacaaaat 4260
atttatcaaa tgaatgttaa ttttttttta attccctgct aaagacgttt tcattagtct 4320
tagagggtat atgctttcta gaacttgttt ttgttaacat gtgctttgat gtaaagaaca 4380
tattttgtat gcaaaacata acttgcatta tggttgtaca atacactata ttgtttaggg 4440
attccggaaa gcagtttaat gcagaaataa ctatatctag tatgcagttc atattgtgaa 4500
tgaagctttg cttttgtaat aaataaataa gactttctaa tgacaaaaaa aaa 4553
<210> 30
<211> 4440
<212> DNA
<213> Mus musculus
<400> 30
cagctgcgac gctgacgaac gctgaggcgg tggcggtggc ggcgacggca gtgaaaaggg 60
ctgtggggat tcctcggtgc ggttgtcagg agatataaca gactttcaac ttaaagaaag 120
aaagaaaaaa aaaagcacca agatgggtga aaagaaacca gagcctttgg actttgtaaa 180
agatttccag gaatacctga cccagcagac gcatcatgtg aacatgattt cgggatcagt 240
tagtggggac aaagaagcag agactcttca gggagctgga acagatggcg atcagaatgg 300
ccttgatcac ccgtctgttg aagtttccct ggatgaaaac tcaggaatgt tagtagacgg 360
gtttgagagg accttcgatg ggaagctcaa gtgtcggtac tgcaactatg ccagcaaagg 420
aacggccagg ctcattgagc acatcaggat ccacacaggc gagaagcctc acaggtgtca 480
cttatgtcca tttgcatctg cttacgagcg ccacctggaa gcccatatgc gctctcacac 540
tggggaaaaa ccatacaaat gtgaattgtg ctccttccgc tgcagtgacc gaagtaacct 600
gtcccaccat cgaaggcgca aacataaaat ggtaccaatt aaaggtacca ggtcttcctt 660
aagcagcaag aaaatgtggg gggttttaca aaagaaaaca agcaatctgg ggtatagcag 720
aagagcacta atcaacttaa gtccaccttc catggtggtc cagaaaccag actaccttaa 780
tgattttaca cacgaaatcc caaatattca gactgactcc tatgaagcta tggctaaaac 840
tacaccaact ggtggcctgc caagggaccc ccaagaactc atggttgaca accctttgaa 900
tcagctctct actttagcag gacagttgtc cagcttgcca ccagaaaacc aaaaccctgc 960
ctctcctgat gtagatgcct gccctgatga aaagcctttc atgattcagc aaccctctgc 1020
ccaagcagtt gtctctgctg tgtcagcaag tattcctcag agctcctccc ccacaagtcc 1080
ggaaccgcgg ccatcgcata gtcagaggaa ctacagtcca gtggcagggc ccagcagtga 1140
accaagtgcc cacaccagta ctcccagcat aggaaacagc cagccaagca ctccagctcc 1200
aaccctgccg gtgcaggatc ctcagcttct acaccactgc cagcactgtg acgtgtactt 1260
tgcagacaac gtcctttaca ctgtccacat ggggtgccat gggtatgaca gcccctttca 1320
gtgtaacgta tgtgggtgca aatgtaaaga caagtacgat tttgcctgtc attttgcaag 1380
agggcaacac aaccagcact gaacacaatc aacattgttc tcacttggtt tggccttttg 1440
ggagtttgta gtttggtttt tagtttgatc atccctaata aggtatatgc taatttaaaa 1500
tttatacatt ctagtctata aaatagaagt ttgatagtga aaaagggttt tgttaacttt 1560
tcataaaagt ctggtcaggg ttatttatgc attagatagt tagatgcatt gctgtctttt 1620
tcatttacac ctatgagagt taaagtacag ttgtaatcag tttcctacac ttgtccataa 1680
ggattcccag ggttatctgt actcctgatg cttcaggata tacattacag ctaatgttct 1740
ttctgccata tgtcaaaatg gcacacttct cataaaatct tttataacat ttcagtgttt 1800
atagacaaac tgcctttaag tttgctccta attaaaatac tattttcatt cacataactt 1860
aagttgaatt agtttcatta caaccaaaac cagtagttat ttcagtgtaa taaatatttc 1920
tcttcaagga gaagcataaa acagttcttt caaatttaaa ttataaaatg aaaatcttgg 1980
aagttgaaat ttggggctaa attgaaaatt gtgtttggta tttgagatat ctgttcattt 2040
aatgtgtaaa catgttagtt tttagctttt catttatata tgtatttata tattttgagt 2100
attattttaa agccacaggt aaatatacta gagtgctaga tgcctttttt caatctgatc 2160
tttcatgtaa attctgcatt cacctgttac tggtgtcagg taagattgac agccacactg 2220
attattttat tcttcccagt ctttgatgac caaagaggaa gtgagcgcat catcccactg 2280
agatgcttcc agagcctccg aggctccttt cctgccctct gtgcataatt gcccgtaatg 2340
tccacgaagg gttggtctag aaacccagag acgtaataag tgaggaaaca gctacaaacc 2400
cagagcatgc ccagacagag cctccttgcc tctccagagc agagcaggcc atggaaagtc 2460
ctccctgtga gtctttatgg acagagacgg tgggatcgtc accacagtgg gaaaggataa 2520
atagagttat tatgaagcac atttaaatgt gtcatttaac ttacttagaa ttagagtggt 2580
tcattttata taggaagcca ttatttttgt attgtgtaat aagtagctta ctctgaagag 2640
agcctggcaa aacaataaaa cattgtcact tactattggt ttctgtgtac cttgcaaatt 2700
tttcattttt atttggttaa tagcttgaaa atattctcaa ttggcttctt aaagaaatac 2760
cctgtcaagc atttattaac caaaaaatag cctcttacag taaataagag ggaactatga 2820
gagtgtctac ccgtgaagcc ccaagtgccc tggtaatgga cctgctctcc ctccctgtgc 2880
tggaaagcca ttccgagggt gcctgtgcgt acacagccag tcttggctcc tcccaactgc 2940
actgttaaag cgcagccccg aagacacttt ctagtgattt tggtctgttg cttaaatcat 3000
ttactagatt agttttaggg caacactttc caaatacata acttgactgt tgtgcttatc 3060
agctgccaga aagaaacagg ttattgttgg gaaaccttgc tgtttttaaa gtttgattca 3120
attaaaagca atacttccaa atagacagtg aaaacttccc aaaagaggaa gaagcccagt 3180
gtactgccgc acatctgtag tcccagctgc ttgaagcaga ggcgggaaga gtgctagagc 3240
ccaggaggtc cctgccaggc cgggcaacac tgcaagacac agtctcaaag gccaagcagc 3300
cgaaagggct ctcctcacag ccagctttat cacctctacg ttctgggcca aacagtgaca 3360
tgggcatttt ggttttccta acaactaacg atgaatgttc tgaaggtaca tttcatttta 3420
aatacggaaa aaacttttca taattacaga caagaaggaa aaacccccga ttttccaata 3480
atataaagag cacagttggt cttccaaagg tgtccatgtg tgaagctaca agtacttcga 3540
aatgcactaa aattttgaag caaatctacc ttaggaactt ttttgaaatt gtacttttaa 3600
aggtttaggc ttttgcttaa atattctgag ttaaattctg tactaggaaa gatgttggat 3660
tctttcctta aatactaaat aagttcctca tcttattttt aatcaaatgt tttatagaaa 3720
tgagttgaga aaagttgacc atgcactatt tatagtactt tgccataaca ggcaatgttc 3780
taaaactaaa tttatttttg tttagtgaac atgagtttag atttttaaag ttggtaattt 3840
atctccacta atattttttt aaagaaactg tgaagagatt aacagaataa ttttatttca 3900
gattttacta atgtagtgtg tagctacaac ttgacattca agtgaagact agacttctgt 3960
tttgaaattt ttccatcagg tagtttcagt ggtttcattt tagaaatgtg tttgcagatg 4020
tttgacaaag ggaatattac taaaaaagaa aagcaaaaaa aaaaaaaact tatcaaatga 4080
agaattgtta gaaaaattta aattccctgc taaagacatt tttgttagtc ttagggggta 4140
ggtatttgct ttctagaact tgtttttgtt gatagtattt gctttctaga acttgttttt 4200
gttgatagct ggatgtatgg aacctgtttt ctatgcgagg tgcaagtctt gcactacagt 4260
tgtaagatat attatattgt ttagggatca agaaagcaat ctatgctgaa gtaactatag 4320
tatgtagttc ctattgtgaa taatgctttg cttttgtaat gtattaataa aaagtaacac 4380
tttctaatga aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4440
<210> 31
<211> 2008
<212> DNA
<213> Homo sapiens
<400> 31
gagacgaaac ttcccgtccc ggcggctctg gcacccaggg tccggcctgc gccttcccgc 60
caggcctgga cactggttca acacctgtga cttcatgtgt gcgcgccggc cacacctgca 120
gtcacacctg tagccccctc tgccaagaga tccataccga ggcagcgtcg gtggctacaa 180
gccctcagtc cacacctgtg gacacctgtg acacctggcc acacgacctg tggccgcggc 240
ctggcgtctg ctgcgacagg agcccttacc tcccctgtta taacacctga ccgccaccta 300
actgcccctg cagaaggagc aatggccttg gctcctgaga ggtaagagcc cggcccaccc 360
tctccagatg ccagtccccg agcgccctgc agccggccct gactctccgc ggccgggcac 420
ccgcagggca gccccacgcg tgctgttcgg agagtggctc cttggagaga tcagcagcgg 480
ctgctatgag gggctgcagt ggctggacga ggcccgcacc tgtttccgcg tgccctggaa 540
gcacttcgcg cgcaaggacc tgagcgaggc cgacgcgcgc atcttcaagg cctgggctgt 600
ggcccgcggc aggtggccgc ctagcagcag gggaggtggc ccgccccccg aggctgagac 660
tgcggagcgc gccggctgga aaaccaactt ccgctgcgca ctgcgcagca cgcgtcgctt 720
cgtgatgctg cgggataact cgggggaccc ggccgacccg cacaaggtgt acgcgctcag 780
ccgggagctg tgctggcgag aaggcccagg cacggaccag actgaggcag aggcccccgc 840
agctgtccca ccaccacagg gtgggccccc agggccattc ctggcacaca cacatgctgg 900
actccaagcc ccaggccccc tccctgcccc agctggtgac aagggggacc tcctgctcca 960
ggcagtgcaa cagagctgcc tggcagacca tctgctgaca gcgtcatggg gggcagatcc 1020
agtcccaacc aaggctcctg gagagggaca agaagggctt cccctgactg gggcctgtgc 1080
tggaggccca gggctccctg ctggggagct gtacgggtgg gcagtagaga cgacccccag 1140
ccccgggccc cagcccgcgg cactaacgac aggcgaggcc gcggccccag agtccccgca 1200
ccaggcagag ccgtacctgt caccctcccc aagcgcctgc accgcggtgc aagagcccag 1260
cccaggggcg ctggacgtga ccatcatgta caagggccgc acggtgctgc agaaggtggt 1320
gggacacccg agctgcacgt tcctatacgg ccccccagac ccagctgtcc gggccacaga 1380
cccccagcag gtagcattcc ccagccctgc cgagctcccg gaccagaagc agctgcgcta 1440
cacggaggaa ctgctgcggc acgtggcccc tgggttgcac ctggagcttc gggggccaca 1500
gctgtgggcc cggcgcatgg gcaagtgcaa ggtgtactgg gaggtgggcg gacccccagg 1560
ctccgccagc ccctccaccc cagcctgcct gctgcctcgg aactgtgaca cccccatctt 1620
cgacttcaga gtcttcttcc aagagctggt ggaattccgg gcacggcagc gccgtggctc 1680
cccacgctat accatctacc tgggcttcgg gcaggacctg tcagctggga ggcccaagga 1740
gaagagcctg gtcctggtga agctggaacc ctggctgtgc cgagtgcacc tagagggcac 1800
gcagcgtgag ggtgtgtctt ccctggatag cagcagcctc agcctctgcc tgtccagcgc 1860
caacagcctc tatgacgaca tcgagtgctt ccttatggag ctggagcagc ccgcctagaa 1920
cccagtctaa tgagaactcc agaaagctgg agcagcccac ctagagctgg ccgcggccgc 1980
ccagtctaat aaaaagaact ccagaaca 2008
<210> 32
<211> 1876
<212> DNA
<213> Mus musculus
<400> 32
tgagataaaa cccgtcccgg cggctccggt accagggtcc agcctgtgac agcccatcca 60
ggctcggacg ctggattaac acctgtgaca tcacgtgtgc gctcccgcta catctgtagt 120
cacatctaca gccaccttgg cagaggaatc tacactgagt tctgaaccta ggtgaccaca 180
agttctcaaa cctcatctgt gaccctcaac accctaatac ctgggtcaca cttgtgaaac 240
tgaaattcct acctgttacc aacacttgta acgtttaaaa cacatttgtg aaacttggtc 300
acactatctg tggctacaac ctaaaaccat agaggcaccc aaggggcctt atttgcaata 360
gctgactgct ccagtgacta caaggcatca cagagtagta gcatctactt tgattctccc 420
agactgcctg tgtagacgga gcaatggctg aagtgagggg ggtccagcga gtgctgtttg 480
gagactggct attgggggag gtcagcagcg gccagtacga ggggctgcag tggctgaacg 540
aggctcgcac agtcttccgc gtaccctgga agcatttcgg tcgtagggat ctggatgaag 600
aagatgcaca gatcttcaag gcctgggctg tggcccgagg gaggtggcca cctagtggag 660
ttaacctgcc acccccagag gctgaggctg ctgagcgaag agagcgaaga ggctggaaga 720
ccaacttccg ctgtgcactc cacagcacag ggcgttttat cttgcgccaa gacaattcag 780
gggatccagt tgatccgcat aaggtgtacg aacttagccg ggagcttgga tctactgtgg 840
gcccagccac ggaaaatagg gaagaagtga gcctcagcaa tgctctgccc acacagggtg 900
tgtccccagg atcatttctg gcaagagaaa atgctgggct ccaaacccca agccctctgc 960
tttctagtga tgccggggac ctcttgcttc aggttctgca gtacagccac atactggaat 1020
ccgagtctgg ggcagacccc gtcccaccac aggctcctgg ccaggagcaa gaccgtgttt 1080
acgaggaacc ctatgcagca tggcaggtgg aagctgtccc cagtcccagg cctcaacagc 1140
cagctctcac cgagcgcagc cttgggttcc tggatgtgac catcatgtac aagggccgca 1200
cagtgctaca ggcagtggtg gggcacccca gatgcgtgtt cctgtacagc cccatggccc 1260
cagcagtaag aacttcagag ccccagccgg tgatctttcc cagtcctgct gagctcccag 1320
atcagaagca gctgcactac acagagacgc ttctccagca tgtgtctccc ggccttcagc 1380
tggagcttcg aggaccgtca ctgtgggccc tgcgtatggg caagtgcaag gtgtactggg 1440
aggtaggcag ccctatgggc actaccggcc cctccacccc accccagctg ctggagcgca 1500
accgccacac ccccatcttc gacttcagca ctttcttccg agaactggag gagtttcggg 1560
ctcggaggcg gcaagggtca ccacactaca ccatctacct gggttttggg caagacttgt 1620
cagcagggag gcccaaggag aagaccctga tcctggtgaa gctggagcca tgggtatgca 1680
aggcatacct ggagggcgtg cagcgtgagg gtgtgtcctc cctggacagc agcagtctcg 1740
gcttgtgctt gtctagcacc aacagtctct acgaagacat cgaacacttc ctcatggacc 1800
tgggtcagtg gccttgactc agaatcccaa ctcccaataa atagttcaaa atcagtggaa 1860
aaaaaaaaaa aaaaaa 1876
<210> 33
<211> 7281
<212> DNA
<213> Homo sapiens
<400> 33
gcagtcacag acacttgagc acacgcgtac acccagacat cttcgggctg ctattggatt 60
gactttgaag gttctgtgtg ggtcgccgtg gctgcatgtt tgaatcaggt ggagaagcac 120
ttcaacgctg gacgaagtaa agattattgt tgttattttt tttttctctc tctctctctc 180
ttaagaaagg aaaatatccc aaggactaat ctgatcgggt cttccttcat caggaacgaa 240
tgcaggaatt tgggaactga gctgtgcaag tgctgaagaa ggagatttgt ttggaggaaa 300
caggaaagag aaagaaaagg aaggaaaaaa tacataattt cagggacgag agagagaaga 360
aaaacgggga ctatggggag aaaaaagatt cagattacga ggattatgga tgaacgtaac 420
agacaggtga catttacaaa gaggaaattt gggttgatga agaaggctta tgagctgagc 480
gtgctgtgtg actgtgagat tgcgctgatc atcttcaaca gcaccaacaa gctgttccag 540
tatgccagca ccgacatgga caaagtgctt ctcaagtaca cggagtacaa cgagccgcat 600
gagagccgga caaactcaga catcgtggag acgttgagaa agaagggcct taatggctgt 660
gacagcccag accccgatgc ggacgattcc gtaggtcaca gccctgagtc tgaggacaag 720
tacaggaaaa ttaacgaaga tattgatcta atgatcagca ggcaaagatt gtgtgctgtt 780
ccacctccca acttcgagat gccagtctcc atcccagtgt ccagccacaa cagtttggtg 840
tacagcaacc ctgtcagctc actgggaaac cccaacctat tgccactggc tcacccttct 900
ctgcagagga atagtatgtc tcctggtgta acacatcgac ctccaagtgc aggtaacaca 960
ggtggtctga tgggtggaga cctcacgtct ggtgcaggca ccagtgcagg gaacgggtat 1020
ggcaatcccc gaaactcacc aggtctgctg gtctcacctg gtaacttgaa caagaatatg 1080
caagcaaaat ctcctccccc aatgaattta ggaatgaata accgtaaacc agatctccga 1140
gttcttattc caccaggcag caagaatacg atgccatcag tgtctgagga tgtcgacctg 1200
cttttgaatc aaaggataaa taactcccag tcggctcagt cattggctac cccagtggtt 1260
tccgtagcaa ctcctacttt accaggacaa ggaatgggag gatatccatc agccatttca 1320
acaacatatg gtaccgagta ctctctgagt agtgcagacc tgtcatctct gtctgggttt 1380
aacaccgcca gcgctcttca ccttggttca gtaactggct ggcaacagca acacctacat 1440
aacatgccac catctgccct cagtcagttg ggagcttgca ctagcactca tttatctcag 1500
agttcaaatc tctccctgcc ttctactcaa agcctcaaca tcaagtcaga acctgtttct 1560
cctcctagag accgtaccac caccccttcg agatacccac aacacacgcg ccacgaggcg 1620
gggagatctc ctgttgacag cttgagcagc tgtagcagtt cgtacgacgg gagcgaccga 1680
gaggatcacc ggaacgaatt ccactccccc attggactca ccagaccttc gccggacgaa 1740
agggaaagtc cctcagtcaa gcgcatgcga ctttctgaag gatgggcaac atgatcagat 1800
tattacttac tagttttttt ttttttcttg cagtgtgtgt gtgtgctata ccttaatggg 1860
gaaggggggt cgatatgcat tatatgtgcc gtgtgtggaa aaaaaaaaag tcaggtactc 1920
tgttttgtaa aagtactttt aaattgcctc agtgatacag tataaagata aacagaaatg 1980
ctgagataag cttagcactt gagttgtaca acagaacact tgtacaaaat agattttaag 2040
gctaacttct tttcactgtt gtgctccttt gcaaaatgta tgttacaata gatagtgtca 2100
tgttgcaggt tcaacgttat ttacatgtaa atagacaaaa ggaaacattt gccaaaagcg 2160
gcagatcttt actgaaagag agagcagctg ttatgcaaca tatagaaaaa tgtatagatg 2220
cttggacaga cccggtaatg ggtggccatt ggtaaatgtt aggaacacac caggtcacct 2280
gacatcccaa gaatgctcac aaacctgcag gcatatcatt ggcgtatggc actcattaaa 2340
aaggatcaga gaccattaaa agaggaccat acctattaaa aaaaaatgtg gagttggagg 2400
gctaacatat ttaattaaat aaataaataa atctgggtct gcatctctta ttaaataaaa 2460
atataaaaat atgtacatta cattttgctt attttcatat aaaaggtaag acagagtttg 2520
caaagcattt gtggcttttt gtagtttact taagccaaaa tgtgtttttt tccccttgat 2580
agcttcgcta atattttaaa cagtcctgta aaaaaccaaa aaggactttt tgtatagaaa 2640
gcactaccct aagccatgaa gaactccatg ctttgctaac caagataact gttttctctt 2700
tgtagaagtt ttgtttttga aatgtgtatt tctaattata taaaatatta agaatctttt 2760
aaaaaaatct gtgaaattaa catgcttgtg tatagctttc taatatatat aatattatgg 2820
taatagcaga agttttgtta tcttaatagc gggagggggg tatatttgtg cagttgcaca 2880
tttgagtaac tattttcttt ctgttttctt ttactctgct tacattttat aagtttaagg 2940
tcagctgtca aaaggataac ctgtggggtt agaacatatc acattgcaac accctaaatt 3000
gtttttaata cattagcaat ctattgggtc aactgacatc cattgtatat actagtttct 3060
ttcatgctat ttttattttg ttttttgcat ttttatcaaa tgcagggccc ctttctgatc 3120
tcaccatttc accatgcatc ttggaattca gtaagtgcat atcctaactt gcccatattc 3180
taaatcatct ggttggtttt cagcctagaa tttgatacgc tttttagaaa tatgcccaga 3240
atagaaaagc tatgttgggg cacatgtcct gcaaatatgg ccctagaaac aagtgatatg 3300
gaatttactt ggtgaataag ttataaattc ccacagaaga aaaatgtgaa agactgggtg 3360
ctagacaaga aggaagcagg taaagggata gttgctttgt catccgtttt taattatttt 3420
aactgaccct tgacaatctt gtcagcaata taggactgtt gaacaatccc ggtgtgtcag 3480
gacccccaaa tgtcacttct gcataaagca tgtatgtcat ctattttttc ttcaataaag 3540
agatttaata gccatttcaa gaaatcccat aaagaacctc tctatgtccc tttttttaat 3600
ttaaaaaaaa tgactcttgt ctaatattcg tctataaggg attaattttc agacccttta 3660
ataagtgagt gccataagaa agtcaatata tattgtttaa aagatatttc agtctaggaa 3720
agattttcct tctcttggaa tgtgaagatc tgtcgattca tctccaatca tatgcattga 3780
catacacagc aaagaagata taggcagtaa tatcaacact gctatatcat gtgtaggaca 3840
tttcttatcc attttttctc ttttacttgc atagttgcta tgtgtttctc attgtaaaag 3900
gctgccgctg ggtggcagaa gccaagagac cttattaact aggctatatt tttcttaact 3960
tgatctgaaa tccacaatta gaccacaatg cacctttggt tgtatccata aaggatgcta 4020
gcctgccttg tactaatgtt ttatatatta aaaaaaaaaa atctatcaac catttcatat 4080
atatcccact actcaaggta tccatggaac atgaaagaat aacatttatg cagaggaaaa 4140
acaaaaacat ccctgaaaat atacacactc atacacacac acgcacaggg gaataaaata 4200
agaaaatcat tttcctcacc atagacttga tcccatcctt acaacccatc cttctaactt 4260
gatgtgtata aaatatgcaa acatttcaca aatgttcttt gtcatttcaa aatactttag 4320
tatatcaata tcagtagata ccagtgggtg ggaaagggtc attacatgaa aatatgaaga 4380
aatagccata ttagtttttt aacctgcaat ttgcctcagc aacaaagaaa aagtgaattt 4440
ttaatgctga agataaagta agctaaagta ccagcagaag ccttggctat ttatagcagt 4500
tctgacaata gttttataag aacatgaaga gaacagaatc acttgaaaat ggatgccagt 4560
catctcttgt tcccactact gaattcttat aaagtggtgg caagataggg aagggataat 4620
ctgagaattt ttaaaagatg atttaatgag aagaagcaca attttgattt tgatgagtca 4680
ctttctgtaa acaatcttgg tctatcttta cccttatacc ttatctgtaa tttaccattt 4740
attgtatttg caaagctagt atggttttta atcacagtaa atcctttgta ttccagactt 4800
tagggcagag ccctgaggga gtattatttt acataacccg tcctagagta acattttagg 4860
caacattctt cattgcaagt aaaagatcca taagtggcat tttacacggc tgcgagtatt 4920
gttatatcta atcctatttt aaaagatttt tggtaatatg aagcttgaat actggtaaca 4980
gtgatgcaat atacgcaagc tgcacaacct gtatattgta tgcattgctg cgtggaggct 5040
gtttatttca acctttttaa aaattgtgtt ttttagtaaa atggcttatt ttttcccaaa 5100
ggtggaattt agcattttgt aatgatgaat ataaaaatac ctgtcatccc cagatcattt 5160
aaaagttaac taaagtgaga atgaaaaaac aaaattccaa gacacttttt aaaagaatgt 5220
ctgccctcac acacttttat ggatttgttt ttcttacata cccatctttt aacttagaga 5280
tagcattttt tgccctcttt attttgttgt ttgtttctcc agagagtaaa cgctttgtag 5340
ttctttcttt aaaaaacatt ttttttaaag aagaagaagc cacttgaacc ctcaataaag 5400
gctgttgcct aagcatggca tacttcatct gttctcattt gtgccatctg ccgtgatgtc 5460
gtcactttta tggcgttaat ttcctgccac tacagatctt ttgaagattg ctggaatact 5520
ggtgtctgtt agaatgcttc agactacaga tgtaattaaa ggcttttctt aatatgtttt 5580
aaccaaagat gtggagcaat ccaagccaca tatcttctac atcaaatttt tccattttgg 5640
ttattttcat aatctggtat tgcattttgc cttccctgtt catacctcaa attgattcat 5700
acctcagttt aattcagaga ggtcagttaa gtgacggatt ctgttgtggt ttgaatgcag 5760
taccagtgtt ctcttcgagc aaagtagacc tgggtcactg taggcatagg acttggattg 5820
cttcagatgg tttgctgtat catttttctt ctttttcttt tcctggggac ttgtttccat 5880
taaatgagag taattaaaat cgcttgtaaa tgagggcata caagcatttg caacaaatat 5940
tcaaatagag gctcacagcg gcataagctg gactttgtcg ccactagatg acaagatgtt 6000
ataactaagt taaaccacat ctgtgtatct caagggactt aattcagctg tctgtagtga 6060
ataaaagtgg gaaattttca aaagtttctc ctgctggaaa taaggtataa tttgtatttt 6120
gcagacaatt cagtaaagtt actggctttc ttagtgatgc agtgtccgtg gtgcattttt 6180
ttaaattaat gttttgctgt ttaaatttat tcaattttat tgtgtttttt aaaaagcagc 6240
ttatgccaca agcacaaatg agctttctca gttttcaact caaaatatta tatgaaaaga 6300
tggatatgtg tgtctgtgtg ggaggggtgt gaattggatg acggttctta gggtattaca 6360
gaattcagcc agtggtggaa gtctaaggtt cttattgaat ggttcaactt ctttatcaaa 6420
gaagttccat gaagatcttt gataacctgt ttaaatgtac agaatttttc aaaagccact 6480
gtgaaaagca gtaccataag ttatttttta actaaaatct gtagaaagtg tttccaaaag 6540
agttcctttt ttcttcttcg aagtaatttc taaaagttga aaacataggc ttataaatct 6600
gaataaatta gtgaattcat acattttaga gactatcaaa tatatccatt attaacattc 6660
aataataatc tctaaagggg aatgtcctta aaaagattga tagaaagatt aatttaaaaa 6720
ctgaaaagga aaacaagaca ccaccagtta gccagctgga gaacttggac ttttgcatta 6780
gtagtgatat ctgctccaaa aagaatgcag ttcgaggaaa tgttgcatgt ggcttcaaaa 6840
tagcagtgct ttctgctttg ttctcttgta ttcattttca gcaaacatgt attaagcaat 6900
tattatatgt aactcatgtg gtgattccag gatgaatgaa gttgtagccc tttctcttag 6960
gaaacttata aactaatagg agataaaagg cattctcagg gaagtctaca aagtgctatg 7020
agggagccac tttggccatc ctggggcaga gcagaccaga ggctcagagc atggacactt 7080
cctcatccac ccagcagaag cctttcactt gattttgaag gtgggcagga ttgagaaagg 7140
cccagaaggg gatgagttca aagctgtttg tgggcatgtg acccctgcag tcacatatgg 7200
ccctagcttg tgtttcgttt agtgttctgc tatcattatc ctgataatat cctgataata 7260
aaattatcct taataatttt a 7281
<210> 34
<211> 6451
<212> DNA
<213> Mus musculus
<400> 34
gagcagttct gtgttctttt gccagcactg acaaaggtct ggttgtcaat gataccttta 60
cagctaaatt tactccagag tgacatgaac aggtgcaccc tggcctgcca gacacttgtg 120
cagagggatc acgcatctca ccgcttgacg atcaaggggg caaagcttcg gtgttcatag 180
aaaaggagag gaggcgagcg cagcccaaac tggggggttt ctcttcaaag ccagctggtc 240
tggctttatt ctacaggaat ttttttacct gtcagagttt ggacaacaaa gccctcagca 300
ggtgctgacg ggaacaactt cctggagaag cagaaaggca ctggtgccaa caaaagcatt 360
gaaaactgtg aagtaacctc tggagagatg aagtgaagcg tggaaggcca atggctgtgg 420
cagtgaagaa gtgcagaggg aacgaatgca gggatttggg aactgagctg tgcgcgtgct 480
gaagaaggaa acgtgtttga aggaaacagg aaagagaaag aaaaggaagg aaaaaataca 540
taatttcagg gacgagagag agaagaaaca cggggactat ggggagaaaa aagattcaga 600
ttacgaggat aatggatgag cgtaacagac aggtgacttt tacgaagagg aaatttggat 660
tgatgaagaa ggcttatgag ctgagcgtgc tgtgcgactg tgagattgca ctgatcatct 720
tcaacagcac caacaagctg ttccagtacg ccagcactga catggataag gtgttgctca 780
agtacaccga gtacaacgag ccgcacgaga gccggacaaa ctcagacatt gtggagacat 840
tgagaaagaa gggcctcaat ggctgtgaca gcccagatcc cgatgcagac gattcagtag 900
gtcacagccc tgagtctgag gacaagtaca ggaaaattaa cgaagatatt gatctaatga 960
tcagcaggca aagattgtgt gctgttccac ctcccagctt tgagatgcca gttaccatcc 1020
cagtgtccag ccataacagt ttggtgtaca gcaatcctgt cagcacactg ggaaacccca 1080
atcttctgcc actggcccac ccgtctctgc agaggaatag tatgtctcct ggtgtaacac 1140
atagacctcc aagtgcaggt aacacaggcg gtctgatggg cggagatctg acatccggtg 1200
caggcaccag cgcagggaat ggatacggca acccccggaa ctcaccaggc ctgctggtct 1260
cacctggtaa cctgaacaag aatatacaag ccaaatctcc tccccctatg aatctaggaa 1320
tgaataatcg taagccagat ctccgcgttc ttatcccacc tggcagcaag aacacgatgc 1380
catcagtgtc tgaggatgtg gatctgctgt tgaatcaaag gataaataac tcccagtcgg 1440
ctcagtcatt ggctaccccg gtggtttccg tagcaactcc tactttacca ggacaaggaa 1500
tgggaggata tccatcagcc atttcaacaa catatggtac tgagtactct ctgagtagcg 1560
cagatctgtc atctctgtct ggcttcaaca ctgccagtgc gctccacctc ggctctgtaa 1620
ctggctggca gcagcagcac ctacataaca tgccgccatc tgccctcagt cagttgggag 1680
cttgcactag cactcattta tctcagagtt caaatctctc cctgccttct actcaaagcc 1740
tcagcatcaa gtcagaacct gtttctcctc ctagagaccg taccaccacc ccttcgagat 1800
acccacaaca caccacgcgc cacgaggcgg ggaggtctcc tgttgacagc ttgagcagct 1860
gtagcagttc ctacgatggg agcgaccgag aggatcaccg gaacgaattc cactccccca 1920
ttggactcac cagaccttcg ccggacgaaa gggaaagtcc ttcagtcaag cgcatgcgac 1980
tctctgaagg atgggcaaca tgatcacatt attacttaat agtttttttt tttcttgcag 2040
tgtgtgtgtg tgctatacct taatggggaa gggggggtcg atatgcatta tatgtgccgt 2100
gtgtggaaaa aaaaaaaaaa gtcaggtact ctgttttgta aaagtacttt taaattgcct 2160
cagtgataca gtataaagat aaacagaaat gctgagatac gcttagcact tgagttgtac 2220
aacagaacac ttgtacaaaa tagattttaa ggctaacttc ttttcactgt tgtgaccctt 2280
tgcaaaatgt atgttacaat agatagtgtc atgttgcagg ttcaacgtta tttacatgta 2340
aatagacaaa aggaaacatt tgccaaaagc ggcagatctt tactgaaaga gagagcagct 2400
gttatgcaac atatagaaaa atgtatagag gtttggacag acccggcaag tggtgactac 2460
cggtaattgt aggaacacgc ctgtcaccta acatccaagc acgctcacaa acctgcaggc 2520
atatcattgg cgtatggcac tcattcaaaa ggatcagaaa ccattcagag aggaccatac 2580
ctaccttaaa agaaaagaga agaaaggaaa ggaaaggaaa gggaaaaaaa agtgtggcgt 2640
ttgagagcta acatatttaa ttaaataaat aaatctgggt ctgcatctct tattaaataa 2700
aaatataaaa atatgtacat tacattttgc ttattttcat ataaaaggta agaaagagtt 2760
tgcaaagcat ttgtggcttt ttgtagttta cttaagccaa aatgtgtttt tccctcaata 2820
gcttcgctaa tattttaaac agtcctgtaa aaacccacca aggacttttt gtatagaaag 2880
cactacccta agccatgagg atctccatgc tttgctaacc aagataactg ttttctcttt 2940
gtagaagttt tgtttttgaa atgtgtattt ctaattatat aaaatattaa gaatctttta 3000
aaaatctgtg aaattaacat gcttgtgtat agctttctaa tatatataat attatggtaa 3060
tggcagaagt tttgttttct taatagcggg aggggggtat atttgtgcag ttgcacattt 3120
gagtaactat tttctttctg atttctttta ctctgcatac attttataag ttcaaggtca 3180
gctgtcaaaa ggataagctg tggggttaga acatattaca ttgcaacatc ctaaattgtt 3240
tttaaaacgt cagcaaacta ttgggtcaac tgacatccat tgtatatact aattggtttc 3300
tttcaaacta tttttttttt tggtttggtt ttgaattgtt ggtttctttt cattttatca 3360
aaagcagggc ccctttcaga tctctcttca tttcaccata catcttggaa ttctgtaagt 3420
ttgtatccta acttgcccat attctaaatt tacatagttt attttcagcc ttgagttgga 3480
tgttttttag aaatatgccc agagtaagaa gctgtgttgg agcctaagtc ctgcaagctg 3540
ggtcctgggg gcgaccgacc tgctttactt gatggataag ttacagagtt ctggaggaga 3600
acaaggtgaa agcctgggtg ctggagagga aggaaacagt taaagggtag ttacttggta 3660
tccaccttca tgattttaac tgacccataa caatgttgtc agcagtatag gactgttgaa 3720
cagcctggtg tgtcaggacc cccaaatgtc acttctgcct aaagcatgta tgtcacctat 3780
ttttttcttc aataaagaaa tttaacagcc atttcaagaa atcccacttt aaaaaaaaaa 3840
aaaaacaaac ctttctctat gtcccccccc ctttttttta attttcaaga taatttaact 3900
cttgtctaat attcttgtgt aagggattaa ttttcagacc cctttaaaag tgagtgccat 3960
aaagagtcaa tatatagtgt tgaagtggta tttcaggcta ggaattattc ccttctcttg 4020
gaatgtgaag atctgtcgat tcatcctgtc attaatcctg acatacagaa caaagaatgc 4080
agtaacatta gccctgccag gtcacgtgta ggacgtgctt atccagtttt ttcccccttt 4140
acctgcatag ttgctacata catgtttctc actgtaaaag gctgccgctg ggtggcagaa 4200
gccaaaagac cttattaacg aggctatatt tttcttaact tgatctgcaa tccagaatta 4260
gaccacaatg cacctttggt ggtatccata taggatgcta gcctgccttg tagtaatgtt 4320
ttatatgtta aaaacaaaat aaagacatca accatttcac atatattcta ctactaaagg 4380
tatcaatgga acatgaagac gagtatttag gcagaagcaa aacaggaaac catccttaca 4440
aacatgctta cctgcacatc tgtttgcatg gtcatgtgta cattcaaaca tgcacataaa 4500
gtgaacaaga aagtcagcca ttatttcacg ccagacttga ttccatcctg agaattcatg 4560
tttataatta aatgtgtgtt aaatatgcaa gcatatcaca aatgttcctt gtcctttcaa 4620
agtgcatttg ttcatcaaga tcaatagaat cttaccagtg ggtaggaaag gatcatataa 4680
aatatgaaga aatagccata ttaaattttt tgctgtcatt tgcctccgca acaaagcgag 4740
tgtaagtgtc taatgctgaa gctagagtga actcatgtgc cagcagaggc ctcctctctt 4800
tatagcaatt ctgacaatag gtttgtttgt ttgtttgttt gtttttacaa actcaagaaa 4860
aacagactca cttgaaaaaa tggatgccag tcacctggtt cccactactg tcgtagcaga 4920
tagcgaaggg acaatctgag acttgtagag atgatttaat gagaagcaca atttttattg 4980
tgaccagtca cgttctatca ccaggcactg tcttgtcttt gcccttgcct tttctgtaac 5040
tcaccattta ttgtatttac aaatctagta agggttttga tcacaccaag ttctttgtat 5100
tgagaagtct agggcagagc tctgggggat tgttatttta cattacctgg cctagagtag 5160
catattagac aacagtcatc attgcaagta ggaggaccgt aaatggcatt ttacatgact 5220
gcaagtattg ttataccgaa tcctatttta aaagagtttt agtaacggtg agctgagaaa 5280
ttctggtcat ggtgagcagc aggcgcaagc catgcagcct gtggactgtg cgcattgata 5340
tgtggaggct gttgatttca acctttttta aacttgtgtt ttttagtaaa attgcttatt 5400
tttttcccaa aggtggaatt taatgttttg tagtgatgaa tatgaaaatg cctgtcatct 5460
ttagatcatt gaaaggttaa ctaacatgag aatttcagag caaattccaa tactctttta 5520
aaaagcgtgt ctgccctctc ttacttctat gtatttgttt atcgacacac tcaccctttc 5580
tgagatagca ttttgctccc ttgatccccc cctttttttg tcccttcgaa gagtaaatgc 5640
tttgtatttc tttctttaaa aaatttactt taaagaagaa gccacttgaa ccttcaataa 5700
aggctgttgc ctaaacatgg cgtacttcat ctgttcccgc ctctgccatc tgctacggtg 5760
tcgtcagttg tatggcatta atttcctgcc actagagata ttttgaagat tgcttgaatg 5820
ctggtgtctg ttagaatgct tctgactaca gatgtaatta aaggcttttc ttactatgtt 5880
ttaaccaaag atgtggagca atccaagccg catatctact gcattaaatt tgtccatttg 5940
gttattcata atcgggtatt gcattttgcc ttccctgtcc atacctcaaa ttgattgata 6000
cctcagttta attcagagag gttcgctaag tgttggattc tagttgtggt ttgaatgcag 6060
cagtgtactc ttgaagtaag caggcaaggg tcactgcagg catgaagctt ggattgcttc 6120
agatggtttg ccgtatcgtt tttcttcctt ttccttttct ggggacttgt ttccattcaa 6180
tgacaattaa aatagcttgt aaatgagggc atacaagcat ttgcaacaag tattcaaata 6240
gaggctcaca gcggcataag ctggactttg tcgccactag atgacaagat ggtataccta 6300
agctaaccac acgtgtgtat ctcaagggac ttaaattcag ctgtctgtag tgaattcaag 6360
tgggaaattt tcaaaagttt ctcctgctgg aaataaggta taatttgtat tttgcagaca 6420
attcagtaaa gttactggct ttcttagtga t 6451
<210> 35
<211> 3684
<212> DNA
<213> Homo sapiens
<400> 35
acactttaat atcaacctgt ttcctcctcc tccttctcct cctcctccgt gacctcctcc 60
tcctctttct cctgagaaac ttcgccccag cggtgcggag cgccgctgcg cagccgggga 120
gggacgcagg caggcggcgg gcagcgggag gcggcagccc ggtgcggtcc ccgcggctct 180
cggcggagcc ccgcgcccgc cgcgccatgg cccgaagacc ccggcacagc atatatagca 240
gtgacgagga tgatgaggac tttgagatgt gtgaccatga ctatgatggg ctgcttccca 300
agtctggaaa gcgtcacttg gggaaaacaa ggtggacccg ggaagaggat gaaaaactga 360
agaagctggt ggaacagaat ggaacagatg actggaaagt tattgccaat tatctcccga 420
atcgaacaga tgtgcagtgc cagcaccgat ggcagaaagt actaaaccct gagctcatca 480
agggtccttg gaccaaagaa gaagatcaga gagtgataga gcttgtacag aaatacggtc 540
cgaaacgttg gtctgttatt gccaagcact taaaggggag aattggaaaa caatgtaggg 600
agaggtggca taaccacttg aatccagaag ttaagaaaac ctcctggaca gaagaggaag 660
acagaattat ttaccaggca cacaagagac tggggaacag atgggcagaa atcgcaaagc 720
tactgcctgg acgaactgat aatgctatca agaaccactg gaattctaca atgcgtcgga 780
aggtcgaaca ggaaggttat ctgcaggagt cttcaaaagc cagccagcca gcagtggcca 840
caagcttcca gaagaacagt catttgatgg gttttgctca ggctccgcct acagctcaac 900
tccctgccac tggccagccc actgttaaca acgactattc ctattaccac atttctgaag 960
cacaaaatgt ctccagtcat gttccatacc ctgtagcgtt acatgtaaat atagtcaatg 1020
tccctcagcc agctgccgca gccattcaga gacactataa tgatgaagac cctgagaagg 1080
aaaagcgaat aaaggaatta gaattgctcc taatgtcaac cgagaatgag ctaaaaggac 1140
agcaggtgct accaacacag aaccacacat gcagctaccc cgggtggcac agcaccacca 1200
ttgccgacca caccagacct catggagaca gtgcacctgt ttcctgtttg ggagaacacc 1260
actccactcc atctctgcca gcggatcctg gctccctacc tgaagaaagc gcctcgccag 1320
caaggtgcat gatcgtccac cagggcacca ttctggataa tgttaagaac ctcttagaat 1380
ttgcagaaac actccaattt atagattctg attcttcatc atggtgtgat ctcagcagtt 1440
ttgaattctt tgaagaagca gatttttcac ctagccaaca tcacacaggc aaagccctac 1500
agcttcagca aagagagggc aatgggacta aacctgcagg agaacctagc ccaagggtga 1560
acaaacgtat gttgagtgag agttcacttg acccacccaa ggtcttacct cctgcaaggc 1620
acagcacaat tccactggtc atccttcgaa aaaaacgggg ccaggccagc cccttagcca 1680
ctggagactg tagctccttc atatttgctg acgtcagcag ttcaactccc aagcgttccc 1740
ctgtcaaaag cctacccttc tctccctcgc agttcttaaa cacttccagt aaccatgaaa 1800
actcagactt ggaaatgcct tctttaactt ccacccccct cattggtcac aaattgactg 1860
ttacaacacc atttcataga gaccagactg tgaaaactca aaaggaaaat actgttttta 1920
gaaccccagc tatcaaaagg tcaatcttag aaagctctcc aagaactcct acaccattca 1980
aacatgcact tgcagctcaa gaaattaaat acggtcccct gaagatgcta cctcagacac 2040
cctctcatct agtagaagat ctgcaggatg tgatcaaaca ggaatctgat gaatctggaa 2100
ttgttgctga gtttcaagaa aatggaccac ccttactgaa gaaaatcaaa caagaggtgg 2160
aatctccaac tgataaatca ggaaacttct tctgctcaca ccactgggaa ggggacagtc 2220
tgaataccca actgttcacg cagacctcgc ctgtggcaga tgcaccgaat attcttacaa 2280
gctccgtttt aatggcacca gcatcagaag atgaagacaa tgttctcaaa gcatttacag 2340
tacctaaaaa caggtccctg gcgagcccct tgcagccttg tagcagtacc tgggaacctg 2400
catcctgtgg aaagatggag gagcagatga catcttccag tcaagctcgt aaatacgtga 2460
atgcattctc agcccggacg ctggtcatgt gagacatttc cagaaaagca ttatggtttt 2520
cagaacactt caagttgact tgggatatat cattcctcaa catgaaactt ttcatgaatg 2580
ggagaagaac ctatttttgt tgtggtacaa cagttgagag cagcaccaag tgcatttagt 2640
tgaatgaagt cttcttggat ttcacccaac taaaaggatt tttaaaaata aataacagtc 2700
ttacctaaat tattaggtaa tgaattgtag ccagttgtta atatcttaat gcagattttt 2760
ttaaaaaaaa cataaaatga tttatctgta ttttaaagga tccaacagat cagtattttt 2820
tcctgtgatg ggttttttga aatttgacac attaaaaggt actccagtat ttcacttttc 2880
tcgatcacta aacatatgca tatattttta aaaatcagta aaagcattac tctaagtgta 2940
gacttaatac catgtgacat ttaatccaga ttgtaaatgc tcatttatgg ttaatgacat 3000
tgaaggtaca tttattgtac caaaccattt tatgagtttt ctgttagctt gctttaaaaa 3060
ttattactgt aagaaatagt tttataaaaa attatatttt tattcagtaa tttaattttg 3120
taaatgccaa atgaaaaacg ttttttgctg ctatggtctt agcctgtaga catgctgcta 3180
gtatcagagg ggcagtagag cttggacaga aagaaaagaa acttggtgtt aggtaattga 3240
ctatgcacta gtatttcaga ctttttaatt ttatatatat atacattttt tttccttctg 3300
caatacattt gaaaacttgt ttgggagact ctgcattttt tattgtggtt tttttgttat 3360
tgttggttta tacaagcatg cgttgcactt cttttttggg agatgtgtgt tgttgatgtt 3420
ctatgttttg ttttgagtgt agcctgactg ttttataatt tgggagttct gcatttgatc 3480
cgcatcccct gtggtttcta agtgtatggt ctcagaactg ttgcatggat cctgtgtttg 3540
caactgggga gacagaaact gtggttgata gccagtcact gccttaagaa catttgatgc 3600
aagatggcca gcactgaact tttgagatat gacggtgtac ttactgcctt gtagcaaaat 3660
aaagatgtgc ccttatttta ccta 3684
<210> 36
<211> 3777
<212> DNA
<213> Mus musculus
<400> 36
gggagtgtcc aaacctcttt gtttgatggc atctgtttac agagttacac tttaatatca 60
acctgtttcc tcctcctcct tctcctcctt ctcctcctcc tcctcggtga cctccttctc 120
ctcccctttc tccggagaaa cttcgccccg gcggtgcgga gcgccgctgc gcagccgggg 180
gaggacgcag gcaaggcgga gggcagcggg aggcggcaac cggtgcggtc cccggggctc 240
ttggcggagc cccggcccgc ctcgccatgg cccggagacc ccgacacagc atctacagta 300
gcgatgaaga tgatgaagac attgagatgt gtgaccatga ctacgatggg ctgctgccca 360
aatctggaaa gcgtcacttg gggaaaacta ggtggacaag ggaagaggat gagaagctga 420
agaagctggt ggaacagaac ggaacagacg actggaaagt cattgccaat tatctgccca 480
accggacaga tgtgcagtgc caacaccggt ggcagaaagt gctgaaccct gaactcatca 540
aaggtccctg gaccaaagaa gaagatcaga gagtcataga gcttgtccag aaatatggtc 600
cgaagcgttg gtctgttatt gccaagcact taaaagggag aattggaaag cagtgtcggg 660
agaggtggca caaccatttg aatccagaag ttaagaaaac ctcctggaca gaagaggagg 720
acagaatcat ttaccaggca cacaagcgtc tggggaacag atgggcagag atcgcaaagc 780
tgctgcccgg acggactgat aatgctatca agaaccactg gaattccacc atgcgtcgca 840
aggtggaaca ggaaggctac ctgcaggagc cttccaaagc cagccagacg ccagtggcca 900
cgagcttcca gaagaacaat catttgatgg ggtttgggca tgcctcacct ccatctcagc 960
tctctccaag tggccagtcc tccgtcaaca gcgaatatcc ctattaccac atcgccgaag 1020
cacaaaacat ctccagtcac gttccctatc ctgtcgcatt gcatgttaat atagtcaacg 1080
tccctcagcc ggctgcggca gccatccaga gacactataa cgacgaagac cctgagaagg 1140
aaaagcgaat aaaggagctg gagttgctcc tgatgtcaac agagaacgag ctgaagggac 1200
agcaggcatt accaacacag aaccacactt gcagctaccc cgggtggcac agcacctcca 1260
ttgtggacca gaccagacct catggggata gtgcacctgt ttcctgtttg ggagaacacc 1320
atgccacccc atctctgcct gcagatcccg gctccctacc tgaagaaagt gcctcaccag 1380
caaggtgcat gatcgtccac cagggcacca ttctggacaa tgttaagaac ctcttagaat 1440
ttgcagaaac actccagttt atagattctg attcttcgtg gtgtgatctc agcagttttg 1500
aattctctga agaagcggca gctttttcac ctagccagca gcccacaggc aaagccttcc 1560
agcttcagca aagagagggc catgggacta gatctgcagg agagcctagc ctgagggtga 1620
ccaggcgagt gctgagcgag gcatccctcg gcccagactc accccaagcg aggcacagca 1680
aggttccgct ggtcgtccta cgaaaaaggc ggggccaggc cagcccccta gccgctggag 1740
agcctagccc ctccctcttt gctgacgtca tcagctcaac tctcaagcgt tcccctgtca 1800
aaagcctacc cttctctccc tcgcagttct tgaacacttc cagcaaccat gaaagctcgg 1860
gcttagatgc acctacctta ccctccactc ctctcattgg tcacaaactg acaccatgtc 1920
gagaccagac tgtgaaaacc cagaaggaaa attccatctt tagaactcca gctatcaaaa 1980
ggtcaatcct cgaaagctct cctcgaactc ccacaccatt caaacatgcc cttgcagctc 2040
aagaaattaa atacggtccc ctgaagatgc tacctcagac cccctcccat gcagtggagg 2100
acctacaaga tgtgattaag caggaatcgg atgaatctgg aattgtggct gagtttcaag 2160
agagtggacc accgttactg aaaaaaatca agcaggaggt ggagtcgcca actgagaaat 2220
cgggaaactt cttctgctca aaccactggg cagagaacag cctgagcacc cagctgttct 2280
cgcaggcgtc tcctgtggca gatgccccaa atattcttac aagctctgtt ttaatgacac 2340
ctgtatcaga agatgaagac aatgtcctca aagcctttac cgtacctaag aacaggcccc 2400
tggtgggtcc cttgcagcca tgcagtggtg cctgggagcc agcatcctgt gggaagacag 2460
aggaccagat gacggcctcc ggtccggctc ggaaatacgt gaacgcgttc tcagctcgaa 2520
ctctggtcat gtgagacatt tccagaaaag cattatggtt ttcagaacac ttaaaagttg 2580
actttcgaca catggctcct cagcgtggag cgctccatgg ctgagagaag agcctgattt 2640
tgttgtggta caacagttga gagcagcacc aagtgcattt ttagttgctt gagatctcac 2700
ttgatttcac acaactaaaa aggatttttt tttttaaaaa taataataat gaataacagt 2760
cttacctaaa ttattaggta atgaattgtg accatttgtt aatatcataa tcagattttt 2820
taaaaaaaat aaaatgattt atttgtattt tagaggatac aacagatcag tatttttgac 2880
tgtggtgaat ttaaaaaaaa aatttacaca aagaaatatc ccagtattcc atgtatctca 2940
gtcactaaac atacacagag agatttttaa aaaccaggag aagcattatt ttgaatgtta 3000
gctaaatccc aagtaatact taatgcaacc ctctaggagc tcatttgtgg ctaataatct 3060
tggaaatatc tttattatac taaaccattt catgaggaga attttgttgt cagcttgctt 3120
gaaaagttat tactgtatga aatagtttta ttgaaaaaat tatattttta ttcagtaatt 3180
taattttgta aatgccaaat ggagaaatgt gttcgctgct atggttttag cctgtagtca 3240
tgctgctagc tagtgtcagg gggcaataga gcttagatgg aaaaaagaga aagagactcg 3300
gtgttagata acggactatg cactagtatt ccagactttt ttatttttat atatatgtac 3360
cttttccttt tgtaattgga aaacttattt gggagaattt tgcatttgtt gtacattttt 3420
gttttttagg attttttttt tttgttgtta ttgtcgattt ataaaagcat tgcacttctt 3480
tttctttttt tgggagattt gtgttgttta tgtcatatgt tttgttttga gttcagcctg 3540
aatgttcatc cgtttgggcg tttttctgac ttggaagaac attctctgta ggtttctaag 3600
tgtacagagc cggaactgcc tcgtggttcc tgggcttcag ggaagacaaa tatggaagtc 3660
aacagccagt ttctgccttg agagcatttg caagaatgct ggccttgaat tctgaaatga 3720
cagtgtatct actgccttgt agcaaaataa agctatcctc ttattttaca tacttcc 3777
<210> 37
<211> 5540
<212> DNA
<213> Homo sapiens
<400> 37
attcgcctca caaacaacca cagaaccaca agtgcggtgc aaactttctc caggaggaca 60
gcaagaagtc tctggttttt aaatggttaa tctccgcagg tcactaccag ccaccgagac 120
caacagagtc atttaaggct gcaagcagta tttacaacag agggtacaag ttctatctga 180
aaaaaaaagg agggactatg gcatcaaaca gcctcttcag cacagtgaca ccatgtcagc 240
aaaacttctt ttgggatccg agcaccagcc ggcgcttcag ccccccctcc agcagcctgc 300
agcccggcaa aatgagcgac gtgagcccgg tggtggctgc gcaacagcag cagcaacagc 360
agcagcagca acagcagcag cagcagcagc aacagcagca gcagcagcag gaggcggcgg 420
cggcggctgc ggcggcggcg gcggctgcgg cggcggcagc tgcagtgccc cggttgcggc 480
cgccccacga caaccgcacc atggtggaga tcatcgccga ccacccggcc gaactcgtcc 540
gcaccgacag ccccaacttc ctgtgctcgg tgctgccctc gcactggcgc tgcaacaaga 600
ccctgcccgt ggccttcaag gtggtagccc tcggagaggt accagatggg actgtggtta 660
ctgtcatggc gggtaacgat gaaaattatt ctgctgagct ccggaatgcc tctgctgtta 720
tgaaaaacca agtagcaagg ttcaacgatc tgagatttgt gggccggagt ggacgaggca 780
agagtttcac cttgaccata accgtcttca caaatcctcc ccaagtagct acctatcaca 840
gagcaattaa agttacagta gatggacctc gggaacccag aaggcacaga cagaagcttg 900
atgactctaa acctagtttg ttctctgacc gcctcagtga tttagggcgc attcctcatc 960
ccagtatgag agtaggtgtc ccgcctcaga acccacggcc ctccctgaac tctgcaccaa 1020
gtccttttaa tccacaagga cagagtcaga ttacagaccc caggcaggca cagtcttccc 1080
cgccgtggtc ctatgaccag tcttacccct cctacctgag ccagatgacg tccccgtcca 1140
tccactctac caccccgctg tcttccacac ggggcactgg gcttcctgcc atcaccgatg 1200
tgcctaggcg catttcagat gatgacactg ccacctctga cttctgcctc tggccttcca 1260
ctctcagtaa gaagagccag gcaggtgctt cagaactggg ccctttttca gaccccaggc 1320
agttcccaag catttcatcc ctcactgaga gccgcttctc caacccacga atgcactatc 1380
cagccacctt tacttacacc ccgccagtca cctcaggcat gtccctcggt atgtccgcca 1440
ccactcacta ccacacctac ctgccaccac cctaccccgg ctcttcccaa agccagagtg 1500
gacccttcca gaccagcagc actccatatc tctactatgg cacttcgtca ggatcctatc 1560
agtttcccat ggtgccgggg ggagaccggt ctccttccag aatgcttccg ccatgcacca 1620
ccacctcgaa tggcagcacg ctattaaatc caaatttgcc taaccagaat gatggtgttg 1680
acgctgatgg aagccacagc agttccccaa ctgttttgaa ttctagtggc agaatggatg 1740
aatctgtttg gcgaccatat tgaaattcct cagcagtggc ccagtggtat ctgggggcca 1800
catcccacac gtatcaatat atacatatat agagagagtg catatatatg tatatcgatt 1860
agctatctac aaagtgccta ttttttagaa gatttttcat tcactcactc agtcatgatc 1920
ttgcagccat aagagggtag atattgagaa gcagaaggct caagagagac aattgcaatc 1980
gagcttcaga ttgtttacta tttaagatgt acttttacaa aggaacaaag aagggaaaag 2040
gtatttttgt ttttgttgtt tggtctgtta tcatcaataa cctgttcata tgccaattca 2100
gagaggtgga ctccaggttc aggagggaga agagcaaagc cgcttcctct ctgtgctttg 2160
aaacttcaca ccctcacggt ggcagctgtg tatggaccag tgccctccgc agacagctca 2220
caaaaccagt tgaggtgcac taaagggaca tgaggtagaa tggatgcttc catcacagta 2280
ccatcattca gaataactct tccaatttct gctttcagac atgctgcagg tcctcatctg 2340
aactgttggg ttcgtttttt tttttttttt tcctgctcca agaaagtgac ttcaaaaata 2400
actgatcagg atagattatt ttattttact ttttaacact ccttctcccc ttttcccact 2460
gaaccaaaaa gaaatcccat ccctaaaacc tgccttctcc ttttatgcaa aactgaaaat 2520
ggcaatacat tattatagcc ataatggtat agatagtgat tgcgtttggc tatgtgttgt 2580
tttctttttt tttaaattat gaatatgtgt aaaatctgag gtaacttgct aacgtgaatg 2640
gtcatataac tttaaagata tatttataat tatttaatga catttggacc cttgaaacat 2700
ttcttagtgt attgatatgt tgacttcggt ctctaaaagt gctctttatt aaataacaaa 2760
tttcttcagt ggtctagagc catatctgaa atattgctaa gcaatttcag ttcatccagg 2820
cacaatgtga ttttaaaaaa tacttccatc tccaaatatt ttagatatag attgtttttg 2880
tgatgtatga aggaaatgtt atgtttagtt ctttcagatc tttgaatgcc tctaacacag 2940
ctttgccttc taaagcggta attagggatt taaaaaacaa cctttagccc tttatcagca 3000
tgaaatgctg gagtgatgtg gttttctaat ttctttgggg taattatgac tcttgtcata 3060
ttaaaaagac aagcacaagt aaatcattga actacagaaa aatgttctgt ggtttcatag 3120
ttaagcaaaa ctctaaatcg ccaggcttca tagcaaagac atagtcagct aaaagccgca 3180
catgtggata gagggttcaa ttatgagaca cctagtacag gagagcaaaa ttgcaccaga 3240
gattcttaac caaccagcct taccaaacaa cacaacaggg gaaccccaat ctgccttacc 3300
caaggcccca ctggcagctt tccacagaat ttgcatttag aggagcagaa tgacatcact 3360
gtcctttggg agtaggtcct ctgaaaaggc agcaggttcc agcaggtagc tgagctgaga 3420
ggacatatgg cccacgggga cctacagaca gcctttgaca tttgtatttc ttacaatgga 3480
gggccaagga gggcaagggg ctgtggagtt tggtgtctac tagtgtgtat gaatttgagc 3540
tagagtcctt ctgtggcatg cactttgacc actcctggca gtcacatggc agatttccaa 3600
gtgcaaatcc ttaatccaaa caaggatcat ctaatgacac caccaggcca atccctgctc 3660
tcctccccga aaagtcaggg tcccttcatt ggaatcctcc acccacccaa gcagaattta 3720
gcagagattt gccttcaaac cctaacggcc cccttgttct ctggtccttc tcaaacccac 3780
ctttgtaggc cacccagcat tgcaggacag cgtgtggggc agctggacct gtgcttcctg 3840
cctgggagtc tcccttggaa ttcatcctga ctccttctaa taaaaatgga tgggaaagca 3900
aaacactttg ccttctaaag gccgtatacc aagtatgctt agataaataa gccacttttc 3960
tattacttaa gtaagaagga agtagtaatt gatactattt attgtttgtg tgtggtagct 4020
tgaagcacac cactgtccat ttatttgtaa gtgtaaaata tgtgtgtttg tttcagcagc 4080
acttaaaaaa gccagtgtct ggttacacat ttcaatttta attaattgac ataaaaatgc 4140
taccgccagt gccagctgca tcctatttaa ttaaaaaggt actatatttg tacattattt 4200
tttaatgtta aaagggcttt tttaagttta cagtacacat accgagtgac tttagggatg 4260
cttttgtgtt gaaatgttac tatagtggct gcaggcagca acccagaaac actttagaag 4320
ctttttttcc ttgggaaaaa ttcaagcact tcttccctcc accctcactc caaccacccc 4380
aatgggggta attcacattt cttagaacaa attctgccct tttttggtct agggattaaa 4440
attttgtttt tctttctttc tttttttttt tttttcactg aacccttaat ttgcactggg 4500
tcatgtgttt gatttgtgat ttcaagacca aagcaaagtc ttactactac tgtggaacca 4560
tgtactagtt cctgggaatt aaaatagcgt ggttctcttt gtagcacaaa cattgctgga 4620
atttgcagtc ttttcaatgc agccacattt ttatccattt cagttgtctc acaaatttta 4680
acccatatca gagttccaga acaggtacca cagctttggt tttagattag tggaataaca 4740
ttcagcccag aactgagaaa ctcaacagat taactatcgt ttgctcttta gacggtctca 4800
ctgcctctca cttgccagag ccctttcaaa atgagcagag aagtccacac cattagggac 4860
catctgtgat aaattcagaa gggaggagat gtgtgtacag ctttaaggat tccctcaatt 4920
ccgaggaaag ggactggccc agaatccagg ttaatacatg gaaacacgaa gcattagcaa 4980
aagtaataat tatacctatg gtatttgaaa gaacaataat aaaagacact tcttccaaac 5040
cttgaatttg ttgtttttag aaaacgaatg catttaaaaa tattttctat gtgagaattt 5100
tttagatgtg tgtttacttc atgtttacaa ataactgttt gctttttaat gcagtacttt 5160
gaaatatatc agccaaaacc ataacttaca ataatttctt aggtattctg aataaaattc 5220
catttctttt ggatatgctt taccattctt aggtttctgt ggaacaaaaa tatttgtagc 5280
attttgtgta aatacaagct ttcattttta ttttttccaa ttgctattgc ccaagaattg 5340
ctttccatgc acatattgta aaaattccgc tttgtgccac aggtcatgat tgtggatgag 5400
tttactctta acttcaaagg gactatttgt attgtatgtt gcaactgtaa attgaattat 5460
ttggcatttt tctcatgatt gtaatattaa tttgaagttt gaatttaatt ttcaataaaa 5520
tggctttttt ggttttgtta 5540
<210> 38
<211> 5740
<212> DNA
<213> Mus musculus
<400> 38
atgcttcatt cgcctcacaa acaaccacag aaccacaagt gcggtgcaaa ctttctccag 60
gaagactgca agaaggctct ggcgtttaaa tggttaatct ctgcaggtca ctaccagcca 120
ccgagaccaa ccgagtcagt gagtgctcta accacagtcc atgcaggaat atttaaggct 180
gcaagcagta tttacaacag agggcacaag ttctatctgg aaaaaaaagg agggactatg 240
gcgtcaaaca gcctcttcag cgcagtgaca ccgtgtcagc aaagcttctt ttgggatccg 300
agcaccagcc ggcgcttcag ccccccctcc agcagcctgc agcccggcaa gatgagcgac 360
gtgagcccgg tggtggctgc gcagcagcag caacagcagc agcagcagca gcaacagcag 420
cagcaacaac agcaacagca acaacagcag cagcagcagc agcagcagga ggcggccgca 480
gcagcagcgg cggcagcggc ggcggcagca gcggcggcgg ccgcagtgcc ccgattgagg 540
ccgccgcacg acaaccgcac catggtggag atcatcgcgg accacccggc cgaactggtc 600
cgcaccgaca gtcccaactt cctgtgctcc gtgctgccct cgcactggcg gtgcaacaag 660
accctgcccg tggccttcaa ggttgtagcc ctcggagagg taccagatgg gactgtggtt 720
accgtcatgg ccgggaatga tgagaactac tccgccgagc tccgaaatgc ctccgctgtt 780
atgaaaaacc aagtagccag gttcaacgat ctgagatttg tgggccggag cggacgaggc 840
aagagtttca ccttgaccat aacagtcttc acaaatcctc cccaagtggc cacttaccac 900
agagctatta aagtgacagt ggacggtccc cgggaaccaa gaaggcacag acagaagctt 960
gatgactcta aacctagttt gttctctgat cgcctcagtg atttagggcg cattcctcat 1020
cccagtatga gagtaggtgt cccgcctcag aacccacggc cctccctgaa ctctgcacca 1080
agtcctttta atccacaagg acagagtcag attacagatc ccaggcaggc acagtcttcc 1140
ccaccgtggt cctatgacca gtcttacccc tcctatctga gccagatgac atccccatcc 1200
atccactcca ccacgccgct gtcttccaca cggggcaccg ggctacctgc catcactgac 1260
gtgcccaggc gtatttcaga tgatgacact gccacctctg acttctgcct ctggccttcc 1320
tctctcagta agaagagcca ggcaggtgct tcagaactgg gccctttttc agaccccagg 1380
cagttcccaa gcatttcatc cctcactgag agccgcttct ccaacccacg aatgcactac 1440
ccagccacct ttacctacac cccgccagtc acgtcaggca tgtccctcgg catgtccgcc 1500
accactcact accacacgta cctgccacca ccctaccccg gctcttccca aagccagagt 1560
ggacccttcc agaccagcag cactccatat ctctactatg gtacttcgtc agcatcctat 1620
cagttcccaa tggtacccgg gggagaccgg tctccttcca ggatggtccc accatgcacc 1680
accacctcga atggcagcac gctattaaat ccaaatttgc ctaaccagaa tgatggtgtt 1740
gacgctgacg gaagccacag cagttcccca actgttttga attctagcgg cagaatggat 1800
gagtctgttt ggcggccata ttgaaattcg tcaaccatgg cccagtggca tgggggccac 1860
atcccgcatg tgttaatata tacatatata aagagagtgc ctatatatgt atattgatta 1920
gctaactaga agatttctca ttcaatccct agtcatgatc ttgcaaccct aagagggtgg 1980
gggcagtcat aactgggttt catattgttt actatttaag atgtcccctt taccaaggaa 2040
caaaccgtca aaggtgttgt ctggtctgtt ttcataagtg acctgttccc acgccggttc 2100
agagaggtgg actctgggtc tgggaggaag gagagacact tcctctctgt gctttgaaac 2160
cacagcctct gctgtgtggc agccggtaca ctctgcagac ccgcttacag agtcagatgt 2220
ggtgcactca gaaagggaca agaggcagag tggctgcttc tgtccgctgc cgtccactct 2280
gccgtccacc tgttccaaag ttttccttca gacttgctgc aggtactcat ttgaactttt 2340
gagttcactt tttttttttc ctattctaag aaagtgactt caaaaatact gatcaggaca 2400
gataatttta ttttaccttt tatattttct cacttccccc atttaaccaa aaagaaatcc 2460
cgttccccct cccccgttcc ttctgcttct ccctttatgc aaactgaaaa tggcaatgcc 2520
ttattattat agccataatg gtatagtgtt tgagttggct gtgtgttatg tgtttttttc 2580
tttttttttc ttttttaaat tatgaatatg tgtaaaatct gaagtaactt gctaacgtga 2640
atggtcatat aactttaaag atatatttat aattatttaa tgacatttgg acatttggaa 2700
catttcttag tgtaatgata tgttgacttc ggtctctaaa agtgtgcttc ttcttcaata 2760
ccaagtttct tcagtgggct agagccatat cggaaatatt gctaagcaat ctcaattcct 2820
tcaggcataa tgtgattttt tttttttttt gaagataact cccatctcca aatagtttag 2880
atgtagtttg ttttcacgat gtatgaagga gatgctctgt ttctttcttt caggcatttg 2940
attgcctctg acacagcttt gccttttaaa gcaataatta gggattaaaa taacaaaaac 3000
aaaacaaaag ccacctatag ccctttaaca cttaacgtgg cccctttact agcatgaaat 3060
gctggagaca tgtggtttcc taatttctcc attttggggg tggtgggagg ggggagggtg 3120
gccattatga ctcttatcat attaaaaagc caagcacaag tgattggttg aactgcagaa 3180
aagtgttctg tggtctctga gttgagcaaa actctaaatt gcaggcttcg tggttgaggg 3240
cctagtcagc tgaaagccac gcgtgtggta aaggctcagg catggcttgg agaacctagg 3300
aacacattag gagcctgcac ctaccagcct caccatacag ccattcaggg gaacccaaaa 3360
agtgccttac ccaaggaggg cccccagcag ctttccagga agtcgaatga agtcgctgtc 3420
ctcggggaac tggtcagctg aagtagcaac cggtagctga tgtcagtaga caacagaacc 3480
tgtggggacc tccaggaaac ctttgacatt ggaggctttc attaggcagg gccaacaaga 3540
gcagggaagg ccatgtaccc attggtatct gccattgtgt gtgagtttga gatccagccc 3600
tccttggagg atgtactgtg atcattcctg gtaccttagg gccaatccct aagtgtggct 3660
tcctaatcca ggccagggat cattcagtga taccaccagg ccaatcccag cattcctcct 3720
gcacaaagtg tttgtgtgtg gggggataga ttggggtggg gccaccttca tttgaatcct 3780
gagtcattct aagagttctg caagcttttg ccttcagcac cctatacccc ctcgctctct 3840
gttccttctc aggttgacct ttgtcccaat gcgggacagt ccagaggcag atggggacct 3900
atgtgtgcct ccaacctgcg ttttcctcag aattcatcct gactccctct gacacagatt 3960
gagggggggg ggaagaaacc caacccgcac caaagcaaaa cactttgcct tctaaaggct 4020
gtgcaccaag tagacgcaga tggtcagccc acctttgtgt ttccttaaga tggaaattgt 4080
aactgatgct atttattgtt tgtgtgtggt agcttgaagc acaccacggt ccatgtgttt 4140
gtctgatacc tatttcagca gcatttacaa aagccagtgt ctggttacac ttttcagttt 4200
tcattaatca acatgaaaat gttaccattg gtgccagctg caccctattt aattttttta 4260
agggcactat atttgtacat ttcgttttta atgttaaagg gcttcttaaa gtttacagta 4320
cagttatcaa gggaatagag gggatgcatt agtgcctaaa tgttattcta gtggctgcag 4380
gcagcaaccc agaagcagtt ttgaaaacag gttgtttccc tctgtcctcc cttatttggg 4440
aaaattcaag tgctttcttc acctttcagg cacctcacgg tgactcccgt tacttagagc 4500
agtctgtcgt cgtcttcttc ttcttcctct tcctcttcct cttcctcttc ctcttcctct 4560
tcctcttcct cttcctcttc ctcttcttct tcttcttctt cttcttcttc ttcttcttct 4620
tcctcctagg gtttaaaatc ccccttcctc ttcccttatc tcttaaactc ttcatttgca 4680
ctgggtcaca cgtatgattt gtggttttaa gaccaaagca atgtcttatt actcttctgg 4740
agccgtttat gtgtactaac caacccttcc ctccacttcc ctgggtttag atgcacacgg 4800
ttctcaaagg agcacaaaca tggccagatt cacagtggga cccacacagc catgttaaaa 4860
aaaaaaacaa aaaaaaacct cttcacttgt ctgagaattt taacctgggc cccaattgct 4920
aacgggcacc atggcttggg tttcaggtta gggaacgttg cccagtgagt aacagaaaga 4980
cttaactgat ttaattagtt tgccctcatc cttcactcca agaccctaag aaaccgatca 5040
gagaaacatc tccacaccat tagaggttga gaagggagga gccatgtggg ggttccctcc 5100
gctcggagga aaggcactga ctgacctagt tagagtggta gcagaagcac ccatggtatc 5160
tgagagagca ataaacaata aaagatgatc ctcccaagct tagaatttgt tgttcttaaa 5220
gaagacgatg catctaaaac aaagaatttt tttttctatg tgggaacttt cttcgttgtc 5280
tgtttacttc atgtttacaa ataattgttt gctttttaat gcagtacttt aaaaaatata 5340
tcagccaaaa ccataactta cagtaatttt tttaggtatt ctgaataaaa ttccatgtct 5400
tttgatatgt ctactgttct taggtttctg tggaacaaca acaacaacaa caacaaaatt 5460
gtagcatttt gtgtaaatac agctttcgtt cttatttttt atttttctga ttgctattgc 5520
ccaagatttg ctttctatgc acgtattgta caaattgtgc tttgtgccac aggtcatgat 5580
cgtggatgag tttactctga acttcaaagg gactatttgt attgtatgtt gcaactgtaa 5640
attgaattat ttggcatttc cccctctcat gattgtaata ttaatttgaa gtttgaattt 5700
aattttcaat aaaaaggctt tttttttcct tttggttttg 5740
<210> 39
<211> 4978
<212> DNA
<213> Homo sapiens
<400> 39
ggtttccgga gctgcggcgg cgcagactgg gagggggagc cgggggttcc gacgtcgcag 60
ccgagggaac aagccccaac cggatcctgg acaggcaccc cggcttggcg ctgtctctcc 120
ccctcggctc ggagaggccc ttcggcctga gggagcctcg ccgcccgtcc ccggcacacg 180
cgcagccccg gcctctcggc ctctgccgga gaaacagttg ggacccctga ttttagcagg 240
atggcccaat ggaatcagct acagcagctt gacacacggt acctggagca gctccatcag 300
ctctacagtg acagcttccc aatggagctg cggcagtttc tggccccttg gattgagagt 360
caagattggg catatgcggc cagcaaagaa tcacatgcca ctttggtgtt tcataatctc 420
ctgggagaga ttgaccagca gtatagccgc ttcctgcaag agtcgaatgt tctctatcag 480
cacaatctac gaagaatcaa gcagtttctt cagagcaggt atcttgagaa gccaatggag 540
attgcccgga ttgtggcccg gtgcctgtgg gaagaatcac gccttctaca gactgcagcc 600
actgcggccc agcaaggggg ccaggccaac caccccacag cagccgtggt gacggagaag 660
cagcagatgc tggagcagca ccttcaggat gtccggaaga gagtgcagga tctagaacag 720
aaaatgaaag tggtagagaa tctccaggat gactttgatt tcaactataa aaccctcaag 780
agtcaaggag acatgcaaga tctgaatgga aacaaccagt cagtgaccag gcagaagatg 840
cagcagctgg aacagatgct cactgcgctg gaccagatgc ggagaagcat cgtgagtgag 900
ctggcggggc ttttgtcagc gatggagtac gtgcagaaaa ctctcacgga cgaggagctg 960
gctgactgga agaggcggca acagattgcc tgcattggag gcccgcccaa catctgccta 1020
gatcggctag aaaactggat aacgtcatta gcagaatctc aacttcagac ccgtcaacaa 1080
attaagaaac tggaggagtt gcagcaaaaa gtttcctaca aaggggaccc cattgtacag 1140
caccggccga tgctggagga gagaatcgtg gagctgttta gaaacttaat gaaaagtgcc 1200
tttgtggtgg agcggcagcc ctgcatgccc atgcatcctg accggcccct cgtcatcaag 1260
accggcgtcc agttcactac taaagtcagg ttgctggtca aattccctga gttgaattat 1320
cagcttaaaa ttaaagtgtg cattgacaaa gactctgggg acgttgcagc tctcagagga 1380
tcccggaaat ttaacattct gggcacaaac acaaaagtga tgaacatgga agaatccaac 1440
aacggcagcc tctctgcaga attcaaacac ttgaccctga gggagcagag atgtgggaat 1500
gggggccgag ccaattgtga tgcttccctg attgtgactg aggagctgca cctgatcacc 1560
tttgagaccg aggtgtatca ccaaggcctc aagattgacc tagagaccca ctccttgcca 1620
gttgtggtga tctccaacat ctgtcagatg ccaaatgcct gggcgtccat cctgtggtac 1680
aacatgctga ccaacaatcc caagaatgta aactttttta ccaagccccc aattggaacc 1740
tgggatcaag tggccgaggt cctgagctgg cagttctcct ccaccaccaa gcgaggactg 1800
agcatcgagc agctgactac actggcagag aaactcttgg gacctggtgt gaattattca 1860
gggtgtcaga tcacatgggc taaattttgc aaagaaaaca tggctggcaa gggcttctcc 1920
ttctgggtct ggctggacaa tatcattgac cttgtgaaaa agtacatcct ggccctttgg 1980
aacgaagggt acatcatggg ctttatcagt aaggagcggg agcgggccat cttgagcact 2040
aagcctccag gcaccttcct gctaagattc agtgaaagca gcaaagaagg aggcgtcact 2100
ttcacttggg tggagaagga catcagcggt aagacccaga tccagtccgt ggaaccatac 2160
acaaagcagc agctgaacaa catgtcattt gctgaaatca tcatgggcta taagatcatg 2220
gatgctacca atatcctggt gtctccactg gtctatctct atcctgacat tcccaaggag 2280
gaggcattcg gaaagtattg tcggccagag agccaggagc atcctgaagc tgacccaggt 2340
agcgctgccc catacctgaa gaccaagttt atctgtgtga caccaacgac ctgcagcaat 2400
accattgacc tgccgatgtc cccccgcact ttagattcat tgatgcagtt tggaaataat 2460
ggtgaaggtg ctgaaccctc agcaggaggg cagtttgagt ccctcacctt tgacatggag 2520
ttgacctcgg agtgcgctac ctcccccatg tgaggagctg agaacggaag ctgcagaaag 2580
atacgactga ggcgcctacc tgcattctgc cacccctcac acagccaaac cccagatcat 2640
ctgaaactac taactttgtg gttccagatt ttttttaatc tcctacttct gctatctttg 2700
agcaatctgg gcacttttaa aaatagagaa atgagtgaat gtgggtgatc tgcttttatc 2760
taaatgcaaa taaggatgtg ttctctgaga cccatgatca ggggatgtgg cggggggtgg 2820
ctagagggag aaaaaggaaa tgtcttgtgt tgttttgttc ccctgccctc ctttctcagc 2880
agctttttgt tattgttgtt gttgttctta gacaagtgcc tcctggtgcc tgcggcatcc 2940
ttctgcctgt ttctgtaagc aaatgccaca ggccacctat agctacatac tcctggcatt 3000
gcacttttta accttgctga catccaaata gaagatagga ctatctaagc cctaggtttc 3060
tttttaaatt aagaaataat aacaattaaa gggcaaaaaa cactgtatca gcatagcctt 3120
tctgtattta agaaacttaa gcagccgggc atggtggctc acgcctgtaa tcccagcact 3180
ttgggaggcc gaggcggatc ataaggtcag gagatcaaga ccatcctggc taacacggtg 3240
aaaccccgtc tctactaaaa gtacaaaaaa ttagctgggt gtggtggtgg gcgcctgtag 3300
tcccagctac tcgggaggct gaggcaggag aatcgcttga acctgagagg cggaggttgc 3360
agtgagccaa aattgcacca ctgcacactg cactccatcc tgggcgacag tctgagactc 3420
tgtctcaaaa aaaaaaaaaa aaaaaagaaa cttcagttaa cagcctcctt ggtgctttaa 3480
gcattcagct tccttcaggc tggtaattta tataatccct gaaacgggct tcaggtcaaa 3540
cccttaagac atctgaagct gcaacctggc ctttggtgtt gaaataggaa ggtttaagga 3600
gaatctaagc attttagact tttttttata aatagactta ttttcctttg taatgtattg 3660
gccttttagt gagtaaggct gggcagaggg tgcttacaac cttgactccc tttctccctg 3720
gacttgatct gctgtttcag aggctaggtt gtttctgtgg gtgccttatc agggctggga 3780
tacttctgat tctggcttcc ttcctgcccc accctcccga ccccagtccc cctgatcctg 3840
ctagaggcat gtctccttgc gtgtctaaag gtccctcatc ctgtttgttt taggaatcct 3900
ggtctcagga cctcatggaa gaagaggggg agagagttac aggttggaca tgatgcacac 3960
tatggggccc cagcgacgtg tctggttgag ctcagggaat atggttctta gccagtttct 4020
tggtgatatc cagtggcact tgtaatggcg tcttcattca gttcatgcag ggcaaaggct 4080
tactgataaa cttgagtctg ccctcgtatg agggtgtata cctggcctcc ctctgaggct 4140
ggtgactcct ccctgctggg gccccacagg tgaggcagaa cagctagagg gcctccccgc 4200
ctgcccgcct tggctggcta gctcgcctct cctgtgcgta tgggaacacc tagcacgtgc 4260
tggatgggct gcctctgact cagaggcatg gccggatttg gcaactcaaa accaccttgc 4320
ctcagctgat cagagtttct gtggaattct gtttgttaaa tcaaattagc tggtctctga 4380
attaaggggg agacgacctt ctctaagatg aacagggttc gccccagtcc tcctgcctgg 4440
agacagttga tgtgtcatgc agagctctta cttctccagc aacactcttc agtacataat 4500
aagcttaact gataaacaga atatttagaa aggtgagact tgggcttacc attgggttta 4560
aatcataggg acctagggcg agggttcagg gcttctctgg agcagatatt gtcaagttca 4620
tggccttagg tagcatgtat ctggtcttaa ctctgattgt agcaaaagtt ctgagaggag 4680
ctgagccctg ttgtggccca ttaaagaaca gggtcctcag gccctgcccg cttcctgtcc 4740
actgccccct ccccatcccc agcccagccg agggaatccc gtgggttgct tacctaccta 4800
taaggtggtt tataagctgc tgtcctggcc actgcattca aattccaatg tgtacttcat 4860
agtgtaaaaa tttatattat tgtgaggttt tttgtctttt tttttttttt ttttttttgg 4920
tatattgctg tatctacttt aacttccaga aataaacgtt atataggaac cgtaaaaa 4978
<210> 40
<211> 4520
<212> DNA
<213> Mus musculus
<400> 40
aattatgcat ggaggcgtgt cttggccagt ggcggctggg tggggattgg ctggaggggc 60
tgtaattcag cggtttccgg agctgcagtg tagacaggga gggggaacct ggggttccga 120
cgtcgcggcg gagggaacga gccctaaccg gatcgctgag gtacaacccc gctcggtgtc 180
gcctgaccgc gtcggctagg agaggccagg cggccctcgg gagcccagca gctcgcgcct 240
ggagtcagcg caggccggcc agtcgggcct cagccccgga gacagtcgag acccctgact 300
gcagcaggat ggctcagtgg aaccagctgc agcagctgga cacacgctac ctggagcagc 360
tgcaccagct gtacagcgac agcttcccca tggagctgcg gcagttcctg gcaccttgga 420
ttgagagtca agactgggca tatgcagcca gcaaagagtc acatgccacg ttggtgtttc 480
ataatctctt gggtgaaatt gaccagcaat atagccgatt cctgcaagag tccaatgtcc 540
tctatcagca caaccttcga agaatcaagc agtttctgca gagcaggtat cttgagaagc 600
caatggaaat tgcccggatc gtggcccgat gcctgtggga agagtctcgc ctcctccaga 660
cggcagccac ggcagcccag caagggggcc aggccaacca cccaacagcc gccgtagtga 720
cagagaagca gcagatgttg gagcagcatc ttcaggatgt ccggaagcga gtgcaggatc 780
tagaacagaa aatgaaggtg gtggagaacc tccaggacga ctttgatttc aactacaaaa 840
ccctcaagag ccaaggagac atgcaggatc tgaatggaaa caaccagtct gtgaccagac 900
agaagatgca gcagctggaa cagatgctca cagccctgga ccagatgcgg agaagcattg 960
tgagtgagct ggcggggctc ttgtcagcaa tggagtacgt gcagaagaca ctgactgatg 1020
aagagctggc tgactggaag aggcggcagc agatcgcgtg catcggaggc cctcccaaca 1080
tctgcctgga ccgtctggaa aactggataa cttcattagc agaatctcaa cttcagaccc 1140
gccaacaaat taagaaactg gaggagctgc agcagaaagt gtcctacaag ggcgacccta 1200
tcgtgcagca ccggcccatg ctggaggaga ggatcgtgga gctgttcaga aacttaatga 1260
agagtgcctt cgtggtggag cggcagccct gcatgcccat gcacccggac cggcccttag 1320
tcatcaagac tggtgtccag tttaccacga aagtcaggtt gctggtcaaa tttcctgagt 1380
tgaattatca gcttaaaatt aaagtgtgca ttgataaaga ctctggggat gttgctgccc 1440
tcagagggtc tcggaaattt aacattctgg gcacgaacac aaaagtgatg aacatggagg 1500
agtctaacaa cggcagcctg tctgcagagt tcaagcacct gacccttagg gagcagagat 1560
gtgggaatgg aggccgtgcc aattgtgatg cctccttgat cgtgactgag gagctgcacc 1620
tgatcacctt cgagactgag gtgtaccacc aaggcctcaa gattgaccta gagacccact 1680
ccttgccagt tgtggtgatc tccaacatct gtcagatgcc aaatgcttgg gcatcaatcc 1740
tgtggtataa catgctgacc aataacccca agaacgtgaa cttcttcact aagccgccaa 1800
ttggaacctg ggaccaagtg gccgaggtgc tcagctggca gttctcgtcc accaccaagc 1860
gggggctgag catcgagcag ctgacaacgc tggctgagaa gctcctaggg cctggtgtga 1920
actactcagg gtgtcagatc acatgggcta aattctgcaa agaaaacatg gctggcaagg 1980
gcttctcctt ctgggtctgg ctagacaata tcatcgacct tgtgaaaaag tatatcttgg 2040
ccctttggaa tgaagggtac atcatgggtt tcatcagcaa ggagcgggag cgggccatcc 2100
taagcacaaa gcccccgggc accttcctac tgcgcttcag cgagagcagc aaagaaggag 2160
gggtcacttt cacttgggtg gaaaaggaca tcagtggcaa gacccagatc cagtctgtag 2220
agccatacac caagcagcag ctgaacaaca tgtcatttgc tgaaatcatc atgggctata 2280
agatcatgga tgcgaccaac atcctggtgt ctccacttgt ctacctctac cccgacattc 2340
ccaaggagga ggcatttgga aagtactgta ggcccgagag ccaggagcac cccgaagccg 2400
acccaggtag tgctgccccg tacctgaaga ccaagttcat ctgtgtgaca ccaacgacct 2460
gcagcaatac cattgacctg ccgatgtccc cccgcacttt agattcattg atgcagtttg 2520
gaaataacgg tgaaggtgct gagccctcag caggagggca gtttgagtcg ctcacgtttg 2580
acatggatct gacctcggag tgtgctacct cccccatgtg aggagctgaa accagaagct 2640
gcagagacgt gacttgagac acctgccccg tgctccaccc ctaagcagcc gaaccccata 2700
tcgtctgaaa ctcctaactt tgtggttcca gatttttttt tttaatttcc tacttctgct 2760
atctttgggc aatctgggca ctttttaaaa tagagaaatg agtgagtgtg ggtgataaac 2820
tgttatgtaa agaggagagc acctctgagt ctggggatgg ggctgagagc agaagggagc 2880
aaggggaaca cctcctgtcc tgcccgcctg ccctcctttt tcagcagctc ggggttggtt 2940
gttagacaag tgcctcctgg tgcccatggc atcctgttgc cccactctgt gagctgatac 3000
cccaggctgg gaactcctgg ctctgcactt tcaaccttgc taatatccac atagaagcta 3060
ggactaagcc cagaggttcc tctttaaatt aaaaaaaaaa aaaataagaa ttaaagggca 3120
aaacacactg acacagcata gcctttccat atcaaggaat actcagttaa cagcctctcc 3180
agcgctgtct tcaggctgat catctatata aaccctggaa tggttgcaga tcaaatctgt 3240
aaaagagatc cgagagctgt ggcttggcct ctggttcaaa cacaaaggct agagagaacc 3300
tagatatccc tgggttttgt ttacccagta tgcttgtcgg ttggaggtgt gaggtaggcc 3360
aagggcactg gaaagccttt gtcatcaccc tactccctcc ccaacccaga ctccagaccc 3420
tgtttcaggg tcagcctgcc ctgtgggtgc cttactgggc ctagggtcaa cctgccttcc 3480
tttcccactt gaccttgctg gtagtatgtc cccttcccat gtccaaaggc cctctgtcct 3540
gcttctattg ggaatccctg cctcaggacc ttgtgtcgag agggattgcc ttacaggttt 3600
gaacctgcct cagactacag gccctcagca aagctcaggg agtatggtcc ttattctatg 3660
cgcttggttc ccagggatat ctgtaaccac agggcaaaag ctgacatata ctccaggtct 3720
gccctcatat gagtggtgta ttcttggcct cccctgagac tggcaactgt ctgctcccca 3780
ttgggtctcc caggtgaggt ggaacacagt tcctgcacct actgtggcct ccatgtcgct 3840
tgcttgcttc gctcactcag cttactggaa cactgagtgt tcaaggcaag cctttcctga 3900
cagaggcatg gctagattca gtgactcaaa gccacctcat tcagctgatc agtgtctgtg 3960
gaattgtttc cttccagtta accagtgtct gaattaaggg cagtgaggac attgtctcca 4020
agacgaactg cttgccttga ccaccccagc cttctgcttc gagacagtta ctgctctccc 4080
accccatcaa tgttctttag ttatacaata agctgaactt ataaactgaa agggtattta 4140
ggaaggcaag gcttgggcat ttttatggct ttcaatcctg gggacccagg aacaaggtga 4200
gggcttctct ggggctggtg ttgtacctca ggggctctgg gaagtctgtg tgcctgggtt 4260
aaccacccat agtgagcccc tggaactgcc cactttccct ctccttggcc ccacttggcc 4320
ccagcctcac ccagcctgca gactgcttag cctttcagtg cagtggcttg tgttctggcc 4380
actgcactca gattccaatg taaactttct agtgtaaaaa tttatattat tgtgggttgt 4440
tttttgttgt tgtttgtttt tgtatattgc tgtaactact ttaacttcca gaaataaaga 4500
ttatatagga actgtctggc 4520
<210> 41
<211> 8232
<212> DNA
<213> Homo sapiens
<400> 41
gatgtctaca gtatcacctt tcttgtagat tggcacttat gcggccaaag gaacaacacc 60
atgttttcta aaaggctgga gaaaatacca caggtgcctc tcctctttcc cttcatcttc 120
atcattttga caaattactc aaagatggag ggtgcagttg aaagccagcc atcatttttt 180
aaaacttctc aggacattgt aacatgcact tgggttgaga actgctactc gagcttctcc 240
aggaggccct tggagcaaat gttttgtaaa caccaatcta agaacattat ctcttggacg 300
ggcatggtgg ctcacacctg taatcccagc actttgggag gccaaggttt gtgtgatttt 360
gctaaaatgc atcaccaaca gcgaatggct gccttaggga cggacaaaga gctgagtgat 420
ttactggatt tcagtgcgat gttttcacct cctgtgagca gtgggaaaaa tggaccaact 480
tctttggcaa gtggacattt tactggctca aatgtagaag acagaagtag ctcagggtcc 540
tgggggaatg gaggacatcc aagcccgtcc aggaactatg gagatgggac tccctatgac 600
cacatgacca gcagggacct tgggtcacat gacaatctct ctccaccttt tgtcaattcc 660
agaatacaaa gtaaaacaga aaggggctca tactcatctt atgggagaga atcaaactta 720
cagggttgcc accagcagag tctccttgga ggtgacatgg atatgggcaa cccaggaacc 780
ctttcgccca ccaaacctgg ttcccagtac tatcagtatt ctagcaataa tccccgaagg 840
aggcctcttc acagtagtgc catggaggta cagacaaaga aagttcgaaa agttcctcca 900
ggtttgccat cttcagtcta tgctccatca gcaagcactg ccgactacaa tagggactcg 960
ccaggctatc cttcctccaa accagcaacc agcactttcc ctagctcctt cttcatgcaa 1020
gatggccatc acagcagtga cccttggagc tcctccagtg ggatgaatca gcctggctat 1080
gcaggaatgt tgggcaactc ttctcatatt ccacagtcca gcagctactg tagcctgcat 1140
ccacatgaac gtttgagcta tccatcacac tcctcagcag acatcaattc cagtcttcct 1200
ccgatgtcca ctttccatcg tagtggtaca aaccattaca gcacctcttc ctgtacgcct 1260
cctgccaacg ggacagacag tataatggca aatagaggaa gcggggcagc cggcagctcc 1320
cagactggag atgctctggg gaaagcactt gcttcgatct attctccaga tcacactaac 1380
aacagctttt catcaaaccc ttcaactcct gttggctctc ctccatctct ctcagcaggc 1440
acagctgttt ggtctagaaa tggaggacag gcctcatcgt ctcctaatta tgaaggaccc 1500
ttacactctt tgcaaagccg aattgaagat cgtttagaaa gactggatga tgctattcat 1560
gttctccgga accatgcagt gggcccatcc acagctatgc ctggtggtca tggggacatg 1620
catggaatca ttggaccttc tcataatgga gccatgggtg gtctgggctc agggtatgga 1680
accggccttc tttcagccaa cagacattca ctcatggtgg ggacccatcg tgaagatggc 1740
gtggccctga gaggcagcca ttctcttctg ccaaaccagg ttccggttcc acagcttcct 1800
gtccagtctg cgacttcccc tgacctgaac ccaccccagg acccttacag aggcatgcca 1860
ccaggactac aggggcagag tgtctcctct ggcagctctg agatcaaatc cgatgacgag 1920
ggtgatgaga acctgcaaga cacgaaatct tcggaggaca agaaattaga tgacgacaag 1980
aaggatatca aatcaattac taggtcaaga tctagcaata atgacgatga ggacctgaca 2040
ccagagcaga aggcagagcg tgagaaggag cggaggatgg ccaacaatgc ccgagagcgt 2100
ctgcgggtcc gtgacatcaa cgaggctttc aaagagctcg gccgcatggt gcagctccac 2160
ctcaagagtg acaagcccca gaccaagctc ctgatcctcc accaggcggt ggccgtcatc 2220
ctcagtctgg agcagcaagt ccgagaaagg aatctgaatc cgaaagctgc gtgtctgaaa 2280
agaagggagg aagagaaggt gtcctcagag cctccccctc tctccttggc cggcccacac 2340
cctggaatgg gagacgcatc gaatcacatg ggacagatgt aaaagggtcc aagttgccac 2400
attgcttcat taaaacaaga gaccacttcc ttaacagctg tattatctta aacccacata 2460
aacacttctc cttaaccccc atttttgtaa tataagacaa gtctgagtag ttatgaatcg 2520
cagacgcaag aggtttcagc attcccaatt atcaaaaaac agaaaaacaa aaaaaagaaa 2580
gaaaaaagtg caacttgagg gacgactttc tttaacatat cattcagaat gtgcaaagca 2640
gtatgtacag gctgagacac agcccagaga ctgaacggca atctttccac actgtggaac 2700
aatgcatttg tgcctaaact tcttttggaa aaaaaaaata taattaattt gtaagtctga 2760
aaaaaaaata tttaatttaa aaaaaattgt aaacttgcaa taatgaaaaa gtgtacttct 2820
gaagaaaact acatgaacgt ttttgttggt attcaagtca gctagtgttt ataattactg 2880
gatattgaat taggggaagc tcggctgccc tagtaacaaa accagcaaac gtcctgatga 2940
caacgaagtg atgacattag ccattcctta gggtaggagg aacagatgga tcttatagac 3000
ctatgacaaa tatatatata aatatatata taaatatata ttaaaaattt agtgactatg 3060
gtaagctttt gttcatttgt ttcagacttt tttctcctgt aaaaaaatag tactgattaa 3120
cttttttaaa agaaagattt tactgtaaat atggattttt ttttttttgg tcttatttct 3180
gtccctttcc ctggtttgtt atcgtaacct gtagtgccaa ctctgcttcc agaggggtag 3240
tgcaggatga aatgctgacc ctgatgttgc ttctcattca taaataagta gaaagttgtt 3300
tctccagtct tttgggaaca caggacttaa aagtcacatc atgtgtagat attacaagca 3360
gcattaccaa gacatggcaa aaagagtttg tctgaattgt aatgttgcgt ttgtgaacct 3420
attctgggat tttcagaggt acaaggttag aatgctacaa tgttaccact gtgccttcca 3480
atgtttatat catcggaaac ataacataat caaagtggct gtgatttaac aaaatgatta 3540
aagtgttacc tacctgtgta gccgaagtag tgtgcagtga ggcgtttctg aatacatggt 3600
cagatttttg gaaaaaaaca aaaacaaaaa aaacaagtaa agttcaaaaa ccgtcaaatg 3660
agaaaattgc aagtagtgtg acagagctga ttgattttgt tgctttcttg attttttttt 3720
tcaaaatggg tttactaaaa tgtagatgac ttaactgcct cctccttcgt ctgaaaaatg 3780
ccaatattca atcatcatgc agcattataa caagccttat aagtcctaaa gcattaagtt 3840
gcactttttt gaggaggggt agtgcagtat ttctctggcc agtatgaatg aagtttatac 3900
ttaccatatt tgatagaaac atagatcaag ctatggcaca gcgactcatc agatagctag 3960
ctttgacgtc tgggcacaat tgaaccaact tccatcgtga atctttataa tgattgactt 4020
tggtgtatag tgcagtaaac aaatagtgct cctagttaag tatttgtcag catccttttg 4080
tctctaactt gtttctattt ttacagccac acaattcttg gcatgtatta agaaaaaaaa 4140
aaatccctgt tcaagtagtt tttccaccta tcagcactga gtaaatgcca taaatccatt 4200
gaaatggtct aaatgttcca tctgttctcc tgttttgcca gttatatagt aatgaaatac 4260
atttgtaaat tttatgcaac aaatggcaaa cgtatcatta ttttgaaatt gtgtatgtaa 4320
aagttatatt tttacatgta gactcttgtt attatgtgtt ttaatacatt gtatcagttt 4380
ttgttttttt ttaaaaactg tggtttaaaa agaagtctca tttaaatgaa atagctacaa 4440
gaatcagaat tttatgttca tttctgaaaa tgtaagaaca aataagatag ttaccacgtg 4500
gtcatctttt acaaacccat aaacattttg attagctgtg tgtgtgttga aaaactgtaa 4560
atatgttcag tagcgataaa actaaaataa ctttgatttg ttgataagtt cctaaaatgt 4620
ggaggtggat taaaacctta ggagaatagc agaaatcaaa cttcatgaaa agttattttg 4680
gggctttcct gtgaaatgta tgaacaaaga ggctcagaga aggacatgga agacaataat 4740
gtatactctc tcctcctccc tgaataatga aaaccatgtg tatttgttcc ctccgtatgt 4800
taaagatttc cttttagtgg tacattctgc actcattttg tatagtctac caaggcgggt 4860
atccctagga acaatattat ataggaagca ggtatactct gatcacattc aggataagtg 4920
tacagaagaa aatacggtgt ttactcttta gggaactgga aacactccct gcattgatgt 4980
acattttaag aatggcactt ttgatacatg ttatcataaa ggtgcttaat agagctgaat 5040
taaagttttt caaatctgta aacaaagcaa aaaagtaaat tgtagtcatt tgattatttt 5100
ttaaattggt gctttatatt ttgttctcac tcagagtaaa agctgcaatt tattgttcac 5160
cagctttgat gtattcatta ctcagtaatg caatacctct attgttgaat tccctttgga 5220
aataagtgaa aattctaacg gccactgaaa gctgctcgct aggttttgct tggtggagaa 5280
acataatctg cacctatcca tattaattgg gttgtatccc cattaaaaaa gaaaaaaagg 5340
gaatgtggcc tttttagtgt gttttttatt gttgttgttt tgtaattatc aaacccaggt 5400
aagatattgg tatcctgcac tggattttca aatgaagttc agcagaagac agttaagatt 5460
aaagtactat acaaaaattt caaaagggtc catactacgc tatctgtatg acgacactta 5520
ggctggggat ctctttcaga aactcggact ttaaaagcaa cttggagcag ttgatccacc 5580
tccacattca agtaatttat gaatatgcag aatagggatc tgttcatcta gaaattttta 5640
ccatttgtct tctgtgtagc tgcaaggaac actaatgttt atacaactgt cagtccaccc 5700
agtggtgcaa ctggttctga ttcagtcttc cgattccttt ttatttttca ctttttccta 5760
tttctgaatt ttttttttta tttgtgatct tgattttgat gaggggttgg ggagtgggga 5820
gggagtcgaa ccaagacttg gagttaagag gattttcatc ttttgcatcc aacaggcaga 5880
atatgatctg tgtccaaaag tgaacttgag tcaggaatga atcaatttca gcataaacaa 5940
gcacaaaaat ttagtctgct ggctgactgg aagcaaaaaa gtcaagatgg aatatgatga 6000
attccaacac aatggggcac caaggccttt aggcctctct ttttattttg ctttggtttt 6060
gtttgttttt ctttagagac atgctctttc tcatgggact tgaagtggac tcatctttgt 6120
gcagtgctgg ttttgccata ctcatttcaa gtattataga catatgtaat ggtgaaaata 6180
tatgaactgt ggcctttttc attcttgtta cttgtgatgc aattaagtga agataagaaa 6240
aaaaaaaaaa aagcagagat ttaccatgta tcagtgcctg gctttttgtt ataaagcttt 6300
gtttgtctag tgctcttttg ctataaaata gactgtagta caccctagta ggaaaaaaaa 6360
aaaactaaat ttaaaaataa aaaatatatt tggcttattt ttcgcaggag caatcctttt 6420
ataccatgaa tattacaaaa aaattgtcag attctgaata tttcttcttt gtagattttt 6480
ggaatcatta tgagtaaaag tttgttactt tattttacta tttaaaagat gttattttac 6540
catgtgttac caagatgaaa ctgtatgggt agcttttttg tttgtttttt gttttgtttt 6600
tgtttttgtt tttgttttta gttgtaggtc gcagcgggga aattttttgc gactgtacac 6660
atagctgcag cattaaaaac ttaaaaaaat tgttaaaaaa aaaaaaaggg aaaacatttc 6720
aaaaaaaaaa aaaaagataa acagttacac cttgttttca atgtgtggct gagtgcctcg 6780
attttttcat gtttttggtg tatttctgat ttgtagaagt gtccaaacag gttgtgtgct 6840
ggagttcctt caagacaaaa acaaacccag cttggtcaag gccattacct gtttcccatc 6900
tgtagttatt cgatgaagtc atgtacatga ccgttctgta gcaataaatg tgccattttt 6960
ataaactgtt tctgacactt gtttcatttc attttgcatt gtccatatag ctatgattct 7020
cttctgtaag taaaacgcat ctatatttca ttttccaagt gttggaggta ttgacagctt 7080
aacaaacaaa acatacaaaa aaaatcacaa aaacaaattg aaaagcaaag cacatgattg 7140
atcaaggaag agatgccctt aatgaaaatg gaacgggatg catgcaaaac aaaaagaaaa 7200
ctgtctagag gattaactaa ttgaaggaat ataattaatg tgtgtgtaac actgaagcta 7260
tgcatttgaa gagctctgaa ctgcaccagt gttttcggtt gtgctgcagg ttgctaagtc 7320
aagtcagcct taaccttttg caccagttgg tcggctgttt ggcagaacat tctcagatct 7380
tttcagtcaa aaatctaaga tgatttattt tgtatcactt tgttaaaagc tgaatattgt 7440
taactacagt taatattaac actgtattta tactttctca aactacatcc gccccaccac 7500
ttctggttgc ctctgttgac tattaatcca gatgtaaaca accagatgtt tttttctaac 7560
ttgtacaaac tgacgtgtgt caactatcat ggaaggaaaa aaatgtacag attaaaatta 7620
ttcagtgtta tgtactgtaa gttaatattt ttgtagaatg gacatcaatc tactttgcaa 7680
aatttggagg ctatttcaac attgcactgt agaaatgtaa agtaatgtat gcaatgtaaa 7740
ggaaagcccg cggtagctga gcgcttcata acagaatgtt ctaatcaagt acgtggtatt 7800
tggggatgtc tccaatattg ctcttgtatt ctttctaatt gggtttagtg actagttgaa 7860
ggaaaatgtt ataacgccat ttggttcaca tgtgaagtgc cctccatagc caaatgttgg 7920
gatttttttt tttttcgttt ttggttggac tgtttgcaga tatttaaatt ttatgaaatt 7980
tccaaagatt ttggttgata accccctttt accttctaaa tgatttgaga tgttcttatg 8040
ttcttactgt gtgttttaaa tatatataaa agagccacaa gcatttagtc ttttagtatt 8100
atatttgatc atataactac tactgaaaag gggtgggggg gaatgtgcct gtgcacccct 8160
acagtatctt gtgtagtgtc tattaacatt gttctctttt agaggaccac attaaaaggt 8220
acattaatct ta 8232
<210> 42
<211> 7462
<212> DNA
<213> Mus musculus
<400> 42
ggagcagccg cggccgcagc gccttctctt tataagccgc agtgcccgga tgtgaatgga 60
ttacaatgta tctttcaggg aaacctatta ttatcaatgt gactcctcgg gggagtcaat 120
gatggtgttg gggaggagga tgatgatgag acgcctctaa acttggaaca agtttaggac 180
tttgaaagag aagagaaaaa aaaatacaac caacaagacc gaagaacaat tataactatc 240
cagtgttgat tatttttata aacaatacga aaaagttgtc ggattttttt ttttaatgat 300
tactttttgg ggggagggaa ttttgttaca gtttgatgat ggaaaatgca aaaaccgagc 360
caggtgcata atcttgtaat ctgtggctaa ccctggaaca ggactgactt ctatttaaaa 420
tactcttttg ggggaacact catgtgagac actaagttct tgcagaagat ttttgtctct 480
ctttttaaag tctctttcct tggaatattg tgagcatatt tgtggccatt gaaggtttgt 540
gtgattttgc taaaatgcat caccaacagc gaatggctgc cttagggacg gacaaagagc 600
tgagtgattt actggatttc agtgcgatgt tttcgcctcc tgtaagcagt gggaaaaatg 660
gaccaacttc tttggcgagt ggacatttca ctggctcaaa tgtagaagac agaagtagct 720
cagggtcctg gggaactgga ggccatccaa gcccgtccag gaactatgga gatgggactc 780
cctatgacca catgactagc agggatcttg ggtcacatga caatctctct ccaccttttg 840
tcaattccag aatacaaagt aaaacagaaa ggggctcata ctcatcttat gggagagaaa 900
acgttcaggg ttgccaccag cagagtctcc tcggagggga catggatatg ggcaatccag 960
gaaccctttc gcccaccaaa cctggctccc agtactatca gtattcaagc aataatgccc 1020
gccggaggcc tcttcacagt agtgccatgg aggtacagac aaagaaagtc cgaaaagttc 1080
ctccgggttt gccgtcttca gtctacgctc cttcagccag cactgccgac tacaacaggg 1140
actcgccagg ctatccttcc tccaagccag cagccagcac tttccctagc tccttcttca 1200
tgcaagatgg ccatcacagc agcgaccctt ggagctcctc cagcgggatg aatcagcccg 1260
gctacggagg gatgctgggc aattcttctc atatcccaca gtccagcagc tactgtagcc 1320
tgcatccaca tgaacgtttg agctatccat cccactcctc ggcagacatc aactccagtc 1380
ttcctccgat gtccacgttc catcgtagtg gcacaaacca ttacagcacc tcttcctgca 1440
caccccctgc caacggaaca gacagtataa tggcaaacag aggaactggg gcagcaggca 1500
gctcgcagac tggagacgct ctagggaaag ccctagcttc gatctattct cctgaccaca 1560
cgaacaacag cttttcctcc aatccttcaa ctcctgtggg ctcccctcct tcactctcag 1620
caggcacagc tgtttggtct agaaatggag gacaggcctc gtcatctccc aattatgaag 1680
gacccttgca ctcactgcaa agccgaatcg aagaccgttt ggaaagactg gacgatgcga 1740
ttcatgttct ccggaaccac gcagtgggcc cgtccacagc tgtgcctggt ggccatgggg 1800
acatgcatgg gatcatggga ccctcccaca acggagcgat gggtagcctg ggctcagggt 1860
acggaactag tcttctctca gccaacagac actcgctcat ggttggggcc caccgtgaag 1920
atggcgtggc tctgagaggc agccattctc tcctgccaaa ccaggttccg gtcccacaac 1980
ttccggtcca gtctgcaact tcccctgact tgaacccacc ccaagaccct tacagaggga 2040
tgccaccagg cctccagggc cagagcgtgt cttctggtag ctctgagatc aaatccgacg 2100
acgagggcga tgagaacctg caagacacaa aatcttctga ggacaagaaa ttagatgacg 2160
acaagaagga tatcaaatca attactaggt caagatctag caataacgat gatgaggacc 2220
tgaccccaga gcagaaggct gagcgcgaga aggaacggag gatggccaat aatgcccgtg 2280
agcgcctgag ggtccgagat atcaacgagg ctttcaagga gcttggccgt atggtgcagc 2340
tccacctgaa gagcgacaag ccccagacca agctcctgat tctccaccag gccgtggctg 2400
tcatcctcag cctggagcag caagttcgag aaaggaatct gaacccgaaa gctgcctgtc 2460
tgaaaagaag ggaggaagag aaggtgtcct cagagcctcc cccactctcc ttggctggcc 2520
cacaccctgg gatgggagac gcagcgaatc acatgggaca gatgtgaaaa ggtccaagtt 2580
gctaccttgc ttcattaaac aagagaccac ttccttaaca gctgtattac cctaaaccca 2640
cataaacact gctccttaac cccgtttttt tttgtaatat aagacaagtc tgagtagtta 2700
tgaatcgcag acgcaagagg tttcagcatt cccaattatc aaaaaacaga aaaacaaaca 2760
aaaaaatgaa tgaaagaaag aaagaaagaa aaaaatgcaa cttgagggac gacttcttta 2820
acatatcact ctgaatgtgc gaagcggtat gtacaggctg agacacagcc cagagactga 2880
atggcaatcc tcccacactg tggagcaatg catttgtgcc taaacttctt ttggaaaaaa 2940
aaaatataat taatttgtaa gtctgaaaaa aatatttaat ttaaaaaaaa attgtaaact 3000
tgcaataatg aaaaagtgta cttctgaaga aaacgacatg aacgtttttg ttggtattca 3060
cgtcagctag tgtttctaat taccggatat tgaatagggg aagcccggct gccctcgtaa 3120
caaaaccagc aaacgtcctg atggcaacga agtgatgaca ttagccattc cttagggtag 3180
gagggacaga tggatgttat agacctatga caaatatata tataaatata tatataaata 3240
tatattaaaa atttagtgac tatggtaagc ttttgttgat ttgtttcaga cttttttctc 3300
ctgtaaaaaa atagtactga ttaacttttt taaaagaaag attttactgt aaatatggat 3360
tttttttttt gtctgatttt tgtcccttcc cccggtttgt tatcgtaacc tgtagtgcca 3420
actctgcttc cggaggggca gtgcaggacg aaatgctgac cctgaagttg cttctcattc 3480
acaaatagta aaaagttgtt tctccagtct tttgggaaca caggacttaa aagtcacatc 3540
atgtgtagga attacatgca gcattgcccg ggcgaggcaa aaagcgtttg tctggcttgt 3600
ggcgctgccc ttgttaccct cccctgggat tttcagaggt acacggttag aatgctacaa 3660
tgttaccact gtgccttcca atgtttatat catcggaaac ataacataat caaagtggct 3720
gtgatttaac aaaaaaaacg attcaagtgt tacctacctg tgtagccgaa gtagtgtgca 3780
gtgaccgaga cgtttctgaa tacatggtca gatttttttt ggaaaaaata caaaaattaa 3840
aaaaaaaaaa aaaaaagaaa aaaagaaaaa aaaactaaaa aagaaagtca agttcaaaaa 3900
ccgtcaaatg agaaaattgc aaggagtgtg acagagctga ttgatttttg ttgctttctt 3960
gatttttttt tcaaaatggg tttactaaaa agtagatgac ttacctgcct cctccttcgt 4020
ctgaaaaaaa aaaaaaatgc caaccaatca tgcagcatta taacaagcct tataagccct 4080
aaagcattaa gttgcacttt tgtgaggagg ggtaacgcag tattctctct ggccagtatg 4140
agtgaagttt atacttaaca tttgatagaa acatagatca aactacggca cagcaactca 4200
tcagatagct agcgttgact ctgggcacaa ttgaaccaat tcccatcgta agtctttcca 4260
acaatggact ttggtgtgta gtgcagtgaa cacataggac tcctacgtaa gcatttgtca 4320
gcatcctttt gtctctaact cggttctgtt ttgacagcca cacaatcttg gcatgtatta 4380
aggaaaaaaa aaatccctgt tgaagtagtt tttccaccta tcagcactga gtaaatgcca 4440
taactccgcg gaaatggtct aaatacccca tttgttgtcc tgaactacca gttacatagt 4500
gacgaaacac atctgtaaat tttatgcaac caatggcaaa cctatcatta ttttgaaact 4560
gtgtatgtaa aagttatatt tttacatgta gactcttgtt attatgtgtt ttaatacatt 4620
gtatcagttt tttgtttttt tttaaactgt gtggttttaa aaagtcattt aaatgaaata 4680
gtgagctaca agaatctgaa atttatgttc atttctgaaa atgtaagaac aaataagata 4740
gttaccacgt ggtcaccttt tacaaaccca tgaacatttt gattagctgt gtgcatgtgt 4800
gtgcgtgtgt gctcttgcgc gtgtgtgtgt gtgtgtgtgt gtgtgtatgt gtgtgtgttg 4860
aaaattgtaa atatgttcag tagcgataaa actaaaatgc tttgatttgt tgagaagttc 4920
ctaaaatgtg gaggtggatt gaaaatgtag gggaatagca ggaatcaaat ctcataaaaa 4980
gttcttcggg gactttgctg tgatgcggtg gcacaaaggt gctccaagaa gggcaaagaa 5040
gaaagacagt aacttcccct cctccctgaa cgatggaaaa catgtgtacg tggtctctca 5100
ccatgttaaa gattttcttt ccgtgataca ttctgcactc attttgtata gtctgccaag 5160
gcgggtatcc ctaggaacaa tattattata taggaaacag gtatcgtccg atcacattca 5220
ggagaagcgt atagaaaaga atatggtgtt tactctttag ggaactggaa atcctccccg 5280
cattgatgga tatcttcaga gtggcacttt tgatacatgt tatcataaag gtgcttacta 5340
aagcagaatc aaagtttttc aactctgtaa acaaagcaaa aaattaaatt tttaaattaa 5400
atcatttgag attttttttt tcaattggtg cttttatatt ttgttctcac tcggacagag 5460
aaaaagctgc aatttcatgt tctcaccagc tttgatgtat tcattacttg gtaatgtaat 5520
atggctattg tcaaattcct tttggaaata agcaaaagac tccccaaagg ccagcagcag 5580
ctgctggcta ctttctgctt ggtgcggaaa cctgatctga ccctctttgt agtaatcagg 5640
tgtatctcca gttttaaaaa gaaggagaaa ggaaatgtgg ccgttttaac gtgttggttt 5700
tgttttgttt tgttttgttt tgttttcctt gttgttattt tgtaattatc aaacccaggt 5760
aagatattgg tattcctgca ctggattttt gaaagaaact tagcagaagt caggattaaa 5820
atactacaca aacatttcat aagtgttcat cctatactag acatacacga aggcggtgag 5880
gcttaggtgc aggatcggtt taagagactt tgaaagcaac ttggaacagt tgatccacct 5940
ccacattaaa gtaaattatg aatatgcaga attagggatc tgtccatctt ggagttgtta 6000
ctctttttgt cttctgtatg gcagtgatga acactaatgc tttgacagct ttcagcccac 6060
ccagtggtcc aactgattcc aattcagtct tccgattcct ggttttgttt tgtctttcca 6120
cttttttttt cctatcttga ttttattgtt attgttattg ttattattat tattattatt 6180
attattaata ttcatgatgt ttgttttgat gagggattgg gaagtgggag ggagtcgaac 6240
tgagactagg ggctgagagg attttttttt ttccatcttt gcatccaaca ggcagaatat 6300
ggtctgtgtc caaaacggaa cttaagtcag gaaggaaacc attcagcata aacaagcaca 6360
acatgtagtc tgccggctga ctggaagcat aaataaataa ataaataaca catacggagg 6420
tgaagatgga atgtgctgga ttccaagaca atggggcacc aaggcctgag ggcctcctct 6480
tgactttgct ttggttatgt ttgttttctt tagagatgtc ttttctcatg ggacttgaag 6540
tgactcatct ctgtgcagta ctggtttcgc catatgctca tttcaagtat tatagacata 6600
tgtaatggtg aaatatatga actgtggcct ttttcattct tgttacttgt gatgcaatta 6660
agtgaagata agaaaaaaaa aaagcagaga tttaccatgt atcagtgcct ggctttttgt 6720
tataaagctt cgtctgtcta gtgctctttt tgctataaaa aatagactgt agtacaccct 6780
agtaggaaaa aaaaactaaa tttaaaaata aaaaaatata tttggcttat ttttcgcagg 6840
agtaatcctt ttataccatg gatattacaa aaaaaaatgt cagattctga gtatttcttc 6900
tttgtagatt tttggaatca ttatgagtaa aagtttgtta ctttattttg ctatttaaaa 6960
gatgttattt taccatgtgt tactgaaagg aaactgtatg gtagagcttc tgtttgtttt 7020
tgttttcagg ttttttttgt ttgtttgttt ttagttgtag gtcgcagtat gaactttttt 7080
tttgtttctc gttatgtttt gttttgtttt tgcgactgta cacatagctg cagcattaaa 7140
aacttttaaa aaattgttta aaaaaaaaga aaaaaaggga aaacgtttta aaaaaaaaga 7200
taaacagtta caccttgttt tcaatgtgtg gctgagtgcc tcaatttttt catgtttttg 7260
gtgtatttct gatttgtaga agtgtccaaa caggttgtgt gccggacttc cttcaagagg 7320
cccacagccc agcttggtct agacctgttc ccatctgtag ttactcgatg aagtcatgta 7380
catgaccgtt ctgtagcaat aaatgtgcca tttttataaa ctgtctctga cacttttttc 7440
atttcacctc tcgtgcacat ag 7462
<210> 43
<211> 6104
<212> DNA
<213> Homo sapiens
<400> 43
gagccgagcg cggtggtgag gccgcctcag cgaaaaaaat gtccgcctga agagacccac 60
aagttctatt cggggggacc gacagcccgc cccgggagga aggggcggcc aggcccgaaa 120
gccgcctccc cctcccagac ccgagagctc gtgcggggca aagtgaaccg agccgctggg 180
cggtgcaagg ggaagcccaa gcccgttctc ccggccaaag tgaactttaa tcggggtggt 240
tggatgcgga gacggggcgg cagaagtggc cgaagatgaa tccccagcaa caacgcatgg 300
ccgctatagg gaccgacaag gagctgagcg acctactgga cttcagtgcg atgttttccc 360
cacctgttaa tagtgggaaa actagaccaa ctacactggg aagcagtcaa ttcagtggat 420
caggtattga tgaaagagga ggtacaacat cttggggaac aagtggtcaa ccaagtcctt 480
cctatgattc atctagaggt tttacagaca gccctcatta cagtgatcac ttgaatgaca 540
gtcgattagg agcccatgaa ggcttgtccc caacaccttt catgaactca aatctgatgg 600
gaaaaacatc agagagaggc tcattttccc tgtacagcag agatactgga ttaccaggct 660
gtcaatctag tctcctgaga caagatctgg ggcttgggag cccagcacag ctatcttctt 720
caggaaaacc tgggacagca tactattcat tctctgctac aagttccagg aggagaccac 780
tccatgactc tgcagcgctt gatcccttgc aagcaaaaaa agtcagaaag gtgcctcctg 840
gtttgccttc ttctgtatat gcaccatccc caaattcaga tgatttcaac cgtgaatctc 900
ctagttatcc atctcctaag ccaccaacca gtatgttcgc tagcactttc tttatgcaag 960
atgggaccca caattcttct gacctttgga gttcatcaaa tgggatgagc cagcctggtt 1020
ttggtggaat tctggggacc tccacttccc acatgtctca atccagtagt tatggcaacc 1080
ttcattcaca tgaccgcttg agttatcctc cacactcagt ttcaccaaca gacataaaca 1140
cgagtcttcc accaatgtcc agctttcatc gcggcagtac cagcagttca ccttacgttg 1200
ctgcctcaca cactcctccc atcaatggat cagacagcat tctaggaacc agagggaatg 1260
ctgctggaag ctcacagaca ggtgatgcac ttggaaaggc tttggcatct atttattctc 1320
ctgaccatac cagcagtagt tttccgtcaa atccatcaac accagttgga tcaccttcac 1380
ctctcacagg taccagtcag tggccaagac ctggagggca agcaccttca tccccaagct 1440
atgaaaactc actccactcc ctgaaaaatc gagttgagca gcaacttcac gagcatttgc 1500
aagatgcaat gtccttctta aaggatgtct gtgagcagtc tcgaatggag gatcgtttag 1560
acagactgga tgatgcaatc catgtgctgc ggaaccatgc tgtgggacct tccaccagtt 1620
tgcctgctgg tcacagtgat atacatagtt tattgggacc atcccataat gcaccaattg 1680
gaagcctcaa ttcaaactat ggaggatcaa gccttgttgc aagcagtcga tcagcttcaa 1740
tggttggaac tcatcgggaa gactctgtca gtctcaatgg caatcattca gtcctgtcta 1800
gtacagtcac tacttcaagc acagacctga accataaaac acaagaaaat tatagaggtg 1860
gcttgcaaag tcagtctgga actgttgtta caacagaaat caagactgaa aacaaagaaa 1920
aggatgaaaa ccttcatgaa cctccttcat cagatgacat gaagtcagat gatgaatcct 1980
cccaaaaaga tatcaaggtt tcatctagag gcagaacaag cagtactaat gaagatgagg 2040
atttgaaccc tgaacagaag atagaaaggg agaaggagag gcggatggct aacaatgcca 2100
gagaacgctt acgcgtgcgg gatattaatg aagcattcaa agagcttggc cgaatgtgtc 2160
agcttcactt gaagagtgaa aaaccccaaa caaaactcct tattcttcat caagccgtgg 2220
cagtcatcct tagtctagaa cagcaagtca gagagaggaa ccttaacccc aaagcagcct 2280
gccttaagag aagggaagaa gaaaaagttt ctgccgtatc ggcagagccg ccaaccacac 2340
tgccaggaac ccatcctggg cttagtgaaa ctaccaaccc tatgggtcat atgtaaacat 2400
cagccagttc cagagttatc agtaggctag atagaaggtg acctctcctc ataaggactt 2460
ggacaactca gattatctga agacacaaac ctgacaggag ggagaagaaa aaacaaaaca 2520
cttgaaccaa gaaactcaaa tgtaatccta cgatcaaagc aactggtcaa cacttccatc 2580
agaagtgaag ataggaagct catcagatag aacatcagcc catgagatgt ttgcaacaaa 2640
tcttttgttg caagcagtgt gtcgcttctg cacaatcaga gactgtctcg atctctccac 2700
tcaccgtgga agttgccttg tgcctaaact gaattgacaa atgcattgta actacaaatt 2760
ttatttattg ttatgaaact gtaaggtcta catataaagg gaaaaagtta atgtggaaag 2820
ctgatctaca ctcagctgat gccagcatac attaaagcgg ttcacgtgca gagaacaaag 2880
cagtgacaac cattggccct tagcattccc ggcataccta ttagtgtctt aaaaaggaag 2940
ggaaaagtct tttgttgccc tctcctatcc tcttgccata tgaatagcgt tttccatgaa 3000
ataggaaaat attacttggt atagcatttc tcttgctctc attttttgat ttatttttat 3060
tttctctttg tgggtgttat atttgatctc taaatctgaa cagtttatgg tcacagtcca 3120
gcctcctccg tgcagccctg tgtgctttgc acatttacct tacagtggta agcagagacc 3180
atctgtgacc atagcctagc tagcatttta aaaggggaaa ttttgttctc taggttttcc 3240
cccaaataaa cattgcttta tttctaataa taaccaagac ttttcaagct tctagatctc 3300
ataggaaagc ttgtaatagc aaaattgtaa attacaaggg aagaatctac tttttagaaa 3360
tcgctttgtt ttccaagcag taagtactac atacagtact tgtaaagtgt tagctgtaag 3420
taagcacaaa atacatttaa aatacaaaga cgattttttc aggctgtgat tatggtgaac 3480
ataacaaaac ccagtagtca ccaaggcagg tagtgtgata aatgaacaca ccactctgag 3540
gctaattacc taatggaata caagagcaat ggtcacccgt atttccttat cctagccttt 3600
atttctctgt catttggatg gctggtcaat ggggaagaat tgagtgggtg atttaatcaa 3660
ctgcaaacca tctgcccctg tcccaaaatg atgagccaga ttagcattaa accagtactt 3720
gtcagtccat cttaatactg ttcattaagg cactctctgt ctctaatcct taggagttgt 3780
tttaaaagac ataatcactt tgaacttcca tgaaacctgt cttccaccac aacaaccctg 3840
ggagagaaaa acatgctaaa ggaggtatct tggcttaata attccttata gccaatatca 3900
acagtggcaa tcagcacaca gaggaaagga cccaaatcac tatgtagctt aaagatttct 3960
gttaatttga aagaacaaaa acaagacaga acttctggta ctctaatcag gatgattcct 4020
aacaagtcag tcatttgtga acttagtgga ctttttggtt actttaattt gcatatattc 4080
tccagttaca tcggactcta tctgtggcct tgttcttcat ttcagtgtta atcagctaaa 4140
cagaagttgt tgcttatgat gtgtgagtga acatatgcca ctgcctggcc tttttttctt 4200
cagagcttgt tgtctttttc gctatattag actttgcagt atgcccagaa gctttccttc 4260
ataaaataga aagaaaaaaa catttggctt atttttcact gtagctagtc ttttatacaa 4320
taatcttgta agaaaatttc ttgaattcta aatattactc tttctagatt tttgaaatca 4380
aaaagttttc agtaaaaagt ttcttacttt attttattat attaggtagt aaaaaatgta 4440
gggttattta ccataacctg ttcattaata tcagaaattt acaatagcat tttaagacca 4500
tagtaggatt ctagcatacc gtgtagtacc tatggagtat tgtaagagct aattgttgga 4560
gatgaattgc ttctcatctt gttctccagt ttccattgtt ggtttattgc agatttgtat 4620
cctgtgtcaa attcaaggta ttattgataa accttttcaa ccagcagcaa gaagttcaaa 4680
tttttttctg tcactgtaac agaaaacaca atatgtatat aacatttatg tagcaataaa 4740
tgtgccatct tttttttaac acagtaaaat agtgagtttt ttacatttct ctttctcaaa 4800
taataatgta ttttgtttta ttttctccat ctcattcgtc ccagaaacac tcacactgct 4860
tttcctaact gcattaccga cattatctgg gaaacccttc aggacagaat caggcttgtg 4920
gagctaagtt ggcaatctgg tctagagctt ctctagcttg tgcttttctc ctcttgccct 4980
cactactgac ggtggccttt taaccttttc ctaaagattg accaaacagc aactagtagt 5040
tatagaaaat ctactcattt gtagatacag agaaaaatga agaagatgga aaaagactca 5100
aaagaggctt tttaagttat tcttcaaagc acttttcaca tttccccata ccctttctca 5160
caaaaaaagt gtcataatta agtaatggta ttgtttactg tttaaaagtt aaaagatcaa 5220
aaatttgctt ttatcccagt ttttaaccac aaaaaaaagc gtagggatta tccatgagga 5280
cttcatgcca agcaagaacc tcaaacaaac tagacaaact ttttttttga cagtgaatga 5340
ctttttgtag gacctgtgcg tgcgaaaccc atggcaattg tcacatcctc ttggtatgct 5400
ggcagattgc ttctcttggt gaattatgaa atccactgtt cacattgggt gcctaacaga 5460
acattttgct tcttgtggga tttagtgaaa actattaaac ttgttaagtt gattttatac 5520
aaaacgataa ataaaaagct ctaagaagaa aatgtataat cttagagctg aaataaaata 5580
tagagaccat ctagtaaatg acctcattaa tatatctgtg aaaactgaga ctcagattgt 5640
atgtctctaa gaacacataa ttagtaacag atcaagacac ttaaaacttt ccctacaaaa 5700
cctccctgcc ttgactttct ctttctcttt gcagatttct aggccgcttc tgctcagtgt 5760
cttcattttc ttccatattt gttttatttc atttttcttt tctatagttc atgttttctt 5820
tttccttgga aactcaaaat ttaaacacac gtcgtgtgtg tgtgtgtgtg tgtgtctgtg 5880
tgtgtgtgac ttaaagaatc ttaagctttg gcattaaata gtcctcgatt caaatctaag 5940
ctcaacatct gattaacttc attttcctat ctgaaaaatg gagataacat tagaattgtg 6000
taagtattga atgaaacaat gtatggaaag ctcttatggt tcttgtcacc taagaagtac 6060
ttaataaatg ataaatattt ttaaataaat aatattataa ccaa 6104
<210> 44
<211> 4707
<212> DNA
<213> Mus musculus
<400> 44
ggaaaaaaaa aaaaatgtcc gcctgaggag acccacaagt tctatcgggg ggacagccag 60
cccgcccggg gagccacggg cggctaagcc cgagagccgc ccgagtcgcg ccgactcaag 120
cactcgcggg ggcccgaggc aacgcagccg ccggcggcgc gtggggaggg ggaaagcctg 180
agcccgcgct cccggccaaa gtgaacttta atcgggaagg ttggatgcgg agcccgggcg 240
gcaggacctg ctagaagtgg ctgaagatga atccccagca gcagcgcatg gccgcgatag 300
ggaccgacaa ggagctgagc gacctgctgg acttcagtgc gatgttttct ccacctgtta 360
atagtgggaa aacgagacca acaacactgg gaagtagtca gttcagcggg tcaggtatgg 420
atgagcgtgg aggaacaaca tcttggggaa caagtggtca accaagcccc tcctatgatt 480
catctagagg ttttacagac agccctcatt acagtgatca cttgaatgac agtcgattag 540
gaacccacga aggcttgtcc ccaacacctt tcatgaactc aaatctgata gggaaaacat 600
cagagagagg ctcattttcc ctgtacagca gagactctgg actctcaggc tgtcagtcta 660
gtctcctgag acaagatcta ggacttggga gcccggcaca gctgtcttct tcaggaaagc 720
ctggaacacc atactactca ttctctgcca caagttcgag aagaagaccg ctccatgatt 780
ctgtagccct agatccttta caagcgaaga aagtaagaaa ggtgcctcct ggcctacctt 840
cttctgtata tgcaccatcc ccaaattctg acgatttcaa ccgtgaatct cctagttacc 900
catctcccaa gccaccaacc agtatgttcg ctagcacttt ctttatgcaa gatgggaccc 960
acagttcttc tgacctttgg agttcatcga atgggatgag ccagcctggt tttggtggaa 1020
ttctggggac ctccacatcc cacatgtctc agtccagtag ttatggcagc cttcattcac 1080
atgaccgctt gagttatcct ccacactcag tgtcaccaac agacataaac acaagtcttc 1140
cgccaatgtc cagcttccac cgtggtagta ccagcagctc accatatgtt gccgcctcac 1200
atactcctcc catcaatgga tcagatagca tcctaggaac cagagggaat gctgctggaa 1260
gctcacagac gggtgatgca cttgggaagg ccttggcatc tatttattcc cctgaccaca 1320
caagcagtag ttttccatca aacccatcaa caccagtggg atctccttca cctctcacag 1380
gtaccagtca gtggcccaga gctggagggc aagctccttc atctccaagc tatgaaaact 1440
cacttcactc cctgaaaaat cgagttgagc agcaacttca cgagcatttg caagatgcaa 1500
tgtccttctt aaaggatgtc tgtgagcagt ctcgaatgga agaccgctta gacaggctgg 1560
atgatgctat ccatgtgcta cgaaaccatg cagttggacc ttctaccagt ctgcctacta 1620
gccacagtga catacacagt ttgctgggac catcccataa tgcatcaatt ggaaacctca 1680
attcaaacta tggaggatcc agccttgtta caaatagtcg atcagcttcg atggtcggaa 1740
cacatcggga agattcagtc agtctcaatg gcaatcattc ggtcctgtct agtactgttg 1800
ctgcctcaaa cacagaactg aaccataaaa caccagaaaa tttcagaggt ggtgtacaaa 1860
atcagtctgg aagtgttgtt ccaacagaaa tcaagactga aaacaaagaa aaagatgaaa 1920
accttcatga acctccttca tcagatgaca tgaaatcaga tgatgagtcc tcccagaaag 1980
acatcaaggt ctcatctagg ggcagaacaa gcagtaccaa tgaagacgag gatctgaatc 2040
cagaacagaa aatcgaaagg gagaaggaaa ggcggatggc taacaatgcc agagagcgcc 2100
tgcgcgtgcg ggatattaac gaggcgttca aggagcttgg ccgaatgtgt cagcttcatt 2160
tgaagagtga aaaacctcag acaaaacttc tcattcttca tcaggccgtg gcagtcatcc 2220
ttagtctaga acagcaagtg agagagagga acctcaaccc caaagcagcc tgccttaaga 2280
gaagagaaga agaaaaagtc tctgctgcgt cagcagagcc gcccaacacg ttgccaggag 2340
cccatcctgg gcttagtgag tctaccaacc ctatgggtca tctgtaaaca tcagccagtt 2400
ccagagtcat cagtaggcta aatagaaggt gacctctcct cataagattt ggacaactca 2460
gattatctga agacacaaac ctggcaggag ggagaagaaa aagcaaaaca cttgaaacca 2520
gaaactcata tgtaatcctg tgatcaaagc aactggtcag cacttcatca gacgtgagca 2580
taggaagctc agcagagacc gtcggccgtg aggtgtttgc agcatatcac tctgctgtaa 2640
tcagtgtgtc gcttctgcac aatcagagac tgtctcatct ctccactcaa cgtggaagtt 2700
gccttgtgcc taaactgaat tgacaaatgc attgtaacta caaattttat ttattgttat 2760
ggaactgtga ggtctacata taaagggaaa agttcatgtg ggaagctgat gtacactcag 2820
ctgatgccag cattgttaaa gctgttcaca gagcagtggc aaccattggc ccttagcatt 2880
cccggcatac ctgttagtgt cttaaaaagg aagggagtcc tttgttgccc tctccgacct 2940
tcgccatatg aatagtgatt tccatgaaat aggaaaaata ttacttcgta tagcatttct 3000
ctcttgtttt tttcactcat ttttatttcc tctttgtggg tgttatattt gatctgagtc 3060
tgcatagttt atggtcacag tccagaaccc tccttgcagt cctgtatgct ttgttcatgt 3120
ccttgaagtg ataagcagac accatctgtg accatagcct agctaatatt ttgaaagggg 3180
aagttttgtc ccctggattt gcccccaaat aaacattgct ttatttctaa taatcactaa 3240
gacttttcag gcttctaggt ttcatagtaa agctataata gcaagaagtg taacttacaa 3300
gggagagttt actttttagg aattgctttg ttttccgagc agtaagtact acacaatata 3360
gtacttgtaa agtgttagct gataagtaag cacagaatgc attcagtaca atacaaagat 3420
gacttttcct ggtgagtctc cgggacaggc agtgtgatga atgcactcaa ccgctctgag 3480
gctaattacc tatggaatcc aagagcaatg gtcacggttc cttaccctag ctttacttct 3540
gtcctttgag ttggctggtc cgtggggggt ggggcaggag ggtgacttaa tcacctgcaa 3600
accacctgcc cccaccccaa gaagagccag attagcaccg agctgtacct gtcagtctgt 3660
cttagcatta tgcattaagg caccctctgt ctctaatccc ttacagttgt ttttaagaca 3720
cagtaatcac tttaaacttc catgaaatct gtcttccacc acagcaccct gggagagaaa 3780
aacatgctaa gcgtgatggt cttggctaag taactcctta aagccaatag cagtggcagt 3840
ctgcacagaa gaaaaatccc aagtcgttct gtaacttaga gacaccggag aattttgaaa 3900
gaacaaaaac catgaagaca gcacttcaga tcctccatca ggactctggt gaacacgtca 3960
gtctttggcg aacttagtgg acttaatttg tatatgttct ccagttagat cagactctat 4020
ctgtggcctt gttcttcatt tcagtgttaa tcagctaaaa cagcagttgt tgctatgatg 4080
tgtgagtgaa cataagccac tgcctggcct tttttcttca gagcttgtcg tctttttcgc 4140
tatattagac tttgcagtat gcccagaagc tttccttcat aaaatagaaa gaaaaaaaca 4200
tttggcttat ttttcactgt agctagtctt ttatacaata atcttgtaag aaaatttctt 4260
gaattctaaa tattactctt tctagatttt tgaaatcaaa agttttcagt aaaaagtttc 4320
ttactttatt ttattatatt aggtagttaa agaaaatgta gggttattta ccataacctg 4380
ttcattaata tcagaaattt acaatagcat tttaagagca tagtaggttc tagcatacca 4440
tgtagttcct atggagtatt gtgagagcga attgttggag atgagctgct tttcatcttg 4500
ttctccagtt tccattgttg gtttattgca gatttgtatt ctgtgtcaaa ttcaaggtat 4560
tattgataaa ccttttcaac cagcagcaag aagttcaaat ttcttttttc tgtcgctgta 4620
acagaaaaca cagtatgtat ataacattta tgtagcaata aatgtgccat cctttttttt 4680
aacatagtaa actagtgagt tttttac 4707
<210> 45
<211> 4116
<212> DNA
<213> Homo sapiens
<400> 45
gtttcgcttt cctgcgcaga gtctgcggag gggctcggct gcaccggggg gatcgcgcct 60
ggcagacccc agaccgagca gaggcgaccc agcgcgctcg ggagaggctg caccgccgcg 120
cccccgccta gcccttccgg atcctgcgcg cagaaaagtt tcatttgctg tatgccatcc 180
tcgagagctg tctaggttaa cgttcgcact ctgtgtatat aacctcgaca gtcttggcac 240
ctaacgtgct gtgcgtagct gctcctttgg ttgaatcccc aggcccttgt tggggcacaa 300
ggtggcagga tgtctcagtg gtacgaactt cagcagcttg actcaaaatt cctggagcag 360
gttcaccagc tttatgatga cagttttccc atggaaatca gacagtacct ggcacagtgg 420
ttagaaaagc aagactggga gcacgctgcc aatgatgttt catttgccac catccgtttt 480
catgacctcc tgtcacagct ggatgatcaa tatagtcgct tttctttgga gaataacttc 540
ttgctacagc ataacataag gaaaagcaag cgtaatcttc aggataattt tcaggaagac 600
ccaatccaga tgtctatgat catttacagc tgtctgaagg aagaaaggaa aattctggaa 660
aacgcccaga gatttaatca ggctcagtcg gggaatattc agagcacagt gatgttagac 720
aaacagaaag agcttgacag taaagtcaga aatgtgaagg acaaggttat gtgtatagag 780
catgaaatca agagcctgga agatttacaa gatgaatatg acttcaaatg caaaaccttg 840
cagaacagag aacacgagac caatggtgtg gcaaagagtg atcagaaaca agaacagctg 900
ttactcaaga agatgtattt aatgcttgac aataagagaa aggaagtagt tcacaaaata 960
atagagttgc tgaatgtcac tgaacttacc cagaatgccc tgattaatga tgaactagtg 1020
gagtggaagc ggagacagca gagcgcctgt attggggggc cgcccaatgc ttgcttggat 1080
cagctgcaga actggttcac tatagttgcg gagagtctgc agcaagttcg gcagcagctt 1140
aaaaagttgg aggaattgga acagaaatac acctacgaac atgaccctat cacaaaaaac 1200
aaacaagtgt tatgggaccg caccttcagt cttttccagc agctcattca gagctcgttt 1260
gtggtggaaa gacagccctg catgccaacg caccctcaga ggccgctggt cttgaagaca 1320
ggggtccagt tcactgtgaa gttgagactg ttggtgaaat tgcaagagct gaattataat 1380
ttgaaagtca aagtcttatt tgataaagat gtgaatgaga gaaatacagt aaaaggattt 1440
aggaagttca acattttggg cacgcacaca aaagtgatga acatggagga gtccaccaat 1500
ggcagtctgg cggctgaatt tcggcacctg caattgaaag aacagaaaaa tgctggcacc 1560
agaacgaatg agggtcctct catcgttact gaagagcttc actcccttag ttttgaaacc 1620
caattgtgcc agcctggttt ggtaattgac ctcgagacga cctctctgcc cgttgtggtg 1680
atctccaacg tcagccagct cccgagcggt tgggcctcca tcctttggta caacatgctg 1740
gtggcggaac ccaggaatct gtccttcttc ctgactccac catgtgcacg atgggctcag 1800
ctttcagaag tgctgagttg gcagttttct tctgtcacca aaagaggtct caatgtggac 1860
cagctgaaca tgttgggaga gaagcttctt ggtcctaacg ccagccccga tggtctcatt 1920
ccgtggacga ggttttgtaa ggaaaatata aatgataaaa attttccctt ctggctttgg 1980
attgaaagca tcctagaact cattaaaaaa cacctgctcc ctctctggaa tgatgggtgc 2040
atcatgggct tcatcagcaa ggagcgagag cgtgccctgt tgaaggacca gcagccgggg 2100
accttcctgc tgcggttcag tgagagctcc cgggaagggg ccatcacatt cacatgggtg 2160
gagcggtccc agaacggagg cgaacctgac ttccatgcgg ttgaacccta cacgaagaaa 2220
gaactttctg ctgttacttt ccctgacatc attcgcaatt acaaagtcat ggctgctgag 2280
aatattcctg agaatcccct gaagtatctg tatccaaata ttgacaaaga ccatgccttt 2340
ggaaagtatt actccaggcc aaaggaagca ccagagccaa tggaacttga tggccctaaa 2400
ggaactggat atatcaagac tgagttgatt tctgtgtctg aagttcaccc ttctagactt 2460
cagaccacag acaacctgct ccccatgtct cctgaggagt ttgacgaggt gtctcggata 2520
gtgggctctg tagaattcga cagtatgatg aacacagtat agagcatgaa tttttttcat 2580
cttctctggc gacagttttc cttctcatct gtgattccct cctgctactc tgttccttca 2640
catcctgtgt ttctagggaa atgaaagaaa ggccagcaaa ttcgctgcaa cctgttgata 2700
gcaagtgaat ttttctctaa ctcagaaaca tcagttactc tgaagggcat catgcatctt 2760
actgaaggta aaattgaaag gcattctctg aagagtgggt ttcacaagtg aaaaacatcc 2820
agatacaccc aaagtatcag gacgagaatg agggtccttt gggaaaggag aagttaagca 2880
acatctagca aatgttatgc ataaagtcag tgcccaactg ttataggttg ttggataaat 2940
cagtggttat ttagggaact gcttgacgta ggaacggtaa atttctgtgg gagaattctt 3000
acatgttttc tttgctttaa gtgtaactgg cagttttcca ttggtttacc tgtgaaatag 3060
ttcaaagcca agtttatata caattatatc agtcctcttt caaaggtagc catcatggat 3120
ctggtagggg gaaaatgtgt attttattac atctttcaca ttggctattt aaagacaaag 3180
acaaattctg tttcttgaga agagaatatt agctttactg tttgttatgg cttaatgaca 3240
ctagctaata tcaatagaag gatgtacatt tccaaattca caagttgtgt ttgatatcca 3300
aagctgaata cattctgctt tcatcttggt cacatacaat tatttttaca gttctcccaa 3360
gggagttagg ctattcacaa ccactcattc aaaagttgaa attaaccata gatgtagata 3420
aactcagaaa tttaattcat gtttcttaaa tgggctactt tgtccttttt gttattaggg 3480
tggtatttag tctattagcc acaaaattgg gaaaggagta gaaaaagcag taactgacaa 3540
cttgaataat acaccagaga taatatgaga atcagatcat ttcaaaactc atttcctatg 3600
taactgcatt gagaactgca tatgtttcgc tgatatatgt gtttttcaca tttgcgaatg 3660
gttccattct ctctcctgta ctttttccag acactttttt gagtggatga tgtttcgtga 3720
agtatactgt atttttacct ttttccttcc ttatcactga cacaaaaagt agattaagag 3780
atgggtttga caaggttctt cccttttaca tactgctgtc tatgtggctg tatcttgttt 3840
ttccactact gctaccacaa ctatattatc atgcaaatgc tgtattcttc tttggtggag 3900
ataaagattt cttgagtttt gttttaaaat taaagctaaa gtatctgtat tgcattaaat 3960
ataatatgca cacagtgctt tccgtggcac tgcatacaat ctgaggcctc ctctctcagt 4020
ttttatatag atggcgagaa cctaagtttc agttgatttt acaattgaaa tgactaaaaa 4080
acaaagaaga caacattaaa acaatattgt ttctaa 4116
<210> 46
<211> 5150
<212> DNA
<213> Mus musculus
<400> 46
aggtgcggat ccgggtgcgg gtgcgggtgg aagtggggcg ccctctcctc ggacctgggg 60
tctgctgccc acaggtgacc tgtcatcccg cagagagaac gccaggagcc ggatcgcttg 120
cccaactctt ggcgctgctt ggctctctta tcctgccgtt ctcacttcta ggtcgtttca 180
gctctgctcc ataccctgag ccggcgccac gccgccgcgc atgcaactgg catataactt 240
gctgtgtgtg gtgattgctt gtgttgaatc ccgaacctgc acccggagac agcccaagga 300
tgtcacagtg gttcgagctt cagcagctgg actccaagtt cctggagcag gtccaccagc 360
tgtacgatga cagtttcccc atggaaatca gacagtacct ggcccagtgg ctggaaaagc 420
aagactggga gcacgctgcc tatgatgtct cgtttgcgac catccgcttc catgacctcc 480
tctcacagct ggacgaccag tacagccgct tttctctgga gaataatttc ttgttgcagc 540
acaacatacg gaaaagcaag cgtaatctcc aggataactt ccaagaagat cccgtacaga 600
tgtccatgat catctacaac tgtctgaagg aagaaaggaa gattttggaa aatgcccaaa 660
gatttaatca ggcccaggag ggaaatattc agaacactgt gatgttagat aaacagaagg 720
agctggacag taaagtcaga aatgtgaagg atcaagtcat gtgcatagag caggaaatca 780
agaccctaga agaattacaa gatgaatatg actttaaatg caaaacctct cagaacagag 840
aaggtgaagc caatggtgtg gcgaagagcg accaaaaaca ggaacagctg ctgctccaca 900
agatgttttt aatgcttgac aataagagaa aggagataat tcacaaaatc agagagttgc 960
tgaattccat cgagctcact cagaacactc tgattaatga cgagctcgtg gagtggaagc 1020
gaaggcagca gagcgcctgc atcgggggac cgcccaacgc ctgcctggat cagctgcaaa 1080
gctggttcac cattgttgca gagaccctgc agcagatccg tcagcagctt aaaaagctgg 1140
aggagttgga acagaaattc acctatgagc ccgaccctat tacaaaaaac aagcaggtgt 1200
tgtcagatcg aaccttcctc ctcttccagc agctcattca gagctccttc gtggtagaac 1260
gacagccgtg catgcccact cacccgcaga ggcccctggt cttgaagact ggggtacagt 1320
tcactgtcaa gctgagactg ttggtgaaat tgcaagagct gaactataac ttgaaagtga 1380
aagtctcatt tgacaaagat gtgaacgaga aaaacacagt taaaggattt cggaagttca 1440
acatcttggg tacgcacaca aaagtgatga acatggaaga atccaccaac ggaagtctgg 1500
cagctgagtt ccgacacctg caactgaagg aacagaaaaa cgctgggaac agaactaatg 1560
aggggcctct cattgtcacc gaagaacttc actctcttag ctttgaaacc cagttgtgcc 1620
agccaggctt ggtgattgac ctggaggtct ttgttccctt tcagaccacc tctcttcctg 1680
tcgtggtgat ctccaacgtc agccagctcc ccagtggctg ggcgtctatc ctgtggtaca 1740
acatgctggt gacagagccc aggaatctct ccttcttcct gaaccccccg tgcgcgtggt 1800
ggtcccagct ctcagaggtg ttgagttggc agttttcatc agtcaccaag agaggtctga 1860
acgcagacca gctgagcatg ctgggagaga agctgctggg ccctaatgct ggccctgatg 1920
gtcttattcc atggacaagg ttttgtaagg aaaatattaa tgataaaaat ttctccttct 1980
ggccttggat tgacaccatc ctagagctca ttaagaagca cctgctgtgc ctctggaatg 2040
atgggtgcat tatgggcttc atcagcaagg agcgagaacg cgctctgctc aaggaccagc 2100
agccagggac gttcctgctt agattcagtg agagctcccg ggaaggggcc atcacattca 2160
catgggtgga acggtcccag aacggaggtg aacctgactt ccatgccgtg gagccctaca 2220
cgaaaaaaga actttcagct gttactttcc cagatattat tcgcaactac aaagtcatgg 2280
ctgccgagaa cataccagag aatcccctga agtatctgta ccccaatatt gacaaagacc 2340
acgcctttgg gaagtattat tccagaccaa aggaagcacc agaaccgatg gagcttgacg 2400
accctaagcg aactggatac atcaagactg agttgatttc tgtgtctgaa gtccaccctt 2460
ctagacttca gaccacagac aacctgcttc ccatgtctcc agaggagttt gatgagatgt 2520
cccggatagt gggccccgaa tttgacagta tgatgagcac agtataaaca cgaatttctc 2580
tctggcgaca tttttttccc atctgtgatt ccttcctgct actgttcctt catatgcagt 2640
atttctaggg aaatgcaaga aagaaagagc atcacatttg ctgagcactg ctggtagaaa 2700
gtggatattt ctctaattag aaacctgtta ctctgaagga cttcatgcat cttactgaag 2760
gtgaaatgga aagtcactta acacaaaatg gattttgtaa acaaagacca agagatccac 2820
ccaagcacca ggactagagt gcgagtattt ggggcaaggt gaggagaacg gtcactttag 2880
taatggtctg taatcagtgc ccaagtgctg cacatcactg gaaagagaca tacttatggg 2940
ggaggggcct tcttgatgga ggaatgtttc tgtcccggga gacattggca cttcccctct 3000
cctggatggc cggaagtctt ccactgtttt acatatggca cagttcaaag tcaactttag 3060
atccaatgct ctatcaaact atagtgggca tccttcatgt gagtgggaag aaaacaaccg 3120
tgctccttac tgcagcttct gccaaggcat ggttgctctc ctcagggact agctttgttg 3180
gtggcaatgg ctacacaaaa ctaaacacca acagaagtaa gaccattttc atgagtactc 3240
catcaagtta aagggttttt gttgtctttt tggtcatgga ttgaataaaa ttgtctttgc 3300
acatccatta agggggccag ctttcttaaa gcaatttttc ttttttttta actaaaatta 3360
gatataggtg aactcatgtt ttttagtggg ctgaacttat cggttttagc tggttgtctt 3420
aattagccat aaacttggag aaagcagtga cttcttgaat ccttagccaa atatgagtat 3480
cagataattt tattattttt ttttcgagac agggtttctc tgtgtagccc tggctattct 3540
ggaactcact ctgtagatca ggctggcctg gaactcagaa atccgcctgt ctctgcctcc 3600
cgagtgctgg gattaaaggt gtgcaccacc aatgcctggt gagataactt taaagaactc 3660
cctataaatg catgagaacc actgttactg atgaatgtgg ttttttgaca actacattca 3720
caaatggcct gtcttgtgtt ttgtcaccgt tttgagggat gatgttttgt ggcacgtgtg 3780
tgatcacagc ctgatggttc tggtcgtggg ttggttcttc tgggccagct ttcacagact 3840
gctgcgcagc tgcacctaca gtgctgcccc ataatactgt ttcactttgg tgaagatcag 3900
cccaccttac accccgagtg caggtgtgaa ccacggtaag tgtgcacagt ccttagggaa 3960
aacagggacg cagaggcctg cctcctctct tttccatgcc aaaatgaaat gaccaagaaa 4020
caaaacattt aaaaagttgt ttctaaatgc tgagacctaa ccattgctta tatactgttg 4080
tctgttgaaa cagtttgtta caatttcatt ctgttgaact aggtgagact ttaagaaatg 4140
ttgaaattat gttaatttcc tattattatt taatataaag atatttaaaa tgtctagtgt 4200
tatgagttgg tttaatatat atctcatgta tgtatcagtc ctattttaag cgctttttaa 4260
aaaagacttg tttaggtata tattttatgt atatgggtgt tttatctgaa tgtatggaca 4320
ccagaagaga gcactgggtc ccatgagact acagtcaaat gggatcacag tcagatgcaa 4380
ttttgagctg ccatgtgggt gctgggattt gaactcaggg cctctggaag aacagccagt 4440
gcttttaact gctgaaccat ctcttgggac gcctatgggt cctattttaa aggaagaccg 4500
atatttccca agtgtcaccc ttgcttactc tactgcagac acaggaacta tggcagttta 4560
aggtaggtca gcgggcaggc ccagcggtga ggcctctctg aggtagaggc ctggggatca 4620
ggcgtttagt cattcaaggc cggcagggct ccatgggatc acatccaagt cagggcaaga 4680
catccactta cactttcagg tagctgcctg ttagacgtca ccaagcatgt cctagcttaa 4740
gtatgacgag gatggcattt tctaagtaca gagcatatat gtagcacttg ggataagctg 4800
atctagggac ttcctgaggc ggcagagctt aaagtggact ccattgactg cttggagact 4860
actgtggaat gaaggcatgt ctcagtaaac agaacaaacc tgtggcatct gtctgcctca 4920
gggaggcatc agacaaagct ggaaaggatt tagaaaattc ttttacctac tctgggagct 4980
gggaggctgt ccttcatccc gagggcatta tttatctgaa ggcatctttt gtttaagatt 5040
cattcatttg ttcctcaaat atgttcagtg cctgccttgc accaggcact attctagatg 5100
cgttgaaggc actaataaaa gaaatgcctc acagtaaaaa aaaaaaaaaa 5150
<210> 47
<211> 5961
<212> DNA
<213> Homo sapiens
<400> 47
aaagtgaatg gcgaaggact gaagggatcc ccccttcggg tccccggccg ccctgttcac 60
cctcgttcat cctcctttcc gaagctcgct ctcgaaggca ggagcgaccg gcgcctttgg 120
ctgaggagga ggagaaggag gaatcgcgcc aggcggagcg tcaggtcccg ttttcctctc 180
cggcgtctcc aatacaaaga ttacggtgca gaaggaaatt gcactcgtct cctccgcgcc 240
cccggtaccc aacacaatgc accagccgcc tgagtccacc gccgcggccg ccgccgctgc 300
agacattagc gctaggaaga tggcgcaccc ggcaatgttc cctcgaaggg gcagcggtag 360
tggcagcgcc tctgctctca atgcagcagg taccggcgtc ggtagtaatg ccacatcttc 420
cgaggatttt ccgcctccgt cgctgcttca gccgccgccc cctgcagcat cttctacgtc 480
gggaccacag cctccgcctc cacaaagcct gaacctcctt tcgcaggctc agctgcaggc 540
acagcctctt gcgccaggcg gaactcaaat gaaaaagaaa agtggcttcc agataactag 600
cgttactcct gctcagatct ccgctagtat cagctctaac aacagtatag cagaggacac 660
tgagagctat gatgatctgg atgaatctca cacggaagat ctctcttctt cggagatcct 720
tgatgtgtca ctttccaggg ctactgactt aggggagccc gaacgcagct cctcagaaga 780
gaccctaaat aacttccagg aagccgagac acctggggca gtctctccca accagcccca 840
ccttcctcag cctcatttgc ctcaccttcc acaacagaat gttgtgatca atgggaatgc 900
tcatccacac cacctccatc accaccatca gattcatcat gggcaccacc tccaacatgg 960
tcaccaccat ccatctcatg ttgctgtggc cagtgcatcc attactggtg ggccaccctc 1020
aagcccagta tctagaaaac tctctacaac tggaagctct gacagtatca caccagttgc 1080
accaacttct gctgtatcat ccagtggttc acctgcatct gtaatgacta atatgcgtgc 1140
tccaagtact acaggtggaa taggtataaa ttctgttact ggcactagta cagtaaataa 1200
tgttaacatt actgctgtgg gtagttttaa tcctaatgtg acaagcagca tgcttggtaa 1260
tgttaatata agtacaagca atattcctag tgctgctggt gtgagtgttg ggcctggagt 1320
taccagtggt gttaatgtga atatcttgag tggcatgggc aatggtacta tttcttcctc 1380
tgctgctgtt agcagtgttc ctaatgcagc tgcagggatg actgggggat cggtttcaag 1440
tcagcagcaa caaccaacag ttaacacttc gaggttcaga gttgtgaagt tagattctag 1500
ttctgagccc tttaaaaaag gtagatggac ttgcactgag ttctatgaaa aagaaaatgc 1560
tgtacctgct acagaaggtg tgctgataaa taaagtggtg gagactgtaa agcaaaatcc 1620
gatagaagtg acttctgaaa gggagagcac tagtgggagt tcagtgagca gtagtgtcag 1680
cacactgagt cactatacag agagtgtggg aagtggagag atgggagccc ctactgtggt 1740
ggtgcagcag cagcagcagc aacaacaaca acaacagcaa caaccagctc tccaaggtgt 1800
gaccctccaa cagatggatt ttggtagcac tggtccacag agtattccag cagttagtat 1860
accacagagt atttctcagt cacagatctc acaagtacaa ttacagtctc aagaactgag 1920
ctatcagcaa aagcaaggtc ttcagccagt acctctgcaa gccactatga gtgctgcaac 1980
tggtatccag ccatcgcctg taaatgtggt tggtgtaact tcagctttag gtcagcagcc 2040
ttccatttcc agtttggctc aaccccagct accatattct caggcggctc ctccagtgca 2100
aactcccctt ccaggggcac caccacccca acagttacag tatggacaac agcaaccaat 2160
ggtttctaca cagatggccc caggccatgt caaatcagtg actcaaaatc ctgcttcaga 2220
gtatgtacaa cagcagccaa ttcttcaaac agcaatgtcc tccggacagc ccagttctgc 2280
aggagtagga gcaggaacaa cagtgattcc tgtggctcag ccacagggta tccagctgcc 2340
agtgcagccc acagcagtcc cagcacaacc tgcaggggca tctgtccagc ctgttggcca 2400
ggctccggca gcagtgtctg ctgtacctac tggcagtcag attgcaaata ttggtcagca 2460
agcaaacata cctactgcag tgcagcagcc ctctacccag gttccacctt cagttattca 2520
gcagggtgct cctccatctt cgcaagtggt tccacctgct caaactggga ttattcatca 2580
gggagttcaa actagtgctc caagccttcc tcaacaattg gttattgcat cccaaagttc 2640
cttgttaact gtgcctcccc agccacaagg agtagaacca gtagctcaag gaattgtttc 2700
acagcagttg cctgcagtta gttctttgcc ctctgctagt agtatttctg ttacaagtca 2760
ggttagttca actggtcctt ctggaatgcc ttctgcccca acaaacttgg ttccaccaca 2820
aaatatagca caaacccctg ctacccaaaa tggtaatttg gttcaaagtg ttagtcaacc 2880
tcccttgata gcaactaata caaatttgcc tttggcacaa cagataccac taagttctac 2940
ccagttctcc gcacaatcat tagctcaggc aattggaagc caaattgaag atgccaggcg 3000
tgcagcggag ccctccttag ttggcttacc tcagactatc agtggtgaca gtgggggaat 3060
gtcagcagtt tcagatggga gtagcagcag cctagcagcc tctgcttctc ttttcccgtt 3120
gaaggtgcta ccgctgacga cacccctggt ggatggcgag gatgagagct cctctggtgc 3180
aagtgtggta gctattgaca acaaaatcga gcaagctatg gatctagtga aaagccattt 3240
gatgtatgcg gtcagagaag aagtggaggt cctcaaagag caaatcaaag aactaataga 3300
gaaaaattcc cagctggagc aggagaacaa tctgctgaag acactggcca gtcctgagca 3360
gcttgcccag tttcaggccc agctgcagac tggctccccc cctgccacca cccagccaca 3420
gggcaccaca cagccccccg cccagccagc atcgcagggc tcaggaccaa ccgcatagct 3480
gcctatgccc ccgcagaact ggctgctgcg tgtgaactga acagacggag aagatgtgct 3540
agggagaatc tgcctccaca gtcacccatt tcattgctcg ctgcgaaaga gacgtgagac 3600
tgacatatgc cattatctct tttccagtat taaacactca tatgcttatg gcttggagaa 3660
atttcttagt tgggtgaatt aaaggttaat ccgagaatta gcatggatat accgggacct 3720
catgcagctt ggcagatatc tgagaaatgg tttaattcat gctcaggagc tgtgtgcctt 3780
tccatccctt ccggctccct acccctcact tccaagggtt ctctctcctg cttgcgctta 3840
gtgtcctaca tggggttgtg aagcgatgga gctcctcact ggactcgcct ctctcctctc 3900
ctccccccag gaggaacttg aaaggagggt aaaaagacta aaatgagggg gaacagagtt 3960
cactgtacaa atttgacaac tgtcaccaaa attcataaaa aacaatagta ctgtgcctct 4020
ttcttctcaa acaatggatg acacaaaact atgagagtga caaaatggtg acaggtagct 4080
gggacctagg ctatcttacc atgaaggttg ttttgcttat tgtatatttg tgtatgtagt 4140
gtaactattt tgtacaatag aggactgtaa ctactattta ggttgtacag attgaaattt 4200
agttgtttca ttggctgtct gaggaggtgt ggacttttat atatagatct acataaaaac 4260
tgctacatga caaaaaccac acctaaagaa attttaagaa tttggcacag ttactcactt 4320
tgtgtaatct gaaatctagc tgctgaatac gctgaagtaa atccttgttc actgaagtct 4380
ttcaattgag ctggttgaat actttgaaaa atgctcagtt ctaactaatg aaatggattt 4440
cccagtaggg gtttctgcat atcacctgta tagtagttat atgcatatgt ttctgtgcat 4500
gttctctaca caattgtaag gtgtcactgt atttaactgt tgcacttgtc aactttcaat 4560
aaagcatata aatgttgata aacaagtgtt tttcatatga ccctgttaac ataatggcag 4620
tcatttccac aactgtttcc aggtaaagtt aacaatttga ctagtaaaat cctgaagggc 4680
agtggaatga ttggaaaagt aggggcgtga tttgactgca tgaagtaaaa ggaaattgac 4740
acattgagtt gttcagcagg taagagaaga gacagtggag gagtccagct caattctaac 4800
tactgtgtga cttggacagg ttgcttcact cctggacgga tgtaggggtt tgaaagagat 4860
gatctcttac attccccttt ggctttaaaa ttctaggagt ccttgaaaat cttaattttt 4920
tactgaactg agaggaagaa ggagccttat tctgtgtata attggaataa gcagatctag 4980
gatcaaaaga cggaagttgg agaagctgat ttccacttta agaaccctgt caccctgggt 5040
tgggatgttt ctcctagtgt aggatgagtt tctagctcct gggataattc gttttgtcta 5100
agcaaaagat gatttgaggt gggaccagat gagcaaggat gtccttgcag ttgattctgc 5160
atgactataa aacaggccaa aattaaaacc acgaaggaat cctgaggcag attggcccct 5220
ggcacctgag gagtgagcct gagggatccc actctgcagt aggagtaacg tgagcgagca 5280
agtgaatggg gtgggtttac cggctctgta atctatcaac ctagggcctc agcagtggcc 5340
ccctgcccag taggaattgg accaatccca agttctaagg cttgtcttaa gtccttgcag 5400
aacaaggaca aactttctga atcattcatt tctctcatct agagctggtg ggagattgag 5460
aggtgaatgg gacatccaag atccctaaaa agaattgttc gatagcgtgc atgtgttata 5520
aagtggtgac acgggcatcc tgttgaaatg atggatggct cactgccata ggctgatagc 5580
agttgtcata aagatatttt gggggaattt gaaaaggacg taaagaaaaa tctttcatat 5640
tggcttgttg gttatataac ttcaaattta ataaaggaat acttacgtag taattacatt 5700
tccttgaaaa aactatagtg aatagaaatc cctagccatt tcatttttta tgtttttaat 5760
gaagatcttt aaaataccat aggtggtaat cgtggaaaat ttgaaaaatc tcatgtcagt 5820
gtattaagat ggtggagaag tttttttctc cattatttaa tggaactttg ggtcttttta 5880
ttaaaaatgt gagactcatg aaattttggc agctgaatat ttgtgaaata agaatgaatt 5940
attaaaagat gtctttccat a 5961
<210> 48
<211> 4601
<212> DNA
<213> Mus musculus
<400> 48
ctggaggggg aagtgaatgg cgaaggactg aaggggtccc ccttcggttc cccagccacc 60
tggttcaccc ggttcatcct cccttcccga agttagccct cgaaggcacg agcagccggc 120
gccttcggca gaggaggagg aggaggaggg atcgcgtcgg gcggagcttc aggtcctgtt 180
cgtctctccg gcttctccat acaaagatta cggtgcagaa ggaaattgca cttgcctcct 240
ccgccccccg gtacccagca caatgcacca gccgccggag tccaccgccg cggcggccgc 300
tgctgcagac attagtgcta ggaagatggc gcacccggca atgttccctc gaaggggcag 360
cggtggtggc agcgcctctg ctctcaatgc agcaggtacg ggcgtcagtg gtgctgctcc 420
atcttctgaa gattttcctc ctccttcgct gctccagccg ccgcctcctg ctgcatcttc 480
cacgcaggga ccccagcctc cgcctccaca aagcctgaac ctcctctcgc aggctcagct 540
gcagggacag cctcttgcgc caggcggaac tcagatgaaa aagaaaagtg gcttccagat 600
aactagcgtt actccggctc agatctctgc cagcatcagc tccaacaaca gcatcgcgga 660
ggacaccgag agctacgacg atctggatga gtcgcacacg gaagatctct cctcttccga 720
gatcctcgac gtctcccttt ccagggccac tgacttaggt gagcctgaac gaagctcctc 780
agaggagact ctgaataact tccaggaagc tgagacacct ggggcagtct ctcctaacca 840
gccccacctt cctcagcctc atttgcctca ccttccacaa cagaacgttg tgatcaatgg 900
gaatgcccat ccccaccacc tccatcatca ccatcaccct catcatgggc accaccttca 960
ccatgggcac catcattcat cacatgctgc tgtggccggt ccatccattc ccggagggcc 1020
accctcgagc ccagtgtcca ggaaactctc tacaactgga agttctgatg gtggtgtgcc 1080
agtcgcacct cctcctgcag taccatcgag tggcttacca gcatcagtga tgacgaacat 1140
ccgtactcca agtactacag gaagcctagg tataaattcg gttactggca cgagcgctac 1200
gaataatgtt aacattgctg ctgtgggtag tttcagtccc agtgtgacga acagcgtgca 1260
tggtaatgct aatataaata caagcaatat ccctaatgct gctagcataa gtggtgggcc 1320
tggagttacc agtgttgtta attcgagtat cttgagtggc atgggcaatg gtaccgtttc 1380
ttcctctcct gttgctaaca gtgtccttaa tgcagctgca ggtatcactg tgggagtggt 1440
ttccagtcag cagcagcagc agcagcagca gcaaccaaca gttaacacat cgaggttcag 1500
ggttgtgaag ttagactcta cttctgaacc ctttaaaaaa ggtcgatgga cttgcacaga 1560
attctatgag aaggaaaacg ctgtgccagc tacagaaggc gtggccgtca ataaagtggt 1620
ggagacggtg aagcaaaccc ccacggaagc atcgtcctcg gagagggaga gcactagtgg 1680
gagttctgtg agcagtagtg tgagcacact gagtcactac acggagagtg tgggaagtgg 1740
agagatgatg ggagccccgg ctgtggtggc gccgcagcag ccgccgctac caccagcgcc 1800
tccaggtctt caaggtgtgg ctctccaaca gctagagttc agtagccctg ctccacagag 1860
tattgcggcg gttagtatgc cacagagtat ttctcagtca cagatgtcac aagtacagtt 1920
acagcctcaa gagttgagct ttcagcagaa gcagactctt cagcctgtcc ctctgcaagc 1980
caccatgagt gccgcaactg gtatccagcc ttcccctgtc agcgtggtcg gcatcacggc 2040
ggctgtaggt cagcagcctt ctgtttccag cctggctcaa ccgcagctgc catattctca 2100
gacagctcct cccgtgcaaa ctcctcttcc aggggcacca ccccagcagt tacaatatgg 2160
gcagcagcaa ccaatggttc ctgcgcagat agccccaggc catggccagc cagtgactca 2220
aaatccaact tcagagtatg tgcagcagca gcagcagcca atatttcaag cagcattgtc 2280
ctctgggcag tccagttcca cgggcacggg ggcaggaata tcagtgattc ctgtggctca 2340
ggcacagggg atccagctgc cagggcagcc cacagcagta caaacacaac ctgcaggggc 2400
ggctgggcag cccattggcc aggctcaaac agcagtgtcc actgtaccaa ctggcggtca 2460
gattgcaagt atcggtcaac aggcaaacat acccactgca gtacagcagc cctctaccca 2520
agttacacct tcagttattc agcaaggtgc tcctccatct tcacaagtag tcctacctgc 2580
tccaaccggg atcattcatc agggagttca aacccgtgct tcaagccttc cacaacaatt 2640
ggtcattgca ccccagagta ccttggtaac tgtgcctccc cagccacagg gagtagaaac 2700
cgtggcccaa ggggttgttt cccagcagtt gcccacaggc agtcctctgc cctctgctag 2760
cactatttct gttacaaatc aggttagttc agccgctcct tctggaatgc cttctgtccc 2820
aacaaactta gttccaccac agaatatagc acaaccccca gccacccaaa atggcagttt 2880
ggttcaaagt gttagtcaat ctcccttgat agccactaac ataaatttgc ctttggcaca 2940
acagatacca ctaagttcta ctcagttctc tacacaatca ttagctcagg ccattggaag 3000
ccaaatggaa gatgccaggc gcccagcgga gccctcctta ggcggcttac ctcagactat 3060
gagtggtgac agtgggggaa tgtcagcagt ttcagatggg agtagcagca gcctagcagc 3120
ccctgcttct ctcttcccgt tgaaggtgct accgctgaca acacccctgg tggatggcga 3180
ggacgagagc tctggtgcaa gtgtggtagc tatcgacaac aaaatagagc aagctatgga 3240
tctggtgaaa agccatttga tgtatgcggt gagggaggaa gtggaagttc tgaaggagca 3300
gatcaaagaa ctaatagaga aaaactccca gctggagcag gagaacaatc tgctgaagac 3360
gctggccagt ccggagcagc tcgcccagtt tcaggcccag ctgcagactg gctcccctcc 3420
ggccaccacg cagccacagg ggaccacaca gccccctgca cagccagcat cccagggctc 3480
aggatcaacc gcatagcctc ctaggcccca acagaactgg ctgctgctgc tgctgtctga 3540
actgaacaga ccgaagagat gtgctagaga gaagccgcct ccacagtcac ccatttcatt 3600
gctgtctacg aaagagacgt gagactcaca cgctgttctc gctttctccc cagtattaag 3660
cactcataag cttttggctt gaagaaatgt actagttgag tgaattaaag gttaatcaga 3720
gagtgagcag ggatgtgccc tgtgcaacgt ggcagatgtc tgaggaatgg tttaattgac 3780
cccgaggagc tctgtgcctt ttcaaccctc cccagccgcc caccctgctt ctgagagctc 3840
gggcggctcg ccttcgtggg gctcgcctgc gtggggttcg gaaagtgggc tgctcctgga 3900
ttctgcgctc tcttctcctt cccttcaaag aactcggaga ggccagaaac aagactgcaa 3960
tggggggcgg ggggagggat gatgcagtcc ttatacaaaa ccgacaactg tcaccaaagc 4020
ttataaaaca cgatagtact gtccctcttt tctgaaccat cagaagacac aaaactgtta 4080
gtgacacaac ggtgacaggt agctgggacc taggctatct tattatgaag gttgttttgc 4140
ttgttgtata tttgtgtatg tagtgtaacg aatttgtacc atagaggact gtccgtaact 4200
actgtttagc ttctacacat tgaaatgtag atgtttcatt ggctgtctga aaaggtgtgg 4260
cttgtccttc ctagagagat ctacttaaaa actgctttgt gacaaaaacc acacctgaag 4320
aaattttaag aatttggccc agttagtcac tctgtgtaat cccggaatct agctgctgaa 4380
gtcttgcgaa gtaaactccc cgtgaccgat gtcagttaag ctggtgatac ctggagaagt 4440
ggtcagttgc taaggaagtg gatttcccag taggggtttc tgcacctcac ctgtatagtc 4500
gttctgcgca tgtcccccac acagtcccca ctgtatttac ctgttctact tgtcaccttt 4560
caataaagca tatcaaatgt tgatacaaaa aaaaaaaaaa a 4601
<210> 49
<211> 436
<212> PRT
<213> Homo sapiens
<400> 49
Met Ala Gly Val Pro Glu Ser Leu Asn Leu Met Cys Asp Arg Asn Gly
1 5 10 15
Gly Arg Arg Leu Arg Gln Trp Leu Ile Glu Gln Ile Asp Ser Ser Met
20 25 30
Tyr Pro Gly Leu Ile Trp Glu Asn Glu Glu Lys Ser Met Phe Arg Ile
35 40 45
Pro Trp Lys His Ala Gly Lys Gln Asp Tyr Asn Gln Glu Val Asp Ala
50 55 60
Ser Ile Phe Lys Ala Trp Ala Val Phe Lys Gly Lys Phe Lys Glu Gly
65 70 75 80
Asp Lys Ala Glu Pro Ala Thr Trp Lys Thr Arg Leu Arg Cys Ala Leu
85 90 95
Asn Lys Ser Pro Asp Phe Glu Glu Val Thr Asp Arg Ser Gln Leu Asp
100 105 110
Ile Ser Glu Pro Tyr Lys Val Tyr Arg Ile Val Pro Glu Glu Glu Gln
115 120 125
Lys Cys Lys Leu Gly Val Ala Thr Ala Gly Cys Val Asn Glu Val Thr
130 135 140
Glu Met Glu Cys Gly Arg Ser Glu Ile Asp Glu Leu Ile Lys Glu Pro
145 150 155 160
Ser Val Asp Asp Tyr Met Gly Met Ile Lys Arg Ser Pro Ser Pro Pro
165 170 175
Glu Ala Cys Arg Ser Gln Leu Leu Pro Asp Trp Trp Ala Gln Gln Pro
180 185 190
Ser Thr Gly Val Pro Leu Val Thr Gly Tyr Thr Thr Tyr Asp Ala His
195 200 205
His Ser Ala Phe Ser Gln Met Val Ile Ser Phe Tyr Tyr Gly Gly Lys
210 215 220
Leu Val Gly Gln Ala Thr Thr Thr Cys Pro Glu Gly Cys Arg Leu Ser
225 230 235 240
Leu Ser Gln Pro Gly Leu Pro Gly Thr Lys Leu Tyr Gly Pro Glu Gly
245 250 255
Leu Glu Leu Val Arg Phe Pro Pro Ala Asp Ala Ile Pro Ser Glu Arg
260 265 270
Gln Arg Gln Val Thr Arg Lys Leu Phe Gly His Leu Glu Arg Gly Val
275 280 285
Leu Leu His Ser Ser Arg Gln Gly Val Phe Val Lys Arg Leu Cys Gln
290 295 300
Gly Arg Val Phe Cys Ser Gly Asn Ala Val Val Cys Lys Gly Arg Pro
305 310 315 320
Asn Lys Leu Glu Arg Asp Glu Val Val Gln Val Phe Asp Thr Ser Gln
325 330 335
Phe Phe Arg Glu Leu Gln Gln Phe Tyr Asn Ser Gln Gly Arg Leu Pro
340 345 350
Asp Gly Arg Val Val Leu Cys Phe Gly Glu Glu Phe Pro Asp Met Ala
355 360 365
Pro Leu Arg Ser Lys Leu Ile Leu Val Gln Ile Glu Gln Leu Tyr Val
370 375 380
Arg Gln Leu Ala Glu Glu Ala Gly Lys Ser Cys Gly Ala Gly Ser Val
385 390 395 400
Met Gln Ala Pro Glu Glu Pro Pro Pro Asp Gln Val Phe Arg Met Phe
405 410 415
Pro Asp Ile Cys Ala Ser His Gln Arg Ser Phe Phe Arg Glu Asn Gln
420 425 430
Gln Ile Thr Val
435
<210> 50
<211> 424
<212> PRT
<213> Mus musculus
<400> 50
Met Cys Asp Arg Asn Gly Gly Arg Arg Leu Arg Gln Trp Leu Ile Glu
1 5 10 15
Gln Ile Asp Ser Ser Met Tyr Pro Gly Leu Ile Trp Glu Asn Asp Glu
20 25 30
Lys Thr Met Phe Arg Ile Pro Trp Lys His Ala Gly Lys Gln Asp Tyr
35 40 45
Asn Gln Glu Val Asp Ala Ser Ile Phe Lys Ala Trp Ala Val Phe Lys
50 55 60
Gly Lys Phe Lys Glu Gly Asp Lys Ala Glu Pro Ala Thr Trp Lys Thr
65 70 75 80
Arg Leu Arg Cys Ala Leu Asn Lys Ser Pro Asp Phe Glu Glu Val Thr
85 90 95
Asp Arg Ser Gln Leu Asp Ile Ser Glu Pro Tyr Lys Val Tyr Arg Ile
100 105 110
Val Pro Glu Glu Glu Gln Lys Cys Lys Leu Gly Val Ala Pro Ala Gly
115 120 125
Cys Met Ser Glu Val Pro Glu Met Glu Cys Gly Arg Ser Glu Ile Glu
130 135 140
Glu Leu Ile Lys Glu Pro Ser Val Asp Glu Tyr Met Gly Met Thr Lys
145 150 155 160
Arg Ser Pro Ser Pro Pro Glu Ala Cys Arg Ser Gln Ile Leu Pro Asp
165 170 175
Trp Trp Val Gln Gln Pro Ser Ala Gly Leu Pro Leu Val Thr Gly Tyr
180 185 190
Ala Ala Tyr Asp Thr His His Ser Ala Phe Ser Gln Met Val Ile Ser
195 200 205
Phe Tyr Tyr Gly Gly Lys Leu Val Gly Gln Ala Thr Thr Thr Cys Leu
210 215 220
Glu Gly Cys Arg Leu Ser Leu Ser Gln Pro Gly Leu Pro Lys Leu Tyr
225 230 235 240
Gly Pro Asp Gly Leu Glu Pro Val Cys Phe Pro Thr Ala Asp Thr Ile
245 250 255
Pro Ser Glu Arg Gln Arg Gln Val Thr Arg Lys Leu Phe Gly His Leu
260 265 270
Glu Arg Gly Val Leu Leu His Ser Asn Arg Lys Gly Val Phe Val Lys
275 280 285
Arg Leu Cys Gln Gly Arg Val Phe Cys Ser Gly Asn Ala Val Val Cys
290 295 300
Lys Gly Arg Pro Asn Lys Leu Glu Arg Asp Glu Val Val Gln Val Phe
305 310 315 320
Asp Thr Asn Gln Phe Ile Arg Glu Leu Gln Gln Phe Tyr Ala Thr Gln
325 330 335
Ser Arg Leu Pro Asp Ser Arg Val Val Leu Cys Phe Gly Glu Glu Phe
340 345 350
Pro Asp Thr Val Pro Leu Arg Ser Lys Leu Ile Leu Val Gln Val Glu
355 360 365
Gln Leu Tyr Ala Arg Gln Leu Val Glu Glu Ala Gly Lys Ser Cys Gly
370 375 380
Ala Gly Ser Leu Met Pro Ala Leu Glu Glu Pro Gln Pro Asp Gln Ala
385 390 395 400
Phe Arg Met Phe Pro Asp Ile Cys Thr Ser His Gln Arg Pro Phe Phe
405 410 415
Arg Glu Asn Gln Gln Ile Thr Val
420
<210> 51
<211> 262
<212> PRT
<213> Homo sapiens
<400> 51
Met Leu Ala Leu Glu Ala Ala Gln Leu Asp Gly Pro His Phe Ser Cys
1 5 10 15
Leu Tyr Pro Asp Gly Val Phe Tyr Asp Leu Asp Ser Cys Lys His Ser
20 25 30
Ser Tyr Pro Asp Ser Glu Gly Ala Pro Asp Ser Leu Trp Asp Trp Thr
35 40 45
Val Ala Pro Pro Val Pro Ala Thr Pro Tyr Glu Ala Phe Asp Pro Ala
50 55 60
Ala Ala Ala Phe Ser His Pro Gln Ala Ala Gln Leu Cys Tyr Glu Pro
65 70 75 80
Pro Thr Tyr Ser Pro Ala Gly Asn Leu Glu Leu Ala Pro Ser Leu Glu
85 90 95
Ala Pro Gly Pro Gly Leu Pro Ala Tyr Pro Thr Glu Asn Phe Ala Ser
100 105 110
Gln Thr Leu Val Pro Pro Ala Tyr Ala Pro Tyr Pro Ser Pro Val Leu
115 120 125
Ser Glu Glu Glu Asp Leu Pro Leu Asp Ser Pro Ala Leu Glu Val Ser
130 135 140
Asp Ser Glu Ser Asp Glu Ala Leu Val Ala Gly Pro Glu Gly Lys Gly
145 150 155 160
Ser Glu Ala Gly Thr Arg Lys Lys Leu Arg Leu Tyr Gln Phe Leu Leu
165 170 175
Gly Leu Leu Thr Arg Gly Asp Met Arg Glu Cys Val Trp Trp Val Glu
180 185 190
Pro Gly Ala Gly Val Phe Gln Phe Ser Ser Lys His Lys Glu Leu Leu
195 200 205
Ala Arg Arg Trp Gly Gln Gln Lys Gly Asn Arg Lys Arg Met Thr Tyr
210 215 220
Gln Lys Leu Ala Arg Ala Leu Arg Asn Tyr Ala Lys Thr Gly Glu Ile
225 230 235 240
Arg Lys Val Lys Arg Lys Leu Thr Tyr Gln Phe Asp Ser Ala Leu Leu
245 250 255
Pro Ala Val Arg Arg Ala
260
<210> 52
<211> 267
<212> PRT
<213> Mus musculus
<400> 52
Met Leu Ala Leu Glu Ala Ala Gln Leu Asp Gly Pro His Leu Ser Cys
1 5 10 15
Leu Tyr Pro Glu Gly Val Phe Tyr Asp Leu Asp Ser Cys Lys Pro Phe
20 25 30
Ser Tyr Pro Asp Ser Asp Gly Gly Leu Asp Ser Thr Trp Gly Trp Thr
35 40 45
Glu Ala Pro Pro Ala Pro Ala Ile Ala Pro Tyr Glu Ala Phe Asp Pro
50 55 60
Ala Thr Ala Ala Phe Ser His Ser Gln Thr Val Gln Leu Cys Tyr Ser
65 70 75 80
His Gly Pro Asn Pro Ser Thr Tyr Ser Pro Met Gly Thr Leu Asp Pro
85 90 95
Ala Pro Ser Leu Glu Ala Pro Gly Pro Gly Leu Gln Val Tyr Pro Pro
100 105 110
Glu Asp Phe Thr Ser Gln Thr Leu Gly Ser Leu Ala Tyr Ala Pro Tyr
115 120 125
Pro Ser Pro Val Leu Ser Glu Glu Glu Asp Ile Met Leu Asp Ser Pro
130 135 140
Ala Leu Glu Val Ser Asp Ser Glu Ser Asp Glu Ala Leu Leu Ala Gly
145 150 155 160
Ser Glu Gly Arg Gly Ser Glu Ala Gly Ala Arg Lys Lys Leu Arg Leu
165 170 175
Tyr Gln Phe Leu Leu Gly Leu Leu Leu Arg Gly Asp Met Arg Glu Cys
180 185 190
Val Trp Trp Val Glu Pro Gly Ala Gly Val Phe Gln Phe Ser Ser Lys
195 200 205
His Lys Glu Leu Leu Ala Arg Arg Trp Gly Gln Gln Lys Gly Asn Arg
210 215 220
Lys Arg Met Thr Tyr Gln Lys Leu Ala Arg Ala Leu Arg Asn Tyr Ala
225 230 235 240
Lys Thr Gly Glu Ile Arg Lys Val Lys Arg Lys Leu Thr Tyr Gln Phe
245 250 255
Asp Ser Ala Leu Leu Pro Ala Ser Arg His Val
260 265
<210> 53
<211> 648
<212> PRT
<213> Homo sapiens
<400> 53
Met Ala Ala Pro Val Lys Gly Asn Arg Lys Gln Ser Thr Glu Gly Asp
1 5 10 15
Ala Leu Asp Pro Pro Ala Ser Pro Lys Pro Ala Gly Lys Gln Asn Gly
20 25 30
Ile Gln Asn Pro Ile Ser Leu Glu Asp Ser Pro Glu Ala Gly Gly Glu
35 40 45
Arg Glu Glu Glu Gln Glu Arg Glu Glu Glu Gln Ala Phe Leu Val Ser
50 55 60
Leu Tyr Lys Phe Met Lys Glu Arg His Thr Pro Ile Glu Arg Val Pro
65 70 75 80
His Leu Gly Phe Lys Gln Ile Asn Leu Trp Lys Ile Tyr Lys Ala Val
85 90 95
Glu Lys Leu Gly Ala Tyr Glu Leu Gln Ser Met Ala Leu Gly Glu Arg
100 105 110
Ile Gly Trp Pro Leu Leu Glu Pro Gln Ser Ser Cys Gln Thr Ala Val
115 120 125
Leu Arg Val Pro Ala Arg Ala Ala Gly Ala Ala Arg Thr Pro Pro Pro
130 135 140
Gly Gly Ala Arg Arg Pro Arg Pro His Glu Val Pro Leu Gln Val Thr
145 150 155 160
Gly Arg Arg Leu Trp Lys Asn Val Tyr Asp Glu Leu Gly Gly Ser Pro
165 170 175
Gly Ser Thr Ser Ala Ala Thr Cys Thr Arg Arg His Tyr Glu Arg Leu
180 185 190
Val Leu Pro Tyr Val Arg His Leu Lys Gly Glu Asp Asp Lys Pro Leu
195 200 205
Pro Thr Ser Lys Pro Arg Lys Gln Tyr Lys Met Ala Lys Glu Asn Arg
210 215 220
Gly Asp Asp Gly Ala Thr Glu Arg Pro Lys Lys Ala Lys Glu Glu Arg
225 230 235 240
Arg Met Asp Gln Met Met Pro Gly Lys Thr Lys Ala Asp Ala Ala Asp
245 250 255
Pro Ala Pro Leu Pro Ser Gln Glu Pro Pro Arg Asn Ser Thr Glu Gln
260 265 270
Gln Gly Leu Ala Ser Gly Ser Ser Val Ser Phe Val Gly Ala Ser Gly
275 280 285
Cys Pro Glu Ala Tyr Lys Arg Leu Leu Ser Ser Phe Tyr Cys Lys Gly
290 295 300
Thr His Gly Ile Met Ser Pro Leu Ala Lys Lys Lys Leu Leu Ala Gln
305 310 315 320
Val Ser Lys Val Glu Ala Leu Gln Cys Gln Glu Glu Gly Cys Arg His
325 330 335
Gly Ala Glu Pro Gln Ala Ser Pro Ala Val His Leu Pro Glu Ser Pro
340 345 350
Gln Ser Pro Lys Gly Leu Thr Glu Asn Ser Arg His Arg Leu Thr Pro
355 360 365
Gln Glu Gly Leu Gln Ala Pro Gly Gly Ser Leu Arg Glu Glu Ala Gln
370 375 380
Ala Gly Pro Cys Pro Ala Ala Pro Ile Phe Lys Gly Cys Phe Tyr Thr
385 390 395 400
His Pro Thr Glu Val Leu Lys Pro Val Ser Gln His Pro Arg Asp Phe
405 410 415
Phe Ser Arg Leu Lys Asp Gly Val Leu Leu Gly Pro Pro Gly Lys Glu
420 425 430
Gly Leu Ser Val Lys Glu Pro Gln Leu Val Trp Gly Gly Asp Ala Asn
435 440 445
Arg Pro Ser Ala Phe His Lys Gly Gly Ser Arg Lys Gly Ile Leu Tyr
450 455 460
Pro Lys Pro Lys Ala Cys Trp Val Ser Pro Met Ala Lys Val Pro Ala
465 470 475 480
Glu Ser Pro Thr Leu Pro Pro Thr Phe Pro Ser Ser Pro Gly Leu Gly
485 490 495
Ser Lys Arg Ser Leu Glu Glu Glu Gly Ala Ala His Ser Gly Lys Arg
500 505 510
Leu Arg Ala Val Ser Pro Phe Leu Lys Glu Ala Asp Ala Lys Lys Cys
515 520 525
Gly Ala Lys Pro Ala Gly Ser Gly Leu Val Ser Cys Leu Leu Gly Pro
530 535 540
Ala Leu Gly Pro Val Pro Pro Glu Ala Tyr Arg Gly Thr Met Leu His
545 550 555 560
Cys Pro Leu Asn Phe Thr Gly Thr Pro Gly Pro Leu Lys Gly Gln Ala
565 570 575
Ala Leu Pro Phe Ser Pro Leu Val Ile Pro Ala Phe Pro Ala His Phe
580 585 590
Leu Ala Thr Ala Gly Pro Ser Pro Met Ala Ala Gly Leu Met His Phe
595 600 605
Pro Pro Thr Ser Phe Asp Ser Ala Leu Arg His Arg Leu Cys Pro Ala
610 615 620
Ser Ser Ala Trp His Ala Pro Pro Val Thr Thr Tyr Ala Ala Pro His
625 630 635 640
Phe Phe His Leu Asn Thr Lys Leu
645
<210> 54
<211> 590
<212> PRT
<213> Mus musculus
<400> 54
Met Ala Ala Pro Pro Ala Lys Gly Asn Thr Glu Gln Ser Glu Glu Gly
1 5 10 15
Asp Leu Pro Gln Leu Pro Val Ser Pro Lys Pro Asp Asp Glu Gln Ser
20 25 30
Arg Ser Gln Ser Pro Thr Gln Leu Gln Asp Ser Pro Glu Ala Gly Gly
35 40 45
Glu Gln Glu Glu Glu Gln Ala Phe Leu Val Ser Leu Tyr Lys Phe Met
50 55 60
Lys Glu Arg His Thr Pro Ile Glu Arg Val Pro His Leu Gly Phe Lys
65 70 75 80
Gln Ile Asn Leu Trp Lys Ile Tyr Lys Ala Val Glu Lys Leu Gly Ala
85 90 95
Tyr Glu Leu Val Thr Gly Arg Arg Leu Trp Lys Asn Val Tyr Asp Glu
100 105 110
Leu Gly Gly Ser Pro Gly Ser Thr Ser Ala Ala Thr Cys Thr Arg Arg
115 120 125
His Tyr Glu Arg Leu Val Leu Pro Tyr Val Arg His Leu Lys Gly Glu
130 135 140
Asp Asp Lys Pro Leu Pro Pro Thr Lys Pro Arg Lys Gln Tyr Lys Met
145 150 155 160
Ala Lys Glu Leu Arg Gly Asp Asp Gly Thr Thr Glu Lys Leu Lys Lys
165 170 175
Ala Lys Asp Ser Glu Glu Arg Arg Val Glu Gln Thr Thr Pro Gly Lys
180 185 190
Thr Lys Ser Asp Ala Thr Gly Gln Thr Gln Leu Pro Cys Gln Gly Ser
195 200 205
Ser Arg Asp Ser Thr Glu Gln Leu Gly Pro Val Ser Gly Pro Ser Pro
210 215 220
Pro Leu Thr Gly Ala Ser Ser Cys Pro Glu Ala Tyr Lys Arg Leu Leu
225 230 235 240
Ser Ser Phe Tyr Cys Lys Gly Ala His Gly Ile Met Ser Pro Leu Ala
245 250 255
Lys Lys Lys Leu Leu Ala Gln Val Ser Lys Ala Glu Ala Leu Gln Cys
260 265 270
Gln Glu Glu Gly Cys Arg His Gly Ala Arg Ser Pro Asn Lys Asp Ile
275 280 285
Gln Asp Ser Pro Gln Asn Leu Arg Gly Pro Ala Glu Asn Ser Glu His
290 295 300
Gln Leu Thr Pro Arg Glu Gly Leu Gln Ala Pro Gly Gly Ser Thr Arg
305 310 315 320
Met Glu Ala Gln Val Gly Pro Cys Pro Thr Ala Pro Met Phe Ser Gly
325 330 335
Cys Phe His Ala Tyr Pro Thr Glu Val Leu Lys Pro Val Ser Gln His
340 345 350
Pro Arg Asp Phe Phe Ser Gly Leu Lys Asp Arg Val Leu Leu Gly Pro
355 360 365
Pro Gly Lys Glu Glu Gly Pro Thr Thr Lys Glu Ser His Leu Val Trp
370 375 380
Gly Gly Asp Ala Asn His Pro Ser Ala Phe His Lys Gly Ser Thr Arg
385 390 395 400
Lys Arg Ser Phe Tyr Pro Lys Pro Lys Ala Cys Trp Val Ser Pro Met
405 410 415
Ala Lys Val Pro Thr Glu Arg Pro Gly Ala Pro Ser Pro His Pro Ser
420 425 430
Ser Pro Gly Leu Gly Ser Lys Arg Gly Leu Glu Glu Glu Gly Phe Ala
435 440 445
His Gly Gly Lys Lys Leu Arg Ala Val Ser Pro Phe Leu Lys Glu Val
450 455 460
Asp Ser Lys Glu Thr Gly Gly Lys Pro Ala Ala Pro Gly Leu Ala Val
465 470 475 480
Ser Cys Leu Leu Gly Pro Thr Pro Gly Pro Thr Pro Pro Glu Ala Tyr
485 490 495
Arg Gly Thr Met Leu Arg Cys Pro Leu Asn Phe Thr Gly Ser Ala Asp
500 505 510
Pro Leu Lys Gly Gln Ala Ser Leu Pro Phe Ser Pro Leu Val Ile Pro
515 520 525
Ala Phe Pro Ala His Leu Leu Ala Thr Thr Gly Ser Ser Pro Met Ala
530 535 540
Ala Ser Leu Met His Phe Pro Pro Thr Pro Tyr Asp Ala Val Leu Arg
545 550 555 560
Asn Arg Leu Gly Pro Ala Ser Ser Ala Trp His Met Pro Pro Val Thr
565 570 575
Thr Tyr Ala Ala Pro His Phe Phe His Leu Asn Thr Lys Leu
580 585 590
<210> 55
<211> 835
<212> PRT
<213> Homo sapiens
<400> 55
Met Ser Arg Arg Lys Gln Gly Lys Pro Gln His Leu Ser Lys Arg Glu
1 5 10 15
Phe Ser Pro Glu Pro Leu Glu Ala Ile Leu Thr Asp Asp Glu Pro Asp
20 25 30
His Gly Pro Leu Gly Ala Pro Glu Gly Asp His Asp Leu Leu Thr Cys
35 40 45
Gly Gln Cys Gln Met Asn Phe Pro Leu Gly Asp Ile Leu Ile Phe Ile
50 55 60
Glu His Lys Arg Lys Gln Cys Asn Gly Ser Leu Cys Leu Glu Lys Ala
65 70 75 80
Val Asp Lys Pro Pro Ser Pro Ser Pro Ile Glu Met Lys Lys Ala Ser
85 90 95
Asn Pro Val Glu Val Gly Ile Gln Val Thr Pro Glu Asp Asp Asp Cys
100 105 110
Leu Ser Thr Ser Ser Arg Gly Ile Cys Pro Lys Gln Glu His Ile Ala
115 120 125
Asp Lys Leu Leu His Trp Arg Gly Leu Ser Ser Pro Arg Ser Ala His
130 135 140
Gly Ala Leu Ile Pro Thr Pro Gly Met Ser Ala Glu Tyr Ala Pro Gln
145 150 155 160
Gly Ile Cys Lys Asp Glu Pro Ser Ser Tyr Thr Cys Thr Thr Cys Lys
165 170 175
Gln Pro Phe Thr Ser Ala Trp Phe Leu Leu Gln His Ala Gln Asn Thr
180 185 190
His Gly Leu Arg Ile Tyr Leu Glu Ser Glu His Gly Ser Pro Leu Thr
195 200 205
Pro Arg Val Gly Ile Pro Ser Gly Leu Gly Ala Glu Cys Pro Ser Gln
210 215 220
Pro Pro Leu His Gly Ile His Ile Ala Asp Asn Asn Pro Phe Asn Leu
225 230 235 240
Leu Arg Ile Pro Gly Ser Val Ser Arg Glu Ala Ser Gly Leu Ala Glu
245 250 255
Gly Arg Phe Pro Pro Thr Pro Pro Leu Phe Ser Pro Pro Pro Arg His
260 265 270
His Leu Asp Pro His Arg Ile Glu Arg Leu Gly Ala Glu Glu Met Ala
275 280 285
Leu Ala Thr His His Pro Ser Ala Phe Asp Arg Val Leu Arg Leu Asn
290 295 300
Pro Met Ala Met Glu Pro Pro Ala Met Asp Phe Ser Arg Arg Leu Arg
305 310 315 320
Glu Leu Ala Gly Asn Thr Ser Ser Pro Pro Leu Ser Pro Gly Arg Pro
325 330 335
Ser Pro Met Gln Arg Leu Leu Gln Pro Phe Gln Pro Gly Ser Lys Pro
340 345 350
Pro Phe Leu Ala Thr Pro Pro Leu Pro Pro Leu Gln Ser Ala Pro Pro
355 360 365
Pro Ser Gln Pro Pro Val Lys Ser Lys Ser Cys Glu Phe Cys Gly Lys
370 375 380
Thr Phe Lys Phe Gln Ser Asn Leu Val Val His Arg Arg Ser His Thr
385 390 395 400
Gly Glu Lys Pro Tyr Lys Cys Asn Leu Cys Asp His Ala Cys Thr Gln
405 410 415
Ala Ser Lys Leu Lys Arg His Met Lys Thr His Met His Lys Ser Ser
420 425 430
Pro Met Thr Val Lys Ser Asp Asp Gly Leu Ser Thr Ala Ser Ser Pro
435 440 445
Glu Pro Gly Thr Ser Asp Leu Val Gly Ser Ala Ser Ser Ala Leu Lys
450 455 460
Ser Val Val Ala Lys Phe Lys Ser Glu Asn Asp Pro Asn Leu Ile Pro
465 470 475 480
Glu Asn Gly Asp Glu Glu Glu Glu Glu Asp Asp Glu Glu Glu Glu Glu
485 490 495
Glu Glu Glu Glu Glu Glu Glu Glu Leu Thr Glu Ser Glu Arg Val Asp
500 505 510
Tyr Gly Phe Gly Leu Ser Leu Glu Ala Ala Arg His His Glu Asn Ser
515 520 525
Ser Arg Gly Ala Val Val Gly Val Gly Asp Glu Ser Arg Ala Leu Pro
530 535 540
Asp Val Met Gln Gly Met Val Leu Ser Ser Met Gln His Phe Ser Glu
545 550 555 560
Ala Phe His Gln Val Leu Gly Glu Lys His Lys Arg Gly His Leu Ala
565 570 575
Glu Ala Glu Gly His Arg Asp Thr Cys Asp Glu Asp Ser Val Ala Gly
580 585 590
Glu Ser Asp Arg Ile Asp Asp Gly Thr Val Asn Gly Arg Gly Cys Ser
595 600 605
Pro Gly Glu Ser Ala Ser Gly Gly Leu Ser Lys Lys Leu Leu Leu Gly
610 615 620
Ser Pro Ser Ser Leu Ser Pro Phe Ser Lys Arg Ile Lys Leu Glu Lys
625 630 635 640
Glu Phe Asp Leu Pro Pro Ala Ala Met Pro Asn Thr Glu Asn Val Tyr
645 650 655
Ser Gln Trp Leu Ala Gly Tyr Ala Ala Ser Arg Gln Leu Lys Asp Pro
660 665 670
Phe Leu Ser Phe Gly Asp Ser Arg Gln Ser Pro Phe Ala Ser Ser Ser
675 680 685
Glu His Ser Ser Glu Asn Gly Ser Leu Arg Phe Ser Thr Pro Pro Gly
690 695 700
Glu Leu Asp Gly Gly Ile Ser Gly Arg Ser Gly Thr Gly Ser Gly Gly
705 710 715 720
Ser Thr Pro His Ile Ser Gly Pro Gly Pro Gly Arg Pro Ser Ser Lys
725 730 735
Glu Gly Arg Arg Ser Asp Thr Cys Glu Tyr Cys Gly Lys Val Phe Lys
740 745 750
Asn Cys Ser Asn Leu Thr Val His Arg Arg Ser His Thr Gly Glu Arg
755 760 765
Pro Tyr Lys Cys Glu Leu Cys Asn Tyr Ala Cys Ala Gln Ser Ser Lys
770 775 780
Leu Thr Arg His Met Lys Thr His Gly Gln Val Gly Lys Asp Val Tyr
785 790 795 800
Lys Cys Glu Ile Cys Lys Met Pro Phe Ser Val Tyr Ser Thr Leu Glu
805 810 815
Lys His Met Lys Lys Trp His Ser Asp Arg Val Leu Asn Asn Asp Ile
820 825 830
Lys Thr Glu
835
<210> 56
<211> 773
<212> PRT
<213> Mus musculus
<400> 56
Met Ser Arg Arg Lys Gln Gly Lys Pro Gln His Leu Ser Lys Arg Glu
1 5 10 15
Phe Ser Pro Glu Pro Leu Glu Ala Ile Leu Thr Asp Asp Glu Pro Asp
20 25 30
His Gly Pro Leu Gly Ala Pro Glu Gly Asp His Asp Leu Leu Thr Cys
35 40 45
Gly Gln Cys Gln Met Asn Phe Pro Leu Gly Asp Ile Leu Ile Phe Ile
50 55 60
Glu His Lys Arg Lys Gln Cys Asn Gly Ser Leu Cys Leu Glu Lys Gly
65 70 75 80
Val Asp Lys Pro Pro Ser Pro Ser Pro Ile Glu Met Lys Lys Ala Ser
85 90 95
Asn Pro Val Glu Val Gly Ile Gln Val Thr Pro Glu Asp Asp Asp Cys
100 105 110
Leu Ser Thr Ser Ser Arg Gly Ile Cys Pro Lys Gln Glu His Ile Ala
115 120 125
Asp Lys Leu Leu His Trp Arg Gly Leu Ser Ser Pro Arg Ser Ala His
130 135 140
Gly Ala Leu Ile Pro Thr Pro Gly Met Ser Ala Glu Tyr Ala Pro Gln
145 150 155 160
Gly Ile Cys Lys Asp Glu Pro Ser Ser Tyr Thr Cys Thr Thr Cys Lys
165 170 175
Gln Pro Phe Thr Ser Ala Trp Phe Leu Leu Gln His Ala Gln Asn Thr
180 185 190
His Gly Leu Arg Ile Tyr Leu Glu Ser Glu His Gly Ser Pro Leu Thr
195 200 205
Pro Arg Val Gly Ile Pro Ser Gly Leu Gly Ala Glu Cys Pro Ser Gln
210 215 220
Pro Pro Leu His Gly Ile His Ile Ala Asp Asn Asn Pro Phe Asn Leu
225 230 235 240
Leu Arg Ile Pro Gly Ser Val Ser Arg Glu Ala Ser Gly Leu Ala Glu
245 250 255
Gly Arg Phe Pro Pro Thr Pro Pro Leu Phe Ser Pro Pro Pro Arg His
260 265 270
His Leu Asp Pro His Arg Ile Glu Arg Leu Gly Ala Glu Glu Met Ala
275 280 285
Leu Ala Thr His His Pro Ser Ala Phe Asp Arg Val Leu Arg Leu Asn
290 295 300
Pro Met Ala Met Glu Pro Pro Ala Met Asp Phe Ser Arg Arg Leu Arg
305 310 315 320
Glu Leu Ala Gly Asn Thr Ser Ser Pro Pro Leu Ser Pro Gly Arg Pro
325 330 335
Ser Pro Met Gln Arg Leu Leu Gln Pro Phe Gln Pro Gly Ser Lys Pro
340 345 350
Pro Phe Leu Ala Thr Pro Pro Leu Pro Pro Leu Gln Ser Ala Pro Pro
355 360 365
Pro Ser Gln Pro Pro Val Lys Ser Lys Ser Cys Glu Phe Cys Gly Lys
370 375 380
Thr Phe Lys Phe Gln Ser Asn Leu Val Val His Arg Arg Ser His Thr
385 390 395 400
Gly Glu Lys Pro Tyr Lys Cys Asn Leu Cys Asp His Ala Cys Thr Gln
405 410 415
Ala Ser Lys Leu Lys Arg His Met Lys Thr His Met His Lys Ser Ser
420 425 430
Pro Met Thr Val Lys Ser Asp Asp Gly Leu Ser Thr Ala Ser Ser Pro
435 440 445
Glu Pro Gly Thr Ser Asp Leu Val Gly Ser Ala Ser Ser Ala Leu Lys
450 455 460
Ser Val Val Ala Lys Phe Lys Ser Glu Asn Asp Pro Asn Leu Ile Pro
465 470 475 480
Glu Asn Gly Asp Glu Glu Glu Glu Glu Asp Asp Glu Glu Glu Glu Glu
485 490 495
Glu Glu Glu Glu Glu Glu Glu Glu Leu Thr Glu Ser Glu Arg Val Asp
500 505 510
Tyr Gly Phe Gly Leu Ser Leu Glu Ala Ala Arg His His Glu Asn Ser
515 520 525
Ser Arg Gly Ala Val Val Gly Val Gly Asp Glu Gly Arg Ala Leu Pro
530 535 540
Asp Val Met Gln Gly Met Val Leu Ser Ser Met Gln His Phe Ser Glu
545 550 555 560
Ala Phe His Gln Val Leu Gly Glu Lys His Lys Arg Ser His Leu Ala
565 570 575
Glu Ala Glu Gly His Arg Asp Thr Cys Asp Glu Asp Ser Val Ala Gly
580 585 590
Glu Ser Asp Arg Ile Asp Asp Gly Thr Val Asn Gly Arg Gly Cys Ser
595 600 605
Pro Gly Glu Ser Ala Ser Gly Gly Leu Ser Lys Lys Leu Leu Leu Gly
610 615 620
Ser Pro Ser Ser Leu Ser Pro Phe Ser Lys Arg Ile Lys Leu Glu Lys
625 630 635 640
Glu Phe Asp Leu Pro Pro Ala Ala Met Pro Asn Thr Glu Asn Val Tyr
645 650 655
Ser Gln Trp Leu Ala Gly Tyr Ala Ala Ser Arg Gln Leu Lys Asp Pro
660 665 670
Phe Leu Thr Phe Gly Asp Ser Arg Gln Ser Pro Phe Ala Ser Ser Ser
675 680 685
Glu His Ser Ser Glu Asn Gly Ser Leu Arg Phe Ser Thr Pro Pro Gly
690 695 700
Glu Leu Asp Gly Gly Ile Ser Gly Arg Ser Gly Thr Gly Ser Gly Gly
705 710 715 720
Ser Thr Pro His Ile Ser Gly Pro Gly Pro Gly Arg Pro Ser Ser Lys
725 730 735
Glu Gly Arg Arg Ser Asp Thr Cys Pro Ser His Thr Pro Val Arg Arg
740 745 750
Ser Thr Pro Arg Ala Gln Asp Val Trp Gln Phe Ser Asp Gly Ser Ser
755 760 765
Arg Thr Leu Lys Phe
770
<210> 57
<211> 653
<212> PRT
<213> Homo sapiens
<400> 57
Met Pro Ala Ser Arg Leu Arg Asp Arg Ala Ala Ser Ser Ala Ser Gly
1 5 10 15
Ser Thr Cys Gly Ser Met Ser Gln Thr His Pro Val Leu Glu Ser Gly
20 25 30
Leu Leu Ala Ser Ala Gly Cys Ser Ala Pro Arg Gly Pro Arg Lys Gly
35 40 45
Gly Pro Ala Pro Val Asp Arg Lys Ala Lys Ala Ser Ala Met Pro Asp
50 55 60
Ser Pro Ala Glu Val Lys Thr Gln Pro Arg Ser Thr Pro Pro Ser Met
65 70 75 80
Pro Pro Pro Pro Pro Ala Ala Ser Gln Gly Ala Thr Arg Pro Pro Ser
85 90 95
Phe Thr Pro His Thr His Arg Glu Asp Gly Pro Ala Thr Leu Pro His
100 105 110
Gly Arg Phe His Gly Cys Leu Lys Trp Ser Met Val Cys Leu Leu Met
115 120 125
Asn Gly Ser Ser His Ser Pro Thr Ala Ile Asn Gly Ala Pro Cys Thr
130 135 140
Pro Asn Gly Phe Ser Asn Gly Pro Ala Thr Ser Ser Thr Ala Ser Leu
145 150 155 160
Ser Thr Gln His Leu Pro Pro Ala Cys Gly Ala Arg Gln Leu Ser Lys
165 170 175
Leu Lys Arg Phe Leu Thr Thr Leu Gln Gln Phe Gly Ser Asp Ile Ser
180 185 190
Pro Glu Ile Gly Glu Arg Val Arg Thr Leu Val Leu Gly Leu Val Asn
195 200 205
Ser Thr Leu Thr Ile Glu Glu Phe His Ser Lys Leu Gln Glu Ala Thr
210 215 220
Asn Phe Pro Leu Arg Pro Phe Val Ile Pro Phe Leu Lys Ala Asn Leu
225 230 235 240
Pro Leu Leu Gln Arg Glu Leu Leu His Cys Ala Arg Leu Ala Lys Gln
245 250 255
Thr Pro Ala Gln Tyr Leu Ala Gln His Glu Gln Leu Leu Leu Asp Ala
260 265 270
Ser Ala Ser Ser Pro Ile Asp Ser Ser Glu Leu Leu Leu Glu Val Asn
275 280 285
Glu Asn Gly Lys Arg Arg Thr Pro Asp Arg Thr Lys Glu Asn Gly Ser
290 295 300
Asp Arg Asp Pro Leu His Pro Glu His Leu Ser Lys Arg Pro Cys Thr
305 310 315 320
Leu Asn Pro Ala Gln Arg Tyr Ser Pro Ser Asn Gly Pro Pro Gln Pro
325 330 335
Thr Pro Pro Pro His Tyr Arg Leu Glu Asp Ile Ala Met Ala His His
340 345 350
Phe Arg Asp Ala Tyr Arg His Pro Asp Pro Arg Glu Leu Arg Glu Arg
355 360 365
His Arg Pro Leu Val Val Pro Gly Ser Arg Gln Glu Glu Val Ile Asp
370 375 380
His Lys Leu Thr Glu Arg Glu Trp Ala Glu Glu Trp Lys His Leu Asn
385 390 395 400
Asn Leu Leu Asn Cys Ile Met Asp Met Val Glu Lys Thr Arg Arg Ser
405 410 415
Leu Thr Val Leu Arg Arg Cys Gln Glu Ala Asp Arg Glu Glu Leu Asn
420 425 430
His Trp Ala Arg Arg Tyr Ser Asp Ala Glu Asp Thr Lys Lys Gly Pro
435 440 445
Ala Pro Ala Ala Ala Arg Pro Arg Ser Ser Ser Ala Gly Pro Glu Gly
450 455 460
Pro Gln Leu Asp Val Pro Arg Glu Phe Leu Pro Arg Thr Leu Thr Gly
465 470 475 480
Tyr Val Pro Glu Asp Ile Trp Arg Lys Ala Glu Glu Ala Val Asn Glu
485 490 495
Val Lys Arg Gln Ala Met Ser Glu Leu Gln Lys Ala Val Ser Asp Ala
500 505 510
Glu Arg Lys Ala His Glu Leu Ile Thr Thr Glu Arg Ala Lys Met Glu
515 520 525
Arg Ala Leu Ala Glu Ala Lys Arg Gln Ala Ser Glu Asp Ala Leu Thr
530 535 540
Val Ile Asn Gln Gln Glu Asp Ser Ser Glu Ser Cys Trp Asn Cys Gly
545 550 555 560
Arg Lys Ala Ser Glu Thr Cys Ser Gly Cys Asn Ala Ala Arg Tyr Cys
565 570 575
Gly Ser Phe Cys Gln His Arg Asp Trp Glu Lys His His His Val Cys
580 585 590
Gly Gln Ser Leu Gln Gly Pro Thr Ala Val Val Ala Asp Pro Val Pro
595 600 605
Gly Pro Pro Glu Ala Ala His Ser Leu Gly Pro Ser Leu Pro Val Gly
610 615 620
Ala Ala Ser Pro Ser Glu Ala Gly Ser Ala Gly Pro Ser Arg Pro Gly
625 630 635 640
Ser Pro Ser Pro Pro Gly Pro Leu Asp Thr Val Pro Arg
645 650
<210> 58
<211> 620
<212> PRT
<213> Mus musculus
<400> 58
Met Ser Gln Ala Ser Thr Thr Thr Leu Glu Ser Gly Ala Leu Leu Ser
1 5 10 15
Gly Pro Arg Gly Leu Gln Asn Gly Ser Pro Ala His Arg Lys Glu Lys
20 25 30
Ala Ala Ala Met Pro Asp Ser Pro Ala Glu Val Lys Thr Gln Pro Arg
35 40 45
Ser Thr Pro Pro Ser Met Pro Pro Pro Pro Pro Thr Ser Ser Gln Gly
50 55 60
Ala Thr Arg Pro Pro Ser Phe Thr Pro His Thr His Gly Glu Asp Gly
65 70 75 80
Pro Ala Thr Ser Leu Pro His Gly Arg Phe His Gly Cys Leu Lys Trp
85 90 95
Ser Met Val Cys Leu Leu Met Asn Gly Ser Ser His Ser Pro Thr Ala
100 105 110
Ile His Gly Ala Pro Ser Thr Pro Asn Gly Phe Ser Asn Gly Pro Ala
115 120 125
Thr Ser Ser Thr Ala Ser Leu Ser Thr Gln His Leu Pro Pro Ala Cys
130 135 140
Gly Ala Arg Gln Leu Ser Lys Leu Lys Arg Phe Leu Thr Thr Leu Gln
145 150 155 160
Gln Phe Gly Ser Asp Ile Ser Pro Glu Ile Gly Glu Arg Val Arg Thr
165 170 175
Leu Val Leu Gly Leu Val Asn Ser Thr Leu Thr Ile Glu Glu Phe His
180 185 190
Ala Lys Leu Gln Glu Ala Thr Asn Phe Pro Leu Arg Pro Phe Val Ile
195 200 205
Pro Phe Leu Lys Ala Asn Leu Pro Leu Leu Gln Arg Glu Leu Leu His
210 215 220
Cys Ala Arg Leu Ala Lys Gln Thr Pro Ala Gln Tyr Leu Ala Gln His
225 230 235 240
Glu Gln Leu Leu Leu Asp Ala Ser Ala Thr Ser Pro Val Asp Ser Ser
245 250 255
Glu Leu Leu Leu Glu Val Asn Glu Asn Gly Lys Arg Arg Thr Pro Asp
260 265 270
Arg Thr Lys Glu Asn Gly Ser Asp Arg Asp Pro Leu His Pro Asp His
275 280 285
Leu Ser Lys Arg Ser Cys Thr Leu Ser Pro Ala Gln Arg Cys Ser Pro
290 295 300
Ser Asn Gly Leu Pro His Pro Thr Pro Pro Pro Pro Pro His Tyr Arg
305 310 315 320
Leu Glu Asp Met Ala Met Ala His His Phe Arg Asp Ser Tyr Arg His
325 330 335
Pro Asp Pro Arg Glu Leu Arg Glu Arg His Arg Pro Leu Ala Ile Pro
340 345 350
Gly Ser Arg Gln Glu Glu Val Ile Asp His Arg Leu Thr Glu Arg Glu
355 360 365
Trp Ala Glu Glu Trp Lys His Leu Asn Ser Leu Leu Asn Cys Ile Met
370 375 380
Asp Met Val Glu Lys Thr Arg Arg Ser Leu Thr Val Leu Arg Arg Cys
385 390 395 400
Gln Glu Ala Asp Arg Glu Glu Leu Asn His Trp Ile Arg Cys Tyr Ser
405 410 415
Asp Ser Glu Glu Gly Lys Lys Gly Pro Thr Pro Ile Ser Ala Arg Ser
420 425 430
Leu Asn Ser Cys Ser Gly Pro Glu Gly Ser Gln Leu Asp Val His Arg
435 440 445
Asp Phe Thr Pro Arg Thr Leu Ser Gly Tyr Met Pro Glu Glu Ile Trp
450 455 460
Arg Lys Ala Glu Glu Ala Val Asn Glu Val Lys Arg Gln Ala Met Ser
465 470 475 480
Glu Leu Gln Lys Ala Val Ser Asp Ala Glu Arg Lys Ala His Glu Leu
485 490 495
Ile Thr Thr Glu Arg Ala Lys Met Glu Arg Ala Leu Ala Glu Ala Lys
500 505 510
Arg Gln Ala Ser Glu Asp Ala Leu Thr Val Ile Asn Gln Gln Glu Asp
515 520 525
Ser Ser Glu Ser Cys Trp Asn Cys Gly Arg Lys Ala Ser Glu Thr Cys
530 535 540
Ser Gly Cys Asn Ala Ala Arg Tyr Cys Gly Ser Phe Cys Gln His Lys
545 550 555 560
Asp Trp Glu Lys His His His Val Cys Gly Gln Ser Leu Gln Gly Pro
565 570 575
Ala Ala Ala Val Ala Asp Pro Leu Pro Gly Gln Pro Asp Ala Thr Ala
580 585 590
Ser Pro Ser Glu Ala Gly Ser Ala Gly Pro Ser Arg Pro Cys Ser Pro
595 600 605
Gly Pro Pro Gly Pro Leu Asp Ala Ala Val Pro Arg
610 615 620
<210> 59
<211> 520
<212> PRT
<213> Homo sapiens
<400> 59
Met Glu Val Leu Glu Ser Gly Glu Gln Gly Val Leu Gln Trp Asp Arg
1 5 10 15
Lys Leu Ser Glu Leu Ser Glu Pro Gly Asp Gly Glu Ala Leu Met Tyr
20 25 30
His Thr His Phe Ser Glu Leu Leu Asp Glu Phe Ser Gln Asn Val Leu
35 40 45
Gly Gln Leu Leu Asn Asp Pro Phe Leu Ser Glu Lys Ser Val Ser Met
50 55 60
Glu Val Glu Pro Ser Pro Thr Ser Pro Ala Pro Leu Ile Gln Ala Glu
65 70 75 80
His Ser Tyr Ser Leu Cys Glu Glu Pro Arg Ala Gln Ser Pro Phe Thr
85 90 95
His Ile Thr Thr Ser Asp Ser Phe Asn Asp Asp Glu Val Glu Ser Glu
100 105 110
Lys Trp Tyr Leu Ser Thr Asp Phe Pro Ser Thr Ser Ile Lys Thr Glu
115 120 125
Pro Val Thr Asp Glu Pro Pro Pro Gly Leu Val Pro Ser Val Thr Leu
130 135 140
Thr Ile Thr Ala Ile Ser Thr Pro Leu Glu Lys Glu Glu Pro Pro Leu
145 150 155 160
Glu Met Asn Thr Gly Val Asp Ser Ser Cys Gln Thr Ile Ile Pro Lys
165 170 175
Ile Lys Leu Glu Pro His Glu Val Asp Gln Phe Leu Asn Phe Ser Pro
180 185 190
Lys Glu Ala Pro Val Asp His Leu His Leu Pro Pro Thr Pro Pro Ser
195 200 205
Ser His Gly Ser Asp Ser Glu Gly Ser Leu Ser Pro Asn Pro Arg Leu
210 215 220
His Pro Phe Ser Leu Pro Gln Thr His Ser Pro Ser Arg Ala Ala Pro
225 230 235 240
Arg Ala Pro Ser Ala Leu Ser Ser Ser Pro Leu Leu Thr Ala Pro His
245 250 255
Lys Leu Gln Gly Ser Gly Pro Leu Val Leu Thr Glu Glu Glu Lys Arg
260 265 270
Thr Leu Ile Ala Glu Gly Tyr Pro Ile Pro Thr Lys Leu Pro Leu Ser
275 280 285
Lys Ser Glu Glu Lys Ala Leu Lys Lys Ile Arg Arg Lys Ile Lys Asn
290 295 300
Lys Ile Ser Ala Gln Glu Ser Arg Arg Lys Lys Lys Glu Tyr Met Asp
305 310 315 320
Ser Leu Glu Lys Lys Val Glu Ser Cys Ser Thr Glu Asn Leu Glu Leu
325 330 335
Arg Lys Lys Val Glu Val Leu Glu Asn Thr Asn Arg Thr Leu Leu Gln
340 345 350
Gln Leu Gln Lys Leu Gln Thr Leu Val Met Gly Lys Val Ser Arg Thr
355 360 365
Cys Lys Leu Ala Gly Thr Gln Thr Gly Thr Cys Leu Met Val Val Val
370 375 380
Leu Cys Phe Ala Val Ala Phe Gly Ser Phe Phe Gln Gly Tyr Gly Pro
385 390 395 400
Tyr Pro Ser Ala Thr Lys Met Ala Leu Pro Ser Gln His Ser Leu Gln
405 410 415
Glu Pro Tyr Thr Ala Ser Val Val Arg Ser Arg Asn Leu Leu Ile Tyr
420 425 430
Glu Glu His Ser Pro Pro Glu Glu Ser Ser Ser Pro Gly Ser Ala Gly
435 440 445
Glu Leu Gly Gly Trp Asp Arg Gly Ser Ser Leu Leu Arg Val Ser Gly
450 455 460
Leu Glu Ser Arg Pro Asp Val Asp Leu Pro His Phe Ile Ile Ser Asn
465 470 475 480
Glu Thr Ser Leu Glu Lys Ser Val Leu Leu Glu Leu Gln Gln His Leu
485 490 495
Val Ser Ala Lys Leu Glu Gly Asn Glu Thr Leu Lys Val Val Glu Leu
500 505 510
Asp Arg Arg Val Asn Thr Thr Phe
515 520
<210> 60
<211> 521
<212> PRT
<213> Mus musculus
<400> 60
Met Glu Val Leu Glu Ser Gly Glu Gln Ser Val Leu Gln Trp Asp Arg
1 5 10 15
Lys Leu Ser Glu Leu Ser Glu Pro Gly Glu Thr Glu Ala Leu Met Tyr
20 25 30
His Thr His Phe Ser Glu Leu Leu Asp Glu Phe Ser Gln Asn Val Leu
35 40 45
Gly Gln Leu Leu Ser Asp Pro Phe Leu Ser Glu Lys Ser Glu Ser Met
50 55 60
Glu Val Glu Pro Ser Pro Thr Ser Pro Ala Pro Leu Ile Gln Ala Glu
65 70 75 80
His Ser Tyr Ser Leu Ser Glu Glu Pro Arg Thr Gln Ser Pro Phe Thr
85 90 95
His Ala Ala Thr Ser Asp Ser Phe Asn Asp Glu Glu Val Glu Ser Glu
100 105 110
Lys Trp Tyr Leu Ser Thr Glu Phe Pro Ser Ala Thr Ile Lys Thr Glu
115 120 125
Pro Ile Thr Glu Glu Gln Pro Pro Gly Leu Val Pro Ser Val Thr Leu
130 135 140
Thr Ile Thr Ala Ile Ser Thr Pro Phe Glu Lys Glu Glu Ser Pro Leu
145 150 155 160
Asp Met Asn Ala Gly Gly Asp Ser Ser Cys Gln Thr Leu Ile Pro Lys
165 170 175
Ile Lys Leu Glu Pro His Glu Val Asp Gln Phe Leu Asn Phe Ser Pro
180 185 190
Lys Glu Ala Ser Val Asp Gln Leu His Leu Pro Pro Thr Pro Pro Ser
195 200 205
Ser His Ser Ser Asp Ser Glu Gly Ser Leu Ser Pro Asn Pro Arg Leu
210 215 220
His Pro Phe Ser Leu Ser Gln Ala His Ser Pro Ala Arg Ala Met Pro
225 230 235 240
Arg Gly Pro Ser Ala Leu Ser Thr Ser Pro Leu Leu Thr Ala Pro His
245 250 255
Lys Leu Gln Gly Ser Gly Pro Leu Val Leu Thr Glu Glu Glu Lys Arg
260 265 270
Thr Leu Val Ala Glu Gly Tyr Pro Ile Pro Thr Lys Leu Pro Leu Thr
275 280 285
Lys Ser Glu Glu Lys Ala Leu Lys Lys Ile Arg Arg Lys Ile Lys Asn
290 295 300
Lys Ile Ser Ala Gln Glu Ser Arg Arg Lys Lys Lys Glu Tyr Met Asp
305 310 315 320
Ser Leu Glu Lys Lys Val Glu Ser Cys Ser Thr Glu Asn Leu Glu Leu
325 330 335
Arg Lys Lys Val Glu Val Leu Glu Asn Thr Asn Arg Thr Leu Leu Gln
340 345 350
Gln Leu Gln Lys Leu Gln Thr Leu Val Met Gly Lys Val Ser Arg Thr
355 360 365
Cys Lys Leu Ala Gly Thr Gln Thr Gly Thr Cys Leu Met Val Val Val
370 375 380
Leu Cys Phe Ala Val Ala Phe Gly Ser Phe Phe Gln Gly Tyr Gly Pro
385 390 395 400
Tyr Pro Ser Ala Thr Lys Met Ala Leu Pro Ser Gln His Pro Leu Ser
405 410 415
Glu Pro Tyr Thr Ala Ser Val Val Arg Ser Arg Asn Leu Leu Ile Tyr
420 425 430
Glu Glu His Ala Pro Leu Glu Glu Ser Ser Ser Pro Ala Ser Ala Gly
435 440 445
Glu Leu Gly Gly Trp Asp Arg Gly Ser Ser Leu Leu Arg Ala Ser Ser
450 455 460
Gly Leu Glu Ala Leu Pro Glu Val Asp Leu Pro His Phe Leu Ile Ser
465 470 475 480
Asn Glu Thr Ser Leu Glu Lys Ser Val Leu Leu Glu Leu Gln Gln His
485 490 495
Leu Val Ser Ser Lys Leu Glu Gly Asn Glu Thr Leu Lys Val Val Glu
500 505 510
Leu Glu Arg Arg Val Asn Ala Thr Phe
515 520
<210> 61
<211> 485
<212> PRT
<213> Homo sapiens
<400> 61
Met Ser Tyr Phe Val Asp Ser Ala Gly Ser Ser Pro Val Pro Tyr Ser
1 5 10 15
Ala Pro Arg Pro Ala Val Val Arg Gln Gly Pro Ser Asn Thr Tyr Glu
20 25 30
Asp Pro Arg Met Asn Cys Gly Phe Gln Ser Asn Tyr His Gln Gln Arg
35 40 45
Pro Cys Tyr Pro Phe Trp Asp Glu Met Ala Thr Gln Glu Val Pro Thr
50 55 60
Gly Leu Glu His Cys Val Ser Asp Met Glu Cys Ala Asp Val Pro Leu
65 70 75 80
Leu Thr Pro Ser Ser Lys Glu Met Met Ser Gln Ala Leu Lys Ala Thr
85 90 95
Phe Ser Gly Phe Thr Lys Glu Gln Gln Arg Leu Gly Ile Pro Lys Asp
100 105 110
Pro Arg Gln Trp Thr Glu Thr His Val Arg Asp Trp Val Met Trp Ala
115 120 125
Val Asn Glu Phe Ser Leu Lys Gly Val Asp Phe Gln Lys Phe Cys Met
130 135 140
Asn Gly Ala Ala Leu Cys Ala Leu Gly Lys Asp Cys Phe Leu Glu Leu
145 150 155 160
Ala Pro Asp Phe Val Gly Asp Ile Leu Trp Glu His Leu Glu Ile Leu
165 170 175
Gln Lys Glu Asp Val Lys Pro Tyr Gln Val Asn Gly Val Asn Pro Ala
180 185 190
Tyr Pro Glu Ser Arg Tyr Thr Ser Asp Tyr Phe Ile Ser Tyr Gly Ile
195 200 205
Glu His Ala Gln Cys Val Pro Pro Ser Glu Phe Ser Glu Pro Ser Phe
210 215 220
Ile Thr Glu Ser Tyr Gln Thr Leu His Pro Ile Ser Ser Glu Glu Leu
225 230 235 240
Leu Ser Leu Lys Tyr Glu Asn Asp Tyr Pro Ser Val Ile Leu Arg Asp
245 250 255
Pro Leu Gln Thr Asp Thr Leu Gln Asn Asp Tyr Phe Ala Ile Lys Gln
260 265 270
Glu Val Val Thr Pro Asp Asn Met Cys Met Gly Arg Thr Ser Arg Gly
275 280 285
Lys Leu Gly Gly Gln Asp Ser Phe Glu Ser Ile Glu Ser Tyr Asp Ser
290 295 300
Cys Asp Arg Leu Thr Gln Ser Trp Ser Ser Gln Ser Ser Phe Asn Ser
305 310 315 320
Leu Gln Arg Val Pro Ser Tyr Asp Ser Phe Asp Ser Glu Asp Tyr Pro
325 330 335
Ala Ala Leu Pro Asn His Lys Pro Lys Gly Thr Phe Lys Asp Tyr Val
340 345 350
Arg Asp Arg Ala Asp Leu Asn Lys Asp Lys Pro Val Ile Pro Ala Ala
355 360 365
Ala Leu Ala Gly Tyr Thr Gly Ser Gly Pro Ile Gln Leu Trp Gln Phe
370 375 380
Leu Leu Glu Leu Leu Thr Asp Lys Ser Cys Gln Ser Phe Ile Ser Trp
385 390 395 400
Thr Gly Asp Gly Trp Glu Phe Lys Leu Ser Asp Pro Asp Glu Val Ala
405 410 415
Arg Arg Trp Gly Lys Arg Lys Asn Lys Pro Lys Met Asn Tyr Glu Lys
420 425 430
Leu Ser Arg Gly Leu Arg Tyr Tyr Tyr Asp Lys Asn Ile Ile His Lys
435 440 445
Thr Ala Gly Lys Arg Tyr Val Tyr Arg Phe Val Cys Asp Leu Gln Ser
450 455 460
Leu Leu Gly Tyr Thr Pro Glu Glu Leu His Ala Met Leu Asp Val Lys
465 470 475 480
Pro Asp Ala Asp Glu
485
<210> 62
<211> 440
<212> PRT
<213> Mus musculus
<400> 62
Met Lys Ala Ala Val Asp Leu Lys Pro Thr Leu Thr Ile Ile Lys Thr
1 5 10 15
Glu Lys Val Asp Leu Glu Leu Phe Pro Ser Pro Asp Met Glu Cys Ala
20 25 30
Asp Val Pro Leu Leu Thr Pro Ser Ser Lys Glu Met Met Ser Gln Ala
35 40 45
Leu Lys Ala Thr Phe Ser Gly Phe Thr Lys Glu Gln Gln Arg Leu Gly
50 55 60
Ile Pro Lys Asp Pro Arg Gln Trp Thr Glu Thr His Val Arg Asp Trp
65 70 75 80
Val Met Trp Ala Val Asn Glu Phe Ser Leu Lys Gly Val Asp Phe Gln
85 90 95
Lys Phe Cys Met Ser Gly Ala Ala Leu Cys Ala Leu Gly Lys Glu Cys
100 105 110
Phe Leu Glu Leu Ala Pro Asp Phe Val Gly Asp Ile Leu Trp Glu His
115 120 125
Leu Glu Ile Leu Gln Lys Glu Asp Val Lys Pro Tyr Gln Val Asn Gly
130 135 140
Ala Asn Pro Thr Tyr Pro Glu Ser Cys Tyr Thr Ser Asp Tyr Phe Ile
145 150 155 160
Ser Tyr Gly Ile Glu His Ala Gln Cys Val Pro Pro Ser Glu Phe Ser
165 170 175
Glu Pro Ser Phe Ile Thr Glu Ser Tyr Gln Thr Leu His Pro Ile Ser
180 185 190
Ser Glu Glu Leu Leu Ser Leu Lys Tyr Glu Asn Asp Tyr Pro Ser Val
195 200 205
Ile Leu Gln Asp Pro Leu Gln Thr Asp Thr Leu Gln Thr Asp Tyr Phe
210 215 220
Ala Ile Lys Gln Glu Val Leu Thr Pro Asp Asn Met Cys Leu Gly Arg
225 230 235 240
Ala Ser Arg Gly Lys Leu Gly Gly Gln Asp Ser Phe Glu Ser Val Glu
245 250 255
Ser Tyr Asp Ser Cys Asp Arg Leu Thr Gln Ser Trp Ser Ser Gln Ser
260 265 270
Ser Phe Asn Ser Leu Gln Arg Val Pro Ser Tyr Asp Ser Phe Asp Tyr
275 280 285
Glu Asp Tyr Pro Ala Ala Leu Pro Asn His Lys Pro Lys Gly Thr Phe
290 295 300
Lys Asp Tyr Val Arg Asp Arg Ala Asp Leu Asn Lys Asp Lys Pro Val
305 310 315 320
Ile Pro Ala Ala Ala Leu Ala Gly Tyr Thr Gly Ser Gly Pro Ile Gln
325 330 335
Leu Trp Gln Phe Leu Leu Glu Leu Leu Thr Asp Lys Ser Cys Gln Ser
340 345 350
Phe Ile Ser Trp Thr Gly Asp Gly Trp Glu Phe Lys Leu Ser Asp Pro
355 360 365
Asp Glu Val Ala Arg Arg Trp Gly Lys Arg Lys Asn Lys Pro Lys Met
370 375 380
Asn Tyr Glu Lys Leu Ser Arg Gly Leu Arg Tyr Tyr Tyr Asp Lys Asn
385 390 395 400
Ile Ile His Lys Thr Ala Gly Lys Arg Tyr Val Tyr Arg Phe Val Cys
405 410 415
Asp Leu Gln Ser Leu Leu Gly Tyr Thr Pro Glu Glu Leu His Ala Met
420 425 430
Leu Asp Val Lys Pro Asp Ala Asp
435 440
<210> 63
<211> 1123
<212> PRT
<213> Homo sapiens
<400> 63
Met Asn Ser Pro Asn Glu Ser Ala Asp Gly Met Ser Gly Arg Glu Pro
1 5 10 15
Ser Leu Glu Ile Leu Pro Arg Thr Ser Leu His Ser Ile Pro Val Thr
20 25 30
Val Glu Val Lys Pro Val Leu Pro Arg Ala Met Pro Ser Ser Met Gly
35 40 45
Gly Gly Gly Gly Gly Ser Pro Ser Pro Val Glu Leu Arg Gly Ala Leu
50 55 60
Val Gly Ser Val Asp Pro Thr Leu Arg Glu Gln Gln Leu Gln Gln Glu
65 70 75 80
Leu Leu Ala Leu Lys Gln Gln Gln Gln Leu Gln Lys Gln Leu Leu Phe
85 90 95
Ala Glu Phe Gln Lys Gln His Asp His Leu Thr Arg Gln His Glu Val
100 105 110
Gln Leu Gln Lys His Leu Lys Gln Gln Gln Glu Met Leu Ala Ala Lys
115 120 125
Gln Gln Gln Glu Met Leu Ala Ala Lys Arg Gln Gln Glu Leu Glu Gln
130 135 140
Gln Arg Gln Arg Glu Gln Gln Arg Gln Glu Glu Leu Glu Lys Gln Arg
145 150 155 160
Leu Glu Gln Gln Leu Leu Ile Leu Arg Asn Lys Glu Lys Ser Lys Glu
165 170 175
Ser Ala Ile Ala Ser Thr Glu Val Lys Leu Arg Leu Gln Glu Phe Leu
180 185 190
Leu Ser Lys Ser Lys Glu Pro Thr Pro Gly Gly Leu Asn His Ser Leu
195 200 205
Pro Gln His Pro Lys Cys Trp Gly Ala His His Ala Ser Leu Asp Gln
210 215 220
Ser Ser Pro Pro Gln Ser Gly Pro Pro Gly Thr Pro Pro Ser Tyr Lys
225 230 235 240
Leu Pro Leu Pro Gly Pro Tyr Asp Ser Arg Asp Asp Phe Pro Leu Arg
245 250 255
Lys Thr Ala Ser Glu Pro Asn Leu Lys Val Arg Ser Arg Leu Lys Gln
260 265 270
Lys Val Ala Glu Arg Arg Ser Ser Pro Leu Leu Arg Arg Lys Asp Gly
275 280 285
Thr Val Ile Ser Thr Phe Lys Lys Arg Ala Val Glu Ile Thr Gly Ala
290 295 300
Gly Pro Gly Ala Ser Ser Val Cys Asn Ser Ala Pro Gly Ser Gly Pro
305 310 315 320
Ser Ser Pro Asn Ser Ser His Ser Thr Ile Ala Glu Asn Gly Phe Thr
325 330 335
Gly Ser Val Pro Asn Ile Pro Thr Glu Met Leu Pro Gln His Arg Ala
340 345 350
Leu Pro Leu Asp Ser Ser Pro Asn Gln Phe Ser Leu Tyr Thr Ser Pro
355 360 365
Ser Leu Pro Asn Ile Ser Leu Gly Leu Gln Ala Thr Val Thr Val Thr
370 375 380
Asn Ser His Leu Thr Ala Ser Pro Lys Leu Ser Thr Gln Gln Glu Ala
385 390 395 400
Glu Arg Gln Ala Leu Gln Ser Leu Arg Gln Gly Gly Thr Leu Thr Gly
405 410 415
Lys Phe Met Ser Thr Ser Ser Ile Pro Gly Cys Leu Leu Gly Val Ala
420 425 430
Leu Glu Gly Asp Gly Ser Pro His Gly His Ala Ser Leu Leu Gln His
435 440 445
Val Leu Leu Leu Glu Gln Ala Arg Gln Gln Ser Thr Leu Ile Ala Val
450 455 460
Pro Leu His Gly Gln Ser Pro Leu Val Thr Gly Glu Arg Val Ala Thr
465 470 475 480
Ser Met Arg Thr Val Gly Lys Leu Pro Arg His Arg Pro Leu Ser Arg
485 490 495
Thr Gln Ser Ser Pro Leu Pro Gln Ser Pro Gln Ala Leu Gln Gln Leu
500 505 510
Val Met Gln Gln Gln His Gln Gln Phe Leu Glu Lys Gln Lys Gln Gln
515 520 525
Gln Leu Gln Leu Gly Lys Ile Leu Thr Lys Thr Gly Glu Leu Pro Arg
530 535 540
Gln Pro Thr Thr His Pro Glu Glu Thr Glu Glu Glu Leu Thr Glu Gln
545 550 555 560
Gln Glu Val Leu Leu Gly Glu Gly Ala Leu Thr Met Pro Arg Glu Gly
565 570 575
Ser Thr Glu Ser Glu Ser Thr Gln Glu Asp Leu Glu Glu Glu Asp Glu
580 585 590
Glu Asp Asp Gly Glu Glu Glu Glu Asp Cys Ile Gln Val Lys Asp Glu
595 600 605
Glu Gly Glu Ser Gly Ala Glu Glu Gly Pro Asp Leu Glu Glu Pro Gly
610 615 620
Ala Gly Tyr Lys Lys Leu Phe Ser Asp Ala Gln Pro Leu Gln Pro Leu
625 630 635 640
Gln Val Tyr Gln Ala Pro Leu Ser Leu Ala Thr Val Pro His Gln Ala
645 650 655
Leu Gly Arg Thr Gln Ser Ser Pro Ala Ala Pro Gly Gly Met Lys Ser
660 665 670
Pro Pro Asp Gln Pro Val Lys His Leu Phe Thr Thr Gly Val Val Tyr
675 680 685
Asp Thr Phe Met Leu Lys His Gln Cys Met Cys Gly Asn Thr His Val
690 695 700
His Pro Glu His Ala Gly Arg Ile Gln Ser Ile Trp Ser Arg Leu Gln
705 710 715 720
Glu Thr Gly Leu Leu Ser Lys Cys Glu Arg Ile Arg Gly Arg Lys Ala
725 730 735
Thr Leu Asp Glu Ile Gln Thr Val His Ser Glu Tyr His Thr Leu Leu
740 745 750
Tyr Gly Thr Ser Pro Leu Asn Arg Gln Lys Leu Asp Ser Lys Lys Leu
755 760 765
Leu Gly Pro Ile Ser Gln Lys Met Tyr Ala Val Leu Pro Cys Gly Gly
770 775 780
Ile Gly Val Asp Ser Asp Thr Val Trp Asn Glu Met His Ser Ser Ser
785 790 795 800
Ala Val Arg Met Ala Val Gly Cys Leu Leu Glu Leu Ala Phe Lys Val
805 810 815
Ala Ala Gly Glu Leu Lys Asn Gly Phe Ala Ile Ile Arg Pro Pro Gly
820 825 830
His His Ala Glu Glu Ser Thr Ala Met Gly Phe Cys Phe Phe Asn Ser
835 840 845
Val Ala Ile Thr Ala Lys Leu Leu Gln Gln Lys Leu Asn Val Gly Lys
850 855 860
Val Leu Ile Val Asp Trp Asp Ile His His Gly Asn Gly Thr Gln Gln
865 870 875 880
Ala Phe Tyr Asn Asp Pro Ser Val Leu Tyr Ile Ser Leu His Arg Tyr
885 890 895
Asp Asn Gly Asn Phe Phe Pro Gly Ser Gly Ala Pro Glu Glu Val Gly
900 905 910
Gly Gly Pro Gly Val Gly Tyr Asn Val Asn Val Ala Trp Thr Gly Gly
915 920 925
Val Asp Pro Pro Ile Gly Asp Val Glu Tyr Leu Thr Ala Phe Arg Thr
930 935 940
Val Val Met Pro Ile Ala His Glu Phe Ser Pro Asp Val Val Leu Val
945 950 955 960
Ser Ala Gly Phe Asp Ala Val Glu Gly His Leu Ser Pro Leu Gly Gly
965 970 975
Tyr Ser Val Thr Ala Arg Cys Phe Gly His Leu Thr Arg Gln Leu Met
980 985 990
Thr Leu Ala Gly Gly Arg Val Val Leu Ala Leu Glu Gly Gly His Asp
995 1000 1005
Leu Thr Ala Ile Cys Asp Ala Ser Glu Ala Cys Val Ser Ala Leu
1010 1015 1020
Leu Ser Val Glu Leu Gln Pro Leu Asp Glu Ala Val Leu Gln Gln
1025 1030 1035
Lys Pro Asn Ile Asn Ala Val Ala Thr Leu Glu Lys Val Ile Glu
1040 1045 1050
Ile Gln Ser Lys His Trp Ser Cys Val Gln Lys Phe Ala Ala Gly
1055 1060 1065
Leu Gly Arg Ser Leu Arg Glu Ala Gln Ala Gly Glu Thr Glu Glu
1070 1075 1080
Ala Glu Thr Val Ser Ala Met Ala Leu Leu Ser Val Gly Ala Glu
1085 1090 1095
Gln Ala Gln Ala Ala Ala Ala Arg Glu His Ser Pro Arg Pro Ala
1100 1105 1110
Glu Glu Pro Met Glu Gln Glu Pro Ala Leu
1115 1120
<210> 64
<211> 1121
<212> PRT
<213> Mus musculus
<400> 64
Met Leu Leu Val Pro Lys Ala Gln Gly Leu Val Glu Met Leu Gln Thr
1 5 10 15
Ile Tyr Glu Thr Glu Ser Cys Phe Ser Ala Asp Gly Met Ser Gly Arg
20 25 30
Glu Pro Ser Leu Glu Ile Leu Pro Arg Thr Pro Leu His Ser Ile Pro
35 40 45
Val Ala Val Glu Val Lys Pro Val Leu Pro Gly Ala Met Pro Ser Ser
50 55 60
Met Gly Gly Gly Gly Gly Gly Ser Pro Ser Pro Val Glu Leu Arg Gly
65 70 75 80
Ala Leu Ala Gly Pro Met Asp Pro Ala Leu Arg Glu Gln Gln Leu Gln
85 90 95
Gln Glu Leu Leu Val Leu Lys Gln Gln Gln Gln Leu Gln Lys Gln Leu
100 105 110
Leu Phe Ala Glu Phe Gln Lys Gln His Asp His Leu Thr Arg Gln His
115 120 125
Glu Val Gln Leu Gln Lys His Leu Lys Gln Gln Gln Glu Met Leu Ala
130 135 140
Ala Lys Arg Gln Gln Glu Leu Glu Gln Gln Arg Gln Arg Glu Gln Gln
145 150 155 160
Arg Gln Glu Glu Leu Glu Lys Gln Arg Leu Glu Gln Gln Leu Leu Ile
165 170 175
Leu Arg Asn Lys Glu Lys Ser Lys Glu Ser Ala Ile Ala Ser Thr Glu
180 185 190
Val Lys Leu Arg Leu Gln Glu Phe Leu Leu Ser Lys Ser Lys Glu Pro
195 200 205
Thr Pro Gly Gly Leu Asn His Ser Leu Pro Gln His Pro Lys Cys Trp
210 215 220
Gly Ala His His Ala Ser Leu Asp Gln Ser Ser Pro Pro Gln Ser Gly
225 230 235 240
Pro Pro Gly Thr Pro Pro Ser Tyr Lys Leu Pro Leu Leu Gly Pro Tyr
245 250 255
Asp Ser Arg Asp Asp Phe Pro Leu Arg Lys Thr Ala Ser Glu Pro Asn
260 265 270
Leu Lys Val Arg Ser Arg Leu Lys Gln Lys Val Ala Glu Arg Arg Ser
275 280 285
Ser Pro Leu Leu Arg Arg Lys Asp Gly Thr Val Ile Ser Thr Phe Lys
290 295 300
Lys Arg Ala Val Glu Ile Thr Gly Thr Gly Pro Gly Val Ser Ser Val
305 310 315 320
Cys Asn Ser Ala Pro Gly Ser Gly Pro Ser Ser Pro Asn Ser Ser His
325 330 335
Ser Thr Ile Ala Glu Asn Gly Phe Thr Gly Ser Val Pro Asn Ile Pro
340 345 350
Thr Glu Met Ile Pro Gln His Arg Ala Leu Pro Leu Asp Ser Ser Pro
355 360 365
Asn Gln Phe Ser Leu Tyr Thr Ser Pro Ser Leu Pro Asn Ile Ser Leu
370 375 380
Gly Leu Gln Ala Thr Val Thr Val Thr Asn Ser His Leu Thr Ala Ser
385 390 395 400
Pro Lys Leu Ser Thr Gln Gln Glu Ala Glu Arg Gln Ala Leu Gln Ser
405 410 415
Leu Arg Gln Gly Gly Thr Leu Thr Gly Lys Phe Met Ser Thr Ser Ser
420 425 430
Ile Pro Gly Cys Leu Leu Gly Val Ala Leu Glu Gly Asp Thr Ser Pro
435 440 445
His Gly His Ala Ser Leu Leu Gln His Val Leu Leu Leu Glu Gln Ala
450 455 460
Arg Gln Gln Ser Thr Leu Ile Ala Val Pro Leu His Gly Gln Ser Pro
465 470 475 480
Leu Val Thr Gly Glu Arg Val Ala Thr Ser Met Arg Thr Val Gly Lys
485 490 495
Leu Pro Arg His Arg Pro Leu Ser Arg Thr Gln Ser Ser Pro Leu Pro
500 505 510
Gln Ser Pro Gln Ala Leu Gln Gln Leu Val Met Gln Gln Gln His Gln
515 520 525
Gln Phe Leu Glu Lys Gln Lys Gln Gln Gln Met Gln Leu Gly Lys Ile
530 535 540
Leu Thr Lys Thr Gly Glu Leu Ser Arg Gln Pro Thr Thr His Pro Glu
545 550 555 560
Glu Thr Glu Glu Glu Leu Thr Glu Gln Gln Glu Ala Leu Leu Gly Glu
565 570 575
Gly Ala Leu Thr Ile Pro Arg Glu Gly Ser Thr Glu Ser Glu Ser Thr
580 585 590
Gln Glu Asp Leu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu
595 600 605
Asp Cys Ile Gln Val Lys Asp Glu Asp Gly Glu Ser Gly Pro Asp Glu
610 615 620
Gly Pro Asp Leu Glu Glu Ser Ser Ala Gly Tyr Lys Lys Leu Phe Ala
625 630 635 640
Asp Ala Gln Gln Leu Gln Pro Leu Gln Val Tyr Gln Ala Pro Leu Ser
645 650 655
Leu Ala Thr Val Pro His Gln Ala Leu Gly Arg Thr Gln Ser Ser Pro
660 665 670
Ala Ala Pro Gly Ser Met Lys Ser Pro Thr Asp Gln Pro Thr Val Val
675 680 685
Lys His Leu Phe Thr Thr Gly Val Val Tyr Asp Thr Phe Met Leu Lys
690 695 700
His Gln Cys Met Cys Gly Asn Thr His Val His Pro Glu His Ala Gly
705 710 715 720
Arg Ile Gln Ser Ile Trp Ser Arg Leu Gln Glu Thr Gly Leu Leu Gly
725 730 735
Lys Cys Glu Arg Ile Arg Gly Arg Lys Ala Thr Leu Asp Glu Ile Gln
740 745 750
Thr Val His Ser Glu Tyr His Thr Leu Leu Tyr Gly Thr Ser Pro Leu
755 760 765
Asn Arg Gln Lys Leu Asp Ser Lys Lys Leu Leu Gly Pro Ile Ser Gln
770 775 780
Lys Met Tyr Ala Met Leu Pro Cys Gly Gly Ile Gly Val Asp Ser Asp
785 790 795 800
Thr Val Trp Asn Glu Met His Ser Ser Ser Ala Val Arg Met Ala Val
805 810 815
Gly Cys Leu Val Glu Leu Ala Phe Lys Val Ala Ala Gly Glu Leu Lys
820 825 830
Asn Gly Phe Ala Ile Ile Arg Pro Pro Gly His His Ala Glu Glu Ser
835 840 845
Thr Ala Met Gly Phe Cys Phe Phe Asn Ser Val Ala Ile Thr Ala Lys
850 855 860
Leu Leu Gln Gln Lys Leu Ser Val Gly Lys Val Leu Ile Val Asp Trp
865 870 875 880
Asp Ile His His Gly Asn Gly Thr Gln Gln Ala Phe Tyr Asn Asp Pro
885 890 895
Ser Val Leu Tyr Ile Ser Leu His Arg Tyr Asp Asn Gly Asn Phe Phe
900 905 910
Pro Gly Ser Gly Ala Pro Glu Glu Val Gly Gly Gly Pro Gly Val Gly
915 920 925
Tyr Asn Val Asn Val Ala Trp Thr Gly Gly Val Asp Pro Pro Ile Gly
930 935 940
Asp Val Glu Tyr Leu Thr Ala Phe Arg Thr Val Val Met Pro Ile Ala
945 950 955 960
Gln Glu Phe Ser Pro Asp Val Val Leu Val Ser Ala Gly Phe Asp Ala
965 970 975
Val Glu Gly His Leu Ser Pro Leu Gly Gly Tyr Ser Val Thr Ala Arg
980 985 990
Cys Phe Gly His Leu Thr Arg Gln Leu Met Thr Leu Ala Gly Gly Arg
995 1000 1005
Val Val Leu Ala Leu Glu Gly Gly His Asp Leu Thr Ala Ile Cys
1010 1015 1020
Asp Ala Ser Glu Ala Cys Val Ser Ala Leu Leu Ser Val Glu Leu
1025 1030 1035
Gln Pro Leu Asp Glu Ala Val Leu Gln Gln Lys Pro Ser Val Asn
1040 1045 1050
Ala Val Ala Thr Leu Glu Lys Val Ile Glu Ile Gln Ser Lys His
1055 1060 1065
Trp Ser Cys Val Gln Arg Phe Ala Ala Gly Leu Gly Cys Ser Leu
1070 1075 1080
Arg Glu Ala Gln Thr Gly Glu Lys Glu Glu Ala Glu Thr Val Ser
1085 1090 1095
Ala Met Ala Leu Leu Ser Val Gly Ala Glu Gln Ala Gln Ala Val
1100 1105 1110
Ala Thr Gln Glu His Ser Pro Arg
1115 1120
<210> 65
<211> 270
<212> PRT
<213> Homo sapiens
<400> 65
Met Gln Tyr Pro His Pro Gly Pro Ala Ala Gly Ala Val Gly Val Pro
1 5 10 15
Leu Tyr Ala Pro Thr Pro Leu Leu Gln Pro Ala His Pro Thr Pro Phe
20 25 30
Tyr Ile Glu Asp Ile Leu Gly Arg Gly Pro Ala Ala Pro Thr Pro Ala
35 40 45
Pro Thr Leu Pro Ser Pro Asn Ser Ser Phe Thr Ser Leu Val Ser Pro
50 55 60
Tyr Arg Thr Pro Val Tyr Glu Pro Thr Pro Ile His Pro Ala Phe Ser
65 70 75 80
His His Ser Ala Ala Ala Leu Ala Ala Ala Tyr Gly Pro Gly Gly Phe
85 90 95
Gly Gly Pro Leu Tyr Pro Phe Pro Arg Thr Val Asn Asp Tyr Thr His
100 105 110
Ala Leu Leu Arg His Asp Pro Leu Gly Lys Pro Leu Leu Trp Ser Pro
115 120 125
Phe Leu Gln Arg Pro Leu His Lys Arg Lys Gly Gly Gln Val Arg Phe
130 135 140
Ser Asn Asp Gln Thr Ile Glu Leu Glu Lys Lys Phe Glu Thr Gln Lys
145 150 155 160
Tyr Leu Ser Pro Pro Glu Arg Lys Arg Leu Ala Lys Met Leu Gln Leu
165 170 175
Ser Glu Arg Gln Val Lys Thr Trp Phe Gln Asn Arg Arg Ala Lys Trp
180 185 190
Arg Arg Leu Lys Gln Glu Asn Pro Gln Ser Asn Lys Lys Glu Glu Leu
195 200 205
Glu Ser Leu Asp Ser Ser Cys Asp Gln Arg Gln Asp Leu Pro Ser Glu
210 215 220
Gln Asn Lys Gly Ala Ser Leu Asp Ser Ser Gln Cys Ser Pro Ser Pro
225 230 235 240
Ala Ser Gln Glu Asp Leu Glu Ser Glu Ile Ser Glu Asp Ser Asp Gln
245 250 255
Glu Val Asp Ile Glu Gly Asp Lys Ser Tyr Phe Asn Ala Gly
260 265 270
<210> 66
<211> 271
<212> PRT
<213> Mus musculus
<400> 66
Met Gln Phe Pro His Pro Gly Pro Ala Ala Ala Pro Ala Val Gly Val
1 5 10 15
Pro Leu Tyr Ala Pro Thr Pro Leu Leu Gln Pro Ala His Pro Thr Pro
20 25 30
Phe Tyr Ile Asp Asp Ile Leu Gly Arg Gly Pro Ala Ala Pro Thr Pro
35 40 45
Thr Pro Thr Leu Pro Ser Pro Asn Ser Ser Phe Thr Ser Leu Val Ser
50 55 60
Ser Tyr Arg Thr Pro Val Tyr Glu Pro Thr Pro Val His Pro Ala Phe
65 70 75 80
Ser His His Pro Ala Ala Ala Leu Ala Ala Ala Tyr Gly Pro Ser Gly
85 90 95
Phe Gly Gly Pro Leu Tyr Pro Phe Pro Arg Thr Val Asn Asp Tyr Thr
100 105 110
His Ala Leu Leu Arg His Asp Pro Leu Gly Lys Pro Leu Leu Trp Ser
115 120 125
Pro Phe Leu Gln Arg Pro Leu His Lys Arg Lys Gly Gly Gln Val Arg
130 135 140
Phe Ser Asn Asp Gln Thr Val Glu Leu Glu Lys Lys Phe Glu Thr Gln
145 150 155 160
Lys Tyr Leu Ser Pro Pro Glu Arg Lys Arg Leu Ala Lys Met Leu Gln
165 170 175
Leu Ser Glu Arg Gln Val Lys Thr Trp Phe Gln Asn Arg Arg Ala Lys
180 185 190
Trp Arg Arg Leu Lys Gln Glu Asn Pro Gln Ser Asn Lys Lys Asp Ala
195 200 205
Leu Asp Ser Leu Asp Thr Ser Cys Glu Gln Gly Gln Asp Leu Pro Ser
210 215 220
Glu Gln Asn Lys Gly Ala Ser Leu Asp Arg Ser Gln Cys Ser Pro Ser
225 230 235 240
Pro Ala Ser Gln Glu Asp Pro Asp Ser Glu Ile Ser Glu Asp Ser Asp
245 250 255
Gln Glu Val Asp Ile Glu Gly Asp Lys Gly Tyr Phe Asn Ala Gly
260 265 270
<210> 67
<211> 270
<212> PRT
<213> Homo sapiens
<400> 67
Met Ser Ser Tyr Phe Val Asn Ser Phe Cys Gly Arg Tyr Pro Asn Gly
1 5 10 15
Pro Asp Tyr Gln Leu His Asn Tyr Gly Asp His Ser Ser Val Ser Glu
20 25 30
Gln Phe Arg Asp Ser Ala Ser Met His Ser Gly Arg Tyr Gly Tyr Gly
35 40 45
Tyr Asn Gly Met Asp Leu Ser Val Gly Arg Ser Gly Ser Gly His Phe
50 55 60
Gly Ser Gly Glu Arg Ala Arg Ser Tyr Ala Ala Ser Ala Ser Ala Ala
65 70 75 80
Pro Ala Glu Pro Arg Tyr Ser Gln Pro Ala Thr Ser Thr His Ser Pro
85 90 95
Gln Pro Asp Pro Leu Pro Cys Ser Ala Val Ala Pro Ser Pro Gly Ser
100 105 110
Asp Ser His His Gly Gly Lys Asn Ser Leu Ser Asn Ser Ser Gly Ala
115 120 125
Ser Ala Asp Ala Gly Ser Thr His Ile Ser Ser Arg Glu Gly Val Gly
130 135 140
Thr Ala Ser Gly Ala Glu Glu Asp Ala Pro Ala Ser Ser Glu Gln Ala
145 150 155 160
Ser Ala Gln Ser Glu Pro Ser Pro Ala Pro Pro Ala Gln Pro Gln Ile
165 170 175
Tyr Pro Trp Met Arg Lys Leu His Ile Ser His Asp Asn Ile Gly Gly
180 185 190
Pro Glu Gly Lys Arg Ala Arg Thr Ala Tyr Thr Arg Tyr Gln Thr Leu
195 200 205
Glu Leu Glu Lys Glu Phe His Phe Asn Arg Tyr Leu Thr Arg Arg Arg
210 215 220
Arg Ile Glu Ile Ala His Ala Leu Cys Leu Ser Glu Arg Gln Ile Lys
225 230 235 240
Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys Asp Asn Lys Leu
245 250 255
Lys Ser Met Ser Met Ala Ala Ala Gly Gly Ala Phe Arg Pro
260 265 270
<210> 68
<211> 270
<212> PRT
<213> Mus musculus
<400> 68
Met Ser Ser Tyr Phe Val Asn Ser Phe Cys Gly Arg Tyr Pro Asn Gly
1 5 10 15
Pro Asp Tyr Gln Leu His Asn Tyr Gly Asp His Ser Ser Val Ser Glu
20 25 30
Gln Phe Arg Asp Ser Ala Ser Met His Ser Gly Arg Tyr Gly Tyr Gly
35 40 45
Tyr Asn Gly Met Asp Leu Ser Val Gly Arg Ser Gly Ser Gly His Phe
50 55 60
Gly Ser Gly Glu Arg Ala Arg Ser Tyr Ala Ala Gly Ala Ser Ala Ala
65 70 75 80
Pro Ala Glu Pro Arg Tyr Ser Gln Pro Ala Thr Ser Thr His Ser Pro
85 90 95
Pro Pro Asp Pro Leu Pro Cys Ser Ala Val Ala Pro Ser Pro Gly Ser
100 105 110
Asp Ser His His Gly Gly Lys Asn Ser Leu Gly Asn Ser Ser Gly Ala
115 120 125
Ser Ala Asn Ala Gly Ser Thr His Ile Ser Ser Arg Glu Gly Val Gly
130 135 140
Thr Ala Ser Ala Ala Glu Glu Asp Ala Pro Ala Ser Ser Glu Gln Ala
145 150 155 160
Gly Ala Gln Ser Glu Pro Ser Pro Ala Pro Pro Ala Gln Pro Gln Ile
165 170 175
Tyr Pro Trp Met Arg Lys Leu His Ile Ser His Asp Asn Ile Gly Gly
180 185 190
Pro Glu Gly Lys Arg Ala Arg Thr Ala Tyr Thr Arg Tyr Gln Thr Leu
195 200 205
Glu Leu Glu Lys Glu Phe His Phe Asn Arg Tyr Leu Thr Arg Arg Arg
210 215 220
Arg Ile Glu Ile Ala His Ala Leu Cys Leu Ser Glu Arg Gln Ile Lys
225 230 235 240
Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys Asp Asn Lys Leu
245 250 255
Lys Ser Met Ser Met Ala Ala Ala Gly Gly Ala Phe Arg Pro
260 265 270
<210> 69
<211> 119
<212> PRT
<213> Homo sapiens
<400> 69
Met Lys Ala Leu Ser Pro Val Arg Gly Cys Tyr Glu Ala Val Cys Cys
1 5 10 15
Leu Ser Glu Arg Ser Leu Ala Ile Ala Arg Gly Arg Gly Lys Gly Pro
20 25 30
Ala Ala Glu Glu Pro Leu Ser Leu Leu Asp Asp Met Asn His Cys Tyr
35 40 45
Ser Arg Leu Arg Glu Leu Val Pro Gly Val Pro Arg Gly Thr Gln Leu
50 55 60
Ser Gln Val Glu Ile Leu Gln Arg Val Ile Asp Tyr Ile Leu Asp Leu
65 70 75 80
Gln Val Val Leu Ala Glu Pro Ala Pro Gly Pro Pro Asp Gly Pro His
85 90 95
Leu Pro Ile Gln Thr Ala Glu Leu Thr Pro Glu Leu Val Ile Ser Asn
100 105 110
Asp Lys Arg Ser Phe Cys His
115
<210> 70
<211> 119
<212> PRT
<213> Mus musculus
<400> 70
Met Lys Ala Leu Ser Pro Val Arg Gly Cys Tyr Glu Ala Val Cys Cys
1 5 10 15
Leu Ser Glu Arg Ser Leu Ala Ile Ala Arg Gly Arg Gly Lys Ser Pro
20 25 30
Ser Thr Glu Glu Pro Leu Ser Leu Leu Asp Asp Met Asn His Cys Tyr
35 40 45
Ser Arg Leu Arg Glu Leu Val Pro Gly Val Pro Arg Gly Thr Gln Leu
50 55 60
Ser Gln Val Glu Ile Leu Gln Arg Val Ile Asp Tyr Ile Leu Asp Leu
65 70 75 80
Gln Val Val Leu Ala Glu Pro Ala Pro Gly Pro Pro Asp Gly Pro His
85 90 95
Leu Pro Ile Gln Thr Ala Glu Leu Thr Pro Glu Leu Val Ile Ser Lys
100 105 110
Asp Lys Arg Ser Phe Cys His
115
<210> 71
<211> 519
<212> PRT
<213> Homo sapiens
<400> 71
Met Asp Ala Asp Glu Gly Gln Asp Met Ser Gln Val Ser Gly Lys Glu
1 5 10 15
Ser Pro Pro Val Ser Asp Thr Pro Asp Glu Gly Asp Glu Pro Met Pro
20 25 30
Ile Pro Glu Asp Leu Ser Thr Thr Ser Gly Gly Gln Gln Ser Ser Lys
35 40 45
Ser Asp Arg Val Val Ala Ser Asn Val Lys Val Glu Thr Gln Ser Asp
50 55 60
Glu Glu Asn Gly Arg Ala Cys Glu Met Asn Gly Glu Glu Cys Ala Glu
65 70 75 80
Asp Leu Arg Met Leu Asp Ala Ser Gly Glu Lys Met Asn Gly Ser His
85 90 95
Arg Asp Gln Gly Ser Ser Ala Leu Ser Gly Val Gly Gly Ile Arg Leu
100 105 110
Pro Asn Gly Lys Leu Lys Cys Asp Ile Cys Gly Ile Ile Cys Ile Gly
115 120 125
Pro Asn Val Leu Met Val His Lys Arg Ser His Thr Gly Glu Arg Pro
130 135 140
Phe Gln Cys Asn Gln Cys Gly Ala Ser Phe Thr Gln Lys Gly Asn Leu
145 150 155 160
Leu Arg His Ile Lys Leu His Ser Gly Glu Lys Pro Phe Lys Cys His
165 170 175
Leu Cys Asn Tyr Ala Cys Arg Arg Arg Asp Ala Leu Thr Gly His Leu
180 185 190
Arg Thr His Ser Val Gly Lys Pro His Lys Cys Gly Tyr Cys Gly Arg
195 200 205
Ser Tyr Lys Gln Arg Ser Ser Leu Glu Glu His Lys Glu Arg Cys His
210 215 220
Asn Tyr Leu Glu Ser Met Gly Leu Pro Gly Thr Leu Tyr Pro Val Ile
225 230 235 240
Lys Glu Glu Thr Asn His Ser Glu Met Ala Glu Asp Leu Cys Lys Ile
245 250 255
Gly Ser Glu Arg Ser Leu Val Leu Asp Arg Leu Ala Ser Asn Val Ala
260 265 270
Lys Arg Lys Ser Ser Met Pro Gln Lys Phe Leu Gly Asp Lys Gly Leu
275 280 285
Ser Asp Thr Pro Tyr Asp Ser Ser Ala Ser Tyr Glu Lys Glu Asn Glu
290 295 300
Met Met Lys Ser His Val Met Asp Gln Ala Ile Asn Asn Ala Ile Asn
305 310 315 320
Tyr Leu Gly Ala Glu Ser Leu Arg Pro Leu Val Gln Thr Pro Pro Gly
325 330 335
Gly Ser Glu Val Val Pro Val Ile Ser Pro Met Tyr Gln Leu His Lys
340 345 350
Pro Leu Ala Glu Gly Thr Pro Arg Ser Asn His Ser Ala Gln Asp Ser
355 360 365
Ala Val Glu Asn Leu Leu Leu Leu Ser Lys Ala Lys Leu Val Pro Ser
370 375 380
Glu Arg Glu Ala Ser Pro Ser Asn Ser Cys Gln Asp Ser Thr Asp Thr
385 390 395 400
Glu Ser Asn Asn Glu Glu Gln Arg Ser Gly Leu Ile Tyr Leu Thr Asn
405 410 415
His Ile Ala Pro His Ala Arg Asn Gly Leu Ser Leu Lys Glu Glu His
420 425 430
Arg Ala Tyr Asp Leu Leu Arg Ala Ala Ser Glu Asn Ser Gln Asp Ala
435 440 445
Leu Arg Val Val Ser Thr Ser Gly Glu Gln Met Lys Val Tyr Lys Cys
450 455 460
Glu His Cys Arg Val Leu Phe Leu Asp His Val Met Tyr Thr Ile His
465 470 475 480
Met Gly Cys His Gly Phe Arg Asp Pro Phe Glu Cys Asn Met Cys Gly
485 490 495
Tyr His Ser Gln Asp Arg Tyr Glu Phe Ser Ser His Ile Thr Arg Gly
500 505 510
Glu His Arg Phe His Met Ser
515
<210> 72
<211> 515
<212> PRT
<213> Mus musculus
<400> 72
Met Asp Val Asp Glu Gly Gln Asp Met Ser Gln Val Ser Gly Lys Glu
1 5 10 15
Ser Pro Pro Val Ser Asp Thr Pro Asp Glu Gly Asp Glu Pro Met Pro
20 25 30
Val Pro Glu Asp Leu Ser Thr Thr Ser Gly Ala Gln Gln Asn Ser Lys
35 40 45
Ser Asp Arg Gly Met Ala Ser Asn Val Lys Val Glu Thr Gln Ser Asp
50 55 60
Glu Glu Asn Gly Arg Ala Cys Glu Met Asn Gly Glu Glu Cys Ala Glu
65 70 75 80
Asp Leu Arg Met Leu Asp Ala Ser Gly Glu Lys Met Asn Gly Ser His
85 90 95
Arg Asp Gln Gly Ser Ser Ala Leu Ser Gly Val Gly Gly Ile Arg Leu
100 105 110
Pro Asn Gly Lys Leu Lys Cys Asp Ile Cys Gly Ile Val Cys Ile Gly
115 120 125
Pro Asn Val Leu Met Val His Lys Arg Ser His Thr Gly Glu Arg Pro
130 135 140
Phe Gln Cys Asn Gln Cys Gly Ala Ser Phe Thr Gln Lys Gly Asn Leu
145 150 155 160
Leu Arg His Ile Lys Leu His Ser Gly Glu Lys Pro Phe Lys Cys His
165 170 175
Leu Cys Asn Tyr Ala Cys Arg Arg Arg Asp Ala Leu Thr Gly His Leu
180 185 190
Arg Thr His Ser Val Gly Lys Pro His Lys Cys Gly Tyr Cys Gly Arg
195 200 205
Ser Tyr Lys Gln Arg Ser Ser Leu Glu Glu His Lys Glu Arg Cys His
210 215 220
Asn Tyr Leu Glu Ser Met Gly Leu Pro Gly Met Tyr Pro Val Ile Lys
225 230 235 240
Glu Glu Thr Asn His Asn Glu Met Ala Glu Asp Leu Cys Lys Ile Gly
245 250 255
Ala Glu Arg Ser Leu Val Leu Asp Arg Leu Ala Ser Asn Val Ala Lys
260 265 270
Arg Lys Ser Ser Met Pro Gln Lys Phe Leu Gly Asp Lys Cys Leu Ser
275 280 285
Asp Met Pro Tyr Asp Ser Ala Asn Tyr Glu Lys Glu Asp Met Met Thr
290 295 300
Ser His Val Met Asp Gln Ala Ile Asn Asn Ala Ile Asn Tyr Leu Gly
305 310 315 320
Ala Glu Ser Leu Arg Pro Leu Val Gln Thr Pro Pro Gly Ser Ser Glu
325 330 335
Val Val Pro Val Ile Ser Ser Met Tyr Gln Leu His Lys Pro Pro Ser
340 345 350
Asp Gly Pro Pro Arg Ser Asn His Ser Ala Gln Asp Ala Val Asp Asn
355 360 365
Leu Leu Leu Leu Ser Lys Ala Lys Ser Val Ser Ser Glu Arg Glu Ala
370 375 380
Ser Pro Ser Asn Ser Cys Gln Asp Ser Thr Asp Thr Glu Ser Asn Ala
385 390 395 400
Glu Glu Gln Arg Ser Gly Leu Ile Tyr Leu Thr Asn His Ile Asn Pro
405 410 415
His Ala Arg Asn Gly Leu Ala Leu Lys Glu Glu Gln Arg Ala Tyr Glu
420 425 430
Val Leu Arg Ala Ala Ser Glu Asn Ser Gln Asp Ala Phe Arg Val Val
435 440 445
Ser Thr Ser Gly Glu Gln Leu Lys Val Tyr Lys Cys Glu His Cys Arg
450 455 460
Val Leu Phe Leu Asp His Val Met Tyr Thr Ile His Met Gly Cys His
465 470 475 480
Gly Phe Arg Asp Pro Phe Glu Cys Asn Met Cys Gly Tyr His Ser Gln
485 490 495
Asp Arg Tyr Glu Phe Ser Ser His Ile Thr Arg Gly Glu His Arg Tyr
500 505 510
His Leu Ser
515
<210> 73
<211> 526
<212> PRT
<213> Homo sapiens
<400> 73
Met Glu Thr Glu Ala Ile Asp Gly Tyr Ile Thr Cys Asp Asn Glu Leu
1 5 10 15
Ser Pro Glu Arg Glu His Ser Asn Met Ala Ile Asp Leu Thr Ser Ser
20 25 30
Thr Pro Asn Gly Gln His Ala Ser Pro Ser His Met Thr Ser Thr Asn
35 40 45
Ser Val Lys Leu Glu Met Gln Ser Asp Glu Glu Cys Asp Arg Lys Pro
50 55 60
Leu Ser Arg Glu Asp Glu Ile Arg Gly His Asp Glu Gly Ser Ser Leu
65 70 75 80
Glu Glu Pro Leu Ile Glu Ser Ser Glu Val Ala Asp Asn Arg Lys Val
85 90 95
Gln Glu Leu Gln Gly Glu Gly Gly Ile Arg Leu Pro Asn Gly Lys Leu
100 105 110
Lys Cys Asp Val Cys Gly Met Val Cys Ile Gly Pro Asn Val Leu Met
115 120 125
Val His Lys Arg Ser His Thr Gly Glu Arg Pro Phe His Cys Asn Gln
130 135 140
Cys Gly Ala Ser Phe Thr Gln Lys Gly Asn Leu Leu Arg His Ile Lys
145 150 155 160
Leu His Ser Gly Glu Lys Pro Phe Lys Cys Pro Phe Cys Ser Tyr Ala
165 170 175
Cys Arg Arg Arg Asp Ala Leu Thr Gly His Leu Arg Thr His Ser Val
180 185 190
Gly Lys Pro His Lys Cys Asn Tyr Cys Gly Arg Ser Tyr Lys Gln Arg
195 200 205
Ser Ser Leu Glu Glu His Lys Glu Arg Cys His Asn Tyr Leu Gln Asn
210 215 220
Val Ser Met Glu Ala Ala Gly Gln Val Met Ser His His Val Pro Pro
225 230 235 240
Met Glu Asp Cys Lys Glu Gln Glu Pro Ile Met Asp Asn Asn Ile Ser
245 250 255
Leu Val Pro Phe Glu Arg Pro Ala Val Ile Glu Lys Leu Thr Gly Asn
260 265 270
Met Gly Lys Arg Lys Ser Ser Thr Pro Gln Lys Phe Val Gly Glu Lys
275 280 285
Leu Met Arg Phe Ser Tyr Pro Asp Ile His Phe Asp Met Asn Leu Thr
290 295 300
Tyr Glu Lys Glu Ala Glu Leu Met Gln Ser His Met Met Asp Gln Ala
305 310 315 320
Ile Asn Asn Ala Ile Thr Tyr Leu Gly Ala Glu Ala Leu His Pro Leu
325 330 335
Met Gln His Pro Pro Ser Thr Ile Ala Glu Val Ala Pro Val Ile Ser
340 345 350
Ser Ala Tyr Ser Gln Val Tyr His Pro Asn Arg Ile Glu Arg Pro Ile
355 360 365
Ser Arg Glu Thr Ala Asp Ser His Glu Asn Asn Met Asp Gly Pro Ile
370 375 380
Ser Leu Ile Arg Pro Lys Ser Arg Pro Gln Glu Arg Glu Ala Ser Pro
385 390 395 400
Ser Asn Ser Cys Leu Asp Ser Thr Asp Ser Glu Ser Ser His Asp Asp
405 410 415
His Gln Ser Tyr Gln Gly His Pro Ala Leu Asn Pro Lys Arg Lys Gln
420 425 430
Ser Pro Ala Tyr Met Lys Glu Asp Val Lys Ala Leu Asp Thr Thr Lys
435 440 445
Ala Pro Lys Gly Ser Leu Lys Asp Ile Tyr Lys Val Phe Asn Gly Glu
450 455 460
Gly Glu Gln Ile Arg Ala Phe Lys Cys Glu His Cys Arg Val Leu Phe
465 470 475 480
Leu Asp His Val Met Tyr Thr Ile His Met Gly Cys His Gly Tyr Arg
485 490 495
Asp Pro Leu Glu Cys Asn Ile Cys Gly Tyr Arg Ser Gln Asp Arg Tyr
500 505 510
Glu Phe Ser Ser His Ile Val Arg Gly Glu His Thr Phe His
515 520 525
<210> 74
<211> 526
<212> PRT
<213> Mus musculus
<400> 74
Met Glu Thr Asp Ala Ile Asp Gly Tyr Ile Thr Cys Asp Asn Glu Leu
1 5 10 15
Ser Pro Glu Gly Glu His Ala Asn Met Ala Ile Asp Leu Thr Ser Ser
20 25 30
Thr Pro Asn Gly Gln His Ala Ser Pro Ser His Met Thr Ser Thr Asn
35 40 45
Ser Val Lys Leu Glu Met Gln Ser Asp Glu Glu Cys Asp Arg Gln Pro
50 55 60
Leu Ser Arg Glu Asp Glu Ile Arg Gly His Asp Glu Gly Ser Ser Leu
65 70 75 80
Glu Glu Pro Leu Ile Glu Ser Ser Glu Val Ala Asp Asn Arg Lys Val
85 90 95
Gln Asp Leu Gln Gly Glu Gly Gly Ile Arg Leu Pro Asn Gly Lys Leu
100 105 110
Lys Cys Asp Val Cys Gly Met Val Cys Ile Gly Pro Asn Val Leu Met
115 120 125
Val His Lys Arg Ser His Thr Gly Glu Arg Pro Phe His Cys Asn Gln
130 135 140
Cys Gly Ala Ser Phe Thr Gln Lys Gly Asn Leu Leu Arg His Ile Lys
145 150 155 160
Leu His Ser Gly Glu Lys Pro Phe Lys Cys Pro Phe Cys Ser Tyr Ala
165 170 175
Cys Arg Arg Arg Asp Ala Leu Thr Gly His Leu Arg Thr His Ser Val
180 185 190
Gly Lys Pro His Lys Cys Asn Tyr Cys Gly Arg Ser Tyr Lys Gln Arg
195 200 205
Ser Ser Leu Glu Glu His Lys Glu Arg Cys His Asn Tyr Leu Gln Asn
210 215 220
Val Ser Met Glu Ala Ala Gly Gln Val Met Ser His His Val Pro Pro
225 230 235 240
Met Glu Asp Cys Lys Glu Gln Glu Pro Ile Met Asp Asn Asn Ile Ser
245 250 255
Leu Val Pro Phe Glu Arg Pro Ala Val Ile Glu Lys Leu Thr Ala Asn
260 265 270
Met Gly Lys Arg Lys Ser Ser Thr Pro Gln Lys Phe Val Gly Glu Lys
275 280 285
Leu Met Arg Phe Ser Tyr Pro Asp Ile His Phe Asp Met Asn Leu Thr
290 295 300
Tyr Glu Lys Glu Ala Glu Leu Met Gln Ser His Met Met Asp Gln Ala
305 310 315 320
Ile Asn Asn Ala Ile Thr Tyr Leu Gly Ala Glu Ala Leu His Pro Leu
325 330 335
Met Gln His Ala Pro Ser Thr Ile Ala Glu Val Ala Pro Val Ile Ser
340 345 350
Ser Ala Tyr Ser Gln Val Tyr His Pro Asn Arg Ile Glu Arg Pro Ile
355 360 365
Ser Arg Glu Thr Ser Asp Ser His Glu Asn Asn Met Asp Gly Pro Ile
370 375 380
Ser Leu Ile Arg Pro Lys Ser Arg Pro Gln Glu Arg Glu Ala Ser Pro
385 390 395 400
Ser Asn Ser Cys Leu Asp Ser Thr Asp Ser Glu Ser Ser His Asp Asp
405 410 415
Arg Gln Ser Tyr Gln Gly Asn Pro Ala Leu Asn Pro Lys Arg Lys Gln
420 425 430
Ser Pro Ala Tyr Met Lys Glu Asp Val Lys Ala Leu Asp Ala Thr Lys
435 440 445
Ala Pro Lys Gly Ser Leu Lys Asp Ile Tyr Lys Val Phe Asn Gly Glu
450 455 460
Gly Glu Gln Ile Arg Ala Phe Lys Cys Glu His Cys Arg Val Leu Phe
465 470 475 480
Leu Asp His Val Met Tyr Thr Ile His Met Gly Cys His Gly Tyr Arg
485 490 495
Asp Pro Leu Glu Cys Asn Ile Cys Gly Tyr Arg Ser Gln Asp Arg Tyr
500 505 510
Glu Phe Ser Ser His Ile Val Arg Gly Glu His Thr Phe His
515 520 525
<210> 75
<211> 509
<212> PRT
<213> Homo sapiens
<400> 75
Met Glu Asp Ile Gln Thr Asn Ala Glu Leu Lys Ser Thr Gln Glu Gln
1 5 10 15
Ser Val Pro Ala Glu Ser Ala Ala Val Leu Asn Asp Tyr Ser Leu Thr
20 25 30
Lys Ser His Glu Met Glu Asn Val Asp Ser Gly Glu Gly Pro Ala Asn
35 40 45
Glu Asp Glu Asp Ile Gly Asp Asp Ser Met Lys Val Lys Asp Glu Tyr
50 55 60
Ser Glu Arg Asp Glu Asn Val Leu Lys Ser Glu Pro Met Gly Asn Ala
65 70 75 80
Glu Glu Pro Glu Ile Pro Tyr Ser Tyr Ser Arg Glu Tyr Asn Glu Tyr
85 90 95
Glu Asn Ile Lys Leu Glu Arg His Val Val Ser Phe Asp Ser Ser Arg
100 105 110
Pro Thr Ser Gly Lys Met Asn Cys Asp Val Cys Gly Leu Ser Cys Ile
115 120 125
Ser Phe Asn Val Leu Met Val His Lys Arg Ser His Thr Gly Glu Arg
130 135 140
Pro Phe Gln Cys Asn Gln Cys Gly Ala Ser Phe Thr Gln Lys Gly Asn
145 150 155 160
Leu Leu Arg His Ile Lys Leu His Thr Gly Glu Lys Pro Phe Lys Cys
165 170 175
His Leu Cys Asn Tyr Ala Cys Gln Arg Arg Asp Ala Leu Thr Gly His
180 185 190
Leu Arg Thr His Ser Val Glu Lys Pro Tyr Lys Cys Glu Phe Cys Gly
195 200 205
Arg Ser Tyr Lys Gln Arg Ser Ser Leu Glu Glu His Lys Glu Arg Cys
210 215 220
Arg Thr Phe Leu Gln Ser Thr Asp Pro Gly Asp Thr Ala Ser Ala Glu
225 230 235 240
Ala Arg His Ile Lys Ala Glu Met Gly Ser Glu Arg Ala Leu Val Leu
245 250 255
Asp Arg Leu Ala Ser Asn Val Ala Lys Arg Lys Ser Ser Met Pro Gln
260 265 270
Lys Phe Ile Gly Glu Lys Arg His Cys Phe Asp Val Asn Tyr Asn Ser
275 280 285
Ser Tyr Met Tyr Glu Lys Glu Ser Glu Leu Ile Gln Thr Arg Met Met
290 295 300
Asp Gln Ala Ile Asn Asn Ala Ile Ser Tyr Leu Gly Ala Glu Ala Leu
305 310 315 320
Arg Pro Leu Val Gln Thr Pro Pro Ala Pro Thr Ser Glu Met Val Pro
325 330 335
Val Ile Ser Ser Met Tyr Pro Ile Ala Leu Thr Arg Ala Glu Met Ser
340 345 350
Asn Gly Ala Pro Gln Glu Leu Glu Lys Lys Ser Ile His Leu Pro Glu
355 360 365
Lys Ser Val Pro Ser Glu Arg Gly Leu Ser Pro Asn Asn Ser Gly His
370 375 380
Asp Ser Thr Asp Thr Asp Ser Asn His Glu Glu Arg Gln Asn His Ile
385 390 395 400
Tyr Gln Gln Asn His Met Val Leu Ser Arg Ala Arg Asn Gly Met Pro
405 410 415
Leu Leu Lys Glu Val Pro Arg Ser Tyr Glu Leu Leu Lys Pro Pro Pro
420 425 430
Ile Cys Pro Arg Asp Ser Val Lys Val Ile Asn Lys Glu Gly Glu Val
435 440 445
Met Asp Val Tyr Arg Cys Asp His Cys Arg Val Leu Phe Leu Asp Tyr
450 455 460
Val Met Phe Thr Ile His Met Gly Cys His Gly Phe Arg Asp Pro Phe
465 470 475 480
Glu Cys Asn Met Cys Gly Tyr Arg Ser His Asp Arg Tyr Glu Phe Ser
485 490 495
Ser His Ile Ala Arg Gly Glu His Arg Ala Leu Leu Lys
500 505
<210> 76
<211> 507
<212> PRT
<213> Mus musculus
<400> 76
Met Glu Asp Ile Gln Pro Thr Val Glu Leu Lys Ser Thr Glu Glu Gln
1 5 10 15
Pro Leu Pro Thr Glu Ser Pro Asp Ala Leu Asn Asp Tyr Ser Leu Pro
20 25 30
Lys Pro His Glu Ile Glu Asn Val Asp Ser Arg Glu Ala Pro Ala Asn
35 40 45
Glu Asp Glu Asp Ala Gly Glu Asp Ser Met Lys Val Lys Asp Glu Tyr
50 55 60
Ser Asp Arg Asp Glu Asn Ile Met Lys Pro Glu Pro Met Gly Asp Ala
65 70 75 80
Glu Glu Ser Glu Met Pro Tyr Ser Tyr Ala Arg Glu Tyr Ser Asp Tyr
85 90 95
Glu Ser Ile Lys Leu Glu Arg His Val Pro Tyr Asp Asn Ser Arg Pro
100 105 110
Thr Gly Gly Lys Met Asn Cys Asp Val Cys Gly Leu Ser Cys Ile Ser
115 120 125
Phe Asn Val Leu Met Val His Lys Arg Ser His Thr Gly Glu Arg Pro
130 135 140
Phe Gln Cys Asn Gln Cys Gly Ala Ser Phe Thr Gln Lys Gly Asn Leu
145 150 155 160
Leu Arg His Ile Lys Leu His Thr Gly Glu Lys Pro Phe Lys Cys His
165 170 175
Leu Cys Asn Tyr Ala Cys Gln Arg Arg Asp Ala Leu Thr Gly His Leu
180 185 190
Arg Thr His Ser Val Glu Lys Pro Tyr Lys Cys Glu Phe Cys Gly Arg
195 200 205
Ser Tyr Lys Gln Arg Ser Ser Leu Glu Glu His Lys Glu Arg Cys Arg
210 215 220
Ala Phe Leu Gln Asn Pro Asp Leu Gly Asp Ala Ala Ser Val Glu Ala
225 230 235 240
Arg His Ile Lys Ala Glu Met Gly Ser Glu Arg Ala Leu Val Leu Asp
245 250 255
Arg Leu Ala Ser Asn Val Ala Lys Arg Lys Ser Ser Met Pro Gln Lys
260 265 270
Phe Ile Gly Glu Lys Arg His Cys Phe Asp Ala Asn Tyr Asn Pro Gly
275 280 285
Tyr Met Tyr Glu Lys Glu Asn Glu Met Met Gln Thr Arg Met Met Asp
290 295 300
Gln Ala Ile Asn Asn Ala Ile Ser Tyr Leu Gly Ala Glu Ala Leu Arg
305 310 315 320
Pro Leu Val Gln Thr Pro Pro Ala Pro Thr Ser Glu Met Val Pro Val
325 330 335
Ile Ser Ser Val Tyr Pro Ile Ala Leu Thr Arg Ala Asp Met Pro Asn
340 345 350
Gly Ala Pro Gln Glu Met Glu Lys Lys Arg Ile Leu Leu Pro Glu Lys
355 360 365
Ile Leu Pro Ser Glu Arg Gly Leu Ser Pro Asn Asn Ser Ala Gln Asp
370 375 380
Ser Thr Asp Thr Asp Ser Asn His Glu Asp Arg Gln His Leu Tyr Gln
385 390 395 400
Gln Ser His Val Val Leu Pro Gln Ala Arg Asn Gly Met Pro Leu Leu
405 410 415
Lys Glu Val Pro Arg Ser Phe Glu Leu Leu Lys Pro Pro Pro Ile Cys
420 425 430
Leu Arg Asp Ser Ile Lys Val Ile Asn Lys Glu Gly Glu Val Met Asp
435 440 445
Val Phe Arg Cys Asp His Cys His Val Leu Phe Leu Asp Tyr Val Met
450 455 460
Phe Thr Ile His Met Gly Cys His Gly Phe Arg Asp Pro Phe Glu Cys
465 470 475 480
Asn Met Cys Gly Tyr Arg Ser His Asp Arg Tyr Glu Phe Ser Ser His
485 490 495
Ile Ala Arg Gly Glu His Arg Ala Met Leu Lys
500 505
<210> 77
<211> 419
<212> PRT
<213> Homo sapiens
<400> 77
Met Gly Glu Lys Lys Pro Glu Pro Leu Asp Phe Val Lys Asp Phe Gln
1 5 10 15
Glu Tyr Leu Thr Gln Gln Thr His His Val Asn Met Ile Ser Gly Ser
20 25 30
Val Ser Gly Asp Lys Glu Ala Glu Ala Leu Gln Gly Ala Gly Thr Asp
35 40 45
Gly Asp Gln Asn Gly Leu Asp His Pro Ser Val Glu Val Ser Leu Asp
50 55 60
Glu Asn Ser Gly Met Leu Val Asp Gly Phe Glu Arg Thr Phe Asp Gly
65 70 75 80
Lys Leu Lys Cys Arg Tyr Cys Asn Tyr Ala Ser Lys Gly Thr Ala Arg
85 90 95
Leu Ile Glu His Ile Arg Ile His Thr Gly Glu Lys Pro His Arg Cys
100 105 110
His Leu Cys Pro Phe Ala Ser Ala Tyr Glu Arg His Leu Glu Ala His
115 120 125
Met Arg Ser His Thr Gly Glu Lys Pro Tyr Lys Cys Glu Leu Cys Ser
130 135 140
Phe Arg Cys Ser Asp Arg Ser Asn Leu Ser His His Arg Arg Arg Lys
145 150 155 160
His Lys Met Val Pro Ile Lys Gly Thr Arg Ser Ser Leu Ser Ser Lys
165 170 175
Lys Met Trp Gly Val Leu Gln Lys Lys Thr Ser Asn Leu Gly Tyr Ser
180 185 190
Arg Arg Ala Leu Ile Asn Leu Ser Pro Pro Ser Met Val Val Gln Lys
195 200 205
Pro Asp Tyr Leu Asn Asp Phe Thr His Glu Ile Pro Asn Ile Gln Thr
210 215 220
Asp Ser Tyr Glu Ser Met Ala Lys Thr Thr Pro Thr Gly Gly Leu Pro
225 230 235 240
Arg Asp Pro Gln Glu Leu Met Val Asp Asn Pro Leu Asn Gln Leu Ser
245 250 255
Thr Leu Ala Gly Gln Leu Ser Ser Leu Pro Pro Glu Asn Gln Asn Pro
260 265 270
Ala Ser Pro Asp Val Val Pro Cys Pro Asp Glu Lys Pro Phe Met Ile
275 280 285
Gln Gln Pro Ser Thr Gln Ala Val Val Ser Ala Val Ser Ala Ser Ile
290 295 300
Pro Gln Ser Ser Ser Pro Thr Ser Pro Glu Pro Arg Pro Ser His Ser
305 310 315 320
Gln Arg Asn Tyr Ser Pro Val Ala Gly Pro Ser Ser Glu Pro Ser Ala
325 330 335
His Thr Ser Thr Pro Ser Ile Gly Asn Ser Gln Pro Ser Thr Pro Ala
340 345 350
Pro Ala Leu Pro Val Gln Asp Pro Gln Leu Leu His His Cys Gln His
355 360 365
Cys Asp Met Tyr Phe Ala Asp Asn Ile Leu Tyr Thr Ile His Met Gly
370 375 380
Cys His Gly Tyr Glu Asn Pro Phe Gln Cys Asn Ile Cys Gly Cys Lys
385 390 395 400
Cys Lys Asn Lys Tyr Asp Phe Ala Cys His Phe Ala Arg Gly Gln His
405 410 415
Asn Gln His
<210> 78
<211> 419
<212> PRT
<213> Mus musculus
<400> 78
Met Gly Glu Lys Lys Pro Glu Pro Leu Asp Phe Val Lys Asp Phe Gln
1 5 10 15
Glu Tyr Leu Thr Gln Gln Thr His His Val Asn Met Ile Ser Gly Ser
20 25 30
Val Ser Gly Asp Lys Glu Ala Glu Thr Leu Gln Gly Ala Gly Thr Asp
35 40 45
Gly Asp Gln Asn Gly Leu Asp His Pro Ser Val Glu Val Ser Leu Asp
50 55 60
Glu Asn Ser Gly Met Leu Val Asp Gly Phe Glu Arg Thr Phe Asp Gly
65 70 75 80
Lys Leu Lys Cys Arg Tyr Cys Asn Tyr Ala Ser Lys Gly Thr Ala Arg
85 90 95
Leu Ile Glu His Ile Arg Ile His Thr Gly Glu Lys Pro His Arg Cys
100 105 110
His Leu Cys Pro Phe Ala Ser Ala Tyr Glu Arg His Leu Glu Ala His
115 120 125
Met Arg Ser His Thr Gly Glu Lys Pro Tyr Lys Cys Glu Leu Cys Ser
130 135 140
Phe Arg Cys Ser Asp Arg Ser Asn Leu Ser His His Arg Arg Arg Lys
145 150 155 160
His Lys Met Val Pro Ile Lys Gly Thr Arg Ser Ser Leu Ser Ser Lys
165 170 175
Lys Met Trp Gly Val Leu Gln Lys Lys Thr Ser Asn Leu Gly Tyr Ser
180 185 190
Arg Arg Ala Leu Ile Asn Leu Ser Pro Pro Ser Met Val Val Gln Lys
195 200 205
Pro Asp Tyr Leu Asn Asp Phe Thr His Glu Ile Pro Asn Ile Gln Thr
210 215 220
Asp Ser Tyr Glu Ala Met Ala Lys Thr Thr Pro Thr Gly Gly Leu Pro
225 230 235 240
Arg Asp Pro Gln Glu Leu Met Val Asp Asn Pro Leu Asn Gln Leu Ser
245 250 255
Thr Leu Ala Gly Gln Leu Ser Ser Leu Pro Pro Glu Asn Gln Asn Pro
260 265 270
Ala Ser Pro Asp Val Asp Ala Cys Pro Asp Glu Lys Pro Phe Met Ile
275 280 285
Gln Gln Pro Ser Ala Gln Ala Val Val Ser Ala Val Ser Ala Ser Ile
290 295 300
Pro Gln Ser Ser Ser Pro Thr Ser Pro Glu Pro Arg Pro Ser His Ser
305 310 315 320
Gln Arg Asn Tyr Ser Pro Val Ala Gly Pro Ser Ser Glu Pro Ser Ala
325 330 335
His Thr Ser Thr Pro Ser Ile Gly Asn Ser Gln Pro Ser Thr Pro Ala
340 345 350
Pro Thr Leu Pro Val Gln Asp Pro Gln Leu Leu His His Cys Gln His
355 360 365
Cys Asp Val Tyr Phe Ala Asp Asn Val Leu Tyr Thr Val His Met Gly
370 375 380
Cys His Gly Tyr Asp Ser Pro Phe Gln Cys Asn Val Cys Gly Cys Lys
385 390 395 400
Cys Lys Asp Lys Tyr Asp Phe Ala Cys His Phe Ala Arg Gly Gln His
405 410 415
Asn Gln His
<210> 79
<211> 516
<212> PRT
<213> Homo sapiens
<400> 79
Met Pro Val Pro Glu Arg Pro Ala Ala Gly Pro Asp Ser Pro Arg Pro
1 5 10 15
Gly Thr Arg Arg Ala Ala Pro Arg Val Leu Phe Gly Glu Trp Leu Leu
20 25 30
Gly Glu Ile Ser Ser Gly Cys Tyr Glu Gly Leu Gln Trp Leu Asp Glu
35 40 45
Ala Arg Thr Cys Phe Arg Val Pro Trp Lys His Phe Ala Arg Lys Asp
50 55 60
Leu Ser Glu Ala Asp Ala Arg Ile Phe Lys Ala Trp Ala Val Ala Arg
65 70 75 80
Gly Arg Trp Pro Pro Ser Ser Arg Gly Gly Gly Pro Pro Pro Glu Ala
85 90 95
Glu Thr Ala Glu Arg Ala Gly Trp Lys Thr Asn Phe Arg Cys Ala Leu
100 105 110
Arg Ser Thr Arg Arg Phe Val Met Leu Arg Asp Asn Ser Gly Asp Pro
115 120 125
Ala Asp Pro His Lys Val Tyr Ala Leu Ser Arg Glu Leu Cys Trp Arg
130 135 140
Glu Gly Pro Gly Thr Asp Gln Thr Glu Ala Glu Ala Pro Ala Ala Val
145 150 155 160
Pro Pro Pro Gln Gly Gly Pro Pro Gly Pro Phe Leu Ala His Thr His
165 170 175
Ala Gly Leu Gln Ala Pro Gly Pro Leu Pro Ala Pro Ala Gly Asp Lys
180 185 190
Gly Asp Leu Leu Leu Gln Ala Val Gln Gln Ser Cys Leu Ala Asp His
195 200 205
Leu Leu Thr Ala Ser Trp Gly Ala Asp Pro Val Pro Thr Lys Ala Pro
210 215 220
Gly Glu Gly Gln Glu Gly Leu Pro Leu Thr Gly Ala Cys Ala Gly Gly
225 230 235 240
Pro Gly Leu Pro Ala Gly Glu Leu Tyr Gly Trp Ala Val Glu Thr Thr
245 250 255
Pro Ser Pro Gly Pro Gln Pro Ala Ala Leu Thr Thr Gly Glu Ala Ala
260 265 270
Ala Pro Glu Ser Pro His Gln Ala Glu Pro Tyr Leu Ser Pro Ser Pro
275 280 285
Ser Ala Cys Thr Ala Val Gln Glu Pro Ser Pro Gly Ala Leu Asp Val
290 295 300
Thr Ile Met Tyr Lys Gly Arg Thr Val Leu Gln Lys Val Val Gly His
305 310 315 320
Pro Ser Cys Thr Phe Leu Tyr Gly Pro Pro Asp Pro Ala Val Arg Ala
325 330 335
Thr Asp Pro Gln Gln Val Ala Phe Pro Ser Pro Ala Glu Leu Pro Asp
340 345 350
Gln Lys Gln Leu Arg Tyr Thr Glu Glu Leu Leu Arg His Val Ala Pro
355 360 365
Gly Leu His Leu Glu Leu Arg Gly Pro Gln Leu Trp Ala Arg Arg Met
370 375 380
Gly Lys Cys Lys Val Tyr Trp Glu Val Gly Gly Pro Pro Gly Ser Ala
385 390 395 400
Ser Pro Ser Thr Pro Ala Cys Leu Leu Pro Arg Asn Cys Asp Thr Pro
405 410 415
Ile Phe Asp Phe Arg Val Phe Phe Gln Glu Leu Val Glu Phe Arg Ala
420 425 430
Arg Gln Arg Arg Gly Ser Pro Arg Tyr Thr Ile Tyr Leu Gly Phe Gly
435 440 445
Gln Asp Leu Ser Ala Gly Arg Pro Lys Glu Lys Ser Leu Val Leu Val
450 455 460
Lys Leu Glu Pro Trp Leu Cys Arg Val His Leu Glu Gly Thr Gln Arg
465 470 475 480
Glu Gly Val Ser Ser Leu Asp Ser Ser Ser Leu Ser Leu Cys Leu Ser
485 490 495
Ser Ala Asn Ser Leu Tyr Asp Asp Ile Glu Cys Phe Leu Met Glu Leu
500 505 510
Glu Gln Pro Ala
515
<210> 80
<211> 457
<212> PRT
<213> Mus musculus
<400> 80
Met Ala Glu Val Arg Gly Val Gln Arg Val Leu Phe Gly Asp Trp Leu
1 5 10 15
Leu Gly Glu Val Ser Ser Gly Gln Tyr Glu Gly Leu Gln Trp Leu Asn
20 25 30
Glu Ala Arg Thr Val Phe Arg Val Pro Trp Lys His Phe Gly Arg Arg
35 40 45
Asp Leu Asp Glu Glu Asp Ala Gln Ile Phe Lys Ala Trp Ala Val Ala
50 55 60
Arg Gly Arg Trp Pro Pro Ser Gly Val Asn Leu Pro Pro Pro Glu Ala
65 70 75 80
Glu Ala Ala Glu Arg Arg Glu Arg Arg Gly Trp Lys Thr Asn Phe Arg
85 90 95
Cys Ala Leu His Ser Thr Gly Arg Phe Ile Leu Arg Gln Asp Asn Ser
100 105 110
Gly Asp Pro Val Asp Pro His Lys Val Tyr Glu Leu Ser Arg Glu Leu
115 120 125
Gly Ser Thr Val Gly Pro Ala Thr Glu Asn Arg Glu Glu Val Ser Leu
130 135 140
Ser Asn Ala Leu Pro Thr Gln Gly Val Ser Pro Gly Ser Phe Leu Ala
145 150 155 160
Arg Glu Asn Ala Gly Leu Gln Thr Pro Ser Pro Leu Leu Ser Ser Asp
165 170 175
Ala Gly Asp Leu Leu Leu Gln Val Leu Gln Tyr Ser His Ile Leu Glu
180 185 190
Ser Glu Ser Gly Ala Asp Pro Val Pro Pro Gln Ala Pro Gly Gln Glu
195 200 205
Gln Asp Arg Val Tyr Glu Glu Pro Tyr Ala Ala Trp Gln Val Glu Ala
210 215 220
Val Pro Ser Pro Arg Pro Gln Gln Pro Ala Leu Thr Glu Arg Ser Leu
225 230 235 240
Gly Phe Leu Asp Val Thr Ile Met Tyr Lys Gly Arg Thr Val Leu Gln
245 250 255
Ala Val Val Gly His Pro Arg Cys Val Phe Leu Tyr Ser Pro Met Ala
260 265 270
Pro Ala Val Arg Thr Ser Glu Pro Gln Pro Val Ile Phe Pro Ser Pro
275 280 285
Ala Glu Leu Pro Asp Gln Lys Gln Leu His Tyr Thr Glu Thr Leu Leu
290 295 300
Gln His Val Ser Pro Gly Leu Gln Leu Glu Leu Arg Gly Pro Ser Leu
305 310 315 320
Trp Ala Leu Arg Met Gly Lys Cys Lys Val Tyr Trp Glu Val Gly Ser
325 330 335
Pro Met Gly Thr Thr Gly Pro Ser Thr Pro Pro Gln Leu Leu Glu Arg
340 345 350
Asn Arg His Thr Pro Ile Phe Asp Phe Ser Thr Phe Phe Arg Glu Leu
355 360 365
Glu Glu Phe Arg Ala Arg Arg Arg Gln Gly Ser Pro His Tyr Thr Ile
370 375 380
Tyr Leu Gly Phe Gly Gln Asp Leu Ser Ala Gly Arg Pro Lys Glu Lys
385 390 395 400
Thr Leu Ile Leu Val Lys Leu Glu Pro Trp Val Cys Lys Ala Tyr Leu
405 410 415
Glu Gly Val Gln Arg Glu Gly Val Ser Ser Leu Asp Ser Ser Ser Leu
420 425 430
Gly Leu Cys Leu Ser Ser Thr Asn Ser Leu Tyr Glu Asp Ile Glu His
435 440 445
Phe Leu Met Asp Leu Gly Gln Trp Pro
450 455
<210> 81
<211> 473
<212> PRT
<213> Homo sapiens
<400> 81
Met Gly Arg Lys Lys Ile Gln Ile Thr Arg Ile Met Asp Glu Arg Asn
1 5 10 15
Arg Gln Val Thr Phe Thr Lys Arg Lys Phe Gly Leu Met Lys Lys Ala
20 25 30
Tyr Glu Leu Ser Val Leu Cys Asp Cys Glu Ile Ala Leu Ile Ile Phe
35 40 45
Asn Ser Thr Asn Lys Leu Phe Gln Tyr Ala Ser Thr Asp Met Asp Lys
50 55 60
Val Leu Leu Lys Tyr Thr Glu Tyr Asn Glu Pro His Glu Ser Arg Thr
65 70 75 80
Asn Ser Asp Ile Val Glu Thr Leu Arg Lys Lys Gly Leu Asn Gly Cys
85 90 95
Asp Ser Pro Asp Pro Asp Ala Asp Asp Ser Val Gly His Ser Pro Glu
100 105 110
Ser Glu Asp Lys Tyr Arg Lys Ile Asn Glu Asp Ile Asp Leu Met Ile
115 120 125
Ser Arg Gln Arg Leu Cys Ala Val Pro Pro Pro Asn Phe Glu Met Pro
130 135 140
Val Ser Ile Pro Val Ser Ser His Asn Ser Leu Val Tyr Ser Asn Pro
145 150 155 160
Val Ser Ser Leu Gly Asn Pro Asn Leu Leu Pro Leu Ala His Pro Ser
165 170 175
Leu Gln Arg Asn Ser Met Ser Pro Gly Val Thr His Arg Pro Pro Ser
180 185 190
Ala Gly Asn Thr Gly Gly Leu Met Gly Gly Asp Leu Thr Ser Gly Ala
195 200 205
Gly Thr Ser Ala Gly Asn Gly Tyr Gly Asn Pro Arg Asn Ser Pro Gly
210 215 220
Leu Leu Val Ser Pro Gly Asn Leu Asn Lys Asn Met Gln Ala Lys Ser
225 230 235 240
Pro Pro Pro Met Asn Leu Gly Met Asn Asn Arg Lys Pro Asp Leu Arg
245 250 255
Val Leu Ile Pro Pro Gly Ser Lys Asn Thr Met Pro Ser Val Ser Glu
260 265 270
Asp Val Asp Leu Leu Leu Asn Gln Arg Ile Asn Asn Ser Gln Ser Ala
275 280 285
Gln Ser Leu Ala Thr Pro Val Val Ser Val Ala Thr Pro Thr Leu Pro
290 295 300
Gly Gln Gly Met Gly Gly Tyr Pro Ser Ala Ile Ser Thr Thr Tyr Gly
305 310 315 320
Thr Glu Tyr Ser Leu Ser Ser Ala Asp Leu Ser Ser Leu Ser Gly Phe
325 330 335
Asn Thr Ala Ser Ala Leu His Leu Gly Ser Val Thr Gly Trp Gln Gln
340 345 350
Gln His Leu His Asn Met Pro Pro Ser Ala Leu Ser Gln Leu Gly Ala
355 360 365
Cys Thr Ser Thr His Leu Ser Gln Ser Ser Asn Leu Ser Leu Pro Ser
370 375 380
Thr Gln Ser Leu Asn Ile Lys Ser Glu Pro Val Ser Pro Pro Arg Asp
385 390 395 400
Arg Thr Thr Thr Pro Ser Arg Tyr Pro Gln His Thr Arg His Glu Ala
405 410 415
Gly Arg Ser Pro Val Asp Ser Leu Ser Ser Cys Ser Ser Ser Tyr Asp
420 425 430
Gly Ser Asp Arg Glu Asp His Arg Asn Glu Phe His Ser Pro Ile Gly
435 440 445
Leu Thr Arg Pro Ser Pro Asp Glu Arg Glu Ser Pro Ser Val Lys Arg
450 455 460
Met Arg Leu Ser Glu Gly Trp Ala Thr
465 470
<210> 82
<211> 466
<212> PRT
<213> Mus musculus
<400> 82
Met Gly Arg Lys Lys Ile Gln Ile Thr Arg Ile Met Asp Glu Arg Asn
1 5 10 15
Arg Gln Val Thr Phe Thr Lys Arg Lys Phe Gly Leu Met Lys Lys Ala
20 25 30
Tyr Glu Leu Ser Val Leu Cys Asp Cys Glu Ile Ala Leu Ile Ile Phe
35 40 45
Asn Ser Thr Asn Lys Leu Phe Gln Tyr Ala Ser Thr Asp Met Asp Lys
50 55 60
Val Leu Leu Lys Tyr Thr Glu Tyr Asn Glu Pro His Glu Ser Arg Thr
65 70 75 80
Asn Ser Asp Ile Val Glu Thr Leu Arg Lys Lys Gly Leu Asn Gly Cys
85 90 95
Asp Ser Pro Asp Pro Asp Ala Asp Asp Ser Val Gly His Ser Pro Glu
100 105 110
Ser Glu Asp Lys Tyr Arg Lys Ile Asn Glu Asp Ile Asp Leu Met Ile
115 120 125
Ser Arg Gln Arg Leu Cys Ala Val Pro Pro Pro Ser Phe Glu Met Pro
130 135 140
Val Thr Ile Pro Val Ser Ser His Asn Ser Leu Val Tyr Ser Asn Pro
145 150 155 160
Val Ser Thr Leu Gly Asn Pro Asn Leu Leu Pro Leu Ala His Pro Ser
165 170 175
Leu Gln Arg Asn Ser Met Ser Pro Gly Val Thr His Arg Pro Pro Ser
180 185 190
Ala Gly Asn Thr Gly Gly Leu Met Gly Gly Asp Leu Thr Ser Gly Ala
195 200 205
Gly Thr Ser Ala Gly Asn Gly Tyr Gly Asn Pro Arg Asn Ser Pro Gly
210 215 220
Leu Leu Val Ser Pro Gly Asn Leu Asn Lys Asn Ile Gln Ala Lys Ser
225 230 235 240
Pro Pro Pro Met Asn Leu Gly Met Asn Asn Arg Lys Pro Asp Leu Arg
245 250 255
Val Leu Ile Pro Pro Gly Ser Lys Asn Thr Met Pro Ser Val Asn Gln
260 265 270
Arg Ile Asn Asn Ser Gln Ser Ala Gln Ser Leu Ala Thr Pro Val Val
275 280 285
Ser Val Ala Thr Pro Thr Leu Pro Gly Gln Gly Met Gly Gly Tyr Pro
290 295 300
Ser Ala Ile Ser Thr Thr Tyr Gly Thr Glu Tyr Ser Leu Ser Ser Ala
305 310 315 320
Asp Leu Ser Ser Leu Ser Gly Phe Asn Thr Ala Ser Ala Leu His Leu
325 330 335
Gly Ser Val Thr Gly Trp Gln Gln Gln His Leu His Asn Met Pro Pro
340 345 350
Ser Ala Leu Ser Gln Leu Gly Ala Cys Thr Ser Thr His Leu Ser Gln
355 360 365
Ser Ser Asn Leu Ser Leu Pro Ser Thr Gln Ser Leu Ser Ile Lys Ser
370 375 380
Glu Pro Val Ser Pro Pro Arg Asp Arg Thr Thr Thr Pro Ser Arg Tyr
385 390 395 400
Pro Gln His Thr Thr Arg His Glu Ala Gly Arg Ser Pro Val Asp Ser
405 410 415
Leu Ser Ser Cys Ser Ser Ser Tyr Asp Gly Ser Asp Arg Glu Asp His
420 425 430
Arg Asn Glu Phe His Ser Pro Ile Gly Leu Thr Arg Pro Ser Pro Asp
435 440 445
Glu Arg Glu Ser Pro Ser Val Lys Arg Met Arg Leu Ser Glu Gly Trp
450 455 460
Ala Thr
465
<210> 83
<211> 761
<212> PRT
<213> Homo sapiens
<400> 83
Met Ala Arg Arg Pro Arg His Ser Ile Tyr Ser Ser Asp Glu Asp Asp
1 5 10 15
Glu Asp Phe Glu Met Cys Asp His Asp Tyr Asp Gly Leu Leu Pro Lys
20 25 30
Ser Gly Lys Arg His Leu Gly Lys Thr Arg Trp Thr Arg Glu Glu Asp
35 40 45
Glu Lys Leu Lys Lys Leu Val Glu Gln Asn Gly Thr Asp Asp Trp Lys
50 55 60
Val Ile Ala Asn Tyr Leu Pro Asn Arg Thr Asp Val Gln Cys Gln His
65 70 75 80
Arg Trp Gln Lys Val Leu Asn Pro Glu Leu Ile Lys Gly Pro Trp Thr
85 90 95
Lys Glu Glu Asp Gln Arg Val Ile Glu Leu Val Gln Lys Tyr Gly Pro
100 105 110
Lys Arg Trp Ser Val Ile Ala Lys His Leu Lys Gly Arg Ile Gly Lys
115 120 125
Gln Cys Arg Glu Arg Trp His Asn His Leu Asn Pro Glu Val Lys Lys
130 135 140
Thr Ser Trp Thr Glu Glu Glu Asp Arg Ile Ile Tyr Gln Ala His Lys
145 150 155 160
Arg Leu Gly Asn Arg Trp Ala Glu Ile Ala Lys Leu Leu Pro Gly Arg
165 170 175
Thr Asp Asn Ala Ile Lys Asn His Trp Asn Ser Thr Met Arg Arg Lys
180 185 190
Val Glu Gln Glu Gly Tyr Leu Gln Glu Ser Ser Lys Ala Ser Gln Pro
195 200 205
Ala Val Ala Thr Ser Phe Gln Lys Asn Ser His Leu Met Gly Phe Ala
210 215 220
Gln Ala Pro Pro Thr Ala Gln Leu Pro Ala Thr Gly Gln Pro Thr Val
225 230 235 240
Asn Asn Asp Tyr Ser Tyr Tyr His Ile Ser Glu Ala Gln Asn Val Ser
245 250 255
Ser His Val Pro Tyr Pro Val Ala Leu His Val Asn Ile Val Asn Val
260 265 270
Pro Gln Pro Ala Ala Ala Ala Ile Gln Arg His Tyr Asn Asp Glu Asp
275 280 285
Pro Glu Lys Glu Lys Arg Ile Lys Glu Leu Glu Leu Leu Leu Met Ser
290 295 300
Thr Glu Asn Glu Leu Lys Gly Gln Gln Val Leu Pro Thr Gln Asn His
305 310 315 320
Thr Cys Ser Tyr Pro Gly Trp His Ser Thr Thr Ile Ala Asp His Thr
325 330 335
Arg Pro His Gly Asp Ser Ala Pro Val Ser Cys Leu Gly Glu His His
340 345 350
Ser Thr Pro Ser Leu Pro Ala Asp Pro Gly Ser Leu Pro Glu Glu Ser
355 360 365
Ala Ser Pro Ala Arg Cys Met Ile Val His Gln Gly Thr Ile Leu Asp
370 375 380
Asn Val Lys Asn Leu Leu Glu Phe Ala Glu Thr Leu Gln Phe Ile Asp
385 390 395 400
Ser Asp Ser Ser Ser Trp Cys Asp Leu Ser Ser Phe Glu Phe Phe Glu
405 410 415
Glu Ala Asp Phe Ser Pro Ser Gln His His Thr Gly Lys Ala Leu Gln
420 425 430
Leu Gln Gln Arg Glu Gly Asn Gly Thr Lys Pro Ala Gly Glu Pro Ser
435 440 445
Pro Arg Val Asn Lys Arg Met Leu Ser Glu Ser Ser Leu Asp Pro Pro
450 455 460
Lys Val Leu Pro Pro Ala Arg His Ser Thr Ile Pro Leu Val Ile Leu
465 470 475 480
Arg Lys Lys Arg Gly Gln Ala Ser Pro Leu Ala Thr Gly Asp Cys Ser
485 490 495
Ser Phe Ile Phe Ala Asp Val Ser Ser Ser Thr Pro Lys Arg Ser Pro
500 505 510
Val Lys Ser Leu Pro Phe Ser Pro Ser Gln Phe Leu Asn Thr Ser Ser
515 520 525
Asn His Glu Asn Ser Asp Leu Glu Met Pro Ser Leu Thr Ser Thr Pro
530 535 540
Leu Ile Gly His Lys Leu Thr Val Thr Thr Pro Phe His Arg Asp Gln
545 550 555 560
Thr Val Lys Thr Gln Lys Glu Asn Thr Val Phe Arg Thr Pro Ala Ile
565 570 575
Lys Arg Ser Ile Leu Glu Ser Ser Pro Arg Thr Pro Thr Pro Phe Lys
580 585 590
His Ala Leu Ala Ala Gln Glu Ile Lys Tyr Gly Pro Leu Lys Met Leu
595 600 605
Pro Gln Thr Pro Ser His Leu Val Glu Asp Leu Gln Asp Val Ile Lys
610 615 620
Gln Glu Ser Asp Glu Ser Gly Ile Val Ala Glu Phe Gln Glu Asn Gly
625 630 635 640
Pro Pro Leu Leu Lys Lys Ile Lys Gln Glu Val Glu Ser Pro Thr Asp
645 650 655
Lys Ser Gly Asn Phe Phe Cys Ser His His Trp Glu Gly Asp Ser Leu
660 665 670
Asn Thr Gln Leu Phe Thr Gln Thr Ser Pro Val Ala Asp Ala Pro Asn
675 680 685
Ile Leu Thr Ser Ser Val Leu Met Ala Pro Ala Ser Glu Asp Glu Asp
690 695 700
Asn Val Leu Lys Ala Phe Thr Val Pro Lys Asn Arg Ser Leu Ala Ser
705 710 715 720
Pro Leu Gln Pro Cys Ser Ser Thr Trp Glu Pro Ala Ser Cys Gly Lys
725 730 735
Met Glu Glu Gln Met Thr Ser Ser Ser Gln Ala Arg Lys Tyr Val Asn
740 745 750
Ala Phe Ser Ala Arg Thr Leu Val Met
755 760
<210> 84
<211> 755
<212> PRT
<213> Mus musculus
<400> 84
Met Ala Arg Arg Pro Arg His Ser Ile Tyr Ser Ser Asp Glu Asp Asp
1 5 10 15
Glu Asp Ile Glu Met Cys Asp His Asp Tyr Asp Gly Leu Leu Pro Lys
20 25 30
Ser Gly Lys Arg His Leu Gly Lys Thr Arg Trp Thr Arg Glu Glu Asp
35 40 45
Glu Lys Leu Lys Lys Leu Val Glu Gln Asn Gly Thr Asp Asp Trp Lys
50 55 60
Val Ile Ala Asn Tyr Leu Pro Asn Arg Thr Asp Val Gln Cys Gln His
65 70 75 80
Arg Trp Gln Lys Val Leu Asn Pro Glu Leu Ile Lys Gly Pro Trp Thr
85 90 95
Lys Glu Glu Asp Gln Arg Val Ile Glu Leu Val Gln Lys Tyr Gly Pro
100 105 110
Lys Arg Trp Ser Val Ile Ala Lys His Leu Lys Gly Arg Ile Gly Lys
115 120 125
Gln Cys Arg Glu Arg Trp His Asn His Leu Asn Pro Glu Val Lys Lys
130 135 140
Thr Ser Trp Thr Glu Glu Glu Asp Arg Ile Ile Tyr Gln Ala His Lys
145 150 155 160
Arg Leu Gly Asn Arg Trp Ala Glu Ile Ala Lys Leu Leu Pro Gly Arg
165 170 175
Thr Asp Asn Ala Ile Lys Asn His Trp Asn Ser Thr Met Arg Arg Lys
180 185 190
Val Glu Gln Glu Gly Tyr Leu Gln Glu Pro Ser Lys Ala Ser Gln Thr
195 200 205
Pro Val Ala Thr Ser Phe Gln Lys Asn Asn His Leu Met Gly Phe Gly
210 215 220
His Ala Ser Pro Pro Ser Gln Leu Ser Pro Ser Gly Gln Ser Ser Val
225 230 235 240
Asn Ser Glu Tyr Pro Tyr Tyr His Ile Ala Glu Ala Gln Asn Ile Ser
245 250 255
Ser His Val Pro Tyr Pro Val Ala Leu His Val Asn Ile Val Asn Val
260 265 270
Pro Gln Pro Ala Ala Ala Ala Ile Gln Arg His Tyr Asn Asp Glu Asp
275 280 285
Pro Glu Lys Glu Lys Arg Ile Lys Glu Leu Glu Leu Leu Leu Met Ser
290 295 300
Thr Glu Asn Glu Leu Lys Gly Gln Gln Ala Leu Pro Thr Gln Asn His
305 310 315 320
Thr Cys Ser Tyr Pro Gly Trp His Ser Thr Ser Ile Val Asp Gln Thr
325 330 335
Arg Pro His Gly Asp Ser Ala Pro Val Ser Cys Leu Gly Glu His His
340 345 350
Ala Thr Pro Ser Leu Pro Ala Asp Pro Gly Ser Leu Pro Glu Glu Ser
355 360 365
Ala Ser Pro Ala Arg Cys Met Ile Val His Gln Gly Thr Ile Leu Asp
370 375 380
Asn Val Lys Asn Leu Leu Glu Phe Ala Glu Thr Leu Gln Phe Ile Asp
385 390 395 400
Ser Asp Ser Ser Trp Cys Asp Leu Ser Ser Phe Glu Phe Ser Glu Glu
405 410 415
Ala Ala Ala Phe Ser Pro Ser Gln Gln Pro Thr Gly Lys Ala Phe Gln
420 425 430
Leu Gln Gln Arg Glu Gly His Gly Thr Arg Ser Ala Gly Glu Pro Ser
435 440 445
Leu Arg Val Thr Arg Arg Val Leu Ser Glu Ala Ser Leu Gly Pro Asp
450 455 460
Ser Pro Gln Ala Arg His Ser Lys Val Pro Leu Val Val Leu Arg Lys
465 470 475 480
Arg Arg Gly Gln Ala Ser Pro Leu Ala Ala Gly Glu Pro Ser Pro Ser
485 490 495
Leu Phe Ala Asp Val Ile Ser Ser Thr Leu Lys Arg Ser Pro Val Lys
500 505 510
Ser Leu Pro Phe Ser Pro Ser Gln Phe Leu Asn Thr Ser Ser Asn His
515 520 525
Glu Ser Ser Gly Leu Asp Ala Pro Thr Leu Pro Ser Thr Pro Leu Ile
530 535 540
Gly His Lys Leu Thr Pro Cys Arg Asp Gln Thr Val Lys Thr Gln Lys
545 550 555 560
Glu Asn Ser Ile Phe Arg Thr Pro Ala Ile Lys Arg Ser Ile Leu Glu
565 570 575
Ser Ser Pro Arg Thr Pro Thr Pro Phe Lys His Ala Leu Ala Ala Gln
580 585 590
Glu Ile Lys Tyr Gly Pro Leu Lys Met Leu Pro Gln Thr Pro Ser His
595 600 605
Ala Val Glu Asp Leu Gln Asp Val Ile Lys Gln Glu Ser Asp Glu Ser
610 615 620
Gly Ile Val Ala Glu Phe Gln Glu Ser Gly Pro Pro Leu Leu Lys Lys
625 630 635 640
Ile Lys Gln Glu Val Glu Ser Pro Thr Glu Lys Ser Gly Asn Phe Phe
645 650 655
Cys Ser Asn His Trp Ala Glu Asn Ser Leu Ser Thr Gln Leu Phe Ser
660 665 670
Gln Ala Ser Pro Val Ala Asp Ala Pro Asn Ile Leu Thr Ser Ser Val
675 680 685
Leu Met Thr Pro Val Ser Glu Asp Glu Asp Asn Val Leu Lys Ala Phe
690 695 700
Thr Val Pro Lys Asn Arg Pro Leu Val Gly Pro Leu Gln Pro Cys Ser
705 710 715 720
Gly Ala Trp Glu Pro Ala Ser Cys Gly Lys Thr Glu Asp Gln Met Thr
725 730 735
Ala Ser Gly Pro Ala Arg Lys Tyr Val Asn Ala Phe Ser Ala Arg Thr
740 745 750
Leu Val Met
755
<210> 85
<211> 521
<212> PRT
<213> Homo sapiens
<400> 85
Met Ala Ser Asn Ser Leu Phe Ser Thr Val Thr Pro Cys Gln Gln Asn
1 5 10 15
Phe Phe Trp Asp Pro Ser Thr Ser Arg Arg Phe Ser Pro Pro Ser Ser
20 25 30
Ser Leu Gln Pro Gly Lys Met Ser Asp Val Ser Pro Val Val Ala Ala
35 40 45
Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln
50 55 60
Gln Gln Gln Gln Gln Gln Gln Glu Ala Ala Ala Ala Ala Ala Ala Ala
65 70 75 80
Ala Ala Ala Ala Ala Ala Ala Ala Ala Val Pro Arg Leu Arg Pro Pro
85 90 95
His Asp Asn Arg Thr Met Val Glu Ile Ile Ala Asp His Pro Ala Glu
100 105 110
Leu Val Arg Thr Asp Ser Pro Asn Phe Leu Cys Ser Val Leu Pro Ser
115 120 125
His Trp Arg Cys Asn Lys Thr Leu Pro Val Ala Phe Lys Val Val Ala
130 135 140
Leu Gly Glu Val Pro Asp Gly Thr Val Val Thr Val Met Ala Gly Asn
145 150 155 160
Asp Glu Asn Tyr Ser Ala Glu Leu Arg Asn Ala Ser Ala Val Met Lys
165 170 175
Asn Gln Val Ala Arg Phe Asn Asp Leu Arg Phe Val Gly Arg Ser Gly
180 185 190
Arg Gly Lys Ser Phe Thr Leu Thr Ile Thr Val Phe Thr Asn Pro Pro
195 200 205
Gln Val Ala Thr Tyr His Arg Ala Ile Lys Val Thr Val Asp Gly Pro
210 215 220
Arg Glu Pro Arg Arg His Arg Gln Lys Leu Asp Asp Ser Lys Pro Ser
225 230 235 240
Leu Phe Ser Asp Arg Leu Ser Asp Leu Gly Arg Ile Pro His Pro Ser
245 250 255
Met Arg Val Gly Val Pro Pro Gln Asn Pro Arg Pro Ser Leu Asn Ser
260 265 270
Ala Pro Ser Pro Phe Asn Pro Gln Gly Gln Ser Gln Ile Thr Asp Pro
275 280 285
Arg Gln Ala Gln Ser Ser Pro Pro Trp Ser Tyr Asp Gln Ser Tyr Pro
290 295 300
Ser Tyr Leu Ser Gln Met Thr Ser Pro Ser Ile His Ser Thr Thr Pro
305 310 315 320
Leu Ser Ser Thr Arg Gly Thr Gly Leu Pro Ala Ile Thr Asp Val Pro
325 330 335
Arg Arg Ile Ser Asp Asp Asp Thr Ala Thr Ser Asp Phe Cys Leu Trp
340 345 350
Pro Ser Thr Leu Ser Lys Lys Ser Gln Ala Gly Ala Ser Glu Leu Gly
355 360 365
Pro Phe Ser Asp Pro Arg Gln Phe Pro Ser Ile Ser Ser Leu Thr Glu
370 375 380
Ser Arg Phe Ser Asn Pro Arg Met His Tyr Pro Ala Thr Phe Thr Tyr
385 390 395 400
Thr Pro Pro Val Thr Ser Gly Met Ser Leu Gly Met Ser Ala Thr Thr
405 410 415
His Tyr His Thr Tyr Leu Pro Pro Pro Tyr Pro Gly Ser Ser Gln Ser
420 425 430
Gln Ser Gly Pro Phe Gln Thr Ser Ser Thr Pro Tyr Leu Tyr Tyr Gly
435 440 445
Thr Ser Ser Gly Ser Tyr Gln Phe Pro Met Val Pro Gly Gly Asp Arg
450 455 460
Ser Pro Ser Arg Met Leu Pro Pro Cys Thr Thr Thr Ser Asn Gly Ser
465 470 475 480
Thr Leu Leu Asn Pro Asn Leu Pro Asn Gln Asn Asp Gly Val Asp Ala
485 490 495
Asp Gly Ser His Ser Ser Ser Pro Thr Val Leu Asn Ser Ser Gly Arg
500 505 510
Met Asp Glu Ser Val Trp Arg Pro Tyr
515 520
<210> 86
<211> 528
<212> PRT
<213> Mus musculus
<400> 86
Met Ala Ser Asn Ser Leu Phe Ser Ala Val Thr Pro Cys Gln Gln Ser
1 5 10 15
Phe Phe Trp Asp Pro Ser Thr Ser Arg Arg Phe Ser Pro Pro Ser Ser
20 25 30
Ser Leu Gln Pro Gly Lys Met Ser Asp Val Ser Pro Val Val Ala Ala
35 40 45
Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln
50 55 60
Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Glu Ala Ala
65 70 75 80
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
85 90 95
Val Pro Arg Leu Arg Pro Pro His Asp Asn Arg Thr Met Val Glu Ile
100 105 110
Ile Ala Asp His Pro Ala Glu Leu Val Arg Thr Asp Ser Pro Asn Phe
115 120 125
Leu Cys Ser Val Leu Pro Ser His Trp Arg Cys Asn Lys Thr Leu Pro
130 135 140
Val Ala Phe Lys Val Val Ala Leu Gly Glu Val Pro Asp Gly Thr Val
145 150 155 160
Val Thr Val Met Ala Gly Asn Asp Glu Asn Tyr Ser Ala Glu Leu Arg
165 170 175
Asn Ala Ser Ala Val Met Lys Asn Gln Val Ala Arg Phe Asn Asp Leu
180 185 190
Arg Phe Val Gly Arg Ser Gly Arg Gly Lys Ser Phe Thr Leu Thr Ile
195 200 205
Thr Val Phe Thr Asn Pro Pro Gln Val Ala Thr Tyr His Arg Ala Ile
210 215 220
Lys Val Thr Val Asp Gly Pro Arg Glu Pro Arg Arg His Arg Gln Lys
225 230 235 240
Leu Asp Asp Ser Lys Pro Ser Leu Phe Ser Asp Arg Leu Ser Asp Leu
245 250 255
Gly Arg Ile Pro His Pro Ser Met Arg Val Gly Val Pro Pro Gln Asn
260 265 270
Pro Arg Pro Ser Leu Asn Ser Ala Pro Ser Pro Phe Asn Pro Gln Gly
275 280 285
Gln Ser Gln Ile Thr Asp Pro Arg Gln Ala Gln Ser Ser Pro Pro Trp
290 295 300
Ser Tyr Asp Gln Ser Tyr Pro Ser Tyr Leu Ser Gln Met Thr Ser Pro
305 310 315 320
Ser Ile His Ser Thr Thr Pro Leu Ser Ser Thr Arg Gly Thr Gly Leu
325 330 335
Pro Ala Ile Thr Asp Val Pro Arg Arg Ile Ser Asp Asp Asp Thr Ala
340 345 350
Thr Ser Asp Phe Cys Leu Trp Pro Ser Ser Leu Ser Lys Lys Ser Gln
355 360 365
Ala Gly Ala Ser Glu Leu Gly Pro Phe Ser Asp Pro Arg Gln Phe Pro
370 375 380
Ser Ile Ser Ser Leu Thr Glu Ser Arg Phe Ser Asn Pro Arg Met His
385 390 395 400
Tyr Pro Ala Thr Phe Thr Tyr Thr Pro Pro Val Thr Ser Gly Met Ser
405 410 415
Leu Gly Met Ser Ala Thr Thr His Tyr His Thr Tyr Leu Pro Pro Pro
420 425 430
Tyr Pro Gly Ser Ser Gln Ser Gln Ser Gly Pro Phe Gln Thr Ser Ser
435 440 445
Thr Pro Tyr Leu Tyr Tyr Gly Thr Ser Ser Ala Ser Tyr Gln Phe Pro
450 455 460
Met Val Pro Gly Gly Asp Arg Ser Pro Ser Arg Met Val Pro Pro Cys
465 470 475 480
Thr Thr Thr Ser Asn Gly Ser Thr Leu Leu Asn Pro Asn Leu Pro Asn
485 490 495
Gln Asn Asp Gly Val Asp Ala Asp Gly Ser His Ser Ser Ser Pro Thr
500 505 510
Val Leu Asn Ser Ser Gly Arg Met Asp Glu Ser Val Trp Arg Pro Tyr
515 520 525
<210> 87
<211> 770
<212> PRT
<213> Homo sapiens
<400> 87
Met Ala Gln Trp Asn Gln Leu Gln Gln Leu Asp Thr Arg Tyr Leu Glu
1 5 10 15
Gln Leu His Gln Leu Tyr Ser Asp Ser Phe Pro Met Glu Leu Arg Gln
20 25 30
Phe Leu Ala Pro Trp Ile Glu Ser Gln Asp Trp Ala Tyr Ala Ala Ser
35 40 45
Lys Glu Ser His Ala Thr Leu Val Phe His Asn Leu Leu Gly Glu Ile
50 55 60
Asp Gln Gln Tyr Ser Arg Phe Leu Gln Glu Ser Asn Val Leu Tyr Gln
65 70 75 80
His Asn Leu Arg Arg Ile Lys Gln Phe Leu Gln Ser Arg Tyr Leu Glu
85 90 95
Lys Pro Met Glu Ile Ala Arg Ile Val Ala Arg Cys Leu Trp Glu Glu
100 105 110
Ser Arg Leu Leu Gln Thr Ala Ala Thr Ala Ala Gln Gln Gly Gly Gln
115 120 125
Ala Asn His Pro Thr Ala Ala Val Val Thr Glu Lys Gln Gln Met Leu
130 135 140
Glu Gln His Leu Gln Asp Val Arg Lys Arg Val Gln Asp Leu Glu Gln
145 150 155 160
Lys Met Lys Val Val Glu Asn Leu Gln Asp Asp Phe Asp Phe Asn Tyr
165 170 175
Lys Thr Leu Lys Ser Gln Gly Asp Met Gln Asp Leu Asn Gly Asn Asn
180 185 190
Gln Ser Val Thr Arg Gln Lys Met Gln Gln Leu Glu Gln Met Leu Thr
195 200 205
Ala Leu Asp Gln Met Arg Arg Ser Ile Val Ser Glu Leu Ala Gly Leu
210 215 220
Leu Ser Ala Met Glu Tyr Val Gln Lys Thr Leu Thr Asp Glu Glu Leu
225 230 235 240
Ala Asp Trp Lys Arg Arg Gln Gln Ile Ala Cys Ile Gly Gly Pro Pro
245 250 255
Asn Ile Cys Leu Asp Arg Leu Glu Asn Trp Ile Thr Ser Leu Ala Glu
260 265 270
Ser Gln Leu Gln Thr Arg Gln Gln Ile Lys Lys Leu Glu Glu Leu Gln
275 280 285
Gln Lys Val Ser Tyr Lys Gly Asp Pro Ile Val Gln His Arg Pro Met
290 295 300
Leu Glu Glu Arg Ile Val Glu Leu Phe Arg Asn Leu Met Lys Ser Ala
305 310 315 320
Phe Val Val Glu Arg Gln Pro Cys Met Pro Met His Pro Asp Arg Pro
325 330 335
Leu Val Ile Lys Thr Gly Val Gln Phe Thr Thr Lys Val Arg Leu Leu
340 345 350
Val Lys Phe Pro Glu Leu Asn Tyr Gln Leu Lys Ile Lys Val Cys Ile
355 360 365
Asp Lys Asp Ser Gly Asp Val Ala Ala Leu Arg Gly Ser Arg Lys Phe
370 375 380
Asn Ile Leu Gly Thr Asn Thr Lys Val Met Asn Met Glu Glu Ser Asn
385 390 395 400
Asn Gly Ser Leu Ser Ala Glu Phe Lys His Leu Thr Leu Arg Glu Gln
405 410 415
Arg Cys Gly Asn Gly Gly Arg Ala Asn Cys Asp Ala Ser Leu Ile Val
420 425 430
Thr Glu Glu Leu His Leu Ile Thr Phe Glu Thr Glu Val Tyr His Gln
435 440 445
Gly Leu Lys Ile Asp Leu Glu Thr His Ser Leu Pro Val Val Val Ile
450 455 460
Ser Asn Ile Cys Gln Met Pro Asn Ala Trp Ala Ser Ile Leu Trp Tyr
465 470 475 480
Asn Met Leu Thr Asn Asn Pro Lys Asn Val Asn Phe Phe Thr Lys Pro
485 490 495
Pro Ile Gly Thr Trp Asp Gln Val Ala Glu Val Leu Ser Trp Gln Phe
500 505 510
Ser Ser Thr Thr Lys Arg Gly Leu Ser Ile Glu Gln Leu Thr Thr Leu
515 520 525
Ala Glu Lys Leu Leu Gly Pro Gly Val Asn Tyr Ser Gly Cys Gln Ile
530 535 540
Thr Trp Ala Lys Phe Cys Lys Glu Asn Met Ala Gly Lys Gly Phe Ser
545 550 555 560
Phe Trp Val Trp Leu Asp Asn Ile Ile Asp Leu Val Lys Lys Tyr Ile
565 570 575
Leu Ala Leu Trp Asn Glu Gly Tyr Ile Met Gly Phe Ile Ser Lys Glu
580 585 590
Arg Glu Arg Ala Ile Leu Ser Thr Lys Pro Pro Gly Thr Phe Leu Leu
595 600 605
Arg Phe Ser Glu Ser Ser Lys Glu Gly Gly Val Thr Phe Thr Trp Val
610 615 620
Glu Lys Asp Ile Ser Gly Lys Thr Gln Ile Gln Ser Val Glu Pro Tyr
625 630 635 640
Thr Lys Gln Gln Leu Asn Asn Met Ser Phe Ala Glu Ile Ile Met Gly
645 650 655
Tyr Lys Ile Met Asp Ala Thr Asn Ile Leu Val Ser Pro Leu Val Tyr
660 665 670
Leu Tyr Pro Asp Ile Pro Lys Glu Glu Ala Phe Gly Lys Tyr Cys Arg
675 680 685
Pro Glu Ser Gln Glu His Pro Glu Ala Asp Pro Gly Ser Ala Ala Pro
690 695 700
Tyr Leu Lys Thr Lys Phe Ile Cys Val Thr Pro Thr Thr Cys Ser Asn
705 710 715 720
Thr Ile Asp Leu Pro Met Ser Pro Arg Thr Leu Asp Ser Leu Met Gln
725 730 735
Phe Gly Asn Asn Gly Glu Gly Ala Glu Pro Ser Ala Gly Gly Gln Phe
740 745 750
Glu Ser Leu Thr Phe Asp Met Glu Leu Thr Ser Glu Cys Ala Thr Ser
755 760 765
Pro Met
770
<210> 88
<211> 770
<212> PRT
<213> Mus musculus
<400> 88
Met Ala Gln Trp Asn Gln Leu Gln Gln Leu Asp Thr Arg Tyr Leu Glu
1 5 10 15
Gln Leu His Gln Leu Tyr Ser Asp Ser Phe Pro Met Glu Leu Arg Gln
20 25 30
Phe Leu Ala Pro Trp Ile Glu Ser Gln Asp Trp Ala Tyr Ala Ala Ser
35 40 45
Lys Glu Ser His Ala Thr Leu Val Phe His Asn Leu Leu Gly Glu Ile
50 55 60
Asp Gln Gln Tyr Ser Arg Phe Leu Gln Glu Ser Asn Val Leu Tyr Gln
65 70 75 80
His Asn Leu Arg Arg Ile Lys Gln Phe Leu Gln Ser Arg Tyr Leu Glu
85 90 95
Lys Pro Met Glu Ile Ala Arg Ile Val Ala Arg Cys Leu Trp Glu Glu
100 105 110
Ser Arg Leu Leu Gln Thr Ala Ala Thr Ala Ala Gln Gln Gly Gly Gln
115 120 125
Ala Asn His Pro Thr Ala Ala Val Val Thr Glu Lys Gln Gln Met Leu
130 135 140
Glu Gln His Leu Gln Asp Val Arg Lys Arg Val Gln Asp Leu Glu Gln
145 150 155 160
Lys Met Lys Val Val Glu Asn Leu Gln Asp Asp Phe Asp Phe Asn Tyr
165 170 175
Lys Thr Leu Lys Ser Gln Gly Asp Met Gln Asp Leu Asn Gly Asn Asn
180 185 190
Gln Ser Val Thr Arg Gln Lys Met Gln Gln Leu Glu Gln Met Leu Thr
195 200 205
Ala Leu Asp Gln Met Arg Arg Ser Ile Val Ser Glu Leu Ala Gly Leu
210 215 220
Leu Ser Ala Met Glu Tyr Val Gln Lys Thr Leu Thr Asp Glu Glu Leu
225 230 235 240
Ala Asp Trp Lys Arg Arg Gln Gln Ile Ala Cys Ile Gly Gly Pro Pro
245 250 255
Asn Ile Cys Leu Asp Arg Leu Glu Asn Trp Ile Thr Ser Leu Ala Glu
260 265 270
Ser Gln Leu Gln Thr Arg Gln Gln Ile Lys Lys Leu Glu Glu Leu Gln
275 280 285
Gln Lys Val Ser Tyr Lys Gly Asp Pro Ile Val Gln His Arg Pro Met
290 295 300
Leu Glu Glu Arg Ile Val Glu Leu Phe Arg Asn Leu Met Lys Ser Ala
305 310 315 320
Phe Val Val Glu Arg Gln Pro Cys Met Pro Met His Pro Asp Arg Pro
325 330 335
Leu Val Ile Lys Thr Gly Val Gln Phe Thr Thr Lys Val Arg Leu Leu
340 345 350
Val Lys Phe Pro Glu Leu Asn Tyr Gln Leu Lys Ile Lys Val Cys Ile
355 360 365
Asp Lys Asp Ser Gly Asp Val Ala Ala Leu Arg Gly Ser Arg Lys Phe
370 375 380
Asn Ile Leu Gly Thr Asn Thr Lys Val Met Asn Met Glu Glu Ser Asn
385 390 395 400
Asn Gly Ser Leu Ser Ala Glu Phe Lys His Leu Thr Leu Arg Glu Gln
405 410 415
Arg Cys Gly Asn Gly Gly Arg Ala Asn Cys Asp Ala Ser Leu Ile Val
420 425 430
Thr Glu Glu Leu His Leu Ile Thr Phe Glu Thr Glu Val Tyr His Gln
435 440 445
Gly Leu Lys Ile Asp Leu Glu Thr His Ser Leu Pro Val Val Val Ile
450 455 460
Ser Asn Ile Cys Gln Met Pro Asn Ala Trp Ala Ser Ile Leu Trp Tyr
465 470 475 480
Asn Met Leu Thr Asn Asn Pro Lys Asn Val Asn Phe Phe Thr Lys Pro
485 490 495
Pro Ile Gly Thr Trp Asp Gln Val Ala Glu Val Leu Ser Trp Gln Phe
500 505 510
Ser Ser Thr Thr Lys Arg Gly Leu Ser Ile Glu Gln Leu Thr Thr Leu
515 520 525
Ala Glu Lys Leu Leu Gly Pro Gly Val Asn Tyr Ser Gly Cys Gln Ile
530 535 540
Thr Trp Ala Lys Phe Cys Lys Glu Asn Met Ala Gly Lys Gly Phe Ser
545 550 555 560
Phe Trp Val Trp Leu Asp Asn Ile Ile Asp Leu Val Lys Lys Tyr Ile
565 570 575
Leu Ala Leu Trp Asn Glu Gly Tyr Ile Met Gly Phe Ile Ser Lys Glu
580 585 590
Arg Glu Arg Ala Ile Leu Ser Thr Lys Pro Pro Gly Thr Phe Leu Leu
595 600 605
Arg Phe Ser Glu Ser Ser Lys Glu Gly Gly Val Thr Phe Thr Trp Val
610 615 620
Glu Lys Asp Ile Ser Gly Lys Thr Gln Ile Gln Ser Val Glu Pro Tyr
625 630 635 640
Thr Lys Gln Gln Leu Asn Asn Met Ser Phe Ala Glu Ile Ile Met Gly
645 650 655
Tyr Lys Ile Met Asp Ala Thr Asn Ile Leu Val Ser Pro Leu Val Tyr
660 665 670
Leu Tyr Pro Asp Ile Pro Lys Glu Glu Ala Phe Gly Lys Tyr Cys Arg
675 680 685
Pro Glu Ser Gln Glu His Pro Glu Ala Asp Pro Gly Ser Ala Ala Pro
690 695 700
Tyr Leu Lys Thr Lys Phe Ile Cys Val Thr Pro Thr Thr Cys Ser Asn
705 710 715 720
Thr Ile Asp Leu Pro Met Ser Pro Arg Thr Leu Asp Ser Leu Met Gln
725 730 735
Phe Gly Asn Asn Gly Glu Gly Ala Glu Pro Ser Ala Gly Gly Gln Phe
740 745 750
Glu Ser Leu Thr Phe Asp Met Asp Leu Thr Ser Glu Cys Ala Thr Ser
755 760 765
Pro Met
770
<210> 89
<211> 773
<212> PRT
<213> Homo sapiens
<400> 89
Met Phe Ser Lys Arg Leu Glu Lys Ile Pro Gln Val Pro Leu Leu Phe
1 5 10 15
Pro Phe Ile Phe Ile Ile Leu Thr Asn Tyr Ser Lys Met Glu Gly Ala
20 25 30
Val Glu Ser Gln Pro Ser Phe Phe Lys Thr Ser Gln Asp Ile Val Thr
35 40 45
Cys Thr Trp Val Glu Asn Cys Tyr Ser Ser Phe Ser Arg Arg Pro Leu
50 55 60
Glu Gln Met Phe Cys Lys His Gln Ser Lys Asn Ile Ile Ser Trp Thr
65 70 75 80
Gly Met Val Ala His Thr Cys Asn Pro Ser Thr Leu Gly Gly Gln Gly
85 90 95
Leu Cys Asp Phe Ala Lys Met His His Gln Gln Arg Met Ala Ala Leu
100 105 110
Gly Thr Asp Lys Glu Leu Ser Asp Leu Leu Asp Phe Ser Ala Met Phe
115 120 125
Ser Pro Pro Val Ser Ser Gly Lys Asn Gly Pro Thr Ser Leu Ala Ser
130 135 140
Gly His Phe Thr Gly Ser Asn Val Glu Asp Arg Ser Ser Ser Gly Ser
145 150 155 160
Trp Gly Asn Gly Gly His Pro Ser Pro Ser Arg Asn Tyr Gly Asp Gly
165 170 175
Thr Pro Tyr Asp His Met Thr Ser Arg Asp Leu Gly Ser His Asp Asn
180 185 190
Leu Ser Pro Pro Phe Val Asn Ser Arg Ile Gln Ser Lys Thr Glu Arg
195 200 205
Gly Ser Tyr Ser Ser Tyr Gly Arg Glu Ser Asn Leu Gln Gly Cys His
210 215 220
Gln Gln Ser Leu Leu Gly Gly Asp Met Asp Met Gly Asn Pro Gly Thr
225 230 235 240
Leu Ser Pro Thr Lys Pro Gly Ser Gln Tyr Tyr Gln Tyr Ser Ser Asn
245 250 255
Asn Pro Arg Arg Arg Pro Leu His Ser Ser Ala Met Glu Val Gln Thr
260 265 270
Lys Lys Val Arg Lys Val Pro Pro Gly Leu Pro Ser Ser Val Tyr Ala
275 280 285
Pro Ser Ala Ser Thr Ala Asp Tyr Asn Arg Asp Ser Pro Gly Tyr Pro
290 295 300
Ser Ser Lys Pro Ala Thr Ser Thr Phe Pro Ser Ser Phe Phe Met Gln
305 310 315 320
Asp Gly His His Ser Ser Asp Pro Trp Ser Ser Ser Ser Gly Met Asn
325 330 335
Gln Pro Gly Tyr Ala Gly Met Leu Gly Asn Ser Ser His Ile Pro Gln
340 345 350
Ser Ser Ser Tyr Cys Ser Leu His Pro His Glu Arg Leu Ser Tyr Pro
355 360 365
Ser His Ser Ser Ala Asp Ile Asn Ser Ser Leu Pro Pro Met Ser Thr
370 375 380
Phe His Arg Ser Gly Thr Asn His Tyr Ser Thr Ser Ser Cys Thr Pro
385 390 395 400
Pro Ala Asn Gly Thr Asp Ser Ile Met Ala Asn Arg Gly Ser Gly Ala
405 410 415
Ala Gly Ser Ser Gln Thr Gly Asp Ala Leu Gly Lys Ala Leu Ala Ser
420 425 430
Ile Tyr Ser Pro Asp His Thr Asn Asn Ser Phe Ser Ser Asn Pro Ser
435 440 445
Thr Pro Val Gly Ser Pro Pro Ser Leu Ser Ala Gly Thr Ala Val Trp
450 455 460
Ser Arg Asn Gly Gly Gln Ala Ser Ser Ser Pro Asn Tyr Glu Gly Pro
465 470 475 480
Leu His Ser Leu Gln Ser Arg Ile Glu Asp Arg Leu Glu Arg Leu Asp
485 490 495
Asp Ala Ile His Val Leu Arg Asn His Ala Val Gly Pro Ser Thr Ala
500 505 510
Met Pro Gly Gly His Gly Asp Met His Gly Ile Ile Gly Pro Ser His
515 520 525
Asn Gly Ala Met Gly Gly Leu Gly Ser Gly Tyr Gly Thr Gly Leu Leu
530 535 540
Ser Ala Asn Arg His Ser Leu Met Val Gly Thr His Arg Glu Asp Gly
545 550 555 560
Val Ala Leu Arg Gly Ser His Ser Leu Leu Pro Asn Gln Val Pro Val
565 570 575
Pro Gln Leu Pro Val Gln Ser Ala Thr Ser Pro Asp Leu Asn Pro Pro
580 585 590
Gln Asp Pro Tyr Arg Gly Met Pro Pro Gly Leu Gln Gly Gln Ser Val
595 600 605
Ser Ser Gly Ser Ser Glu Ile Lys Ser Asp Asp Glu Gly Asp Glu Asn
610 615 620
Leu Gln Asp Thr Lys Ser Ser Glu Asp Lys Lys Leu Asp Asp Asp Lys
625 630 635 640
Lys Asp Ile Lys Ser Ile Thr Arg Ser Arg Ser Ser Asn Asn Asp Asp
645 650 655
Glu Asp Leu Thr Pro Glu Gln Lys Ala Glu Arg Glu Lys Glu Arg Arg
660 665 670
Met Ala Asn Asn Ala Arg Glu Arg Leu Arg Val Arg Asp Ile Asn Glu
675 680 685
Ala Phe Lys Glu Leu Gly Arg Met Val Gln Leu His Leu Lys Ser Asp
690 695 700
Lys Pro Gln Thr Lys Leu Leu Ile Leu His Gln Ala Val Ala Val Ile
705 710 715 720
Leu Ser Leu Glu Gln Gln Val Arg Glu Arg Asn Leu Asn Pro Lys Ala
725 730 735
Ala Cys Leu Lys Arg Arg Glu Glu Glu Lys Val Ser Ser Glu Pro Pro
740 745 750
Pro Leu Ser Leu Ala Gly Pro His Pro Gly Met Gly Asp Ala Ser Asn
755 760 765
His Met Gly Gln Met
770
<210> 90
<211> 670
<212> PRT
<213> Mus musculus
<400> 90
Met His His Gln Gln Arg Met Ala Ala Leu Gly Thr Asp Lys Glu Leu
1 5 10 15
Ser Asp Leu Leu Asp Phe Ser Ala Met Phe Ser Pro Pro Val Ser Ser
20 25 30
Gly Lys Asn Gly Pro Thr Ser Leu Ala Ser Gly His Phe Thr Gly Ser
35 40 45
Asn Val Glu Asp Arg Ser Ser Ser Gly Ser Trp Gly Thr Gly Gly His
50 55 60
Pro Ser Pro Ser Arg Asn Tyr Gly Asp Gly Thr Pro Tyr Asp His Met
65 70 75 80
Thr Ser Arg Asp Leu Gly Ser His Asp Asn Leu Ser Pro Pro Phe Val
85 90 95
Asn Ser Arg Ile Gln Ser Lys Thr Glu Arg Gly Ser Tyr Ser Ser Tyr
100 105 110
Gly Arg Glu Asn Val Gln Gly Cys His Gln Gln Ser Leu Leu Gly Gly
115 120 125
Asp Met Asp Met Gly Asn Pro Gly Thr Leu Ser Pro Thr Lys Pro Gly
130 135 140
Ser Gln Tyr Tyr Gln Tyr Ser Ser Asn Asn Ala Arg Arg Arg Pro Leu
145 150 155 160
His Ser Ser Ala Met Glu Val Gln Thr Lys Lys Val Arg Lys Val Pro
165 170 175
Pro Gly Leu Pro Ser Ser Val Tyr Ala Pro Ser Ala Ser Thr Ala Asp
180 185 190
Tyr Asn Arg Asp Ser Pro Gly Tyr Pro Ser Ser Lys Pro Ala Ala Ser
195 200 205
Thr Phe Pro Ser Ser Phe Phe Met Gln Asp Gly His His Ser Ser Asp
210 215 220
Pro Trp Ser Ser Ser Ser Gly Met Asn Gln Pro Gly Tyr Gly Gly Met
225 230 235 240
Leu Gly Asn Ser Ser His Ile Pro Gln Ser Ser Ser Tyr Cys Ser Leu
245 250 255
His Pro His Glu Arg Leu Ser Tyr Pro Ser His Ser Ser Ala Asp Ile
260 265 270
Asn Ser Ser Leu Pro Pro Met Ser Thr Phe His Arg Ser Gly Thr Asn
275 280 285
His Tyr Ser Thr Ser Ser Cys Thr Pro Pro Ala Asn Gly Thr Asp Ser
290 295 300
Ile Met Ala Asn Arg Gly Thr Gly Ala Ala Gly Ser Ser Gln Thr Gly
305 310 315 320
Asp Ala Leu Gly Lys Ala Leu Ala Ser Ile Tyr Ser Pro Asp His Thr
325 330 335
Asn Asn Ser Phe Ser Ser Asn Pro Ser Thr Pro Val Gly Ser Pro Pro
340 345 350
Ser Leu Ser Ala Gly Thr Ala Val Trp Ser Arg Asn Gly Gly Gln Ala
355 360 365
Ser Ser Ser Pro Asn Tyr Glu Gly Pro Leu His Ser Leu Gln Ser Arg
370 375 380
Ile Glu Asp Arg Leu Glu Arg Leu Asp Asp Ala Ile His Val Leu Arg
385 390 395 400
Asn His Ala Val Gly Pro Ser Thr Ala Val Pro Gly Gly His Gly Asp
405 410 415
Met His Gly Ile Met Gly Pro Ser His Asn Gly Ala Met Gly Ser Leu
420 425 430
Gly Ser Gly Tyr Gly Thr Ser Leu Leu Ser Ala Asn Arg His Ser Leu
435 440 445
Met Val Gly Ala His Arg Glu Asp Gly Val Ala Leu Arg Gly Ser His
450 455 460
Ser Leu Leu Pro Asn Gln Val Pro Val Pro Gln Leu Pro Val Gln Ser
465 470 475 480
Ala Thr Ser Pro Asp Leu Asn Pro Pro Gln Asp Pro Tyr Arg Gly Met
485 490 495
Pro Pro Gly Leu Gln Gly Gln Ser Val Ser Ser Gly Ser Ser Glu Ile
500 505 510
Lys Ser Asp Asp Glu Gly Asp Glu Asn Leu Gln Asp Thr Lys Ser Ser
515 520 525
Glu Asp Lys Lys Leu Asp Asp Asp Lys Lys Asp Ile Lys Ser Ile Thr
530 535 540
Arg Ser Arg Ser Ser Asn Asn Asp Asp Glu Asp Leu Thr Pro Glu Gln
545 550 555 560
Lys Ala Glu Arg Glu Lys Glu Arg Arg Met Ala Asn Asn Ala Arg Glu
565 570 575
Arg Leu Arg Val Arg Asp Ile Asn Glu Ala Phe Lys Glu Leu Gly Arg
580 585 590
Met Val Gln Leu His Leu Lys Ser Asp Lys Pro Gln Thr Lys Leu Leu
595 600 605
Ile Leu His Gln Ala Val Ala Val Ile Leu Ser Leu Glu Gln Gln Val
610 615 620
Arg Glu Arg Asn Leu Asn Pro Lys Ala Ala Cys Leu Lys Arg Arg Glu
625 630 635 640
Glu Glu Lys Val Ser Ser Glu Pro Pro Pro Leu Ser Leu Ala Gly Pro
645 650 655
His Pro Gly Met Gly Asp Ala Ala Asn His Met Gly Gln Met
660 665 670
<210> 91
<211> 706
<212> PRT
<213> Homo sapiens
<400> 91
Met Asn Pro Gln Gln Gln Arg Met Ala Ala Ile Gly Thr Asp Lys Glu
1 5 10 15
Leu Ser Asp Leu Leu Asp Phe Ser Ala Met Phe Ser Pro Pro Val Asn
20 25 30
Ser Gly Lys Thr Arg Pro Thr Thr Leu Gly Ser Ser Gln Phe Ser Gly
35 40 45
Ser Gly Ile Asp Glu Arg Gly Gly Thr Thr Ser Trp Gly Thr Ser Gly
50 55 60
Gln Pro Ser Pro Ser Tyr Asp Ser Ser Arg Gly Phe Thr Asp Ser Pro
65 70 75 80
His Tyr Ser Asp His Leu Asn Asp Ser Arg Leu Gly Ala His Glu Gly
85 90 95
Leu Ser Pro Thr Pro Phe Met Asn Ser Asn Leu Met Gly Lys Thr Ser
100 105 110
Glu Arg Gly Ser Phe Ser Leu Tyr Ser Arg Asp Thr Gly Leu Pro Gly
115 120 125
Cys Gln Ser Ser Leu Leu Arg Gln Asp Leu Gly Leu Gly Ser Pro Ala
130 135 140
Gln Leu Ser Ser Ser Gly Lys Pro Gly Thr Ala Tyr Tyr Ser Phe Ser
145 150 155 160
Ala Thr Ser Ser Arg Arg Arg Pro Leu His Asp Ser Ala Ala Leu Asp
165 170 175
Pro Leu Gln Ala Lys Lys Val Arg Lys Val Pro Pro Gly Leu Pro Ser
180 185 190
Ser Val Tyr Ala Pro Ser Pro Asn Ser Asp Asp Phe Asn Arg Glu Ser
195 200 205
Pro Ser Tyr Pro Ser Pro Lys Pro Pro Thr Ser Met Phe Ala Ser Thr
210 215 220
Phe Phe Met Gln Asp Gly Thr His Asn Ser Ser Asp Leu Trp Ser Ser
225 230 235 240
Ser Asn Gly Met Ser Gln Pro Gly Phe Gly Gly Ile Leu Gly Thr Ser
245 250 255
Thr Ser His Met Ser Gln Ser Ser Ser Tyr Gly Asn Leu His Ser His
260 265 270
Asp Arg Leu Ser Tyr Pro Pro His Ser Val Ser Pro Thr Asp Ile Asn
275 280 285
Thr Ser Leu Pro Pro Met Ser Ser Phe His Arg Gly Ser Thr Ser Ser
290 295 300
Ser Pro Tyr Val Ala Ala Ser His Thr Pro Pro Ile Asn Gly Ser Asp
305 310 315 320
Ser Ile Leu Gly Thr Arg Gly Asn Ala Ala Gly Ser Ser Gln Thr Gly
325 330 335
Asp Ala Leu Gly Lys Ala Leu Ala Ser Ile Tyr Ser Pro Asp His Thr
340 345 350
Ser Ser Ser Phe Pro Ser Asn Pro Ser Thr Pro Val Gly Ser Pro Ser
355 360 365
Pro Leu Thr Gly Thr Ser Gln Trp Pro Arg Pro Gly Gly Gln Ala Pro
370 375 380
Ser Ser Pro Ser Tyr Glu Asn Ser Leu His Ser Leu Lys Asn Arg Val
385 390 395 400
Glu Gln Gln Leu His Glu His Leu Gln Asp Ala Met Ser Phe Leu Lys
405 410 415
Asp Val Cys Glu Gln Ser Arg Met Glu Asp Arg Leu Asp Arg Leu Asp
420 425 430
Asp Ala Ile His Val Leu Arg Asn His Ala Val Gly Pro Ser Thr Ser
435 440 445
Leu Pro Ala Gly His Ser Asp Ile His Ser Leu Leu Gly Pro Ser His
450 455 460
Asn Ala Pro Ile Gly Ser Leu Asn Ser Asn Tyr Gly Gly Ser Ser Leu
465 470 475 480
Val Ala Ser Ser Arg Ser Ala Ser Met Val Gly Thr His Arg Glu Asp
485 490 495
Ser Val Ser Leu Asn Gly Asn His Ser Val Leu Ser Ser Thr Val Thr
500 505 510
Thr Ser Ser Thr Asp Leu Asn His Lys Thr Gln Glu Asn Tyr Arg Gly
515 520 525
Gly Leu Gln Ser Gln Ser Gly Thr Val Val Thr Thr Glu Ile Lys Thr
530 535 540
Glu Asn Lys Glu Lys Asp Glu Asn Leu His Glu Pro Pro Ser Ser Asp
545 550 555 560
Asp Met Lys Ser Asp Asp Glu Ser Ser Gln Lys Asp Ile Lys Val Ser
565 570 575
Ser Arg Gly Arg Thr Ser Ser Thr Asn Glu Asp Glu Asp Leu Asn Pro
580 585 590
Glu Gln Lys Ile Glu Arg Glu Lys Glu Arg Arg Met Ala Asn Asn Ala
595 600 605
Arg Glu Arg Leu Arg Val Arg Asp Ile Asn Glu Ala Phe Lys Glu Leu
610 615 620
Gly Arg Met Cys Gln Leu His Leu Lys Ser Glu Lys Pro Gln Thr Lys
625 630 635 640
Leu Leu Ile Leu His Gln Ala Val Ala Val Ile Leu Ser Leu Glu Gln
645 650 655
Gln Val Arg Glu Arg Asn Leu Asn Pro Lys Ala Ala Cys Leu Lys Arg
660 665 670
Arg Glu Glu Glu Lys Val Ser Ala Val Ser Ala Glu Pro Pro Thr Thr
675 680 685
Leu Pro Gly Thr His Pro Gly Leu Ser Glu Thr Thr Asn Pro Met Gly
690 695 700
His Met
705
<210> 92
<211> 706
<212> PRT
<213> Mus musculus
<400> 92
Met Asn Pro Gln Gln Gln Arg Met Ala Ala Ile Gly Thr Asp Lys Glu
1 5 10 15
Leu Ser Asp Leu Leu Asp Phe Ser Ala Met Phe Ser Pro Pro Val Asn
20 25 30
Ser Gly Lys Thr Arg Pro Thr Thr Leu Gly Ser Ser Gln Phe Ser Gly
35 40 45
Ser Gly Met Asp Glu Arg Gly Gly Thr Thr Ser Trp Gly Thr Ser Gly
50 55 60
Gln Pro Ser Pro Ser Tyr Asp Ser Ser Arg Gly Phe Thr Asp Ser Pro
65 70 75 80
His Tyr Ser Asp His Leu Asn Asp Ser Arg Leu Gly Thr His Glu Gly
85 90 95
Leu Ser Pro Thr Pro Phe Met Asn Ser Asn Leu Ile Gly Lys Thr Ser
100 105 110
Glu Arg Gly Ser Phe Ser Leu Tyr Ser Arg Asp Ser Gly Leu Ser Gly
115 120 125
Cys Gln Ser Ser Leu Leu Arg Gln Asp Leu Gly Leu Gly Ser Pro Ala
130 135 140
Gln Leu Ser Ser Ser Gly Lys Pro Gly Thr Pro Tyr Tyr Ser Phe Ser
145 150 155 160
Ala Thr Ser Ser Arg Arg Arg Pro Leu His Asp Ser Val Ala Leu Asp
165 170 175
Pro Leu Gln Ala Lys Lys Val Arg Lys Val Pro Pro Gly Leu Pro Ser
180 185 190
Ser Val Tyr Ala Pro Ser Pro Asn Ser Asp Asp Phe Asn Arg Glu Ser
195 200 205
Pro Ser Tyr Pro Ser Pro Lys Pro Pro Thr Ser Met Phe Ala Ser Thr
210 215 220
Phe Phe Met Gln Asp Gly Thr His Ser Ser Ser Asp Leu Trp Ser Ser
225 230 235 240
Ser Asn Gly Met Ser Gln Pro Gly Phe Gly Gly Ile Leu Gly Thr Ser
245 250 255
Thr Ser His Met Ser Gln Ser Ser Ser Tyr Gly Ser Leu His Ser His
260 265 270
Asp Arg Leu Ser Tyr Pro Pro His Ser Val Ser Pro Thr Asp Ile Asn
275 280 285
Thr Ser Leu Pro Pro Met Ser Ser Phe His Arg Gly Ser Thr Ser Ser
290 295 300
Ser Pro Tyr Val Ala Ala Ser His Thr Pro Pro Ile Asn Gly Ser Asp
305 310 315 320
Ser Ile Leu Gly Thr Arg Gly Asn Ala Ala Gly Ser Ser Gln Thr Gly
325 330 335
Asp Ala Leu Gly Lys Ala Leu Ala Ser Ile Tyr Ser Pro Asp His Thr
340 345 350
Ser Ser Ser Phe Pro Ser Asn Pro Ser Thr Pro Val Gly Ser Pro Ser
355 360 365
Pro Leu Thr Gly Thr Ser Gln Trp Pro Arg Ala Gly Gly Gln Ala Pro
370 375 380
Ser Ser Pro Ser Tyr Glu Asn Ser Leu His Ser Leu Lys Asn Arg Val
385 390 395 400
Glu Gln Gln Leu His Glu His Leu Gln Asp Ala Met Ser Phe Leu Lys
405 410 415
Asp Val Cys Glu Gln Ser Arg Met Glu Asp Arg Leu Asp Arg Leu Asp
420 425 430
Asp Ala Ile His Val Leu Arg Asn His Ala Val Gly Pro Ser Thr Ser
435 440 445
Leu Pro Thr Ser His Ser Asp Ile His Ser Leu Leu Gly Pro Ser His
450 455 460
Asn Ala Ser Ile Gly Asn Leu Asn Ser Asn Tyr Gly Gly Ser Ser Leu
465 470 475 480
Val Thr Asn Ser Arg Ser Ala Ser Met Val Gly Thr His Arg Glu Asp
485 490 495
Ser Val Ser Leu Asn Gly Asn His Ser Val Leu Ser Ser Thr Val Ala
500 505 510
Ala Ser Asn Thr Glu Leu Asn His Lys Thr Pro Glu Asn Phe Arg Gly
515 520 525
Gly Val Gln Asn Gln Ser Gly Ser Val Val Pro Thr Glu Ile Lys Thr
530 535 540
Glu Asn Lys Glu Lys Asp Glu Asn Leu His Glu Pro Pro Ser Ser Asp
545 550 555 560
Asp Met Lys Ser Asp Asp Glu Ser Ser Gln Lys Asp Ile Lys Val Ser
565 570 575
Ser Arg Gly Arg Thr Ser Ser Thr Asn Glu Asp Glu Asp Leu Asn Pro
580 585 590
Glu Gln Lys Ile Glu Arg Glu Lys Glu Arg Arg Met Ala Asn Asn Ala
595 600 605
Arg Glu Arg Leu Arg Val Arg Asp Ile Asn Glu Ala Phe Lys Glu Leu
610 615 620
Gly Arg Met Cys Gln Leu His Leu Lys Ser Glu Lys Pro Gln Thr Lys
625 630 635 640
Leu Leu Ile Leu His Gln Ala Val Ala Val Ile Leu Ser Leu Glu Gln
645 650 655
Gln Val Arg Glu Arg Asn Leu Asn Pro Lys Ala Ala Cys Leu Lys Arg
660 665 670
Arg Glu Glu Glu Lys Val Ser Ala Ala Ser Ala Glu Pro Pro Asn Thr
675 680 685
Leu Pro Gly Ala His Pro Gly Leu Ser Glu Ser Thr Asn Pro Met Gly
690 695 700
His Leu
705
<210> 93
<211> 750
<212> PRT
<213> Homo sapiens
<400> 93
Met Ser Gln Trp Tyr Glu Leu Gln Gln Leu Asp Ser Lys Phe Leu Glu
1 5 10 15
Gln Val His Gln Leu Tyr Asp Asp Ser Phe Pro Met Glu Ile Arg Gln
20 25 30
Tyr Leu Ala Gln Trp Leu Glu Lys Gln Asp Trp Glu His Ala Ala Asn
35 40 45
Asp Val Ser Phe Ala Thr Ile Arg Phe His Asp Leu Leu Ser Gln Leu
50 55 60
Asp Asp Gln Tyr Ser Arg Phe Ser Leu Glu Asn Asn Phe Leu Leu Gln
65 70 75 80
His Asn Ile Arg Lys Ser Lys Arg Asn Leu Gln Asp Asn Phe Gln Glu
85 90 95
Asp Pro Ile Gln Met Ser Met Ile Ile Tyr Ser Cys Leu Lys Glu Glu
100 105 110
Arg Lys Ile Leu Glu Asn Ala Gln Arg Phe Asn Gln Ala Gln Ser Gly
115 120 125
Asn Ile Gln Ser Thr Val Met Leu Asp Lys Gln Lys Glu Leu Asp Ser
130 135 140
Lys Val Arg Asn Val Lys Asp Lys Val Met Cys Ile Glu His Glu Ile
145 150 155 160
Lys Ser Leu Glu Asp Leu Gln Asp Glu Tyr Asp Phe Lys Cys Lys Thr
165 170 175
Leu Gln Asn Arg Glu His Glu Thr Asn Gly Val Ala Lys Ser Asp Gln
180 185 190
Lys Gln Glu Gln Leu Leu Leu Lys Lys Met Tyr Leu Met Leu Asp Asn
195 200 205
Lys Arg Lys Glu Val Val His Lys Ile Ile Glu Leu Leu Asn Val Thr
210 215 220
Glu Leu Thr Gln Asn Ala Leu Ile Asn Asp Glu Leu Val Glu Trp Lys
225 230 235 240
Arg Arg Gln Gln Ser Ala Cys Ile Gly Gly Pro Pro Asn Ala Cys Leu
245 250 255
Asp Gln Leu Gln Asn Trp Phe Thr Ile Val Ala Glu Ser Leu Gln Gln
260 265 270
Val Arg Gln Gln Leu Lys Lys Leu Glu Glu Leu Glu Gln Lys Tyr Thr
275 280 285
Tyr Glu His Asp Pro Ile Thr Lys Asn Lys Gln Val Leu Trp Asp Arg
290 295 300
Thr Phe Ser Leu Phe Gln Gln Leu Ile Gln Ser Ser Phe Val Val Glu
305 310 315 320
Arg Gln Pro Cys Met Pro Thr His Pro Gln Arg Pro Leu Val Leu Lys
325 330 335
Thr Gly Val Gln Phe Thr Val Lys Leu Arg Leu Leu Val Lys Leu Gln
340 345 350
Glu Leu Asn Tyr Asn Leu Lys Val Lys Val Leu Phe Asp Lys Asp Val
355 360 365
Asn Glu Arg Asn Thr Val Lys Gly Phe Arg Lys Phe Asn Ile Leu Gly
370 375 380
Thr His Thr Lys Val Met Asn Met Glu Glu Ser Thr Asn Gly Ser Leu
385 390 395 400
Ala Ala Glu Phe Arg His Leu Gln Leu Lys Glu Gln Lys Asn Ala Gly
405 410 415
Thr Arg Thr Asn Glu Gly Pro Leu Ile Val Thr Glu Glu Leu His Ser
420 425 430
Leu Ser Phe Glu Thr Gln Leu Cys Gln Pro Gly Leu Val Ile Asp Leu
435 440 445
Glu Thr Thr Ser Leu Pro Val Val Val Ile Ser Asn Val Ser Gln Leu
450 455 460
Pro Ser Gly Trp Ala Ser Ile Leu Trp Tyr Asn Met Leu Val Ala Glu
465 470 475 480
Pro Arg Asn Leu Ser Phe Phe Leu Thr Pro Pro Cys Ala Arg Trp Ala
485 490 495
Gln Leu Ser Glu Val Leu Ser Trp Gln Phe Ser Ser Val Thr Lys Arg
500 505 510
Gly Leu Asn Val Asp Gln Leu Asn Met Leu Gly Glu Lys Leu Leu Gly
515 520 525
Pro Asn Ala Ser Pro Asp Gly Leu Ile Pro Trp Thr Arg Phe Cys Lys
530 535 540
Glu Asn Ile Asn Asp Lys Asn Phe Pro Phe Trp Leu Trp Ile Glu Ser
545 550 555 560
Ile Leu Glu Leu Ile Lys Lys His Leu Leu Pro Leu Trp Asn Asp Gly
565 570 575
Cys Ile Met Gly Phe Ile Ser Lys Glu Arg Glu Arg Ala Leu Leu Lys
580 585 590
Asp Gln Gln Pro Gly Thr Phe Leu Leu Arg Phe Ser Glu Ser Ser Arg
595 600 605
Glu Gly Ala Ile Thr Phe Thr Trp Val Glu Arg Ser Gln Asn Gly Gly
610 615 620
Glu Pro Asp Phe His Ala Val Glu Pro Tyr Thr Lys Lys Glu Leu Ser
625 630 635 640
Ala Val Thr Phe Pro Asp Ile Ile Arg Asn Tyr Lys Val Met Ala Ala
645 650 655
Glu Asn Ile Pro Glu Asn Pro Leu Lys Tyr Leu Tyr Pro Asn Ile Asp
660 665 670
Lys Asp His Ala Phe Gly Lys Tyr Tyr Ser Arg Pro Lys Glu Ala Pro
675 680 685
Glu Pro Met Glu Leu Asp Gly Pro Lys Gly Thr Gly Tyr Ile Lys Thr
690 695 700
Glu Leu Ile Ser Val Ser Glu Val His Pro Ser Arg Leu Gln Thr Thr
705 710 715 720
Asp Asn Leu Leu Pro Met Ser Pro Glu Glu Phe Asp Glu Val Ser Arg
725 730 735
Ile Val Gly Ser Val Glu Phe Asp Ser Met Met Asn Thr Val
740 745 750
<210> 94
<211> 755
<212> PRT
<213> Mus musculus
<400> 94
Met Ser Gln Trp Phe Glu Leu Gln Gln Leu Asp Ser Lys Phe Leu Glu
1 5 10 15
Gln Val His Gln Leu Tyr Asp Asp Ser Phe Pro Met Glu Ile Arg Gln
20 25 30
Tyr Leu Ala Gln Trp Leu Glu Lys Gln Asp Trp Glu His Ala Ala Tyr
35 40 45
Asp Val Ser Phe Ala Thr Ile Arg Phe His Asp Leu Leu Ser Gln Leu
50 55 60
Asp Asp Gln Tyr Ser Arg Phe Ser Leu Glu Asn Asn Phe Leu Leu Gln
65 70 75 80
His Asn Ile Arg Lys Ser Lys Arg Asn Leu Gln Asp Asn Phe Gln Glu
85 90 95
Asp Pro Val Gln Met Ser Met Ile Ile Tyr Asn Cys Leu Lys Glu Glu
100 105 110
Arg Lys Ile Leu Glu Asn Ala Gln Arg Phe Asn Gln Ala Gln Glu Gly
115 120 125
Asn Ile Gln Asn Thr Val Met Leu Asp Lys Gln Lys Glu Leu Asp Ser
130 135 140
Lys Val Arg Asn Val Lys Asp Gln Val Met Cys Ile Glu Gln Glu Ile
145 150 155 160
Lys Thr Leu Glu Glu Leu Gln Asp Glu Tyr Asp Phe Lys Cys Lys Thr
165 170 175
Ser Gln Asn Arg Glu Gly Glu Ala Asn Gly Val Ala Lys Ser Asp Gln
180 185 190
Lys Gln Glu Gln Leu Leu Leu His Lys Met Phe Leu Met Leu Asp Asn
195 200 205
Lys Arg Lys Glu Ile Ile His Lys Ile Arg Glu Leu Leu Asn Ser Ile
210 215 220
Glu Leu Thr Gln Asn Thr Leu Ile Asn Asp Glu Leu Val Glu Trp Lys
225 230 235 240
Arg Arg Gln Gln Ser Ala Cys Ile Gly Gly Pro Pro Asn Ala Cys Leu
245 250 255
Asp Gln Leu Gln Ser Trp Phe Thr Ile Val Ala Glu Thr Leu Gln Gln
260 265 270
Ile Arg Gln Gln Leu Lys Lys Leu Glu Glu Leu Glu Gln Lys Phe Thr
275 280 285
Tyr Glu Pro Asp Pro Ile Thr Lys Asn Lys Gln Val Leu Ser Asp Arg
290 295 300
Thr Phe Leu Leu Phe Gln Gln Leu Ile Gln Ser Ser Phe Val Val Glu
305 310 315 320
Arg Gln Pro Cys Met Pro Thr His Pro Gln Arg Pro Leu Val Leu Lys
325 330 335
Thr Gly Val Gln Phe Thr Val Lys Leu Arg Leu Leu Val Lys Leu Gln
340 345 350
Glu Leu Asn Tyr Asn Leu Lys Val Lys Val Ser Phe Asp Lys Asp Val
355 360 365
Asn Glu Lys Asn Thr Val Lys Gly Phe Arg Lys Phe Asn Ile Leu Gly
370 375 380
Thr His Thr Lys Val Met Asn Met Glu Glu Ser Thr Asn Gly Ser Leu
385 390 395 400
Ala Ala Glu Phe Arg His Leu Gln Leu Lys Glu Gln Lys Asn Ala Gly
405 410 415
Asn Arg Thr Asn Glu Gly Pro Leu Ile Val Thr Glu Glu Leu His Ser
420 425 430
Leu Ser Phe Glu Thr Gln Leu Cys Gln Pro Gly Leu Val Ile Asp Leu
435 440 445
Glu Val Phe Val Pro Phe Gln Thr Thr Ser Leu Pro Val Val Val Ile
450 455 460
Ser Asn Val Ser Gln Leu Pro Ser Gly Trp Ala Ser Ile Leu Trp Tyr
465 470 475 480
Asn Met Leu Val Thr Glu Pro Arg Asn Leu Ser Phe Phe Leu Asn Pro
485 490 495
Pro Cys Ala Trp Trp Ser Gln Leu Ser Glu Val Leu Ser Trp Gln Phe
500 505 510
Ser Ser Val Thr Lys Arg Gly Leu Asn Ala Asp Gln Leu Ser Met Leu
515 520 525
Gly Glu Lys Leu Leu Gly Pro Asn Ala Gly Pro Asp Gly Leu Ile Pro
530 535 540
Trp Thr Arg Phe Cys Lys Glu Asn Ile Asn Asp Lys Asn Phe Ser Phe
545 550 555 560
Trp Pro Trp Ile Asp Thr Ile Leu Glu Leu Ile Lys Lys His Leu Leu
565 570 575
Cys Leu Trp Asn Asp Gly Cys Ile Met Gly Phe Ile Ser Lys Glu Arg
580 585 590
Glu Arg Ala Leu Leu Lys Asp Gln Gln Pro Gly Thr Phe Leu Leu Arg
595 600 605
Phe Ser Glu Ser Ser Arg Glu Gly Ala Ile Thr Phe Thr Trp Val Glu
610 615 620
Arg Ser Gln Asn Gly Gly Glu Pro Asp Phe His Ala Val Glu Pro Tyr
625 630 635 640
Thr Lys Lys Glu Leu Ser Ala Val Thr Phe Pro Asp Ile Ile Arg Asn
645 650 655
Tyr Lys Val Met Ala Ala Glu Asn Ile Pro Glu Asn Pro Leu Lys Tyr
660 665 670
Leu Tyr Pro Asn Ile Asp Lys Asp His Ala Phe Gly Lys Tyr Tyr Ser
675 680 685
Arg Pro Lys Glu Ala Pro Glu Pro Met Glu Leu Asp Asp Pro Lys Arg
690 695 700
Thr Gly Tyr Ile Lys Thr Glu Leu Ile Ser Val Ser Glu Val His Pro
705 710 715 720
Ser Arg Leu Gln Thr Thr Asp Asn Leu Leu Pro Met Ser Pro Glu Glu
725 730 735
Phe Asp Glu Met Ser Arg Ile Val Gly Pro Glu Phe Asp Ser Met Met
740 745 750
Ser Thr Val
755
<210> 95
<211> 1073
<212> PRT
<213> Homo sapiens
<400> 95
Met His Gln Pro Pro Glu Ser Thr Ala Ala Ala Ala Ala Ala Ala Asp
1 5 10 15
Ile Ser Ala Arg Lys Met Ala His Pro Ala Met Phe Pro Arg Arg Gly
20 25 30
Ser Gly Ser Gly Ser Ala Ser Ala Leu Asn Ala Ala Gly Thr Gly Val
35 40 45
Gly Ser Asn Ala Thr Ser Ser Glu Asp Phe Pro Pro Pro Ser Leu Leu
50 55 60
Gln Pro Pro Pro Pro Ala Ala Ser Ser Thr Ser Gly Pro Gln Pro Pro
65 70 75 80
Pro Pro Gln Ser Leu Asn Leu Leu Ser Gln Ala Gln Leu Gln Ala Gln
85 90 95
Pro Leu Ala Pro Gly Gly Thr Gln Met Lys Lys Lys Ser Gly Phe Gln
100 105 110
Ile Thr Ser Val Thr Pro Ala Gln Ile Ser Ala Ser Ile Ser Ser Asn
115 120 125
Asn Ser Ile Ala Glu Asp Thr Glu Ser Tyr Asp Asp Leu Asp Glu Ser
130 135 140
His Thr Glu Asp Leu Ser Ser Ser Glu Ile Leu Asp Val Ser Leu Ser
145 150 155 160
Arg Ala Thr Asp Leu Gly Glu Pro Glu Arg Ser Ser Ser Glu Glu Thr
165 170 175
Leu Asn Asn Phe Gln Glu Ala Glu Thr Pro Gly Ala Val Ser Pro Asn
180 185 190
Gln Pro His Leu Pro Gln Pro His Leu Pro His Leu Pro Gln Gln Asn
195 200 205
Val Val Ile Asn Gly Asn Ala His Pro His His Leu His His His His
210 215 220
Gln Ile His His Gly His His Leu Gln His Gly His His His Pro Ser
225 230 235 240
His Val Ala Val Ala Ser Ala Ser Ile Thr Gly Gly Pro Pro Ser Ser
245 250 255
Pro Val Ser Arg Lys Leu Ser Thr Thr Gly Ser Ser Asp Ser Ile Thr
260 265 270
Pro Val Ala Pro Thr Ser Ala Val Ser Ser Ser Gly Ser Pro Ala Ser
275 280 285
Val Met Thr Asn Met Arg Ala Pro Ser Thr Thr Gly Gly Ile Gly Ile
290 295 300
Asn Ser Val Thr Gly Thr Ser Thr Val Asn Asn Val Asn Ile Thr Ala
305 310 315 320
Val Gly Ser Phe Asn Pro Asn Val Thr Ser Ser Met Leu Gly Asn Val
325 330 335
Asn Ile Ser Thr Ser Asn Ile Pro Ser Ala Ala Gly Val Ser Val Gly
340 345 350
Pro Gly Val Thr Ser Gly Val Asn Val Asn Ile Leu Ser Gly Met Gly
355 360 365
Asn Gly Thr Ile Ser Ser Ser Ala Ala Val Ser Ser Val Pro Asn Ala
370 375 380
Ala Ala Gly Met Thr Gly Gly Ser Val Ser Ser Gln Gln Gln Gln Pro
385 390 395 400
Thr Val Asn Thr Ser Arg Phe Arg Val Val Lys Leu Asp Ser Ser Ser
405 410 415
Glu Pro Phe Lys Lys Gly Arg Trp Thr Cys Thr Glu Phe Tyr Glu Lys
420 425 430
Glu Asn Ala Val Pro Ala Thr Glu Gly Val Leu Ile Asn Lys Val Val
435 440 445
Glu Thr Val Lys Gln Asn Pro Ile Glu Val Thr Ser Glu Arg Glu Ser
450 455 460
Thr Ser Gly Ser Ser Val Ser Ser Ser Val Ser Thr Leu Ser His Tyr
465 470 475 480
Thr Glu Ser Val Gly Ser Gly Glu Met Gly Ala Pro Thr Val Val Val
485 490 495
Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Pro Ala Leu
500 505 510
Gln Gly Val Thr Leu Gln Gln Met Asp Phe Gly Ser Thr Gly Pro Gln
515 520 525
Ser Ile Pro Ala Val Ser Ile Pro Gln Ser Ile Ser Gln Ser Gln Ile
530 535 540
Ser Gln Val Gln Leu Gln Ser Gln Glu Leu Ser Tyr Gln Gln Lys Gln
545 550 555 560
Gly Leu Gln Pro Val Pro Leu Gln Ala Thr Met Ser Ala Ala Thr Gly
565 570 575
Ile Gln Pro Ser Pro Val Asn Val Val Gly Val Thr Ser Ala Leu Gly
580 585 590
Gln Gln Pro Ser Ile Ser Ser Leu Ala Gln Pro Gln Leu Pro Tyr Ser
595 600 605
Gln Ala Ala Pro Pro Val Gln Thr Pro Leu Pro Gly Ala Pro Pro Pro
610 615 620
Gln Gln Leu Gln Tyr Gly Gln Gln Gln Pro Met Val Ser Thr Gln Met
625 630 635 640
Ala Pro Gly His Val Lys Ser Val Thr Gln Asn Pro Ala Ser Glu Tyr
645 650 655
Val Gln Gln Gln Pro Ile Leu Gln Thr Ala Met Ser Ser Gly Gln Pro
660 665 670
Ser Ser Ala Gly Val Gly Ala Gly Thr Thr Val Ile Pro Val Ala Gln
675 680 685
Pro Gln Gly Ile Gln Leu Pro Val Gln Pro Thr Ala Val Pro Ala Gln
690 695 700
Pro Ala Gly Ala Ser Val Gln Pro Val Gly Gln Ala Pro Ala Ala Val
705 710 715 720
Ser Ala Val Pro Thr Gly Ser Gln Ile Ala Asn Ile Gly Gln Gln Ala
725 730 735
Asn Ile Pro Thr Ala Val Gln Gln Pro Ser Thr Gln Val Pro Pro Ser
740 745 750
Val Ile Gln Gln Gly Ala Pro Pro Ser Ser Gln Val Val Pro Pro Ala
755 760 765
Gln Thr Gly Ile Ile His Gln Gly Val Gln Thr Ser Ala Pro Ser Leu
770 775 780
Pro Gln Gln Leu Val Ile Ala Ser Gln Ser Ser Leu Leu Thr Val Pro
785 790 795 800
Pro Gln Pro Gln Gly Val Glu Pro Val Ala Gln Gly Ile Val Ser Gln
805 810 815
Gln Leu Pro Ala Val Ser Ser Leu Pro Ser Ala Ser Ser Ile Ser Val
820 825 830
Thr Ser Gln Val Ser Ser Thr Gly Pro Ser Gly Met Pro Ser Ala Pro
835 840 845
Thr Asn Leu Val Pro Pro Gln Asn Ile Ala Gln Thr Pro Ala Thr Gln
850 855 860
Asn Gly Asn Leu Val Gln Ser Val Ser Gln Pro Pro Leu Ile Ala Thr
865 870 875 880
Asn Thr Asn Leu Pro Leu Ala Gln Gln Ile Pro Leu Ser Ser Thr Gln
885 890 895
Phe Ser Ala Gln Ser Leu Ala Gln Ala Ile Gly Ser Gln Ile Glu Asp
900 905 910
Ala Arg Arg Ala Ala Glu Pro Ser Leu Val Gly Leu Pro Gln Thr Ile
915 920 925
Ser Gly Asp Ser Gly Gly Met Ser Ala Val Ser Asp Gly Ser Ser Ser
930 935 940
Ser Leu Ala Ala Ser Ala Ser Leu Phe Pro Leu Lys Val Leu Pro Leu
945 950 955 960
Thr Thr Pro Leu Val Asp Gly Glu Asp Glu Ser Ser Ser Gly Ala Ser
965 970 975
Val Val Ala Ile Asp Asn Lys Ile Glu Gln Ala Met Asp Leu Val Lys
980 985 990
Ser His Leu Met Tyr Ala Val Arg Glu Glu Val Glu Val Leu Lys Glu
995 1000 1005
Gln Ile Lys Glu Leu Ile Glu Lys Asn Ser Gln Leu Glu Gln Glu
1010 1015 1020
Asn Asn Leu Leu Lys Thr Leu Ala Ser Pro Glu Gln Leu Ala Gln
1025 1030 1035
Phe Gln Ala Gln Leu Gln Thr Gly Ser Pro Pro Ala Thr Thr Gln
1040 1045 1050
Pro Gln Gly Thr Thr Gln Pro Pro Ala Gln Pro Ala Ser Gln Gly
1055 1060 1065
Ser Gly Pro Thr Ala
1070
<210> 96
<211> 1077
<212> PRT
<213> Mus musculus
<400> 96
Met His Gln Pro Pro Glu Ser Thr Ala Ala Ala Ala Ala Ala Ala Asp
1 5 10 15
Ile Ser Ala Arg Lys Met Ala His Pro Ala Met Phe Pro Arg Arg Gly
20 25 30
Ser Gly Gly Gly Ser Ala Ser Ala Leu Asn Ala Ala Gly Thr Gly Val
35 40 45
Ser Gly Ala Ala Pro Ser Ser Glu Asp Phe Pro Pro Pro Ser Leu Leu
50 55 60
Gln Pro Pro Pro Pro Ala Ala Ser Ser Thr Gln Gly Pro Gln Pro Pro
65 70 75 80
Pro Pro Gln Ser Leu Asn Leu Leu Ser Gln Ala Gln Leu Gln Gly Gln
85 90 95
Pro Leu Ala Pro Gly Gly Thr Gln Met Lys Lys Lys Ser Gly Phe Gln
100 105 110
Ile Thr Ser Val Thr Pro Ala Gln Ile Ser Ala Ser Ile Ser Ser Asn
115 120 125
Asn Ser Ile Ala Glu Asp Thr Glu Ser Tyr Asp Asp Leu Asp Glu Ser
130 135 140
His Thr Glu Asp Leu Ser Ser Ser Glu Ile Leu Asp Val Ser Leu Ser
145 150 155 160
Arg Ala Thr Asp Leu Gly Glu Pro Glu Arg Ser Ser Ser Glu Glu Thr
165 170 175
Leu Asn Asn Phe Gln Glu Ala Glu Thr Pro Gly Ala Val Ser Pro Asn
180 185 190
Gln Pro His Leu Pro Gln Pro His Leu Pro His Leu Pro Gln Gln Asn
195 200 205
Val Val Ile Asn Gly Asn Ala His Pro His His Leu His His His His
210 215 220
His Pro His His Gly His His Leu His His Gly His His His Ser Ser
225 230 235 240
His Ala Ala Val Ala Gly Pro Ser Ile Pro Gly Gly Pro Pro Ser Ser
245 250 255
Pro Val Ser Arg Lys Leu Ser Thr Thr Gly Ser Ser Asp Gly Gly Val
260 265 270
Pro Val Ala Pro Pro Pro Ala Val Pro Ser Ser Gly Leu Pro Ala Ser
275 280 285
Val Met Thr Asn Ile Arg Thr Pro Ser Thr Thr Gly Ser Leu Gly Ile
290 295 300
Asn Ser Val Thr Gly Thr Ser Ala Thr Asn Asn Val Asn Ile Ala Ala
305 310 315 320
Val Gly Ser Phe Ser Pro Ser Val Thr Asn Ser Val His Gly Asn Ala
325 330 335
Asn Ile Asn Thr Ser Asn Ile Pro Asn Ala Ala Ser Ile Ser Gly Gly
340 345 350
Pro Gly Val Thr Ser Val Val Asn Ser Ser Ile Leu Ser Gly Met Gly
355 360 365
Asn Gly Thr Val Ser Ser Ser Pro Val Ala Asn Ser Val Leu Asn Ala
370 375 380
Ala Ala Gly Ile Thr Val Gly Val Val Ser Ser Gln Gln Gln Gln Gln
385 390 395 400
Gln Gln Gln Gln Pro Thr Val Asn Thr Ser Arg Phe Arg Val Val Lys
405 410 415
Leu Asp Ser Thr Ser Glu Pro Phe Lys Lys Gly Arg Trp Thr Cys Thr
420 425 430
Glu Phe Tyr Glu Lys Glu Asn Ala Val Pro Ala Thr Glu Gly Val Ala
435 440 445
Val Asn Lys Val Val Glu Thr Val Lys Gln Thr Pro Thr Glu Ala Ser
450 455 460
Ser Ser Glu Arg Glu Ser Thr Ser Gly Ser Ser Val Ser Ser Ser Val
465 470 475 480
Ser Thr Leu Ser His Tyr Thr Glu Ser Val Gly Ser Gly Glu Met Met
485 490 495
Gly Ala Pro Ala Val Val Ala Pro Gln Gln Pro Pro Leu Pro Pro Ala
500 505 510
Pro Pro Gly Leu Gln Gly Val Ala Leu Gln Gln Leu Glu Phe Ser Ser
515 520 525
Pro Ala Pro Gln Ser Ile Ala Ala Val Ser Met Pro Gln Ser Ile Ser
530 535 540
Gln Ser Gln Met Ser Gln Val Gln Leu Gln Pro Gln Glu Leu Ser Phe
545 550 555 560
Gln Gln Lys Gln Thr Leu Gln Pro Val Pro Leu Gln Ala Thr Met Ser
565 570 575
Ala Ala Thr Gly Ile Gln Pro Ser Pro Val Ser Val Val Gly Ile Thr
580 585 590
Ala Ala Val Gly Gln Gln Pro Ser Val Ser Ser Leu Ala Gln Pro Gln
595 600 605
Leu Pro Tyr Ser Gln Thr Ala Pro Pro Val Gln Thr Pro Leu Pro Gly
610 615 620
Ala Pro Pro Gln Gln Leu Gln Tyr Gly Gln Gln Gln Pro Met Val Pro
625 630 635 640
Ala Gln Ile Ala Pro Gly His Gly Gln Pro Val Thr Gln Asn Pro Thr
645 650 655
Ser Glu Tyr Val Gln Gln Gln Gln Gln Pro Ile Phe Gln Ala Ala Leu
660 665 670
Ser Ser Gly Gln Ser Ser Ser Thr Gly Thr Gly Ala Gly Ile Ser Val
675 680 685
Ile Pro Val Ala Gln Ala Gln Gly Ile Gln Leu Pro Gly Gln Pro Thr
690 695 700
Ala Val Gln Thr Gln Pro Ala Gly Ala Ala Gly Gln Pro Ile Gly Gln
705 710 715 720
Ala Gln Thr Ala Val Ser Thr Val Pro Thr Gly Gly Gln Ile Ala Ser
725 730 735
Ile Gly Gln Gln Ala Asn Ile Pro Thr Ala Val Gln Gln Pro Ser Thr
740 745 750
Gln Val Thr Pro Ser Val Ile Gln Gln Gly Ala Pro Pro Ser Ser Gln
755 760 765
Val Val Leu Pro Ala Pro Thr Gly Ile Ile His Gln Gly Val Gln Thr
770 775 780
Arg Ala Ser Ser Leu Pro Gln Gln Leu Val Ile Ala Pro Gln Ser Thr
785 790 795 800
Leu Val Thr Val Pro Pro Gln Pro Gln Gly Val Glu Thr Val Ala Gln
805 810 815
Gly Val Val Ser Gln Gln Leu Pro Thr Gly Ser Pro Leu Pro Ser Ala
820 825 830
Ser Thr Ile Ser Val Thr Asn Gln Val Ser Ser Ala Ala Pro Ser Gly
835 840 845
Met Pro Ser Val Pro Thr Asn Leu Val Pro Pro Gln Asn Ile Ala Gln
850 855 860
Pro Pro Ala Thr Gln Asn Gly Ser Leu Val Gln Ser Val Ser Gln Ser
865 870 875 880
Pro Leu Ile Ala Thr Asn Ile Asn Leu Pro Leu Ala Gln Gln Ile Pro
885 890 895
Leu Ser Ser Thr Gln Phe Ser Thr Gln Ser Leu Ala Gln Ala Ile Gly
900 905 910
Ser Gln Met Glu Asp Ala Arg Arg Pro Ala Glu Pro Ser Leu Gly Gly
915 920 925
Leu Pro Gln Thr Met Ser Gly Asp Ser Gly Gly Met Ser Ala Val Ser
930 935 940
Asp Gly Ser Ser Ser Ser Leu Ala Ala Pro Ala Ser Leu Phe Pro Leu
945 950 955 960
Lys Val Leu Pro Leu Thr Thr Pro Leu Val Asp Gly Glu Asp Glu Ser
965 970 975
Ser Gly Ala Ser Val Val Ala Ile Asp Asn Lys Ile Glu Gln Ala Met
980 985 990
Asp Leu Val Lys Ser His Leu Met Tyr Ala Val Arg Glu Glu Val Glu
995 1000 1005
Val Leu Lys Glu Gln Ile Lys Glu Leu Ile Glu Lys Asn Ser Gln
1010 1015 1020
Leu Glu Gln Glu Asn Asn Leu Leu Lys Thr Leu Ala Ser Pro Glu
1025 1030 1035
Gln Leu Ala Gln Phe Gln Ala Gln Leu Gln Thr Gly Ser Pro Pro
1040 1045 1050
Ala Thr Thr Gln Pro Gln Gly Thr Thr Gln Pro Pro Ala Gln Pro
1055 1060 1065
Ala Ser Gln Gly Ser Gly Ser Thr Ala
1070 1075
Claims (32)
- 적어도 2개의 전사 인자(transcription factor): IRF8 및 SPIB를 포함하는 조성물로서,
줄기 세포 또는 분화된 세포(differentiated cell), 또는 이들의 혼합물을 대상체(subject)에서 형질세포양 수지상 세포(plasmacytoid dendritic cell) 또는 인터페론 유형 I-생산 세포로 재프로그래밍(reprogramming)할 때에 사용하기 위한, 조성물. - 제1항에 있어서, 상기 조성물이 ARID5A, BCL11A, CBFA2T3, CREB3L2, ETS1, IKZF1, STAT1, TCF4, TCF12 및 TSC22D1로 이루어진 그룹으로부터 선택된 하나 이상의 기타 전사 인자를 추가로 포함하는, 조성물.
- 제1항 또는 제2항에 있어서, 상기 전사 인자가 개별적으로 IRF8(서열번호 49, 서열번호 50), SPIB(서열번호 51, 서열번호 52), ARID5A(서열번호 53, 서열번호 54), BCL11A(서열번호 55, 서열번호 56), CBFA2T3(서열번호 57, 서열번호 58), CREB3L2(서열번호 59, 서열번호 60), ETS1(서열번호 61, 서열번호 62), IKZF1(서열번호 71, 서열번호 72), TCF4(서열번호 89, 서열번호 90), TCF12(서열번호 91, 서열번호 92), STAT1(서열번호 93, 서열번호 94) 및 TSC22D1(서열번호 95, 서열번호 96)으로 이루어진 그룹으로부터 선택된 서열과 적어도 90% 동일한, 조성물.
- 제1항 내지 제3항 중 어느 한 항에 있어서, 상기 전사 인자의 조합이 하기 조합으로부터 선택되는, 조성물:
IRF8 및 SPIB;
IRF8, SPIB 및 ARID5A;
IRF8, SPIB 및 BCL11A;
IRF8, SPIB 및 CBFA2T3;
IRF8, SPIB 및 CREB3L2;
IRF8, SPIB 및 ETS1;
IRF8, SPIB 및 IKZF1;
IRF8, SPIB 및 STAT1;
IRF8, SPIB 및 TCF4;
IRF8, SPIB 및 TCF12;
IRF8, SPIB 및 TSC22D1 또는 이들의 혼합물. - 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 전사 인자의 조합이 IRF8, SPIB 및 TCF12의 조합인, 조성물.
- 제1항 내지 제5항 중 어느 한 항에 있어서, 상기 전사 인자의 조합이 IRF8, SPIB 및 TSC22D1의 조합인, 조성물.
- 제1항 내지 제6항 중 어느 한 항에 있어서, 상기 세포가 다능성(pluripotent) 줄기 세포, 다분화능(multipotent) 줄기 세포, 분화 세포, 종양 세포, 암 세포 및 이들의 혼합물로 이루어진 그룹으로부터 선택되는, 조성물.
- 제1항 내지 제5항 중 어느 한 항에 있어서, 수의학 또는 인간 의약(human medicine), 특히 항바이러스성 면역 반응 및 면역 병리(pathology), 특히 자가면역 질환 및 면역결핍 상태(condition), 신생물, 특히 암, 즉 고형 또는 혈액 종양, 양성 종양(benign tumour), 악성 종양(malignant tumour), 초기 암(early cancer), 기저 세포 암종(basal cell carcinoma), 자궁경부 이형성증(cervical dysplasia), 연조직 육종(soft tissue sarcoma), 생식 세포 종양(germ cell tumour), 망막모세포종(retinoblastoma), 연령 관련 황반 변성(age-related macular degeneration), 호지킨 림프종(Hodgkin's lymphoma), 혈액암(blood cancer), 전립선암(prostate cancer), 난소암(ovarian cancer), 자궁경부암(cervix cancer), 자궁암(uterus cancer), 질암(vaginal cancer), 유방암(breast cancer), 비인두암(naso-pharynx cancer), 기관암(trachea cancer), 후두암(larynx cancer), 기관지암(bronchi cancer), 세기관지암(bronchioles cancer), 폐암(lung cancer), 중공 장기암(hollow organs cancer), 식도암(esophagus cancer), 위암(stomach cancer), 담관암(bile duct cancer), 장암(intestine cancer), 결장암(colon cancer), 대장암(colorectum cancer), 직장암(rectum cancer), 방광암(bladder cancer), 요관암(ureter cancer), 신장암(kidney cancer), 간암(liver cancer), 담낭암(gall bladder cancer,), 비장암(spleen cancer), 뇌암(brain cancer), 림프계암(lymphatic system cancer), 골암(bone cancer), 췌장암(pancreatic cancer), 백혈병(leukaemia), 피부암(skin cancer) 또는 골수종(myeloma), 감염성 질환(infectious disease), 바이러스성 질환(viral disease) 또는 바이러스성 유발 질환(viral induced disease), 중추 및 말초 신경계 장애(central and peripheral nervous system disorder), 진균(fungal), 세균(viral), 클라미디아(chlamydial), 박테리아(bacterial), 나노박테리아(nanobacterial) 또는 기생충(parasitic) 감염 질환 또는 바이러스성 질환, 또는 바이러스 유발 질환의 진단, 요법 또는 치료에서, 항바이러스제로서 또는 면역원성 조성물로서, 면역요법으로서, 또는 신경퇴행성 질환의 치료 또는 요법에서, 암의 치료 또는 요법에서, 또는 감염성 질환의 치료 또는 요법에서, 또는 바이러스 질환, 또는 바이러스 유도 질환, 피내 및 경피 요법, HIV, SARS 코로나바이러스에 의한 감염, 아시아 독감 바이러스(Asian flu virus), 단순 포진(herpes simplex), 인플루엔자 바이러스, 대상 포진(herpes zoster), 간염(hepatitis), 인간 유두종 바이러스(human papillomavirus), 엡스타인-바르 바이러스(Epstein-Barr virus), 인간 T-림프성 바이러스 또는 바이러스 간염, 아밀로이드 질환, 특히 아밀로이드 질환 A 아밀로이드증(amyloidosis), 알츠하이머병(Alzheimer's disease), 경쇄(AL) 아밀로이드증(Light-Chain (AL) amyloidosis), 제2형 당뇨병(Type-2 Diabetes), 갑상선 수질암(Medullary Carcinoma of the Thyroid), 파킨슨병(Parkinson's disease), 다발성 신경병증(Polyneuropathy), 또는 해면상 뇌병증(Spongiform Encephalopathy)(크로이츠펠트 야콥병(Creutzfeldt Jakob disease)) 또는 약물 스크리닝(drug screening)에 사용하기 위한 조성물.
- 적어도 2개의 전사 인자 SPIB 및 IRF8을 코딩하는(encoding) 작제물(construct) 또는 벡터(vector).
- 제9항에 있어서, 상기 벡터가 바이러스 벡터; 특히 레트로바이러스, 아데노바이러스, 렌티바이러스, 헤르페스 바이러스, 수두 바이러스, 바이러스(paramyxoviral), 랍도바이러스, 알파바이러스, 플라바이러스 또는 아데노-연관 바이러스 벡터인, 작제물 또는 벡터.
- 제9항 또는 제10항에 있어서, 상기 벡터 또는 작제물이 합성 mRNA, 네이키드(naked) 알파바이러스 RNA 레플리콘(replicon) 또는 네이키드 플라비바이러스 RNA 레플리콘인, 작제물 또는 벡터.
- 대상체에서 줄기 세포 또는 분화된 세포, 또는 이들의 혼합물을 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포로 재프로그래밍할 때에 사용하기 위한, 적어도 2개의 전사 인자 IRF8 및 SPIB를 코딩하는 적어도 2개의 폴리뉴클레오티드 서열을 포함하는 하나 이상의 벡터.
- 제12항에 있어서, 상기 벡터가 ARID5A, BCL11A, CBFA2T3, CREB3L2, ETS1, IKZF1, STAT1, TCF4, TCF12 및 TSC22D1로 이루어진 그룹으로부터 선택된 하나 이상의 기타 전사 인자를 추가로 코딩하는, 하나 이상의 벡터.
- 제12항 또는 제13항에 있어서, 상기 전사 인자가 개별적으로, IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4), ARID5A(서열번호 5, 서열번호 6), BCL11A(서열번호 7, 서열번호 8), CBFA2T3(서열번호 9, 서열번호 10), CREB3L2(서열번호 11, 서열번호 12), ETS1(서열번호 13, 서열번호 14), IKZF1(서열번호 23, 서열번호 24), TCF4(서열번호 41, 서열번호 42), TCF12(서열번호 43, 서열번호 44), STAT1(서열번호 45, 서열번호 46) 및 TSC22D1(서열번호 47, 서열번호 48)로 이루어진 그룹으로부터 선택된 서열과 적어도 90% 동일한, 하나 이상의 벡터.
- 제12항 내지 제14항 중 어느 한 항에 있어서, 상기 전사 인자의 조합이 하기 조합으로부터 선택되는, 하나 이상의 벡터:
IRF8 및 SPIB;
IRF8, SPIB 및 ARID5A;
IRF8, SPIB 및 BCL11A;
IRF8, SPIB 및 CBFA2T3;
IRF8, SPIB 및 CREB3L2;
IRF8, SPIB 및 ETS1;
IRF8, SPIB 및 IKZF1;
IRF8, SPIB 및 STAT1;
IRF8, SPIB 및 TCF4;
IRF8, SPIB 및 TCF12;
IRF8, SPIB 및 TSC22D1, 또는 이들의 혼합물. - 제12항 내지 제15항 중 어느 한 항에 있어서, 상기 전사 인자의 조합이 IRF8, SPIB 및 TCF12의 조합인, 하나 이상의 벡터.
- 제12항 내지 제16항 중 어느 한 항에 있어서, 상기 전사 인자의 조합이 IRF8, SPIB 및 TSC22D1의 조합인, 하나 이상의 벡터.
- 제12항 내지 제17항 중 어느 한 항에 있어서, 상기 벡터가 바이러스 벡터; 특히 레트로바이러스, 아데노바이러스, 렌티바이러스, 헤르페스 바이러스, 수두 바이러스, 파라믹소바이러스, 랍도바이러스, 알파바이러스, 플라비바이러스 또는 아데노-연관 바이러스 벡터인, 하나 이상의 벡터.
- 제12항 내지 제18항 중 어느 한 항에 있어서, 상기 벡터가 합성 mRNA, 네이키드 알파바이러스 RNA 레플리콘 또는 네이키드 플라비바이러스 RNA 레플리콘인, 하나 이상의 벡터.
- 제12항 내지 제19항 중 어느 한 항에 있어서, 상기 세포가 다능성 줄기 세포, 다분화능 줄기 세포, 분화된 세포, 종양 세포, 암 세포 및 이들의 혼합물로 이루어진 그룹으로부터 선택되는, 하나 이상의 벡터.
- 제12항 내지 제20항 중 어느 한 항에 있어서, 수의학 또는 인간 의약, 특히 항바이러스성 면역 반응 및 면역 병리, 특히 자가면역 질환 및 면역결핍 상태, 신생물, 특히 암, 즉 고형 또는 혈액 종양, 양성 종양(benign tumour), 악성 종양(malignant tumour), 초기 암(early cancer), 기저 세포 암종(basal cell carcinoma), 자궁경부 이형성증(cervical dysplasia), 연조직 육종(soft tissue sarcoma), 생식 세포 종양(germ cell tumour), 망막모세포종(retinoblastoma), 연령 관련 황반 변성(age-related macular degeneration), 호지킨 림프종(Hodgkin's lymphoma), 혈액암(blood cancer), 전립선암(prostate cancer), 난소암(ovarian cancer), 자궁경부암(cervix cancer), 자궁암(uterus cancer), 질암(vaginal cancer), 유방암(breast cancer), 비인두암(naso-pharynx cancer), 기관암(trachea cancer), 후두암(larynx cancer), 기관지암(bronchi cancer), 세기관지암(bronchioles cancer), 폐암(lung cancer), 중공 장기암(hollow organs cancer), 식도암(esophagus cancer), 위암(stomach cancer), 담관암(bile duct cancer), 장암(intestine cancer), 결장암(colon cancer), 대장암(colorectum cancer), 직장암(rectum cancer), 방광암(bladder cancer), 요관암(ureter cancer), 신장암(kidney cancer), 간암(liver cancer), 담낭암(gall bladder cancer,), 비장암(spleen cancer), 뇌암(brain cancer), 림프계암(lymphatic system cancer), 골암(bone cancer), 췌장암(pancreatic cancer), 백혈병(leukaemia), 피부암(skin cancer) 또는 골수종(myeloma), 감염성 질환(infectious disease), 바이러스성 질환(viral disease) 또는 바이러스성 유발 질환(viral induced disease), 중추 및 말초 신경계 장애(central and peripheral nervous system disorder), 진균(fungal), 세균(viral), 클라미디아(chlamydial), 박테리아(bacterial), 나노박테리아(nanobacterial) 또는 기생충(parasitic) 감염 질환 또는 바이러스성 질환, 또는 바이러스 유발 질환의 진단, 요법 또는 치료에서, 항바이러스제로서 또는 면역원성 조성물로서, 면역요법으로서, 또는 신경퇴행성 질환의 치료 또는 요법에서, 암의 치료 또는 요법에서, 또는 감염성 질환의 치료 또는 요법에서, 또는 바이러스 질환, 또는 바이러스 유도 질환, 피내 및 경피 요법, HIV, SARS 코로나바이러스에 의한 감염, 아시아 독감 바이러스(Asian flu virus), 단순 포진(herpes simplex), 인플루엔자 바이러스, 대상 포진(herpes zoster), 간염(hepatitis), 인간 유두종 바이러스(human papillomavirus), 엡스타인-바르 바이러스(Epstein-Barr virus), 인간 T-림프성 바이러스 또는 바이러스 간염, 아밀로이드 질환, 특히 아밀로이드 질환 A 아밀로이드증(amyloidosis), 알츠하이머병(Alzheimer's disease), 경쇄(AL) 아밀로이드증(Light-Chain (AL) amyloidosis), 제2형 당뇨병(Type-2 Diabetes), 갑상선 수질암(Medullary Carcinoma of the Thyroid), 파킨슨병(Parkinson's disease), 다발성 신경병증(Polyneuropathy), 또는 해면상 뇌병증(Spongiform Encephalopathy)(크로이츠펠트 야콥병(Creutzfeldt Jakob disease)) 또는 약물 스크리닝에 사용하기 위한 하나 이상의 벡터.
- 세포를 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포 내로 재프로그래밍하거나 유도하기 위한 시험관내 방법으로서,
줄기 세포, 분화 세포 및 이들의 혼합물로 이루어진 그룹으로부터 선택된 세포를 IRF8 및 SPIB로 이루어진 그룹으로부터 선택된 적어도 2개의 전사 인자를 포함하는 하나 이상의 벡터로 형질도입하는 단계를 포함하는, 시험관내 방법. - 제22항에 있어서, 상기 하나 이상의 벡터가 ARID5A, BCL11A, CBFA2T3, CREB3L2, ETS1, IKZF1, STAT1, TCF4, TCF12 및 TSC22D1로 이루어진 그룹으로부터 선택된 하나 이상의 전사 인자를 추가로 포함하는, 시험관내 방법.
- 제22항 내지 제23항 중 어느 한 항에 있어서, 상기 전사 인자가 개별적으로 IRF8(서열번호 1, 서열번호 2), SPIB(서열번호 3, 서열번호 4), ARID5A(서열번호 5, 서열번호 6), BCL11A(서열번호 7, 서열번호 8), CBFA2T3(서열번호 9, 서열번호 10), CREB3L2(서열번호 11, 서열번호 12), ETS1(서열번호 13, 서열번호 14), IKZF1(서열번호 23, 서열번호 24), TCF4(서열번호 41, 서열번호 42), TCF12(서열번호 43, 서열번호 44), STAT1(서열번호 45, 서열번호 46) 및 TSC22D1(서열번호 47, 서열번호 48)로 이루어진 그룹으로부터 선택된 서열과 적어도 90% 동일한, 시험관내 방법.
- 제22항 내지 제24항 중 어느 한 항에 있어서, 상기 전사 인자의 조합이 하기 조합으로부터 선택되는, 시험관내 방법:
IRF8 및 SPIB;
IRF8, SPIB 및 ARID5A;
IRF8, SPIB 및 BCL11A;
IRF8, SPIB 및 CBFA2T3;
IRF8, SPIB 및 CREB3L2;
IRF8, SPIB 및 ETS1;
IRF8, SPIB 및 IKZF1;
IRF8, SPIB 및 STAT1;
IRF8, SPIB 및 TCF4;
IRF8, SPIB 및 TCF12;
IRF8, SPIB 및 TSC22D1, 또는 이들의 혼합물. - 제22항 내지 제25항 중 어느 한 항에 있어서, 상기 형질도입된 세포를 적어도 2일, 바람직하게는 적어도 5일, 보다 바람직하게는 적어도 8일, 보다 더 바람직하게는 적어도 9일 동안 배양하는, 시험관내 방법.
- 제22항 내지 제26항 중 어느 한 항에 있어서, 상기 형질도입 단계가 IL-12를 코딩하는 핵산 서열; IL-4를 코딩하는 핵산 서열; IFN-α를 코딩하는 핵산 서열; IFN-β를 코딩하는 핵산 서열; IFN-γ를 코딩하는 핵산 서열; TNF를 코딩하는 핵산 서열; GM-CSF를 코딩하는 핵산 서열; IL-10 RNA를 표적으로 하는 siRNA를 코딩하는 핵산 서열, 및 이들의 혼합물로 이루어진 그룹으로부터 선택된 적어도 하나의 벡터를 추가로 포함하고, 바람직하게는 면역자극성 사이토카인을 코딩하는 핵산을 포함하는, 시험관내 방법.
- 제22항 내지 제27항 중 어느 한 항에 있어서, 상기 세포가 다능성 줄기 세포, 또는 다분화능 줄기 세포, 분화 세포로 이루어진 그룹으로부터 선택된 포유동물 세포, 인간 세포, 비-인간 세포 또는 마우스 세포이고, 상기 다능성 줄기 세포, 다분화능 줄기 세포 또는 분화된 세포가 내배엽 유래 세포, 중배엽 유래 세포, 또는 외배엽 유래 세포, 중간엽 줄기 세포, 조혈 줄기 세포, 장 줄기 세포, 다능성 줄기 세포 및 세포주를 포함하는 다분화능 줄기 세포; 특히 중배엽 유래 세포, 바람직하게는 단핵구 및 이의 혼합물로 이루어진 그룹으로부터 선택되는, 시험관내 방법.
- 제22항 내지 제28항 중 어느 한 항에 기재된 방법에 의해 수득되는, 유도된 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포.
- 약제학적으로 허용되는 부형제, 진통제, 항염증제, 화학요법제, 방사선 요법제, 항생제, 이뇨제, 충전제, 결합제, 붕해제(disintegrant) 또는 윤활제, 또는 이들의 혼합물을 추가로 포함하는 치료 유효량으로 제29항에 따른 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포를 포함하는 조성물.
- 제1항 내지 제8항 및 제30항 중 어느 한 항에 따른 조성물, 및/또는 제29항에 따른 유도 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포, 또는 이의 혼합물을 포함하는, 백신 또는 주사가능한 제형, 특히 원위치 주사제(in-situ injection).
- 하기 성분:
제29항에 따른 유도된 형질세포양 수지상 세포 또는 인터페론 유형 I-생산 세포;
제1항 내지 제8항 및 제30항 중 어느 한 항에 따른 조성물;
제9항 내지 제21항 중 어느 한 항에 따른 벡터 또는 작제물; 또는 이들의 혼합물
중의 적어도 하나를 포함하는 키트(kit).
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PT115833 | 2019-10-10 | ||
| PT11583319 | 2019-10-10 | ||
| EP20151310 | 2020-01-10 | ||
| EP20151310.8 | 2020-01-10 | ||
| PCT/EP2020/078429 WO2021069672A1 (en) | 2019-10-10 | 2020-10-09 | Composition for reprogramming cells into plasmacytoid dendritic cells or interferon type i-producing cells, methods and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20220077916A true KR20220077916A (ko) | 2022-06-09 |
Family
ID=72811870
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020227013673A KR20220077916A (ko) | 2019-10-10 | 2020-10-09 | 세포를 형질세포양 수지상 세포 또는 인터페론 유형 i-생산 세포로 재프로그래밍하기 위한 조성물, 방법 및 이의 용도 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20240052312A1 (ko) |
| EP (1) | EP4041869A1 (ko) |
| JP (1) | JP2023502318A (ko) |
| KR (1) | KR20220077916A (ko) |
| CN (1) | CN114729322A (ko) |
| CA (1) | CA3153052A1 (ko) |
| IL (1) | IL292004B2 (ko) |
| WO (1) | WO2021069672A1 (ko) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20240141294A1 (en) * | 2021-07-02 | 2024-05-02 | Aarhus Universitet | Cgmp compliant production and expansion of plasmacytoid dendritic cells from hematopoietic stem and progenitor cells |
| WO2023176806A1 (ja) * | 2022-03-18 | 2023-09-21 | 国立研究開発法人産業技術総合研究所 | 線維芽細胞または線維芽細胞様細胞を従来型２型樹状細胞にリプログラミングするための方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110088272B (zh) * | 2017-04-05 | 2023-08-04 | 阿斯加德治疗有限公司 | 用于将细胞重编程为树突状细胞或抗原呈递细胞的组合物、其方法和用途 |
| EP3385373A1 (en) * | 2017-04-05 | 2018-10-10 | Centro de Neurociências e Biologia Celular | Compositions for reprogramming cells into dendritic cells or antigen presenting cells, methods and uses thereof |
-
2020
- 2020-10-09 EP EP20789106.0A patent/EP4041869A1/en active Pending
- 2020-10-09 KR KR1020227013673A patent/KR20220077916A/ko unknown
- 2020-10-09 CA CA3153052A patent/CA3153052A1/en active Pending
- 2020-10-09 US US17/766,369 patent/US20240052312A1/en active Pending
- 2020-10-09 CN CN202080080049.6A patent/CN114729322A/zh active Pending
- 2020-10-09 JP JP2022521601A patent/JP2023502318A/ja active Pending
- 2020-10-09 WO PCT/EP2020/078429 patent/WO2021069672A1/en active Search and Examination
-
2022
- 2022-04-06 IL IL292004A patent/IL292004B2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL292004B1 (en) | 2023-03-01 |
| IL292004A (en) | 2022-06-01 |
| CA3153052A1 (en) | 2021-04-15 |
| WO2021069672A1 (en) | 2021-04-15 |
| JP2023502318A (ja) | 2023-01-24 |
| EP4041869A1 (en) | 2022-08-17 |
| US20240052312A1 (en) | 2024-02-15 |
| IL292004B2 (en) | 2023-07-01 |
| CN114729322A (zh) | 2022-07-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2022201329B2 (en) | Genetically modified cells, tissues, and organs for treating disease | |
| CN114176043B (zh) | 用于治疗疾病的遗传修饰的细胞、组织和器官 | |
| KR102252561B1 (ko) | Ｃ/ｅｂｐ 알파 짧은 활성화 ｒｎａ 조성물 및 사용 방법 | |
| AU2016376191A1 (en) | Materials and methods for treatment of amyotrophic lateral sclerosis and/or frontal temporal lobular degeneration | |
| AU2016364667A1 (en) | Materials and methods for treatment of Alpha-1 antitrypsin deficiency | |
| KR20160018525A (ko) | 종양 세포에 의한 면역 억제를 감소시키기 위한 방법 및 조성물 | |
| CN110088272A (zh) | 用于将细胞重编程为树突状细胞或抗原呈递细胞的组合物、其方法和用途 | |
| KR20120082906A (ko) | 자가포식현상-향상 유전자 생성물의 조절을 통한 자가포식현상의 조절 방법 | |
| KR20150122638A (ko) | 면역자극성 수지상 세포를 얻는 방법 | |
| KR20210138587A (ko) | 개선된 면역요법을 위한 조합 유전자 표적 | |
| KR20150122639A (ko) | 면역억제성 수지상 세포를 얻는 방법 | |
| AU2015282825B2 (en) | Method for obtaining globally activated monocytes | |
| KR20230034198A (ko) | 종양 침윤 림프구의 활성화 및 확장 방법 | |
| KR20220077916A (ko) | 세포를 형질세포양 수지상 세포 또는 인터페론 유형 i-생산 세포로 재프로그래밍하기 위한 조성물, 방법 및 이의 용도 | |
| KR102195319B1 (ko) | 상처치료제 스크리닝용 조성물 및 이를 이용한 상처 치료제 스크리닝 방법 | |
| CN115151558A (zh) | 哺乳动物序列中的靶向整合增强基因表达 | |
| US20030207286A1 (en) | Nucleic acid sequences showing enhanced expression in benign neuroblastoma compared with acritical human neuroblastoma | |
| KR20220025806A (ko) | 핵산의 무작위 구성 표적화 통합 | |
| TW202309274A (zh) | 產生成熟角膜內皮細胞之方法 | |
| KR102458464B1 (ko) | Snp를 검출 또는 증폭할 수 있는 제제를 포함하는 소의 마블링 지수 판별용 조성물 및 이를 포함하는 키트 | |
| US20040110194A1 (en) | Genes regulated by human cytokines | |
| JP2001321175A (ja) | 予後良好及び不良なヒト神経芽細胞腫との比較において、予後良好なヒト神経芽細胞腫で発現が増強していることを特徴とする核酸配列 |