JP2000236882A - Mouse nurse cell receptor gene - Google Patents
Mouse nurse cell receptor geneInfo
- Publication number
- JP2000236882A JP2000236882A JP11046603A JP4660399A JP2000236882A JP 2000236882 A JP2000236882 A JP 2000236882A JP 11046603 A JP11046603 A JP 11046603A JP 4660399 A JP4660399 A JP 4660399A JP 2000236882 A JP2000236882 A JP 2000236882A
- Authority
- JP
- Japan
- Prior art keywords
- mouse
- dna
- gly
- ala
- cys
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 210000001915 nurse cell Anatomy 0.000 title claims abstract description 76
- 108020003175 receptors Proteins 0.000 title claims description 85
- 238000000034 method Methods 0.000 claims abstract description 56
- 239000003446 ligand Substances 0.000 claims abstract description 43
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 31
- 230000027455 binding Effects 0.000 claims abstract description 27
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 27
- 238000012216 screening Methods 0.000 claims abstract description 27
- 229920001184 polypeptide Polymers 0.000 claims abstract description 25
- 239000013604 expression vector Substances 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 14
- 208000000398 DiGeorge Syndrome Diseases 0.000 claims abstract description 14
- 208000010543 22q11.2 deletion syndrome Diseases 0.000 claims abstract description 12
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 6
- 102000005962 receptors Human genes 0.000 claims description 81
- 150000001413 amino acids Chemical class 0.000 claims description 31
- 239000002773 nucleotide Substances 0.000 claims description 14
- 125000003729 nucleotide group Chemical group 0.000 claims description 14
- 210000004408 hybridoma Anatomy 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 238000012258 culturing Methods 0.000 claims description 6
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 claims description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 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 2
- 239000001963 growth medium Substances 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 66
- 239000002299 complementary DNA Substances 0.000 abstract description 62
- 108090000623 proteins and genes Proteins 0.000 abstract description 46
- 108020004999 messenger RNA Proteins 0.000 abstract description 28
- 230000003321 amplification Effects 0.000 abstract description 9
- 238000003199 nucleic acid amplification method Methods 0.000 abstract description 9
- 239000013598 vector Substances 0.000 abstract description 7
- 238000010367 cloning Methods 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 230000002463 transducing effect Effects 0.000 abstract 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 84
- 108020004414 DNA Proteins 0.000 description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- 102000004169 proteins and genes Human genes 0.000 description 26
- 238000003752 polymerase chain reaction Methods 0.000 description 25
- 235000018102 proteins Nutrition 0.000 description 25
- 239000000243 solution Substances 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 239000012634 fragment Substances 0.000 description 16
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 14
- 238000005516 engineering process Methods 0.000 description 13
- 239000000556 agonist Substances 0.000 description 12
- 239000005557 antagonist Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 10
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 10
- 101000663183 Homo sapiens Scavenger receptor class F member 1 Proteins 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000000523 sample Substances 0.000 description 10
- 108010007622 LDL Lipoproteins Proteins 0.000 description 9
- 102000007330 LDL Lipoproteins Human genes 0.000 description 9
- 210000004102 animal cell Anatomy 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 8
- 241000238631 Hexapoda Species 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 7
- 230000006870 function Effects 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
- 108010050848 glycylleucine Proteins 0.000 description 7
- 239000013600 plasmid vector Substances 0.000 description 7
- 102000014452 scavenger receptors Human genes 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 6
- 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 6
- 241000588724 Escherichia coli Species 0.000 description 6
- 241000282326 Felis catus Species 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 230000018109 developmental process Effects 0.000 description 6
- 108010036413 histidylglycine Proteins 0.000 description 6
- 108010078070 scavenger receptors Proteins 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 210000001541 thymus gland Anatomy 0.000 description 6
- 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 5
- 241000699800 Cricetinae Species 0.000 description 5
- 102000006382 Ribonucleases Human genes 0.000 description 5
- 108010083644 Ribonucleases Proteins 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 238000002741 site-directed mutagenesis Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 229920000936 Agarose Polymers 0.000 description 4
- MUXONAMCEUBVGA-DCAQKATOSA-N Arg-Arg-Gln Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(O)=O MUXONAMCEUBVGA-DCAQKATOSA-N 0.000 description 4
- 206010003210 Arteriosclerosis Diseases 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- KFMBRBPXHVMDFN-UWVGGRQHSA-N Gly-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCNC(N)=N KFMBRBPXHVMDFN-UWVGGRQHSA-N 0.000 description 4
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 4
- 108010079364 N-glycylalanine Proteins 0.000 description 4
- 239000004677 Nylon Substances 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 108010068380 arginylarginine Proteins 0.000 description 4
- 208000011775 arteriosclerosis disease Diseases 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 108010016616 cysteinylglycine Proteins 0.000 description 4
- 108010060199 cysteinylproline Proteins 0.000 description 4
- 230000004064 dysfunction Effects 0.000 description 4
- 238000001962 electrophoresis Methods 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229920001778 nylon Polymers 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 108010077112 prolyl-proline Proteins 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 108010061238 threonyl-glycine Proteins 0.000 description 4
- 230000002992 thymic effect Effects 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- WJRXVTCKASUIFF-FXQIFTODSA-N Ala-Cys-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WJRXVTCKASUIFF-FXQIFTODSA-N 0.000 description 3
- HPKSHFSEXICTLI-CIUDSAMLSA-N Arg-Glu-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HPKSHFSEXICTLI-CIUDSAMLSA-N 0.000 description 3
- 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 3
- YRKJQKATZOTUEN-ACZMJKKPSA-N Cys-Gln-Cys Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N YRKJQKATZOTUEN-ACZMJKKPSA-N 0.000 description 3
- PYUCNHJQQVSPGN-BQBZGAKWSA-N Gly-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN)CN=C(N)N PYUCNHJQQVSPGN-BQBZGAKWSA-N 0.000 description 3
- 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 3
- 101100118545 Holotrichia diomphalia EGF-like gene Proteins 0.000 description 3
- 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 3
- HYIFFZAQXPUEAU-QWRGUYRKSA-N Leu-Gly-Leu Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(C)C HYIFFZAQXPUEAU-QWRGUYRKSA-N 0.000 description 3
- 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 3
- QWWPYKKLXWOITQ-VOAKCMCISA-N Leu-Thr-Leu 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(C)C QWWPYKKLXWOITQ-VOAKCMCISA-N 0.000 description 3
- YPLVCBKEPJPBDQ-MELADBBJSA-N Lys-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N YPLVCBKEPJPBDQ-MELADBBJSA-N 0.000 description 3
- 102000018697 Membrane Proteins Human genes 0.000 description 3
- 108010052285 Membrane Proteins Proteins 0.000 description 3
- 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 3
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 3
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 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 3
- 208000025747 Rheumatic disease Diseases 0.000 description 3
- 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 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- HPQHHRLWSAMMKG-KATARQTJSA-N Thr-Lys-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)O)N)O HPQHHRLWSAMMKG-KATARQTJSA-N 0.000 description 3
- 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 3
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 3
- 108010047495 alanylglycine Proteins 0.000 description 3
- 108010087924 alanylproline Proteins 0.000 description 3
- 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 3
- 230000006287 biotinylation Effects 0.000 description 3
- 238000007413 biotinylation Methods 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 108010031719 prolyl-serine Proteins 0.000 description 3
- 108010029020 prolylglycine Proteins 0.000 description 3
- 230000000552 rheumatic effect Effects 0.000 description 3
- 108010026333 seryl-proline Proteins 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 210000001258 synovial membrane Anatomy 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 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 2
- YLTKNGYYPIWKHZ-ACZMJKKPSA-N Ala-Ala-Glu Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O YLTKNGYYPIWKHZ-ACZMJKKPSA-N 0.000 description 2
- OILNWMNBLIHXQK-ZLUOBGJFSA-N Ala-Cys-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O OILNWMNBLIHXQK-ZLUOBGJFSA-N 0.000 description 2
- BEMGNWZECGIJOI-WDSKDSINSA-N Ala-Gly-Glu Chemical compound [H]N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O BEMGNWZECGIJOI-WDSKDSINSA-N 0.000 description 2
- 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 2
- OBVSBEYOMDWLRJ-BFHQHQDPSA-N Ala-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N OBVSBEYOMDWLRJ-BFHQHQDPSA-N 0.000 description 2
- 108010076441 Ala-His-His Proteins 0.000 description 2
- 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 2
- 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 2
- 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 2
- 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 2
- AQPVUEJJARLJHB-BQBZGAKWSA-N Arg-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N AQPVUEJJARLJHB-BQBZGAKWSA-N 0.000 description 2
- GRRXPUAICOGISM-RWMBFGLXSA-N Arg-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O GRRXPUAICOGISM-RWMBFGLXSA-N 0.000 description 2
- 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 2
- KPSHWSWFPUDEGF-FXQIFTODSA-N Asp-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC(O)=O KPSHWSWFPUDEGF-FXQIFTODSA-N 0.000 description 2
- 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 2
- XMTDCXXLDZKAGI-ACZMJKKPSA-N Cys-Ala-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CS)N XMTDCXXLDZKAGI-ACZMJKKPSA-N 0.000 description 2
- SMYXEYRYCLIPIL-ZLUOBGJFSA-N Cys-Cys-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(O)=O SMYXEYRYCLIPIL-ZLUOBGJFSA-N 0.000 description 2
- SBORMUFGKSCGEN-XHNCKOQMSA-N Cys-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CS)N)C(=O)O SBORMUFGKSCGEN-XHNCKOQMSA-N 0.000 description 2
- XTHUKRLJRUVVBF-WHFBIAKZSA-N Cys-Gly-Ser Chemical compound SC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O XTHUKRLJRUVVBF-WHFBIAKZSA-N 0.000 description 2
- KPENUVBHAKRDQR-GUBZILKMSA-N Cys-His-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O KPENUVBHAKRDQR-GUBZILKMSA-N 0.000 description 2
- WTNLLMQAFPOCTJ-GARJFASQSA-N Cys-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CS)N)C(=O)O WTNLLMQAFPOCTJ-GARJFASQSA-N 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010058314 Dysplasia Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- XEYMBRRKIFYQMF-GUBZILKMSA-N Gln-Asp-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O XEYMBRRKIFYQMF-GUBZILKMSA-N 0.000 description 2
- WBYHRQBKJGEBQJ-CIUDSAMLSA-N Gln-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)N)N)C(=O)N[C@@H](CS)C(=O)O WBYHRQBKJGEBQJ-CIUDSAMLSA-N 0.000 description 2
- FYBSCGZLICNOBA-XQXXSGGOSA-N Glu-Ala-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FYBSCGZLICNOBA-XQXXSGGOSA-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
- OPAINBJQDQTGJY-JGVFFNPUSA-N Glu-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCC(=O)O)N)C(=O)O OPAINBJQDQTGJY-JGVFFNPUSA-N 0.000 description 2
- SWDNPSMMEWRNOH-HJGDQZAQSA-N Glu-Pro-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O SWDNPSMMEWRNOH-HJGDQZAQSA-N 0.000 description 2
- KIEICAOUSNYOLM-NRPADANISA-N Glu-Val-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O KIEICAOUSNYOLM-NRPADANISA-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
- GQGAFTPXAPKSCF-WHFBIAKZSA-N Gly-Ala-Cys Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)O GQGAFTPXAPKSCF-WHFBIAKZSA-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
- XUDLUKYPXQDCRX-BQBZGAKWSA-N Gly-Arg-Asn Chemical compound [H]NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O XUDLUKYPXQDCRX-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
- SWQALSGKVLYKDT-UHFFFAOYSA-N Gly-Ile-Ala Natural products NCC(=O)NC(C(C)CC)C(=O)NC(C)C(O)=O SWQALSGKVLYKDT-UHFFFAOYSA-N 0.000 description 2
- LIXWIUAORXJNBH-QWRGUYRKSA-N Gly-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)CN LIXWIUAORXJNBH-QWRGUYRKSA-N 0.000 description 2
- 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 2
- LOEANKRDMMVOGZ-YUMQZZPRSA-N Gly-Lys-Asp Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CC(O)=O)C(O)=O LOEANKRDMMVOGZ-YUMQZZPRSA-N 0.000 description 2
- QAMMIGULQSIRCD-IRXDYDNUSA-N Gly-Phe-Tyr Chemical compound C([C@H](NC(=O)C[NH3+])C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C([O-])=O)C1=CC=CC=C1 QAMMIGULQSIRCD-IRXDYDNUSA-N 0.000 description 2
- DNVDEMWIYLVIQU-RCOVLWMOSA-N Gly-Val-Asp Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O DNVDEMWIYLVIQU-RCOVLWMOSA-N 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
- UOAVQQRILDGZEN-SRVKXCTJSA-N His-Asp-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O UOAVQQRILDGZEN-SRVKXCTJSA-N 0.000 description 2
- 208000013038 Hypocalcemia Diseases 0.000 description 2
- 108010065920 Insulin Lispro Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 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 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
- 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 2
- FOBUGKUBUJOWAD-IHPCNDPISA-N Leu-Leu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 FOBUGKUBUJOWAD-IHPCNDPISA-N 0.000 description 2
- 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 2
- LINKCQUOMUDLKN-KATARQTJSA-N Leu-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(C)C)N)O LINKCQUOMUDLKN-KATARQTJSA-N 0.000 description 2
- IXHKPDJKKCUKHS-GARJFASQSA-N Lys-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N IXHKPDJKKCUKHS-GARJFASQSA-N 0.000 description 2
- IKXQOBUBZSOWDY-AVGNSLFASA-N Lys-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CCCCN)N IKXQOBUBZSOWDY-AVGNSLFASA-N 0.000 description 2
- YORIKIDJCPKBON-YUMQZZPRSA-N Met-Glu-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O YORIKIDJCPKBON-YUMQZZPRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- JJHVFCUWLSKADD-ONGXEEELSA-N Phe-Gly-Ala Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](C)C(O)=O JJHVFCUWLSKADD-ONGXEEELSA-N 0.000 description 2
- GCFNFKNPCMBHNT-IRXDYDNUSA-N Phe-Tyr-Gly Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)NCC(=O)O)N GCFNFKNPCMBHNT-IRXDYDNUSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 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 2
- 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 2
- 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 2
- 241000700159 Rattus Species 0.000 description 2
- 102000014400 SH2 domains Human genes 0.000 description 2
- 108050003452 SH2 domains Proteins 0.000 description 2
- 102000000395 SH3 domains Human genes 0.000 description 2
- 108050008861 SH3 domains Proteins 0.000 description 2
- GXXTUIUYTWGPMV-FXQIFTODSA-N Ser-Arg-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O GXXTUIUYTWGPMV-FXQIFTODSA-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
- MQUZANJDFOQOBX-SRVKXCTJSA-N Ser-Phe-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O MQUZANJDFOQOBX-SRVKXCTJSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- UCCNDUPVIFOOQX-CUJWVEQBSA-N Thr-Cys-His Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 UCCNDUPVIFOOQX-CUJWVEQBSA-N 0.000 description 2
- SLUWOCTZVGMURC-BFHQHQDPSA-N Thr-Gly-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O SLUWOCTZVGMURC-BFHQHQDPSA-N 0.000 description 2
- WFAUDCSNCWJJAA-KXNHARMFSA-N Thr-Lys-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(O)=O WFAUDCSNCWJJAA-KXNHARMFSA-N 0.000 description 2
- 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 2
- DDRBQONWVBDQOY-GUBZILKMSA-N Val-Ala-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O DDRBQONWVBDQOY-GUBZILKMSA-N 0.000 description 2
- REJBPZVUHYNMEN-LSJOCFKGSA-N Val-Ala-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N REJBPZVUHYNMEN-LSJOCFKGSA-N 0.000 description 2
- CVUDMNSZAIZFAE-UHFFFAOYSA-N Val-Arg-Pro Natural products NC(N)=NCCCC(NC(=O)C(N)C(C)C)C(=O)N1CCCC1C(O)=O CVUDMNSZAIZFAE-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 2
- 108010018691 arginyl-threonyl-arginine Proteins 0.000 description 2
- 108010093581 aspartyl-proline Proteins 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 238000010804 cDNA synthesis Methods 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000011748 cell maturation Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 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 2
- 108010000434 glycyl-alanyl-leucine Proteins 0.000 description 2
- 108010026364 glycyl-glycyl-leucine Proteins 0.000 description 2
- 108010089804 glycyl-threonine Proteins 0.000 description 2
- 108010077515 glycylproline Proteins 0.000 description 2
- 108010040030 histidinoalanine Proteins 0.000 description 2
- 108010085325 histidylproline Proteins 0.000 description 2
- 230000000705 hypocalcaemia Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 108010043612 kentsin Proteins 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 108010057821 leucylproline Proteins 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 108010025153 lysyl-alanyl-alanine Proteins 0.000 description 2
- 108010054155 lysyllysine Proteins 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 108010093296 prolyl-prolyl-alanine Proteins 0.000 description 2
- 108010087846 prolyl-prolyl-glycine Proteins 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 108010071097 threonyl-lysyl-proline Proteins 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 108010080629 tryptophan-leucine Proteins 0.000 description 2
- 108010038745 tryptophylglycine Proteins 0.000 description 2
- 101150072531 10 gene Proteins 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- BRLRJZRHRJEWJY-VCOUNFBDSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-[3-[3-(4-azido-2-nitroanilino)propyl-methylamino]propyl]pentanamide Chemical compound C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)NCCCN(C)CCCNC1=CC=C(N=[N+]=[N-])C=C1[N+]([O-])=O BRLRJZRHRJEWJY-VCOUNFBDSA-N 0.000 description 1
- FFBLNTOMOSLSQM-AYEYRVMASA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-[3-[3-(4-azido-2-nitroanilino)propyl-methylamino]propyl]pentanamide;acetic acid Chemical compound CC(O)=O.C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)NCCCN(C)CCCNC1=CC=C(N=[N+]=[N-])C=C1[N+]([O-])=O FFBLNTOMOSLSQM-AYEYRVMASA-N 0.000 description 1
- 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 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
- 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
- WRDANSJTFOHBPI-FXQIFTODSA-N Ala-Arg-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N WRDANSJTFOHBPI-FXQIFTODSA-N 0.000 description 1
- JBGSZRYCXBPWGX-BQBZGAKWSA-N Ala-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)C)CCCN=C(N)N JBGSZRYCXBPWGX-BQBZGAKWSA-N 0.000 description 1
- YBPLKDWJFYCZSV-ZLUOBGJFSA-N Ala-Asn-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N YBPLKDWJFYCZSV-ZLUOBGJFSA-N 0.000 description 1
- BUDNAJYVCUHLSV-ZLUOBGJFSA-N Ala-Asp-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O BUDNAJYVCUHLSV-ZLUOBGJFSA-N 0.000 description 1
- HFBFSOAKPUZCCO-ZLUOBGJFSA-N Ala-Cys-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O)N HFBFSOAKPUZCCO-ZLUOBGJFSA-N 0.000 description 1
- FRFDXQWNDZMREB-ACZMJKKPSA-N Ala-Cys-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O FRFDXQWNDZMREB-ACZMJKKPSA-N 0.000 description 1
- YEELWQSXYBJVSV-UWJYBYFXSA-N Ala-Cys-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YEELWQSXYBJVSV-UWJYBYFXSA-N 0.000 description 1
- HMRWQTHUDVXMGH-GUBZILKMSA-N Ala-Glu-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN HMRWQTHUDVXMGH-GUBZILKMSA-N 0.000 description 1
- ZVFVBBGVOILKPO-WHFBIAKZSA-N Ala-Gly-Ala Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O ZVFVBBGVOILKPO-WHFBIAKZSA-N 0.000 description 1
- SIGTYDNEPYEXGK-ZANVPECISA-N Ala-Gly-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)CNC(=O)[C@@H](N)C)C(O)=O)=CNC2=C1 SIGTYDNEPYEXGK-ZANVPECISA-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
- IHMCQESUJVZTKW-UBHSHLNASA-N Ala-Phe-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=CC=C1 IHMCQESUJVZTKW-UBHSHLNASA-N 0.000 description 1
- 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 1
- 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 1
- IPWKGIFRRBGCJO-IMJSIDKUSA-N Ala-Ser Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](CO)C([O-])=O IPWKGIFRRBGCJO-IMJSIDKUSA-N 0.000 description 1
- OMCKWYSDUQBYCN-FXQIFTODSA-N Ala-Ser-Met Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(O)=O OMCKWYSDUQBYCN-FXQIFTODSA-N 0.000 description 1
- PEEYDECOOVQKRZ-DLOVCJGASA-N Ala-Ser-Phe Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PEEYDECOOVQKRZ-DLOVCJGASA-N 0.000 description 1
- 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 1
- WNHNMKOFKCHKKD-BFHQHQDPSA-N Ala-Thr-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O WNHNMKOFKCHKKD-BFHQHQDPSA-N 0.000 description 1
- IETUUAHKCHOQHP-KZVJFYERSA-N Ala-Thr-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](C)N)[C@@H](C)O)C(O)=O IETUUAHKCHOQHP-KZVJFYERSA-N 0.000 description 1
- BOKLLPVAQDSLHC-FXQIFTODSA-N Ala-Val-Cys Chemical compound C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)O)N BOKLLPVAQDSLHC-FXQIFTODSA-N 0.000 description 1
- 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 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- SGYSTDWPNPKJPP-GUBZILKMSA-N Arg-Ala-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SGYSTDWPNPKJPP-GUBZILKMSA-N 0.000 description 1
- VKKYFICVTYKFIO-CIUDSAMLSA-N Arg-Ala-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N VKKYFICVTYKFIO-CIUDSAMLSA-N 0.000 description 1
- XPSGESXVBSQZPL-SRVKXCTJSA-N Arg-Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XPSGESXVBSQZPL-SRVKXCTJSA-N 0.000 description 1
- KJGNDQCYBNBXDA-GUBZILKMSA-N Arg-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N)CN=C(N)N KJGNDQCYBNBXDA-GUBZILKMSA-N 0.000 description 1
- UXJCMQFPDWCHKX-DCAQKATOSA-N Arg-Arg-Glu Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O UXJCMQFPDWCHKX-DCAQKATOSA-N 0.000 description 1
- KMSHNDWHPWXPEC-BQBZGAKWSA-N Arg-Asp-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KMSHNDWHPWXPEC-BQBZGAKWSA-N 0.000 description 1
- OTCJMMRQBVDQRK-DCAQKATOSA-N Arg-Asp-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O OTCJMMRQBVDQRK-DCAQKATOSA-N 0.000 description 1
- SQKPKIJVWHAWNF-DCAQKATOSA-N Arg-Asp-Lys Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(O)=O SQKPKIJVWHAWNF-DCAQKATOSA-N 0.000 description 1
- JTWOBPNAVBESFW-FXQIFTODSA-N Arg-Cys-Asp Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)CN=C(N)N JTWOBPNAVBESFW-FXQIFTODSA-N 0.000 description 1
- QIWYWCYNUMJBTC-CIUDSAMLSA-N Arg-Cys-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O QIWYWCYNUMJBTC-CIUDSAMLSA-N 0.000 description 1
- GDVDRMUYICMNFJ-CIUDSAMLSA-N Arg-Cys-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O GDVDRMUYICMNFJ-CIUDSAMLSA-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
- 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
- HPSVTWMFWCHKFN-GARJFASQSA-N Arg-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O HPSVTWMFWCHKFN-GARJFASQSA-N 0.000 description 1
- 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 1
- PHHRSPBBQUFULD-UWVGGRQHSA-N Arg-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)N PHHRSPBBQUFULD-UWVGGRQHSA-N 0.000 description 1
- MSILNNHVVMMTHZ-UWVGGRQHSA-N Arg-His-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CN=CN1 MSILNNHVVMMTHZ-UWVGGRQHSA-N 0.000 description 1
- 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 1
- GXXWTNKNFFKTJB-NAKRPEOUSA-N Arg-Ile-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O GXXWTNKNFFKTJB-NAKRPEOUSA-N 0.000 description 1
- 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 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
- BTJVOUQWFXABOI-IHRRRGAJSA-N Arg-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCNC(N)=N BTJVOUQWFXABOI-IHRRRGAJSA-N 0.000 description 1
- BSYKSCBTTQKOJG-GUBZILKMSA-N Arg-Pro-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O BSYKSCBTTQKOJG-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
- 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
- ASQKVGRCKOFKIU-KZVJFYERSA-N Arg-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ASQKVGRCKOFKIU-KZVJFYERSA-N 0.000 description 1
- AIFHRTPABBBHKU-RCWTZXSCSA-N Arg-Thr-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O AIFHRTPABBBHKU-RCWTZXSCSA-N 0.000 description 1
- ZJBUILVYSXQNSW-YTWAJWBKSA-N Arg-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ZJBUILVYSXQNSW-YTWAJWBKSA-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
- HZPSDHRYYIORKR-WHFBIAKZSA-N Asn-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CC(N)=O HZPSDHRYYIORKR-WHFBIAKZSA-N 0.000 description 1
- RCENDENBBJFJHZ-ACZMJKKPSA-N Asn-Asn-Gln Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O RCENDENBBJFJHZ-ACZMJKKPSA-N 0.000 description 1
- VWJFQGXPYOPXJH-ZLUOBGJFSA-N Asn-Cys-Asp Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)C(=O)N VWJFQGXPYOPXJH-ZLUOBGJFSA-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
- QGNXYDHVERJIAY-ACZMJKKPSA-N Asn-Gln-Cys Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N QGNXYDHVERJIAY-ACZMJKKPSA-N 0.000 description 1
- ULRPXVNMIIYDDJ-ACZMJKKPSA-N Asn-Glu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)N)N ULRPXVNMIIYDDJ-ACZMJKKPSA-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
- UYXXMIZGHYKYAT-NHCYSSNCSA-N Asn-His-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC(=O)N)N UYXXMIZGHYKYAT-NHCYSSNCSA-N 0.000 description 1
- JBDLMLZNDRLDIX-HJGDQZAQSA-N Asn-Thr-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O JBDLMLZNDRLDIX-HJGDQZAQSA-N 0.000 description 1
- HPNDBHLITCHRSO-WHFBIAKZSA-N Asp-Ala-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)NCC(O)=O HPNDBHLITCHRSO-WHFBIAKZSA-N 0.000 description 1
- ICAYWNTWHRRAQP-FXQIFTODSA-N Asp-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N)CN=C(N)N ICAYWNTWHRRAQP-FXQIFTODSA-N 0.000 description 1
- ILJQISGMGXRZQQ-IHRRRGAJSA-N Asp-Arg-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ILJQISGMGXRZQQ-IHRRRGAJSA-N 0.000 description 1
- XACXDSRQIXRMNS-OLHMAJIHSA-N Asp-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N)O XACXDSRQIXRMNS-OLHMAJIHSA-N 0.000 description 1
- ACEDJCOOPZFUBU-CIUDSAMLSA-N Asp-Cys-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)O)N ACEDJCOOPZFUBU-CIUDSAMLSA-N 0.000 description 1
- CSEJMKNZDCJYGJ-XHNCKOQMSA-N Asp-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)O)N)C(=O)O CSEJMKNZDCJYGJ-XHNCKOQMSA-N 0.000 description 1
- RATOMFTUDRYMKX-ACZMJKKPSA-N Asp-Glu-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N RATOMFTUDRYMKX-ACZMJKKPSA-N 0.000 description 1
- 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 1
- DWOGMPWRQQWPPF-GUBZILKMSA-N Asp-Leu-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O DWOGMPWRQQWPPF-GUBZILKMSA-N 0.000 description 1
- YRZIYQGXTSBRLT-AVGNSLFASA-N Asp-Phe-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O YRZIYQGXTSBRLT-AVGNSLFASA-N 0.000 description 1
- HJZLUGQGJWXJCJ-CIUDSAMLSA-N Asp-Pro-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O HJZLUGQGJWXJCJ-CIUDSAMLSA-N 0.000 description 1
- HICVMZCGVFKTPM-BQBZGAKWSA-N Asp-Pro-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O HICVMZCGVFKTPM-BQBZGAKWSA-N 0.000 description 1
- BKOIIURTQAJHAT-GUBZILKMSA-N Asp-Pro-Pro Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 BKOIIURTQAJHAT-GUBZILKMSA-N 0.000 description 1
- DINOVZWPTMGSRF-QXEWZRGKSA-N Asp-Pro-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O DINOVZWPTMGSRF-QXEWZRGKSA-N 0.000 description 1
- ZBYLEBZCVKLPCY-FXQIFTODSA-N Asp-Ser-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ZBYLEBZCVKLPCY-FXQIFTODSA-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
- RKXVTTIQNKPCHU-KKHAAJSZSA-N Asp-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O RKXVTTIQNKPCHU-KKHAAJSZSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 1
- 102100033040 Carbonic anhydrase 12 Human genes 0.000 description 1
- 208000004652 Cardiovascular Abnormalities Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- CVOZXIPULQQFNY-ZLUOBGJFSA-N Cys-Ala-Cys Chemical compound C[C@H](NC(=O)[C@@H](N)CS)C(=O)N[C@@H](CS)C(O)=O CVOZXIPULQQFNY-ZLUOBGJFSA-N 0.000 description 1
- AEJSNWMRPXAKCW-WHFBIAKZSA-N Cys-Ala-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O AEJSNWMRPXAKCW-WHFBIAKZSA-N 0.000 description 1
- ZOLXQKZHYOHHMD-DLOVCJGASA-N Cys-Ala-Phe Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CS)N ZOLXQKZHYOHHMD-DLOVCJGASA-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
- YFXFOZPXVFPBDH-VZFHVOOUSA-N Cys-Ala-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)CS)C(O)=O YFXFOZPXVFPBDH-VZFHVOOUSA-N 0.000 description 1
- GMXSSZUVDNPRMA-FXQIFTODSA-N Cys-Arg-Asp Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O GMXSSZUVDNPRMA-FXQIFTODSA-N 0.000 description 1
- OCEHKDFAWQIBHH-FXQIFTODSA-N Cys-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N)CN=C(N)N OCEHKDFAWQIBHH-FXQIFTODSA-N 0.000 description 1
- LRZPRGJXAZFXCR-DCAQKATOSA-N Cys-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](CS)N LRZPRGJXAZFXCR-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
- YRJICXCOIBUCRP-CIUDSAMLSA-N Cys-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CS)N YRJICXCOIBUCRP-CIUDSAMLSA-N 0.000 description 1
- CPTUXCUWQIBZIF-ZLUOBGJFSA-N Cys-Asn-Ser Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O CPTUXCUWQIBZIF-ZLUOBGJFSA-N 0.000 description 1
- NDUSUIGBMZCOIL-ZKWXMUAHSA-N Cys-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CS)N NDUSUIGBMZCOIL-ZKWXMUAHSA-N 0.000 description 1
- BIVLWXQGXJLGKG-BIIVOSGPSA-N Cys-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)N)C(=O)O BIVLWXQGXJLGKG-BIIVOSGPSA-N 0.000 description 1
- 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 1
- DZIGZIIJIGGANI-FXQIFTODSA-N Cys-Glu-Gln Chemical compound SC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O DZIGZIIJIGGANI-FXQIFTODSA-N 0.000 description 1
- UUOYKFNULIOCGJ-GUBZILKMSA-N Cys-Glu-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CS)N UUOYKFNULIOCGJ-GUBZILKMSA-N 0.000 description 1
- VCIIDXDOPGHMDQ-WDSKDSINSA-N Cys-Gly-Gln Chemical compound [H]N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O VCIIDXDOPGHMDQ-WDSKDSINSA-N 0.000 description 1
- UPURLDIGQGTUPJ-ZKWXMUAHSA-N Cys-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CS)N UPURLDIGQGTUPJ-ZKWXMUAHSA-N 0.000 description 1
- XVLMKWWVBNESPX-XVYDVKMFSA-N Cys-His-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CS)N XVLMKWWVBNESPX-XVYDVKMFSA-N 0.000 description 1
- RRJOQIBQVZDVCW-SRVKXCTJSA-N Cys-His-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CS)N RRJOQIBQVZDVCW-SRVKXCTJSA-N 0.000 description 1
- DYBIDOHFRRUMLW-CIUDSAMLSA-N Cys-Leu-Cys Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CS)C(=O)N[C@@H](CS)C(O)=O DYBIDOHFRRUMLW-CIUDSAMLSA-N 0.000 description 1
- XZKJEOMFLDVXJG-KATARQTJSA-N Cys-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)N)O XZKJEOMFLDVXJG-KATARQTJSA-N 0.000 description 1
- BNCKELUXXUYRNY-GUBZILKMSA-N Cys-Lys-Glu Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CS)N BNCKELUXXUYRNY-GUBZILKMSA-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
- 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
- ZOKPRHVIFAUJPV-GUBZILKMSA-N Cys-Pro-Arg Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CS)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O ZOKPRHVIFAUJPV-GUBZILKMSA-N 0.000 description 1
- NITLUESFANGEIW-BQBZGAKWSA-N Cys-Pro-Gly Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O NITLUESFANGEIW-BQBZGAKWSA-N 0.000 description 1
- KSMSFCBQBQPFAD-GUBZILKMSA-N Cys-Pro-Pro Chemical compound SC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 KSMSFCBQBQPFAD-GUBZILKMSA-N 0.000 description 1
- KVCJEMHFLGVINV-ZLUOBGJFSA-N Cys-Ser-Asn Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(N)=O KVCJEMHFLGVINV-ZLUOBGJFSA-N 0.000 description 1
- RJPKQCFHEPPTGL-ZLUOBGJFSA-N Cys-Ser-Asp Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O RJPKQCFHEPPTGL-ZLUOBGJFSA-N 0.000 description 1
- ABLQPNMKLMFDQU-BIIVOSGPSA-N Cys-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CS)N)C(=O)O ABLQPNMKLMFDQU-BIIVOSGPSA-N 0.000 description 1
- UKHNKRGNFKSHCG-CUJWVEQBSA-N Cys-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CS)N)O UKHNKRGNFKSHCG-CUJWVEQBSA-N 0.000 description 1
- JIZRUFJGHPIYPS-SRVKXCTJSA-N Cys-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N)O JIZRUFJGHPIYPS-SRVKXCTJSA-N 0.000 description 1
- MHYHLWUGWUBUHF-GUBZILKMSA-N Cys-Val-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CS)N MHYHLWUGWUBUHF-GUBZILKMSA-N 0.000 description 1
- 102000004594 DNA Polymerase I Human genes 0.000 description 1
- 108010017826 DNA Polymerase I Proteins 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 1
- 101100532034 Drosophila melanogaster RTase gene Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 235000006369 Emex spinosa Nutrition 0.000 description 1
- ZFADFBPRMSBPOT-KKUMJFAQSA-N Gln-Arg-Phe Chemical compound N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](Cc1ccccc1)C(O)=O ZFADFBPRMSBPOT-KKUMJFAQSA-N 0.000 description 1
- UZMWDBOHAOSCCH-ACZMJKKPSA-N Gln-Cys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCC(N)=O UZMWDBOHAOSCCH-ACZMJKKPSA-N 0.000 description 1
- IPHGBVYWRKCGKG-FXQIFTODSA-N Gln-Cys-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O IPHGBVYWRKCGKG-FXQIFTODSA-N 0.000 description 1
- MFLMFRZBAJSGHK-ACZMJKKPSA-N Gln-Cys-Ser Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O)N MFLMFRZBAJSGHK-ACZMJKKPSA-N 0.000 description 1
- COYGBRTZEVWZBW-XKBZYTNZSA-N Gln-Cys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCC(N)=O COYGBRTZEVWZBW-XKBZYTNZSA-N 0.000 description 1
- 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 1
- NROSLUJMIQGFKS-IUCAKERBSA-N Gln-His-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCC(=O)N)N NROSLUJMIQGFKS-IUCAKERBSA-N 0.000 description 1
- XZLLTYBONVKGLO-SDDRHHMPSA-N Gln-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)N)N)C(=O)O XZLLTYBONVKGLO-SDDRHHMPSA-N 0.000 description 1
- PDXIOFXRBVDSHD-JBACZVJFSA-N Gln-Phe-Trp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)NC(=O)[C@H](CCC(=O)N)N PDXIOFXRBVDSHD-JBACZVJFSA-N 0.000 description 1
- WLRYGVYQFXRJDA-DCAQKATOSA-N Gln-Pro-Pro Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 WLRYGVYQFXRJDA-DCAQKATOSA-N 0.000 description 1
- VNTGPISAOMAXRK-CIUDSAMLSA-N Gln-Pro-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O VNTGPISAOMAXRK-CIUDSAMLSA-N 0.000 description 1
- OSCLNNWLKKIQJM-WDSKDSINSA-N Gln-Ser-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O OSCLNNWLKKIQJM-WDSKDSINSA-N 0.000 description 1
- ININBLZFFVOQIO-JHEQGTHGSA-N Gln-Thr-Gly Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCC(=O)N)N)O ININBLZFFVOQIO-JHEQGTHGSA-N 0.000 description 1
- 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 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
- 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 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
- MXOODARRORARSU-ACZMJKKPSA-N Glu-Ala-Ser Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)O)N MXOODARRORARSU-ACZMJKKPSA-N 0.000 description 1
- IYAUFWMUCGBFMQ-CIUDSAMLSA-N Glu-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)CN=C(N)N IYAUFWMUCGBFMQ-CIUDSAMLSA-N 0.000 description 1
- KEBACWCLVOXFNC-DCAQKATOSA-N Glu-Arg-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(O)=O KEBACWCLVOXFNC-DCAQKATOSA-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
- NADWTMLCUDMDQI-ACZMJKKPSA-N Glu-Asp-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N NADWTMLCUDMDQI-ACZMJKKPSA-N 0.000 description 1
- FLQAKQOBSPFGKG-CIUDSAMLSA-N Glu-Cys-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FLQAKQOBSPFGKG-CIUDSAMLSA-N 0.000 description 1
- XHWLNISLUFEWNS-CIUDSAMLSA-N Glu-Gln-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O XHWLNISLUFEWNS-CIUDSAMLSA-N 0.000 description 1
- UHVIQGKBMXEVGN-WDSKDSINSA-N Glu-Gly-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O UHVIQGKBMXEVGN-WDSKDSINSA-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
- VXQOONWNIWFOCS-HGNGGELXSA-N Glu-His-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCC(=O)O)N VXQOONWNIWFOCS-HGNGGELXSA-N 0.000 description 1
- OQXDUSZKISQQSS-GUBZILKMSA-N Glu-Lys-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O OQXDUSZKISQQSS-GUBZILKMSA-N 0.000 description 1
- HLYCMRDRWGSTPZ-CIUDSAMLSA-N Glu-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CS)C(=O)O HLYCMRDRWGSTPZ-CIUDSAMLSA-N 0.000 description 1
- 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 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
- JVYNYWXHZWVJEF-NUMRIWBASA-N Glu-Thr-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O JVYNYWXHZWVJEF-NUMRIWBASA-N 0.000 description 1
- DTLLNDVORUEOTM-WDCWCFNPSA-N Glu-Thr-Lys Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O DTLLNDVORUEOTM-WDCWCFNPSA-N 0.000 description 1
- UMZHHILWZBFPGL-LOKLDPHHSA-N Glu-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O UMZHHILWZBFPGL-LOKLDPHHSA-N 0.000 description 1
- GZUKEVBTYNNUQF-WDSKDSINSA-N Gly-Ala-Gln Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GZUKEVBTYNNUQF-WDSKDSINSA-N 0.000 description 1
- RJIVPOXLQFJRTG-LURJTMIESA-N Gly-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N RJIVPOXLQFJRTG-LURJTMIESA-N 0.000 description 1
- XCLCVBYNGXEVDU-WHFBIAKZSA-N Gly-Asn-Ser Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O XCLCVBYNGXEVDU-WHFBIAKZSA-N 0.000 description 1
- IWAXHBCACVWNHT-BQBZGAKWSA-N Gly-Asp-Arg Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IWAXHBCACVWNHT-BQBZGAKWSA-N 0.000 description 1
- QSTLUOIOYLYLLF-WDSKDSINSA-N Gly-Asp-Glu Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QSTLUOIOYLYLLF-WDSKDSINSA-N 0.000 description 1
- 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 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
- SOEATRRYCIPEHA-BQBZGAKWSA-N Gly-Glu-Glu Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SOEATRRYCIPEHA-BQBZGAKWSA-N 0.000 description 1
- XTQFHTHIAKKCTM-YFKPBYRVSA-N Gly-Glu-Gly Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O XTQFHTHIAKKCTM-YFKPBYRVSA-N 0.000 description 1
- 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 1
- BUEFQXUHTUZXHR-LURJTMIESA-N Gly-Gly-Pro zwitterion Chemical compound NCC(=O)NCC(=O)N1CCC[C@H]1C(O)=O BUEFQXUHTUZXHR-LURJTMIESA-N 0.000 description 1
- FQKKPCWTZZEDIC-XPUUQOCRSA-N Gly-His-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 FQKKPCWTZZEDIC-XPUUQOCRSA-N 0.000 description 1
- 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 1
- IVSWQHKONQIOHA-YUMQZZPRSA-N Gly-His-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN IVSWQHKONQIOHA-YUMQZZPRSA-N 0.000 description 1
- SWQALSGKVLYKDT-ZKWXMUAHSA-N Gly-Ile-Ala Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O SWQALSGKVLYKDT-ZKWXMUAHSA-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
- CCBIBMKQNXHNIN-ZETCQYMHSA-N Gly-Leu-Gly Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O CCBIBMKQNXHNIN-ZETCQYMHSA-N 0.000 description 1
- LHYJCVCQPWRMKZ-WEDXCCLWSA-N Gly-Leu-Thr Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LHYJCVCQPWRMKZ-WEDXCCLWSA-N 0.000 description 1
- VLIJYPMATZSOLL-YUMQZZPRSA-N Gly-Lys-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN VLIJYPMATZSOLL-YUMQZZPRSA-N 0.000 description 1
- IUKIDFVOUHZRAK-QWRGUYRKSA-N Gly-Lys-His Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 IUKIDFVOUHZRAK-QWRGUYRKSA-N 0.000 description 1
- ZZJVYSAQQMDIRD-UWVGGRQHSA-N Gly-Pro-His Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O ZZJVYSAQQMDIRD-UWVGGRQHSA-N 0.000 description 1
- 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 1
- 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 1
- BMWFDYIYBAFROD-WPRPVWTQSA-N Gly-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN BMWFDYIYBAFROD-WPRPVWTQSA-N 0.000 description 1
- FGPLUIQCSKGLTI-WDSKDSINSA-N Gly-Ser-Glu Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O FGPLUIQCSKGLTI-WDSKDSINSA-N 0.000 description 1
- 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 1
- ZKJZBRHRWKLVSJ-ZDLURKLDSA-N Gly-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN)O ZKJZBRHRWKLVSJ-ZDLURKLDSA-N 0.000 description 1
- FFALDIDGPLUDKV-ZDLURKLDSA-N Gly-Thr-Ser Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O FFALDIDGPLUDKV-ZDLURKLDSA-N 0.000 description 1
- FOKISINOENBSDM-WLTAIBSBSA-N Gly-Thr-Tyr Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O FOKISINOENBSDM-WLTAIBSBSA-N 0.000 description 1
- JKSMZVCGQWVTBW-STQMWFEESA-N Gly-Trp-Asn Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(O)=O JKSMZVCGQWVTBW-STQMWFEESA-N 0.000 description 1
- WTUSRDZLLWGYAT-KCTSRDHCSA-N Gly-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)CN WTUSRDZLLWGYAT-KCTSRDHCSA-N 0.000 description 1
- WSLHFAFASQFMSK-SFTDATJTSA-N Gly-Trp-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)CN)C(O)=O)=CNC2=C1 WSLHFAFASQFMSK-SFTDATJTSA-N 0.000 description 1
- FULZDMOZUZKGQU-ONGXEEELSA-N Gly-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)CN FULZDMOZUZKGQU-ONGXEEELSA-N 0.000 description 1
- 102100036738 Guanine nucleotide-binding protein subunit alpha-11 Human genes 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- YXBRCTXAEYSCHS-XVYDVKMFSA-N His-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N YXBRCTXAEYSCHS-XVYDVKMFSA-N 0.000 description 1
- JHVCZQFWRLHUQR-DCAQKATOSA-N His-Arg-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N JHVCZQFWRLHUQR-DCAQKATOSA-N 0.000 description 1
- RBOOOLVEKJHUNA-CIUDSAMLSA-N His-Cys-Asn Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O RBOOOLVEKJHUNA-CIUDSAMLSA-N 0.000 description 1
- LDTJBEOANMQRJE-CIUDSAMLSA-N His-Cys-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N LDTJBEOANMQRJE-CIUDSAMLSA-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
- CHZRWFUGWRTUOD-IUCAKERBSA-N His-Gly-Gln Chemical compound C1=C(NC=N1)C[C@@H](C(=O)NCC(=O)N[C@@H](CCC(=O)N)C(=O)O)N CHZRWFUGWRTUOD-IUCAKERBSA-N 0.000 description 1
- 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 1
- OQDLKDUVMTUPPG-AVGNSLFASA-N His-Leu-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O OQDLKDUVMTUPPG-AVGNSLFASA-N 0.000 description 1
- SOYCWSKCUVDLMC-AVGNSLFASA-N His-Pro-Arg Chemical compound N[C@@H](Cc1cnc[nH]1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCNC(=N)N)C(=O)O SOYCWSKCUVDLMC-AVGNSLFASA-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
- CGAMSLMBYJHMDY-ONGXEEELSA-N His-Val-Gly Chemical compound CC(C)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC1=CN=CN1)N CGAMSLMBYJHMDY-ONGXEEELSA-N 0.000 description 1
- 101000867855 Homo sapiens Carbonic anhydrase 12 Proteins 0.000 description 1
- 101100283445 Homo sapiens GNA11 gene Proteins 0.000 description 1
- LKACSKJPTFSBHR-MNXVOIDGSA-N Ile-Gln-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N LKACSKJPTFSBHR-MNXVOIDGSA-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
- QQVXERGIFIRCGW-NAKRPEOUSA-N Ile-Ser-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)O)N QQVXERGIFIRCGW-NAKRPEOUSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- OTAMFXXAGYBAQL-YXMSTPNBSA-N Kentsin Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(O)=O OTAMFXXAGYBAQL-YXMSTPNBSA-N 0.000 description 1
- 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 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 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 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
- LHSGPCFBGJHPCY-UHFFFAOYSA-N L-leucine-L-tyrosine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LHSGPCFBGJHPCY-UHFFFAOYSA-N 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 241000880493 Leptailurus serval Species 0.000 description 1
- BAJIJEGGUYXZGC-CIUDSAMLSA-N Leu-Asn-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N BAJIJEGGUYXZGC-CIUDSAMLSA-N 0.000 description 1
- LJKJVTCIRDCITR-SRVKXCTJSA-N Leu-Cys-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N LJKJVTCIRDCITR-SRVKXCTJSA-N 0.000 description 1
- PNUCWVAGVNLUMW-CIUDSAMLSA-N Leu-Cys-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O PNUCWVAGVNLUMW-CIUDSAMLSA-N 0.000 description 1
- OGUUKPXUTHOIAV-SDDRHHMPSA-N Leu-Glu-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N OGUUKPXUTHOIAV-SDDRHHMPSA-N 0.000 description 1
- BABSVXFGKFLIGW-UWVGGRQHSA-N Leu-Gly-Arg Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCNC(N)=N BABSVXFGKFLIGW-UWVGGRQHSA-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
- LFSQWRSVPNKJGP-WDCWCFNPSA-N Leu-Thr-Glu 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)CCC(O)=O LFSQWRSVPNKJGP-WDCWCFNPSA-N 0.000 description 1
- RIHIGSWBLHSGLV-CQDKDKBSSA-N Leu-Tyr-Ala 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](C)C(O)=O RIHIGSWBLHSGLV-CQDKDKBSSA-N 0.000 description 1
- FZIJIFCXUCZHOL-CIUDSAMLSA-N Lys-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN FZIJIFCXUCZHOL-CIUDSAMLSA-N 0.000 description 1
- 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 1
- SWWCDAGDQHTKIE-RHYQMDGZSA-N Lys-Arg-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SWWCDAGDQHTKIE-RHYQMDGZSA-N 0.000 description 1
- RDIILCRAWOSDOQ-CIUDSAMLSA-N Lys-Cys-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N RDIILCRAWOSDOQ-CIUDSAMLSA-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
- 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
- PGLGNCVOWIORQE-SRVKXCTJSA-N Lys-His-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O PGLGNCVOWIORQE-SRVKXCTJSA-N 0.000 description 1
- UQJOKDAYFULYIX-AVGNSLFASA-N Lys-Pro-Pro Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 UQJOKDAYFULYIX-AVGNSLFASA-N 0.000 description 1
- TVHCDSBMFQYPNA-RHYQMDGZSA-N Lys-Thr-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O TVHCDSBMFQYPNA-RHYQMDGZSA-N 0.000 description 1
- BDFHWFUAQLIMJO-KXNHARMFSA-N Lys-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N)O BDFHWFUAQLIMJO-KXNHARMFSA-N 0.000 description 1
- HONVOXINDBETTI-KKUMJFAQSA-N Lys-Tyr-Cys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CS)C(O)=O)CC1=CC=C(O)C=C1 HONVOXINDBETTI-KKUMJFAQSA-N 0.000 description 1
- GILLQRYAWOMHED-DCAQKATOSA-N Lys-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN GILLQRYAWOMHED-DCAQKATOSA-N 0.000 description 1
- IUYCGMNKIZDRQI-BQBZGAKWSA-N Met-Gly-Ala Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O IUYCGMNKIZDRQI-BQBZGAKWSA-N 0.000 description 1
- HSJIGJRZYUADSS-IHRRRGAJSA-N Met-Lys-Leu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O HSJIGJRZYUADSS-IHRRRGAJSA-N 0.000 description 1
- KRLKICLNEICJGV-STQMWFEESA-N Met-Phe-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 KRLKICLNEICJGV-STQMWFEESA-N 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 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 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 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 1
- 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 1
- YKUGPVXSDOOANW-KKUMJFAQSA-N Phe-Leu-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O YKUGPVXSDOOANW-KKUMJFAQSA-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
- ZVJGAXNBBKPYOE-HKUYNNGSSA-N Phe-Trp-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(O)=O)C1=CC=CC=C1 ZVJGAXNBBKPYOE-HKUYNNGSSA-N 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- VXCHGLYSIOOZIS-GUBZILKMSA-N Pro-Ala-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 VXCHGLYSIOOZIS-GUBZILKMSA-N 0.000 description 1
- 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 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
- NHDVNAKDACFHPX-GUBZILKMSA-N Pro-Arg-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O NHDVNAKDACFHPX-GUBZILKMSA-N 0.000 description 1
- HPXVFFIIGOAQRV-DCAQKATOSA-N Pro-Arg-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O HPXVFFIIGOAQRV-DCAQKATOSA-N 0.000 description 1
- GRIRJQGZZJVANI-CYDGBPFRSA-N Pro-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]1CCCN1 GRIRJQGZZJVANI-CYDGBPFRSA-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
- LANQLYHLMYDWJP-SRVKXCTJSA-N Pro-Gln-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O LANQLYHLMYDWJP-SRVKXCTJSA-N 0.000 description 1
- 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 1
- PULPZRAHVFBVTO-DCAQKATOSA-N Pro-Glu-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PULPZRAHVFBVTO-DCAQKATOSA-N 0.000 description 1
- QNZLIVROMORQFH-BQBZGAKWSA-N Pro-Gly-Cys Chemical compound C1C[C@H](NC1)C(=O)NCC(=O)N[C@@H](CS)C(=O)O QNZLIVROMORQFH-BQBZGAKWSA-N 0.000 description 1
- 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 1
- DXTOOBDIIAJZBJ-BQBZGAKWSA-N Pro-Gly-Ser Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(O)=O DXTOOBDIIAJZBJ-BQBZGAKWSA-N 0.000 description 1
- FFSLAIOXRMOFIZ-GJZGRUSLSA-N Pro-Gly-Trp Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)CNC(=O)[C@@H]1CCCN1 FFSLAIOXRMOFIZ-GJZGRUSLSA-N 0.000 description 1
- HAEGAELAYWSUNC-WPRPVWTQSA-N Pro-Gly-Val Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HAEGAELAYWSUNC-WPRPVWTQSA-N 0.000 description 1
- AJCRQOHDLCBHFA-SRVKXCTJSA-N Pro-His-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O AJCRQOHDLCBHFA-SRVKXCTJSA-N 0.000 description 1
- VWXGFAIZUQBBBG-UWVGGRQHSA-N Pro-His-Gly Chemical compound C([C@@H](C(=O)NCC(=O)[O-])NC(=O)[C@H]1[NH2+]CCC1)C1=CN=CN1 VWXGFAIZUQBBBG-UWVGGRQHSA-N 0.000 description 1
- 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 1
- JLMZKEQFMVORMA-SRVKXCTJSA-N Pro-Pro-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 JLMZKEQFMVORMA-SRVKXCTJSA-N 0.000 description 1
- HWLKHNDRXWTFTN-GUBZILKMSA-N Pro-Pro-Cys Chemical compound C1C[C@H](NC1)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CS)C(=O)O HWLKHNDRXWTFTN-GUBZILKMSA-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
- 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 1
- 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 1
- OWQXAJQZLWHPBH-FXQIFTODSA-N Pro-Ser-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O OWQXAJQZLWHPBH-FXQIFTODSA-N 0.000 description 1
- BGWKULMLUIUPKY-BQBZGAKWSA-N Pro-Ser-Gly Chemical compound OC(=O)CNC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 BGWKULMLUIUPKY-BQBZGAKWSA-N 0.000 description 1
- 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 1
- XSXABUHLKPUVLX-JYJNAYRXSA-N Pro-Ser-Trp Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O XSXABUHLKPUVLX-JYJNAYRXSA-N 0.000 description 1
- 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 1
- 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 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 241000978493 Rumex spinosus Species 0.000 description 1
- 108091015661 Scavenger receptor class F member 1 Proteins 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
- 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 1
- JPIDMRXXNMIVKY-VZFHVOOUSA-N Ser-Ala-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JPIDMRXXNMIVKY-VZFHVOOUSA-N 0.000 description 1
- JJKSSJVYOVRJMZ-FXQIFTODSA-N Ser-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N)CN=C(N)N JJKSSJVYOVRJMZ-FXQIFTODSA-N 0.000 description 1
- 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 1
- RDFQNDHEHVSONI-ZLUOBGJFSA-N Ser-Asn-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O RDFQNDHEHVSONI-ZLUOBGJFSA-N 0.000 description 1
- CTRHXXXHUJTTRZ-ZLUOBGJFSA-N Ser-Asp-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N)C(=O)O CTRHXXXHUJTTRZ-ZLUOBGJFSA-N 0.000 description 1
- ZHYMUFQVKGJNRM-ZLUOBGJFSA-N Ser-Cys-Asn Chemical compound OC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC(N)=O ZHYMUFQVKGJNRM-ZLUOBGJFSA-N 0.000 description 1
- KNCJWSPMTFFJII-ZLUOBGJFSA-N Ser-Cys-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(O)=O KNCJWSPMTFFJII-ZLUOBGJFSA-N 0.000 description 1
- COLJZWUVZIXSSS-CIUDSAMLSA-N Ser-Cys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N COLJZWUVZIXSSS-CIUDSAMLSA-N 0.000 description 1
- HVKMTOIAYDOJPL-NRPADANISA-N Ser-Gln-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O HVKMTOIAYDOJPL-NRPADANISA-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
- UFKPDBLKLOBMRH-XHNCKOQMSA-N Ser-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)N)C(=O)O UFKPDBLKLOBMRH-XHNCKOQMSA-N 0.000 description 1
- UQFYNFTYDHUIMI-WHFBIAKZSA-N Ser-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CO UQFYNFTYDHUIMI-WHFBIAKZSA-N 0.000 description 1
- 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 1
- UIGMAMGZOJVTDN-WHFBIAKZSA-N Ser-Gly-Ser Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O UIGMAMGZOJVTDN-WHFBIAKZSA-N 0.000 description 1
- XNCUYZKGQOCOQH-YUMQZZPRSA-N Ser-Leu-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O XNCUYZKGQOCOQH-YUMQZZPRSA-N 0.000 description 1
- 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 1
- XNXRTQZTFVMJIJ-DCAQKATOSA-N Ser-Met-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O XNXRTQZTFVMJIJ-DCAQKATOSA-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
- UPLYXVPQLJVWMM-KKUMJFAQSA-N Ser-Phe-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O UPLYXVPQLJVWMM-KKUMJFAQSA-N 0.000 description 1
- WBAXJMCUFIXCNI-WDSKDSINSA-N Ser-Pro Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WBAXJMCUFIXCNI-WDSKDSINSA-N 0.000 description 1
- XQAPEISNMXNKGE-FXQIFTODSA-N Ser-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CO)N)C(=O)N[C@@H](CS)C(=O)O XQAPEISNMXNKGE-FXQIFTODSA-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
- 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 1
- 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 1
- XZKQVQKUZMAADP-IMJSIDKUSA-N Ser-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(O)=O XZKQVQKUZMAADP-IMJSIDKUSA-N 0.000 description 1
- 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 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
- 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 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
- 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 1
- ZWSZBWAFDZRBNM-UBHSHLNASA-N Ser-Trp-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O ZWSZBWAFDZRBNM-UBHSHLNASA-N 0.000 description 1
- LLSLRQOEAFCZLW-NRPADANISA-N Ser-Val-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LLSLRQOEAFCZLW-NRPADANISA-N 0.000 description 1
- YEDSOSIKVUMIJE-DCAQKATOSA-N Ser-Val-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O YEDSOSIKVUMIJE-DCAQKATOSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- JMZKMSTYXHFYAK-VEVYYDQMSA-N Thr-Arg-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)O JMZKMSTYXHFYAK-VEVYYDQMSA-N 0.000 description 1
- CEXFELBFVHLYDZ-XGEHTFHBSA-N Thr-Arg-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CEXFELBFVHLYDZ-XGEHTFHBSA-N 0.000 description 1
- JHBHMCMKSPXRHV-NUMRIWBASA-N Thr-Asn-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O JHBHMCMKSPXRHV-NUMRIWBASA-N 0.000 description 1
- LMMDEZPNUTZJAY-GCJQMDKQSA-N Thr-Asp-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O LMMDEZPNUTZJAY-GCJQMDKQSA-N 0.000 description 1
- YBXMGKCLOPDEKA-NUMRIWBASA-N Thr-Asp-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YBXMGKCLOPDEKA-NUMRIWBASA-N 0.000 description 1
- QWMPARMKIDVBLV-VZFHVOOUSA-N Thr-Cys-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O QWMPARMKIDVBLV-VZFHVOOUSA-N 0.000 description 1
- DGOJNGCGEYOBKN-BWBBJGPYSA-N Thr-Cys-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)O)N)O DGOJNGCGEYOBKN-BWBBJGPYSA-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
- MMTOHPRBJKEZHT-BWBBJGPYSA-N Thr-Cys-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O MMTOHPRBJKEZHT-BWBBJGPYSA-N 0.000 description 1
- MPUMPERGHHJGRP-WEDXCCLWSA-N Thr-Gly-Lys Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)O)N)O MPUMPERGHHJGRP-WEDXCCLWSA-N 0.000 description 1
- KBBRNEDOYWMIJP-KYNKHSRBSA-N Thr-Gly-Thr Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O KBBRNEDOYWMIJP-KYNKHSRBSA-N 0.000 description 1
- HEJJDUDEHLPDAW-CUJWVEQBSA-N Thr-His-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CS)C(=O)O)N)O HEJJDUDEHLPDAW-CUJWVEQBSA-N 0.000 description 1
- MEJHFIOYJHTWMK-VOAKCMCISA-N Thr-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)[C@@H](C)O MEJHFIOYJHTWMK-VOAKCMCISA-N 0.000 description 1
- 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 1
- YRJOLUDFVAUXLI-GSSVUCPTSA-N Thr-Thr-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(O)=O YRJOLUDFVAUXLI-GSSVUCPTSA-N 0.000 description 1
- PELIQFPESHBTMA-WLTAIBSBSA-N Thr-Tyr-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 PELIQFPESHBTMA-WLTAIBSBSA-N 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- RSUXQZNWAOTBQF-XIRDDKMYSA-N Trp-Arg-Gln 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](CCC(=O)N)C(=O)O)N RSUXQZNWAOTBQF-XIRDDKMYSA-N 0.000 description 1
- MHNHRNHJMXAVHZ-AAEUAGOBSA-N Trp-Asn-Gly Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)NCC(=O)O)N MHNHRNHJMXAVHZ-AAEUAGOBSA-N 0.000 description 1
- FEZASNVQLJQBHW-CABZTGNLSA-N Trp-Gly-Ala Chemical compound C1=CC=C2C(C[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O)=CNC2=C1 FEZASNVQLJQBHW-CABZTGNLSA-N 0.000 description 1
- HQJOVVWAPQPYDS-ZFWWWQNUSA-N Trp-Gly-Arg Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O HQJOVVWAPQPYDS-ZFWWWQNUSA-N 0.000 description 1
- KIMOCKLJBXHFIN-YLVFBTJISA-N Trp-Ile-Gly Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O)=CNC2=C1 KIMOCKLJBXHFIN-YLVFBTJISA-N 0.000 description 1
- MKDXQPMIQPTTAW-SIXJUCDHSA-N Trp-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N MKDXQPMIQPTTAW-SIXJUCDHSA-N 0.000 description 1
- WNGMGTMSUBARLB-RXVVDRJESA-N Trp-Trp-Gly Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)N)C(=O)NCC(O)=O)=CNC2=C1 WNGMGTMSUBARLB-RXVVDRJESA-N 0.000 description 1
- NIHNMOSRSAYZIT-BPNCWPANSA-N Tyr-Ala-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NIHNMOSRSAYZIT-BPNCWPANSA-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
- KLGFILUOTCBNLJ-IHRRRGAJSA-N Tyr-Cys-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O KLGFILUOTCBNLJ-IHRRRGAJSA-N 0.000 description 1
- QOEZFICGUZTRFX-IHRRRGAJSA-N Tyr-Cys-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O QOEZFICGUZTRFX-IHRRRGAJSA-N 0.000 description 1
- OKDNSNWJEXAMSU-IRXDYDNUSA-N Tyr-Phe-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(O)=O)C1=CC=C(O)C=C1 OKDNSNWJEXAMSU-IRXDYDNUSA-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
- QHDXUYOYTPWCSK-RCOVLWMOSA-N Val-Asp-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N QHDXUYOYTPWCSK-RCOVLWMOSA-N 0.000 description 1
- FRUYSSRPJXNRRB-GUBZILKMSA-N Val-Cys-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N FRUYSSRPJXNRRB-GUBZILKMSA-N 0.000 description 1
- KOPBYUSPXBQIHD-NRPADANISA-N Val-Cys-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KOPBYUSPXBQIHD-NRPADANISA-N 0.000 description 1
- XJFXZQKJQGYFMM-GUBZILKMSA-N Val-Cys-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)O)N XJFXZQKJQGYFMM-GUBZILKMSA-N 0.000 description 1
- JVYIGCARISMLMV-HOCLYGCPSA-N Val-Gly-Trp Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N JVYIGCARISMLMV-HOCLYGCPSA-N 0.000 description 1
- JVGHIFMSFBZDHH-WPRPVWTQSA-N Val-Met-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)O)N JVGHIFMSFBZDHH-WPRPVWTQSA-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
- 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
- SDHZOOIGIUEPDY-JYJNAYRXSA-N Val-Ser-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CO)NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 SDHZOOIGIUEPDY-JYJNAYRXSA-N 0.000 description 1
- BZDGLJPROOOUOZ-XGEHTFHBSA-N Val-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C(C)C)N)O BZDGLJPROOOUOZ-XGEHTFHBSA-N 0.000 description 1
- 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 1
- CFIBZQOLUDURST-IHRRRGAJSA-N Val-Tyr-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CS)C(=O)O)N CFIBZQOLUDURST-IHRRRGAJSA-N 0.000 description 1
- NLNCNKIVJPEFBC-DLOVCJGASA-N Val-Val-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O NLNCNKIVJPEFBC-DLOVCJGASA-N 0.000 description 1
- 101100068489 Vicia faba AGPC gene Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 108010022164 acetyl-LDL Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 238000003277 amino acid sequence analysis Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108010013835 arginine glutamate Proteins 0.000 description 1
- 108010008355 arginyl-glutamine Proteins 0.000 description 1
- 108010001271 arginyl-glutamyl-arginine Proteins 0.000 description 1
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 1
- 108010038633 aspartylglutamate Proteins 0.000 description 1
- 108010047857 aspartylglycine Proteins 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000002318 cardia Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 108010004073 cysteinylcysteine Proteins 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 210000000630 fibrocyte Anatomy 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 108010023364 glycyl-histidyl-arginine Proteins 0.000 description 1
- 108010020688 glycylhistidine Proteins 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 108010084389 glycyltryptophan Proteins 0.000 description 1
- 108010087823 glycyltyrosine Proteins 0.000 description 1
- 108010037850 glycylvaline Proteins 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 108010018006 histidylserine Proteins 0.000 description 1
- 230000001096 hypoplastic effect Effects 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 210000002861 immature t-cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 108010009298 lysylglutamic acid Proteins 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 108010068488 methionylphenylalanine Proteins 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 210000003254 palate Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 108010051242 phenylalanylserine Proteins 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 108010014614 prolyl-glycyl-proline Proteins 0.000 description 1
- 108010015796 prolylisoleucine Proteins 0.000 description 1
- 108010090894 prolylleucine Proteins 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 102220201851 rs143406017 Human genes 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 108010048818 seryl-histidine Proteins 0.000 description 1
- 108010071207 serylmethionine Proteins 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 108010045269 tryptophyltryptophan Proteins 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、マウスナース細胞レセ
プター；本発明のポリペプチドをコードするDNA；本発
明の塩基配列中の連続した少なくとも１４個の塩基を含
み、該塩基配列と特異的に結合するDNA；本発明のポリ
ペプチドを特異的に認識する抗体；本発明の抗体を産生
するハイブリドーマ；本発明のDNAを含む発現ベクタ
ー；本発明の発現ベクターより得られる形質転換体；組
換えマウスナース細胞レセプターの製造方法；本発明の
マウスナース細胞レセプターに特異的に結合するリガン
ドのスクリーニング方法；本発明のマウスナース細胞レ
セプターとリガンドとの結合を阻害する化合物のスクリ
ーニング方法；本発明のスクリーニング方法により得ら
れる医薬；本発明プライマーを含むディジョージ症候群
を検出するためのキット；本発明プライマーを含む自己
免疫疾患を検出するためのキットに関する。The present invention relates to a mouse nurse cell receptor; a DNA encoding the polypeptide of the present invention; and at least 14 contiguous bases in the base sequence of the present invention. An antibody that specifically recognizes the polypeptide of the present invention; a hybridoma producing the antibody of the present invention; an expression vector containing the DNA of the present invention; a transformant obtained from the expression vector of the present invention; A method for producing a nurse cell receptor; a method for screening a ligand that specifically binds to a mouse nurse cell receptor of the present invention; a method for screening a compound that inhibits binding between a mouse nurse cell receptor and a ligand according to the present invention; A kit for detecting DiGeorge syndrome comprising the primer of the present invention; It relates to a kit for detecting autoimmune diseases including invention primers.
【０００２】[0002]
【従来の技術】胸腺は、免疫機能の発達に重要な役割を
果たし、特にT細胞の分化や成熟に不可欠な器官であ
る。胸腺微小環境は、マクロファージ、樹状細胞、線維
細胞、上皮細胞などから構成される。この上皮細胞に、
胸腺ナース細胞が存在している(Wekerle, H. et al., N
ature, 283:402, 1980; Wekerle, H. et al., J. Exp.
Med., 151:929, 1980)。さらに、ナース細胞は胸腺以外
の、ヒトやマウスの皮膚組織（Iwagami, S. etal., I.
Immunol., 153, 2927-2938, 1994）、骨髄（豊崎ら, 炎
症と免疫, 2:643-649, 1994）、リウマチ患者の滑膜
（豊崎ら, 臨床免疫, 27: 167, 1995）、腫瘍の原発巣
及び転移巣（Itoh, T. et al., Eur. J. Immunol., 18,
821-824,1988、Hiai, H. et al., J. Natl. Cancer In
st., 66, 713-722, 1981）に存在することが確認されて
いる。胸腺ナース細胞は、未熟なT細胞を細胞内に多数
抱え込んだ細胞である。従って、このナース細胞は、T
細胞の成熟・分化に関与し、T細胞のpositive selectio
nおよびnegative selectionに関与している可能性があ
るものの、その機能については不明な点が多い。2. Description of the Related Art The thymus plays an important role in the development of immune functions, and is an essential organ particularly for T cell differentiation and maturation. The thymic microenvironment is composed of macrophages, dendritic cells, fibrocytes, epithelial cells, and the like. In this epithelial cell,
Thymic nurse cells are present (Wekerle, H. et al., N
ature, 283: 402, 1980; Wekerle, H. et al., J. Exp.
Med., 151: 929, 1980). Furthermore, nurse cells are derived from human and mouse skin tissues other than the thymus (Iwagami, S. etal., I.
Immunol., 153, 2927-2938, 1994), bone marrow (Toyosaki et al., Inflammation and immunity, 2: 643-649, 1994), synovium of rheumatic patients (Toyosaki et al., Clinical immunity, 27: 167, 1995), tumor Primary and metastatic foci (Itoh, T. et al., Eur. J. Immunol., 18,
821-824, 1988, Hiai, H. et al., J. Natl. Cancer In
st., 66, 713-722, 1981). Thymic nurse cells are cells that have many immature T cells within them. Therefore, this nurse cell
Involved in cell maturation / differentiation, positive selection of T cells
Although it may be involved in n and negative selection, there are many unclear points about its function.
【０００３】一方、ディジョージ症候群は、胸腺の無ま
たは低形成、副甲状腺の無または低形成に起因する低カ
ルシウム血症、顔貌異常、心大血管系異常を特徴とする
先天性自己免疫疾患および臓器形成異常性疾患である。
ディジョージ症候群の多くの症例で、第２２染色体長腕
の欠失が観察されることにより、ディジョージ症候群を
含む臓器形成異常性疾患、特にＣＡＴＣＨ２２（cardia
c defects, abnormalfacies, thymic hypoplasia, clef
t palate, and hypocalcemia on chromosome22）の責任
遺伝子が同じ部位に存在するのではないかと想定されて
いる。On the other hand, DiGeorge syndrome is a congenital autoimmune disease characterized by hypocalcemia, facial abnormalities and cardiovascular abnormalities caused by athymic or hypoplastic thymus, parathyroid gland or hypothyroidism. It is an organ dysplasia disease.
In many cases of DiGeorge's syndrome, the deletion of the long arm of chromosome 22 has been observed, which has led to organ dysplasia diseases including DiGeorge's syndrome, especially CATCH22 (cardia
c defects, abnormalfacies, thymic hypoplasia, clef
It is postulated that the genes responsible for t palate, and hypocalcemia on chromosome22) may be present at the same site.
【０００４】[0004]
【発明が解決しようとする課題】本発明の目的は、マウ
スナース細胞レセプター；本発明のポリペプチドをコー
ドするDNA；本発明の塩基配列中の連続した少なくとも
１４個の塩基を含み、該塩基配列と特異的に結合するDN
A；本発明のポリペプチドを特異的に認識する抗体；本
発明の抗体を産生するハイブリドーマ；本発明のDNAを
含む発現ベクター；本発明の発現ベクターより得られる
形質転換体；組換えマウスナース細胞レセプターの製造
方法；本発明のマウスナース細胞レセプターに特異的に
結合するリガンドのスクリーニング方法；本発明のマウ
スナース細胞レセプターとリガンドとの結合を阻害する
化合物のスクリーニング方法；本発明のスクリーニング
方法により得られる医薬；本発明プライマーを含むディ
ジョージ症候群を検出するためのキット；本発明プライ
マーを含む自己免疫疾患を検出するためのキットを提供
することにある。An object of the present invention is to provide a mouse nurse cell receptor; a DNA encoding the polypeptide of the present invention; and a base sequence comprising at least 14 consecutive bases in the base sequence of the present invention. DN that specifically binds to
A; an antibody that specifically recognizes the polypeptide of the present invention; a hybridoma that produces the antibody of the present invention; an expression vector containing the DNA of the present invention; a transformant obtained from the expression vector of the present invention; a recombinant mouse nurse cell A method for producing a receptor; a method for screening a ligand that specifically binds to a mouse nurse cell receptor of the present invention; a method for screening a compound that inhibits binding between a mouse nurse cell receptor and a ligand according to the present invention; A kit for detecting DiGeorge syndrome containing the primer of the present invention; and a kit for detecting an autoimmune disease containing the primer of the present invention.
【０００５】[0005]
【課題を解決するための手段】本発明者らは、ナース細
胞の機能の解明を目指して鋭意研鑚を重ねてきた。その
結果、マウスナース細胞膜表面に発現するマウスナース
細胞レセプター（以下、マウスB6TNC#10または本レセプ
ターと略する）をコードする遺伝子を見出し、本発明を
完成するに至った。本レセプター遺伝子は、ディジョー
ジ症候群の原因領域に相当するマウスゲノムDNA配列（G
enBank Accesion No.: AC000096）に相同性を示す。ま
た、本レセプターは、遺伝子の塩基配列から予想される
オープンリーディングフレームでは８３３個のアミノ酸
からなるタンパク質である。本レセプターのcDNAと最も
高い相同性を示したのは、アセチル低比重リポタンパク
質（low density lipoprotein: LDL）レセプター（Adac
hi, H. et al., J. Biol.Chem., 272, 31217-31220, 19
97）であり、相同性は、３９％であった。アセチルLDL
レセプターは、アセチルLDLを細胞内へ取り込む機能を
有する（Goldstein, J. L. et al., Proc. Natl. Acad.
Sci. USA, 76, 333-337, 1979）。このような機能を有
するレセプターは、スカベンジャーレセプターと命名さ
れている。スカベンジャーレセプターは、マクロファー
ジの泡沫化に関与し、動脈硬化形成の原因と考えられて
いる。本レセプターもスカベンジャーレセプターファミ
リーに属することが想定される。Means for Solving the Problems The present inventors have intensively studied to elucidate the function of nurse cells. As a result, they found a gene encoding a mouse nurse cell receptor (hereinafter abbreviated as mouse B6TNC # 10 or this receptor) expressed on the mouse nurse cell membrane surface, and completed the present invention. This receptor gene is a mouse genomic DNA sequence (G
enBank Accesion No .: AC000096). This receptor is a protein consisting of 833 amino acids in the open reading frame predicted from the nucleotide sequence of the gene. The highest homology with the cDNA of this receptor is the acetyl low density lipoprotein (LDL) receptor (Adac
hi, H. et al., J. Biol. Chem., 272, 31217-31220, 19
97) and the homology was 39%. Acetyl LDL
The receptor has a function of taking up acetyl LDL into cells (Goldstein, JL et al., Proc. Natl. Acad.
Sci. USA, 76, 333-337, 1979). A receptor having such a function is called a scavenger receptor. Scavenger receptors are involved in macrophage foaming and are thought to be responsible for atherosclerosis formation. This receptor is also assumed to belong to the scavenger receptor family.
【０００６】すなわち、本発明は、配列番号２の１位の
Metから８３３位のSerまでのアミノ酸配列を含むポリペ
プチド；本発明のアミノ酸配列において１もしくは数個
のアミノ酸が置換、欠失、挿入または付加されたアミノ
酸配列を含み、かつマウスナース細胞レセプターである
ポリペプチド；本発明のポリペプチドからなるマウスナ
ース細胞レセプター；本発明のポリペプチドをコードす
るDNA；配列番号１の６５位のAから２５６３位のCまで
の塩基配列を含む本発明のDNA；本発明のDNAとストリン
ジェントな条件でハイブリダイズし、かつマウスナース
細胞レセプターであるポリペプチドをコードするDNA；
本発明のDNAからなるマウスナース細胞レセプター遺伝
子；配列番号１に記載の塩基配列中の連続した少なくと
も１４個の塩基を含み、該塩基配列と特異的に結合する
DNA；配列番号４から１０のいずれかに記載の塩基配列
中の連続した少なくとも１４個の塩基を含む本発明のDN
A；本発明のポリペプチドを特異的に認識する抗体；モ
ノクローナル抗体である、本発明の抗体；本発明のモノ
クローナル抗体を産生するハイブリドーマ；本発明のDN
Aを有する発現ベクター；本発明の発現ベクターを宿主
に導入して得られる形質転換体；本発明の形質転換体を
培養する工程、および生産された組換えタンパク質を培
養培地から回収する工程を包含する、組換えマウスナー
ス細胞レセプターの製造方法；本発明の形質転換体また
は本発明の製造方法より得られたマウスナース細胞レセ
プターを用いた、マウスナース細胞レセプターに特異的
に結合するリガンドのスクリーニング方法；本発明の形
質転換体または本発明の製造方法より得られたマウスナ
ース細胞レセプターと本発明のスクリーニング方法より
得られるリガンドとの結合を阻害する化合物のスクリー
ニング方法；本発明のスクリーニング方法より得られる
医薬；本発明のDNAを含む、ディジョージ症候群を検出
するためのキット；本発明のDNAを含む、自己免疫疾患
を検出するためのキット、に関する。That is, the present invention relates to
A polypeptide comprising an amino acid sequence from Met to Ser at position 833; an amino acid sequence of the present invention comprising an amino acid sequence in which one or several amino acids have been substituted, deleted, inserted or added, and which is a mouse nurse cell receptor A mouse; a nurse cell receptor comprising the polypeptide of the present invention; a DNA encoding the polypeptide of the present invention; a DNA of the present invention comprising a nucleotide sequence from A at position 65 to C at position 2563 of SEQ ID NO: 1; DNA that hybridizes with the DNA of the present invention under stringent conditions and encodes a polypeptide that is a mouse nurse cell receptor;
A mouse nurse cell receptor gene comprising the DNA of the present invention; which contains at least 14 consecutive bases in the nucleotide sequence of SEQ ID NO: 1 and specifically binds to the nucleotide sequence
DNA; DN of the present invention comprising at least 14 consecutive bases in the base sequence of any of SEQ ID NOs: 4 to 10
A; an antibody that specifically recognizes the polypeptide of the present invention; an antibody of the present invention, which is a monoclonal antibody; a hybridoma that produces the monoclonal antibody of the present invention;
An expression vector having A; a transformant obtained by introducing the expression vector of the present invention into a host; a step of culturing the transformant of the present invention, and a step of recovering the produced recombinant protein from the culture medium. Method for producing a recombinant mouse nurse cell receptor; screening method for a ligand that specifically binds to a mouse nurse cell receptor using the transformant of the present invention or the mouse nurse cell receptor obtained by the method of the present invention A method for screening a compound that inhibits the binding between the transformant of the present invention or the mouse nurse cell receptor obtained by the method of the present invention and the ligand obtained by the screening method of the present invention; obtained by the screening method of the present invention. Pharmaceuticals; kit for detecting DiGeorge syndrome, including DNA of the present invention; book A kit for detecting an autoimmune disease, comprising the DNA of the present invention.
【０００７】本発明のポリペプチドは、「配列番号２の
１位のMetから８３３位のSerまでのアミノ酸配列を含む
ポリペプチド」または「該アミノ酸配列において１もし
くは数個のアミノ酸が置換、欠失、挿入または付加され
たアミノ酸配列を含み、かつマウスナース細胞レセプタ
ーであるポリペプチド」を指す。「マウスナース細胞レ
セプター」とは、マウスナース細胞の細胞膜に発現する
タンパク質である。「ナース細胞」とは、リンパ球など
自分自身以外の細胞を細胞内に取り込むことができる能
力がある細胞を言う。マウスナース細胞株としては、B6
TNC（Nanno, M.et al., J. Immunol., 155, 2918, 199
5）、IT-79 MTNC3 (Itoh, T. et al.(1998) Eur. J. Im
munol. 18,821)、Doi Nurse（Iwagami, S. et al. (199
4) J. Immunol. 153,2927）、C3H10T1/2 clone8 (ATCC
No.CCL-226)が例示できる。[0007] The polypeptide of the present invention may be a "polypeptide comprising an amino acid sequence from Met at position 1 to Ser at position 833 of SEQ ID NO: 2" or "one or several amino acids substituted or deleted in the amino acid sequence. , A polypeptide comprising an inserted or added amino acid sequence and being a mouse nurse cell receptor ". "Mouse nurse cell receptor" is a protein expressed on the cell membrane of mouse nurse cells. "Nurse cells" refer to cells capable of taking up cells other than themselves, such as lymphocytes, into cells. B6 as a mouse nurse cell line
TNC (Nanno, M. et al., J. Immunol., 155, 2918, 199
5), IT-79 MTNC3 (Itoh, T. et al. (1998) Eur. J. Im
munol. 18,821), Doi Nurse (Iwagami, S. et al. (199
4) J. Immunol. 153,2927), C3H10T 1/2 clone8 (ATCC
No. CCL-226).
【０００８】本発明のDNAとは、本発明のポリペプチド
をコードするDNAを指す。例えば、配列番号１の６５位
のAから２５６３位のCまでの塩基配列を含むDNAが例示
される。更に、本発明のDNAとストリンジェントな条件
でハイブリダイズし、かつマウスナース細胞レセプター
であるポリペプチドをコードするDNAも、本発明のDNAに
含まれる。「DNAにストリンジェントな条件でハイブリ
ダイズするDNA」は、コード領域のDNAをプローブとして
用いることにより得ることが出来る。ここで、「ストリ
ンジェントな条件でハイブリダイズする」とは、例え
ば、６ｘSSC、0.5%SDSおよび50%ホルムアミドの溶液中
で42℃にて加温した後、0.1xSSC、0.5%SDSの溶液中で68
℃にて洗浄する条件でも依然として陽性のハイブリダイ
ズのシグナルが観察されることを表す。更に、本発明の
DNAには、「配列番号１に記載の塩基配列中の連続した
少なくとも１４個の塩基を含み、該塩基配列と特異的に
結合するDNA」も含まれる。好ましくは、配列番号４か
ら１０のいずれかに記載の塩基配列を含むDNAである。
「特異的に結合する」とは、ハイブリダイスすることを
指す。このようなDNAは、プライマーまたはプローブと
して有用である。このようなDNAを用いることにより、
ディジョージ症候群の検出が可能となる。従って、本発
明のDNAはディジョージ症候群の検出キットを提供する
ものである。更に、本レセプターが欠損した場合には、
ナース細胞によるT細胞の成熟・分化が正常におこなわ
れない可能性がある。従って、本発明のDNAは、本レセ
プターの欠損に起因する自己免疫疾患の検出キットを提
供するものである。[0008] The DNA of the present invention refers to a DNA encoding the polypeptide of the present invention. For example, a DNA containing a base sequence from A at position 65 to C at position 2563 in SEQ ID NO: 1 is exemplified. Furthermore, DNA that hybridizes with the DNA of the present invention under stringent conditions and encodes a polypeptide that is a mouse nurse cell receptor is also included in the DNA of the present invention. “DNA that hybridizes to DNA under stringent conditions” can be obtained by using DNA in the coding region as a probe. Here, "to hybridize under stringent conditions" means, for example, after heating at 42 ° C. in a solution of 6 × SSC, 0.5% SDS and 50% formamide, in a solution of 0.1 × SSC, 0.5% SDS. 68
This shows that a positive hybridization signal is still observed even under the condition of washing at ℃. Furthermore, the present invention
The DNA also includes “a DNA containing at least 14 consecutive bases in the base sequence described in SEQ ID NO: 1 and specifically binding to the base sequence”. Preferably, it is a DNA comprising the nucleotide sequence of any one of SEQ ID NOs: 4 to 10.
"Specifically binds" refers to hybridizing. Such DNAs are useful as primers or probes. By using such DNA,
DiGeorge syndrome can be detected. Therefore, the DNA of the present invention provides a kit for detecting DiGeorge syndrome. Furthermore, when this receptor is deficient,
There is a possibility that the maturation and differentiation of T cells by nurse cells may not be performed normally. Therefore, the DNA of the present invention provides a kit for detecting an autoimmune disease caused by deficiency of the present receptor.
【０００９】本発明の抗体は、本発明のポリペプチドま
たはエピトープを構成しえるペプチド断片に対する抗体
であり、モロクローナル抗体とポリクローナル抗体のい
ずれをも含む。本発明のハイブリドーマは、該モノクロ
ーナル抗体を産生するハイブリドーマである。本発明の
抗体は、アフィニティークロマトグラフィー、cDNAライ
ブラリーのスクリーニング、診断薬・実験用試薬等に有
用である。また、医薬として使用することもできる。The antibody of the present invention is an antibody against the polypeptide of the present invention or a peptide fragment that can constitute an epitope, and includes both a mocloclonal antibody and a polyclonal antibody. The hybridoma of the present invention is a hybridoma that produces the monoclonal antibody. The antibody of the present invention is useful for affinity chromatography, screening of a cDNA library, diagnostic reagents, experimental reagents, and the like. It can also be used as a medicine.
【００１０】本発明には、本発明のDNAを有する発現ベ
クター、該発現ベクターを宿主に導入することにより形
質転換体、該形質転換体を用いた組換えマウスナース細
胞レセプターの製造方法が提供される。「発現ベクタ
ー」としては、例えば、細菌についてはpRSET、pET、pG
EMEX、pKK233-2など、酵母についてはpYES2、昆虫細胞
についてはpVL1393、pFastBac1、動物細胞についてはpE
F-BOS、pSRa、pDR2などが挙げられる。「宿主」として
は、細菌、酵母、昆虫細胞、または動物細胞が挙げられ
る。The present invention provides an expression vector having the DNA of the present invention, a transformant obtained by introducing the expression vector into a host, and a method for producing a recombinant mouse nurse cell receptor using the transformant. You. Examples of “expression vectors” include, for bacteria, pRSET, pET, pG
EMEX, pKK233-2, etc., pYES2 for yeast, pVL1393, pFastBac1 for insect cells, pE for animal cells
F-BOS, pSRa, pDR2 and the like. "Host" includes bacteria, yeast, insect cells, or animal cells.
【００１１】本発明は、本レセプターに特異的に結合す
るリガンドのスクリーニング方法と提供する。リガンド
としては、分泌型ペプチド、細胞膜タンパク質、
脂肪や核酸などの生体内代謝物、などが考えられる。リ
ガンドのスクリーニング方法としては、このようなリガ
ンド候補物質をアイソトープラベルや蛍光ラベルし、本
レセプターを発現する細胞または膜画分との結合試験を
行なう方法が挙げられる。実施例で示すとおり、本レセ
プターは、アセチルLDL（low density lipoprotein）レ
セプターと相同性を示す。アセチルLDLは、変性した脂
肪であり、生体内代謝物に該当する。従って、アセチル
LDLが本レセプターのリガンドである可能性は高い。[0011] The present invention provides a method for screening for a ligand that specifically binds to the present receptor. Ligands include secretory peptides, cell membrane proteins,
In vivo metabolites such as fats and nucleic acids can be considered. Examples of the method for screening a ligand include a method of labeling such a ligand candidate substance with an isotope label or a fluorescent label and performing a binding test with a cell or a membrane fraction expressing the present receptor. As shown in the examples, the present receptor shows homology to the acetyl LDL (low density lipoprotein) receptor. Acetyl LDL is a denatured fat and corresponds to an in vivo metabolite. Therefore, acetyl
It is highly likely that LDL is a ligand for this receptor.
【００１２】リガンドが特定されれば、本マウスナース
細胞レセプターとリガンドの結合を阻害する化合物のス
クリーニングが可能となる。「リガンドの結合を阻害す
る化合物」には、アゴニスト及びアンタゴニストが含ま
れる。該化合物のスクリーニング方法としては、標識し
たリガンド、本レセプターおよび候補化合物をインキュ
ベートし、結合活性を測定する方法が挙げられる。When the ligand is specified, it becomes possible to screen for a compound that inhibits the binding between the mouse nurse cell receptor and the ligand. "Compounds that inhibit ligand binding" include agonists and antagonists. As a method for screening the compound, there is a method of incubating a labeled ligand, the present receptor and a candidate compound, and measuring the binding activity.
【００１３】前述のとおり、本発明のマウスナース細胞
レセプターは、スカベンジャーレセプターとして機能
し、動脈硬化に関与することが予想される。従って、本
発明のペプチドとリガンドとの結合を阻害する化合物
は、動脈硬化の治療に有用であると考えられる。また、
前述のとおり、ナース細胞は、胸腺、皮膚組織、骨髄、
リンパ節、肝臓、脳、リウマチ患者の滑膜、癌の原発巣
及び転移巣に存在することが確認されている。ナース細
胞は、血球系幹細胞の増殖と自己再生能の維持及びリン
パ球の正及び負の選択に関与し、正常な免疫系の発生と
メモリー細胞の維持に関与していると考えられる。よっ
て、ナース細胞膜表面に発現する本レセプターの機能異
常が免疫系の機能異常と自己免疫疾患の発症に関わるこ
とが予想される。そのため、本発明のスクリーニングに
より得られるアゴニストおよびアンタゴニストは、自己
免疫疾患と腫瘍に対する治療に有用であることが考えら
れる。As described above, the mouse nurse cell receptor of the present invention functions as a scavenger receptor and is expected to be involved in arteriosclerosis. Therefore, compounds that inhibit the binding of the peptide to the ligand of the present invention are considered to be useful for treating arteriosclerosis. Also,
As mentioned earlier, nurse cells are derived from thymus, skin tissue, bone marrow,
It has been confirmed to be present in lymph nodes, liver, brain, synovium of rheumatic patients, and primary and metastatic lesions of cancer. Nurse cells are considered to be involved in the proliferation of blood stem cells and maintenance of self-renewal ability and positive and negative selection of lymphocytes, and are involved in the development of a normal immune system and maintenance of memory cells. Therefore, it is expected that the dysfunction of the present receptor expressed on the surface of the nurse cell membrane will contribute to the dysfunction of the immune system and the development of autoimmune diseases. Therefore, the agonists and antagonists obtained by the screening of the present invention are considered to be useful for treating autoimmune diseases and tumors.
【００１４】[0014]
【発明の実施の形態】本発明は、おもにマウスナース細
胞レセプターに関する。以下に本発明タンパク質の調製
工程、抗体の調製工程、リガンドのスクリーニング方
法、アゴニスト及びアンタゴニストのスクリーニング方
法を説明する。本明細書において、特に指示のない限
り、当該分野で公知である遺伝子組換え技術、動物細
胞、昆虫細胞、酵母および大腸菌での組換えタンパク質
の生産技術、発現したタンパク質の分離精製法、分析法
および免疫学的手法が採用される。DETAILED DESCRIPTION OF THE INVENTION The present invention relates primarily to the mouse nurse cell receptor. Hereinafter, the steps of preparing the protein of the present invention, preparing the antibody, screening the ligand, and screening the agonist and antagonist will be described. In the present specification, unless otherwise indicated, unless otherwise indicated, gene recombination techniques, techniques for producing recombinant proteins in animal cells, insect cells, yeast and Escherichia coli, methods for separating and purifying expressed proteins, and methods for analysis And immunological techniques are employed.
【００１５】本発明タンパク質の調製 本発明タンパク質をコードするDNAを含むDNA断片の配列
決定方法を例示する。このDNA断片の配列は、例えば、
マウス細胞株B6TNC（Nanno, M. et al., J. Immunol.,
155, 2918, 1995）などから由来したcDNAから得ること
ができる。そのためには、まず、cDNAから本タンパク質
をコードするcDNAのクローニングを行なうためのプライ
マーが必要である。 （１） マウスナース細胞レセプターをコードするcDNA
断片の単離 ナース細胞特異的に発現する遺伝子を得るため、ナース
細胞（例えば、B6TNC）および非ナース細胞（例えば、L
929細胞）よりmRNAを精製する。ナース細胞mRNAよりfir
st strand cDNAを合成する。得られたFirst strand cDN
Aは一本鎖化する。一方、非ナース細胞mRNAはビオチン
化を行なう。ナース細胞first strand cDNAとビオチン
化非ナース細胞mRNAをインキュベートする。インキュベ
ート後、ストレプトアビジンを添加し、ハイブリダイズ
したcDNAとビオチン化mRNAを抽出する。残ったcDNAはナ
ース細胞特異的cDNAである。このcDNAより二本鎖cDNAを
合成し、プラスミドベクターに挿入する。このプラスミ
ドを大腸菌などに遺伝子導入し、プラスミドDNAを回収
し、cDNA断片の塩基配列を決定する。 Preparation of the Protein of the Present Invention A method for determining the sequence of a DNA fragment containing the DNA encoding the protein of the present invention will be described. The sequence of this DNA fragment is, for example,
Mouse cell line B6TNC (Nanno, M. et al., J. Immunol.,
155, 2918, 1995). For that purpose, first, a primer for cloning a cDNA encoding the present protein from the cDNA is required. (1) cDNA encoding mouse nurse cell receptor
Isolation of Fragments To obtain genes specifically expressed in nurse cells, nurse cells (eg, B6TNC) and non-nurse cells (eg, L
929 cells). Fir than nurse cell mRNA
Synthesize st strand cDNA. First strand cDN obtained
A is single-stranded. On the other hand, non-nurse cell mRNA undergoes biotinylation. Incubate nurse cell first strand cDNA with biotinylated non-nurse cell mRNA. After the incubation, streptavidin is added, and the hybridized cDNA and biotinylated mRNA are extracted. The remaining cDNA is a nurse cell-specific cDNA. A double-stranded cDNA is synthesized from this cDNA and inserted into a plasmid vector. This plasmid is transfected into E. coli or the like, the plasmid DNA is recovered, and the nucleotide sequence of the cDNA fragment is determined.
【００１６】（２）全長マウスB6TNC#10 cDNAの同定 単離されたcDNA断片を元に、ホモロジー検索を行なう。
その結果、ディジョージ症候群遺伝子座に相当するマウ
スゲノムDNA配列と相同性を示した。このマウスゲノムD
NA配列は、アセチルLDLレセプターcDNAと相同性を示
す。そこで、ゲノム配列を元に、プライマーを合成す
る。つぎに、例えばマウス細胞株B6TNC（Nanno, M. et
al., J. Immunol., 155, 2918, 1995）、IT-79 MTNC3
(Itoh, T. et al.(1998) Eur. J. Immunol. 18,821)、Do
i Nurse（Iwagami, S. et al. (1994) J. Immunol. 15
3,2927）、C3H10T1/2clone8 (ATCC No.CCL-226)からTRI
zolTM（LIFE TECHNOLOGIES,INC.社製）を用いてtotal R
NAを調製する。得られたtotal RNAはmRNA purification
Kit（ファルマシア社）を用いて精製し、mRNAを得る。
このmRNAからcDNA末端迅速増幅法（rapid amplificatio
n of cDNA enbs, RACE法）（Frohman et al., Proc. Na
tl.Acad. Sci. USA, 85: 8998-9002, 1988）により5'
側、3'側および5'RACEおよび3'RACEで同定していない領
域のcDNA断片を増幅し、cDNAの全長にわたる塩基配列を
決定する。5'RACEと3'RACEは、5' RACE System for Rap
id Amplification of cDNA Ends（Life Technologies,
Inc.）と合成したプライマーを用いる。5'RACEと3'RACE
で同定していない領域は、Super Script TM Preamplifi
cationSystem for First Strand cDNA Synthesis（Life
Technologies, Inc.）と合成したプライマーを用い
る。得られたそれぞれのDNA断片は、プラスミドベクタ
ーに挿入し、クローニングする。クローニングしたDNA
断片は、ABI Prism TM dRhodamine Terminator Cycle S
equenceing Ready Reaction Kit（Applied Biosystems
社）とABI Prism TM 310 Genetic Analyzer（Applied B
iosystems社）を用いて、塩基配列決定を行なう。決定
した３種類のcDNAクローンの塩基配列に共通する領域を
調べ、これにより、全長cDNAの塩基配列が決定される。(2) Identification of full-length mouse B6TNC # 10 cDNA A homology search is performed based on the isolated cDNA fragment.
As a result, it showed homology to the mouse genomic DNA sequence corresponding to the DiGeorge syndrome locus. This mouse genome D
The NA sequence shows homology to the acetyl LDL receptor cDNA. Therefore, primers are synthesized based on the genome sequence. Next, for example, the mouse cell line B6TNC (Nanno, M. et.
al., J. Immunol., 155, 2918, 1995), IT-79 MTNC3
(Itoh, T. et al. (1998) Eur. J. Immunol. 18,821), Do
i Nurse (Iwagami, S. et al. (1994) J. Immunol. 15
3,2927), C3H10T 1/2 clone8 from (ATCC No.CCL-226) TRI
total R using zol TM (manufactured by LIFE TECHNOLOGIES, INC.)
Prepare NA. The obtained total RNA is mRNA purified
Purify using Kit (Pharmacia) to obtain mRNA.
Rapid amplification of cDNA from this mRNA (rapid amplificatio
n of cDNA enbs, RACE method) (Frohman et al., Proc. Na
5 'according to tl. Acad. Sci. USA, 85: 8998-9002, 1988).
The cDNA fragment in the side, 3 'side, and the region not identified by 5' RACE and 3 'RACE is amplified, and the nucleotide sequence over the full length of the cDNA is determined. 5'RACE and 3'RACE are 5 'RACE System for Rap
id Amplification of cDNA Ends (Life Technologies,
Inc.) and primers synthesized. 5'RACE and 3'RACE
Areas not identified in the above are Super Script TM Preamplifi
cationSystem for First Strand cDNA Synthesis (Life
Technologies, Inc.). Each of the obtained DNA fragments is inserted into a plasmid vector and cloned. Cloned DNA
Fragments, ABI Prism TM dRhodamine Terminator Cycle S
equenceing Ready Reaction Kit (Applied Biosystems
ABI Prism TM 310 Genetic Analyzer (Applied B)
iosystems). The regions common to the base sequences of the determined three types of cDNA clones are examined, and thereby the base sequence of the full-length cDNA is determined.
【００１７】（３）組換え体の発現 得られた全長cDNAを適当な発現ベクターに組み込み、タ
ンパク質を発現するための発現ベクターとする。適切な
発現ベクターとしては、例えば、細菌についてはpRSE
T、pET、pGEMEX、pKK233-2など、酵母についてはpYES
2、昆虫細胞についてはpVL1393、pFastBac1、動物細胞
についてはpEF-BOS、pSRa、pDR2などが挙げられる。こ
の発現ベクターを適当な宿主細胞に導入して、形質転換
体を作製する。宿主細胞としては、細菌、酵母、昆虫細
胞、または動物細胞が挙げられる。大腸菌、酵母では、
強力なプロモーターの下流にタンパク質をコードする遺
伝子を挿入した発現ベクターで形質転換し、これら形質
転換体を培養することによりタンパク質を産生できる。
昆虫細胞、動物細胞では、タンパク質の遺伝子を強力な
プロモーターの下流に挿入し、効果的な選択マーカーと
共に動物細胞に導入し、薬剤に対する耐性により細胞を
選択し、高発現の細胞株を樹立し得る。また、タンパク
質前駆体の遺伝子をウイルスまたはレトロウイルスに組
み込み、この組換えウイルスを動物細胞に感染させるこ
とにより、発現し得る。これら形質転換体を培養するこ
とにより、タンパク質が産生され得る。得られたタンパ
ク質の精製は、当業者に周知の方法、例えば、アフィニ
ティーカラム、イオン交換クロマトグラフィー、ゲル濾
過クロマトグラフィー、逆相クロマトグラフィー、疎水
クルマトグラフィーなどを組み合わせて行なうことがで
きる（Imai et al., J. Biol. Chem., 271: 21514-2152
1, 1996）。(3) Expression of Recombinant The obtained full-length cDNA is incorporated into an appropriate expression vector to prepare an expression vector for expressing a protein. Suitable expression vectors include, for example, pRSE for bacteria.
PYES for yeast, such as T, pET, pGEMEX, pKK233-2
2. Insect cells include pVL1393 and pFastBac1, and animal cells include pEF-BOS, pSRa and pDR2. This expression vector is introduced into a suitable host cell to prepare a transformant. Host cells include bacteria, yeast, insect cells, or animal cells. In E. coli and yeast,
A protein can be produced by transforming with an expression vector having a gene encoding the protein inserted downstream of a strong promoter, and culturing these transformants.
In insect cells and animal cells, a protein gene can be inserted downstream of a strong promoter, introduced into animal cells together with an effective selectable marker, cells can be selected based on drug resistance, and high-expressing cell lines can be established. . Alternatively, it can be expressed by incorporating the protein precursor gene into a virus or retrovirus and infecting animal cells with the recombinant virus. By culturing these transformants, proteins can be produced. The obtained protein can be purified by a method known to those skilled in the art, for example, by a combination of affinity column, ion exchange chromatography, gel filtration chromatography, reverse phase chromatography, hydrophobic chromatography and the like (Imai et al.). al., J. Biol. Chem., 271: 21514-2152
1, 1996).
【００１８】（４）変異体の作成 アミノ酸配列は、任意のアミノ酸配列を欠失させ、所望
のアミノ酸、ないしはアミノ酸配列を導入することによ
って置換される。アミノ酸配列の置換処理には、プロテ
インエンジニアリングとして知られる方法が広く利用で
きるが、例えば、Site-diredted deletion（部位指定削
除）法（Nucl. Acids Res., 11, 1645,1983）、Site-sp
ecific mutagenesis（部位特異的変異）法（Zoller, M.
J. etal., Methods in Enzymol., 100, 468, 1983、Ku
nkel. T.A. et al., Methods in Enzymol., 154, 367-3
82, 1987）、PCR突然変異生成法、制限酵素処理と合成
遺伝子の利用による方法等がある。部位特異的変異法で
あれば、例えばMolecuar Cloning: A Laboratory Manua
l第２版第１−３巻 Sambrook, J.ら著、Cold Spring Ha
rber Laboratory Press出版New York 1989年に記載の部
位特異的変異誘発法やPCR法などの方法を用い、本発明
のDNA配列に変異を導入する。これら方法により変異が
導入されたDNA配列は、適当なベクターおよび宿主系を
用いて、例えばMolecuar Cloning: A Laboratory Manua
l第２版第１−３巻 Sambrook, J.ら著、Cold Spring Ha
rber Laboratory Press出版New York 1989年に記載の方
法により、遺伝子工学的に発現させればよい。例えば、
Mutan TM -SuperExpress Km、Mutan TM -K（宝酒造社
製）、Quik Change Site- Directed Mutagenesis Kit
（Stratagene社製）といったキットが使用できる。(4) Construction of Mutant The amino acid sequence is substituted by deleting any amino acid sequence and introducing a desired amino acid or amino acid sequence. For the amino acid sequence substitution treatment, a method known as protein engineering can be widely used. For example, a site-diredted deletion method (Nucl. Acids Res., 11, 1645, 1983), Site-sp
ecific mutagenesis (site-directed mutagenesis) (Zoller, M .;
J. etal., Methods in Enzymol., 100, 468, 1983, Ku
nkel. TA et al., Methods in Enzymol., 154, 367-3
82, 1987), a PCR mutagenesis method, a method using restriction enzyme treatment and the use of a synthetic gene, and the like. For site-directed mutagenesis, for example, Molecuar Cloning: A Laboratory Manua
lSecond Edition, Volume 1-3, by Sambrook, J. et al., Cold Spring Ha
A mutation is introduced into the DNA sequence of the present invention using a method such as site-directed mutagenesis or PCR described in New York 1989, published by rber Laboratory Press. A DNA sequence into which a mutation has been introduced by these methods can be used, for example, by using an appropriate vector and host system, for example, Molecular Cloning: A Laboratory Manua.
lSecond Edition, Volume 1-3, by Sambrook, J. et al., Cold Spring Ha
Expression may be performed by genetic engineering according to the method described in New York 1989, published by rber Laboratory Press. For example,
Mutan TM -SuperExpress Km, Mutan TM -K (Takara Shuzo), Quik Change Site- Directed Mutagenesis Kit
(Stratagene) can be used.
【００１９】一般に、部位特異的変異法は、まず、タン
パク質をコードするDNA配列をその配列中に含む一本鎖
ベクターを得ることによって実施することができる。所
望の突然変異した配列を持つオリゴヌクレオチドプライ
マーを、一般的には合成によって、例えばクレア等（Cr
ea, R. et al., Proc. Natl. Acsd. Sci. U.S.A., 75,
5765, 1978）の方法によって製造する。次ぎに、このプ
ライマーを一本鎖の本レセプター配列含有ベクターとア
ニーリングし、大腸菌ポリメラーゼIクレノウフラグメ
ントのようなDNA重合酵素を作用させて、突然変異含有
鎖の合成を完成する。このようにして、第一の鎖は元の
非突然変異配列をコードしており、第二の鎖は所望の突
然変異を有しているヘテロ二本鎖が形成される。次い
で、この二本鎖ベクターを用いて、適当な細菌、または
細胞を形質転換し、32P−標識突然変異生成プライマー
から成る放射性プローブへのハイブリダイゼーションを
介してクローンを選択する（Wallace, R.B., Nucleic A
cids Res., 9, 3647, 1981）。選択されたクローンに
は、突然変異した配列を有する組換えベクターを含んで
いる。このようなクローンを選択した後、突然変異した
本レセプターの領域を形質転換に使用される型の発現ベ
クターに入れることができる。In general, the site-directed mutagenesis method can be carried out by first obtaining a single-stranded vector containing a DNA sequence encoding a protein in the sequence. An oligonucleotide primer having the desired mutated sequence is generally synthesized, for example, by Clair et al.
ea, R. et al., Proc. Natl. Acsd. Sci. USA, 75,
5765, 1978). Next, this primer is annealed with a single-stranded vector containing the present receptor sequence, and a DNA polymerase such as Escherichia coli polymerase I Klenow fragment is allowed to act on the primer to complete the synthesis of the mutation-containing strand. In this way, the first strand encodes the original non-mutated sequence and the second strand forms a heteroduplex with the desired mutation. The double-stranded vector is then used to transform appropriate bacteria, or cells, and clones are selected via hybridization to a radioactive probe consisting of 32 P-labeled mutagenic primers (Wallace, RB, Nucleic A
cids Res., 9, 3647, 1981). The selected clone contains the recombinant vector with the mutated sequence. After selecting such a clone, the mutated region of the receptor can be placed in an expression vector of the type used for transformation.
【００２０】本発明タンパク質に対 する抗体の調製 本発明のレセプターに対する抗体は、以下の方法により
作製される。 （１）ポリクローナル抗体の作製 推定されるアミノ酸配列の一部に基づいて通常のペプチ
ド合成機で合成した合成ペプチドや、本レセプターを発
現するベクターで形質転換した細菌、酵母、昆虫細胞、
動物細胞、などにより産生されたタンパク質を通常のタ
ンパク化学的方法で精製し、これらを免疫原とする。こ
の免疫原を用いて、Antibodies; A Laboratory Manual,
Lane,H.D.ら編、Cold Spring Harber Laboratory Pres
s出版 New York 1989年などに記載の方法に従って、適
切な方法で動物を免疫することにより、抗原となるタン
パク質を特異的に認識するポリクローナル抗体を容易に
作製し、精製することができる。ラット、ハムスター、
ウサギなどの動物を免疫し、その血清由来のポリクロー
ナル抗体を作製すればよい。[0020] Antibodies to the receptor of the present invention protein antibodies against preparing the present invention is manufactured by the following method. (1) Preparation of polyclonal antibody Bacteria, yeast, insect cells transformed with a synthetic peptide synthesized by a usual peptide synthesizer based on a part of the deduced amino acid sequence, or a vector expressing the present receptor,
Proteins produced by animal cells and the like are purified by ordinary protein chemical methods, and these are used as immunogens. Using this immunogen, Antibodies; A Laboratory Manual,
Lane, HD et al., Cold Spring Harber Laboratory Pres
By immunizing an animal with an appropriate method according to the method described in New York 1989 or the like, a polyclonal antibody that specifically recognizes a protein serving as an antigen can be easily prepared and purified. Rats, hamsters,
An animal such as a rabbit may be immunized to prepare a polyclonal antibody derived from the serum.
【００２１】（２）モノクローナル抗体 前述の免疫原で免疫したハムスターやラットの脾臓また
はリンパ節からリンパ球を取りだし、ミエローマ細胞と
融合させてKohlerとMilsteinの方法［Nature,256, 495-
497(1975)］またはその改良法であるUedaらの方法［Pro
c.Natl.Acad.Sci.USA, 79:4386-4390, 1982)］に従って
ハイブリドーマを作製した後、該ハイブリドーマから単
クローン抗体を産生させ得る。例えば以下の工程により
本レセプターのモノクルーナル抗体を得ることができ
る： （ａ） タンパク質によるハムスターの免疫、（ｂ）
免疫ハムスターの脾臓の除去および脾臓細胞の分離、
（ｃ） 分離された脾臓細胞とハムスターミエローマ細
胞との融合促進剤（例えばポリエチレングリコール）の
存在下での上記のKohlerらに記載の方法による融合、
（ｄ） 未融合ミエローマ細胞が成長しない選択培地で
の得られたハイブリドーマ細胞の培養、（ｅ） 酵素結
合免疫吸着検定 (ELISA)、ウェスターンブロットなどの
方法による所望の抗体を生産するハイブリドーマ細胞の
選択および限定希釈法等によるクローニング、（ｆ）
モノクローナル抗体を生産するハイブリドーマ細胞を培
養し、モノクルーナル抗体を収穫する。(2) Monoclonal antibody Lymphocytes are extracted from the spleen or lymph node of a hamster or rat immunized with the above-mentioned immunogen, fused with myeloma cells, and subjected to the method of Kohler and Milstein [Nature, 256, 495-
497 (1975)] or a modified method of Ueda et al. [Pro
c. Natl. Acad. Sci. USA, 79: 4386-4390, 1982)], and then a monoclonal antibody can be produced from the hybridoma. For example, a monoclonal antibody of the receptor can be obtained by the following steps: (a) immunization of a hamster with a protein, (b)
Removal of the spleen and isolation of the spleen cells of the immune hamster,
(C) fusion of the isolated spleen cells and hamster myeloma cells in the presence of a fusion promoter (eg, polyethylene glycol) by the method described in Kohler et al.
(D) culturing the obtained hybridoma cells in a selection medium in which unfused myeloma cells do not grow, (e) culturing hybridoma cells producing the desired antibody by a method such as enzyme-linked immunosorbent assay (ELISA), Cloning by selection and limited dilution method, etc., (f)
The hybridoma cells producing the monoclonal antibody are cultured, and the monoclonal antibody is harvested.
【００２２】リガンドのスクリーニング方法 リガンドのスクリーニング方法としては、例えば、放射
性アイソトープ、ペルオキシダーゼやアルカリフォスフ
ァターゼのような酵素あるいは蛍光色素などで標識した
一定量のリガンド候補物質に、本レセプターを発現した
細胞または細胞膜画分を加え、結合試験を行わせる方法
が例示できる。細胞等と結合した標識リガンド候補物質
と細胞等に結合していない標識リガンド候補物質とを適
当な方法で分離し、細胞等と結合した標識リガンド候補
物質の放射能量、酵素活性または蛍光強度を測定する。
これにより、標識リガンド候補物質が、本レセプターの
リガンドとなりうるかどうかを判定することが出来る。
本発明のレセプターのリガンドとしては、分泌型ペプ
チド、細胞膜タンパク質、脂肪や核酸などの生体内
代謝物、などが考えられる。本レセプターは、アセチル
LDLレセプターと相同性を示ため、アセチルLDLが本レセ
プターのリガンドであることが期待できる。 Ligands can be screened by, for example, a cell or cell membrane expressing the receptor in a certain amount of a candidate ligand labeled with a radioisotope, an enzyme such as peroxidase or alkaline phosphatase, or a fluorescent dye. A method of adding a fraction and performing a binding test can be exemplified. Separate the labeled ligand candidate substance bound to cells etc. from the labeled ligand candidate substance not bound to cells etc. by an appropriate method and measure the radioactivity, enzyme activity or fluorescence intensity of the labeled ligand candidate substance bound to cells etc. I do.
Thereby, it can be determined whether or not the labeled ligand candidate substance can be a ligand of the present receptor.
As the ligand of the receptor of the present invention, secretory peptides, cell membrane proteins, in vivo metabolites such as fats and nucleic acids, and the like can be considered. This receptor is acetyl
Since it shows homology to the LDL receptor, it can be expected that acetyl LDL is a ligand for this receptor.
【００２３】アゴニスト及びアンタゴニストのスクリー
ニング方法 本レセプターのリガンドが特定された後、アゴニスト及
びアンタゴニストのスクリーニングは以下の方法により
行なうことができる。排除型の結合実験の場合、一定量
の本レセプターを発現する細胞に一定量の標識リガンド
と各種の濃度の非標識のアゴニスト及びアンタゴニスト
候補化合物を加えて反応させる。洗浄後、細胞を50μl
の1% Triton X-100を含む10 mM Tris-HCl (pH 8.0)など
で溶解し、上清中の放射能量、酵素活性または蛍光強度
を測定する。一定濃度の標識リガンドに対し非標識のア
ゴニスト及びアンタゴニスト候補化合物の濃度を変化さ
せたときの標識リガンドの本レセプター発現細胞への結
合量の変化を調べる。これにより、アゴニスト及びアン
タゴニストの結合阻害活性を検討することができる。飽
和型の結合実験の場合、一定量の本レセプターを発現す
る細胞に各種濃度の標識リガンドと一定量の非標識のア
ゴニスト及びアンタゴニスト候補化合物を加えて反応さ
せる。上記と同様に、洗浄後、細胞を50μlの1% Triton
X-100を含む10 mM Tris-HCl (pH 8.0)などで溶解し、
遠心後、上清中の放射能量、酵素活性または蛍光強度を
測定する。一定濃度の非標識アゴニスト及びアンタゴニ
スト候補化合物に対し標識リガンドの濃度を変化させた
ときの標識リガンドの本レセプター発現細胞への結合量
の変化を調べる。Screening of agonists and antagonists
After ligand training method the receptor has been identified, screening of agonists and antagonists can be performed by the following method. In the case of the exclusion-type binding experiment, a fixed amount of a labeled ligand and various concentrations of unlabeled candidate agonist and antagonist compounds are reacted with a fixed amount of cells expressing the present receptor. After washing, 50 μl of cells
And then dissolve in 10 mM Tris-HCl (pH 8.0) containing 1% Triton X-100, and measure the amount of radioactivity, enzyme activity or fluorescence intensity in the supernatant. The change in the binding amount of the labeled ligand to the present receptor-expressing cell when the concentration of the unlabeled agonist and antagonist candidate compound is changed with respect to the fixed concentration of the labeled ligand is examined. Thereby, the binding inhibitory activity of the agonist and the antagonist can be examined. In the case of a saturation type binding experiment, various concentrations of a labeled ligand and a fixed amount of unlabeled agonist and antagonist candidate compounds are reacted with cells expressing a certain amount of the present receptor. After washing as above, cells are washed with 50 μl of 1% Triton
Dissolve in 10 mM Tris-HCl (pH 8.0) containing X-100, etc.
After centrifugation, the amount of radioactivity, enzyme activity or fluorescence intensity in the supernatant is measured. A change in the amount of the labeled ligand bound to the present receptor-expressing cells when the concentration of the labeled ligand is changed with respect to a fixed concentration of the unlabeled agonist and antagonist candidate compound is examined.
【００２４】[0024]
【実施例】本発明を以下の実施例によりさらに説明す
る。本発明の各工程において用いた一般的な実験手法
（DNAのアガロースゲル電気泳動、ライゲーション反
応、大腸菌の形質転換、DNAの制限酵素による消化、ノ
ザン解析等）はCurrent Protocols in Molecular Biolo
gy (F. M. Ausubel et al. Ed., John Wiley & Sons. I
nc.)によった。The present invention is further described by the following examples. General experimental methods (eg, agarose gel electrophoresis of DNA, ligation reaction, transformation of E. coli, digestion of DNA with restriction enzymes, Northern analysis, etc.) used in each step of the present invention are described in Current Protocols in Molecular Biolo.
gy (FM Ausubel et al. Ed., John Wiley & Sons. I
nc.)
【００２５】実施例１ マウスB6TNC#10 c DNAの単離 （１）ナース細胞特異的遺伝子の単離 マウス細胞株B6TNC（Nanno, M. et al. (1995) J. Immu
nol. 155,2918）および、L929細胞（ATCC No.CCL-1）よ
り、AGPC法（Analytical Biochemistry （1987） 162,
156-159）によりtotal RNAを調製し、PolyATtract syst
em 1000（Promega社製）を用いてmRNAを精製した。B6TN
C mRNAからfirst strand cDNAを合成するためにNot I p
rimer-adapter用いた。 Not I primer-adapter 5'-pGACTAGTTCTAGATCGCGAGCGGCC
GCCC（T）15-3'(配列番号３) Example 1 Isolation of Mouse B6TNC # 10 cDNA (1) Isolation of Nurse Cell-Specific Gene Mouse cell line B6TNC (Nanno, M. et al. (1995) J. Immu
nol. 155, 2918) and L929 cells (ATCC No. CCL-1) by the AGPC method (Analytical Biochemistry (1987) 162,
156-159) to prepare total RNA and use PolyATtract syst
mRNA was purified using em1000 (Promega). B6TN
Not I p to synthesize first strand cDNA from C mRNA
rimer-adapter was used. Not I primer-adapter 5'-pGACTAGTTCTAGATCGCGAGCGGCC
GCCC (T) 15 -3 '(SEQ ID NO: 3)
【００２６】B6TNC mRNA 5 μgにNot I primer-adapter
をアニーリング後、MMLV RTase （LIFE TECHNOLOGIES,I
NC.社製SuperScript Plasumid System）を用いてInstru
ction Manualに従いfirst strand cDNAを合成した。合
成したfirst strand cDNAをフェノール/クロロホルム抽
出、エタノール沈殿・乾燥後50μlのTEに溶解した。こ
れを終濃度0.3 N NaOH、0.025 M EDTAで25℃、一晩処理
し、1本鎖化をおこなった。終濃度100 mM Tris-HCl （p
H8.0）、0.12 N HClなるようにし、中和をおこない、エ
タノール沈殿・乾燥後40μlのDEPC処理水に溶解した。1
本鎖化をおこなったfirst strand cDNAの３'端をグアニ
ン残基の付加をTakara Manualの条件下terminal deoxyn
ucleotidyl transferase (宝酒造社製) 0.3u/μlの濃度
で30℃、30分反応後、終濃度6mMのEDTAを添加した。以
下定法に従いフェノール/クロロホルム抽出、エタノー
ル沈殿・乾燥後20μlのDEPC処理水に溶解した。Not I primer-adapter was added to 5 μg of B6TNC mRNA.
MMLV RTase (LIFE TECHNOLOGIES, I
Instru using NC. SuperScript Plasumid System)
First strand cDNA was synthesized according to the ction Manual. The synthesized first strand cDNA was extracted with phenol / chloroform, precipitated with ethanol, dried, and then dissolved in 50 μl of TE. This was treated overnight at 25 ° C. with a final concentration of 0.3 N NaOH and 0.025 M EDTA to form a single strand. Final concentration 100 mM Tris-HCl (p
H8.0) and 0.12 N HCl, neutralized, ethanol precipitated, dried and dissolved in 40 μl of DEPC-treated water. 1
Addition of a guanine residue to the 3 'end of the first strand cDNA that has been converted to a normal strand is performed using terminal deoxyn under the conditions of Takara Manual.
ucleotidyl transferase (Takara Shuzo) at a concentration of 0.3 u / μl at 30 ° C. for 30 minutes, followed by addition of EDTA at a final concentration of 6 mM. Following phenol / chloroform extraction, ethanol precipitation and drying according to a conventional method, the resultant was dissolved in 20 μl of DEPC-treated water.
【００２７】一方、L929 mRNAのビオチン化をBresatec
社Photobiotin Labelling Kit Manualに従いおこなっ
た。L929 mRNA 15 μg (1 μg/μl)とフォトビオチン酢
酸塩15μg (1 mg/ml) (Bresatec社製、Sigma社製) を加
え、BHRF-300水銀ランプ下10 cmで20分間照射後、2-ブ
タノールで抽出し、エタノール沈殿、８０% エタノール
洗浄、乾燥しD.D.WでmRNA終濃度(1μg/μl)に溶解し
た。さらに、このビオチン化操作を2回（計3回）おこな
った後、D.D.W.でmRNA終濃度(1μg/μl)に溶解した。On the other hand, biotinylation of L929 mRNA
Labeling was performed according to Photobiotin Labelling Kit Manual. After adding 15 μg (1 μg / μl) of L929 mRNA and 15 μg (1 mg / ml) of photobiotin acetate (manufactured by Bresatec, Sigma) for 20 minutes at 10 cm under a BHRF-300 mercury lamp, It was extracted with butanol, precipitated with ethanol, washed with 80% ethanol, dried, and dissolved in DDW to a final mRNA concentration (1 μg / μl). After this biotinylation operation was performed twice (three times in total), the resultant was dissolved in DDW to a final mRNA concentration (1 μg / μl).
【００２８】1本鎖化したB6TNC first strand cDNA（0.
5〜1.5μｇ）とビオチン化L929 mRNA（15μｇ）を合わ
せ、ポリエチレングリコール沈殿、エタノール洗浄、乾
燥後、hybridization buffer(終濃度50 mM Hepes pH 7.
6、2 mM EDTA、0.5 M NaCl、0.2％ SDS)20μlに溶解、
ミネラルオイルを一滴滴下し、95℃、1分間処理し、65
℃、50時間インキュベートした。クロロホルム抽出後、
水層（50μl）に10μgのstreptavidin (1 mg/ml)を加
え、室温、5分間放置し、等量のフェノールで抽出操作
をおこなう。この操作によりビオチン化mRNAとハイブリ
ダイズしたcDNAは有機層および中間層に抽出される。こ
の操作を計３回おこなった。次に、水層（250μl）をエ
ーテル抽出、エタノール沈殿、８０% エタノール洗浄、
乾燥後、20μlのD.D.W.に溶解し、subtracted single s
trand cDNAサンプルとした。The single-stranded B6TNC first strand cDNA (0.
5 to 1.5 μg) and biotinylated L929 mRNA (15 μg) are combined, precipitated with polyethylene glycol, washed with ethanol, dried, and then subjected to hybridization buffer (final concentration 50 mM Hepes pH 7.
6, 2 mM EDTA, 0.5 M NaCl, 0.2% SDS) dissolved in 20 μl,
Add a drop of mineral oil and treat at 95 ° C for 1 minute.
Incubated at 50 ° C for 50 hours. After chloroform extraction
10 μg of streptavidin (1 mg / ml) is added to the aqueous layer (50 μl), left at room temperature for 5 minutes, and extracted with an equal amount of phenol. By this operation, the cDNA hybridized with the biotinylated mRNA is extracted into the organic layer and the intermediate layer. This operation was performed three times in total. Next, the aqueous layer (250 μl) was extracted with ether, precipitated with ethanol, washed with 80% ethanol,
After drying, dissolve in 20 μl of DDW, and
A trand cDNA sample was used.
【００２９】次に、LIFE TECHNOLOGIES Instruction Ma
nualに従い２本鎖cDNAを合成した。subtracted single
strand cDNAサンプルとOligoｄ（pＧ）12-18primer（終
濃度50ng/μl）をアニーリングし、大腸菌 DNA Polymer
ase を用いて２本鎖cDNAを合成後、T４DNA Polymerase
で末端修復をおこない、Not Iで切断した。このサンプ
ルをプラスミドベクターpCDL SRα296 (Takebe, Y. et
al. (1988) Mol. Cell.Biol. 8, 466)のSma I、Not I部
位に挿入した。このプラスミドを大腸菌 JM109に遺伝子
導入し、プラスミドDNAを回収し、塩基配列の決定をお
こなった。決定した塩基配列をGenBankに対してホモロ
ジー検索を行ない、新規遺伝子と考えられるクローンに
ついて、B6TNC細胞での発現特異性を調べるために、B6T
NC細胞およびL929細胞におけるmRNAの発現をノザンブロ
ット法で調べた。その結果、B6TNC細胞に発現し、L929
細胞に発現していないB6TNC細胞特異的遺伝子マウスB6T
NC#10 クローン遺伝子断片を得ることができた。Next, LIFE TECHNOLOGIES Instruction Ma
A double-stranded cDNA was synthesized according to the manual. subtracted single
Annealed strand cDNA sample and Oligod (pG) 12-18 primer (final concentration 50 ng / μl)
After synthesizing double-stranded cDNA using ase, T4 DNA Polymerase
Was used to perform terminal repair, and cut with NotI. This sample was transferred to the plasmid vector pCDL SRα296 (Takebe, Y. et.
al. (1988) Mol. Cell. Biol. 8, 466) at the SmaI and NotI sites. This plasmid was transfected into Escherichia coli JM109, the plasmid DNA was recovered, and the nucleotide sequence was determined. A homology search was performed on the determined base sequence against GenBank, and to determine the expression specificity of B6TNC cells for clones considered as novel genes, B6T
MRNA expression in NC cells and L929 cells was examined by Northern blotting. As a result, it was expressed on B6TNC cells and L929
B6TNC cell-specific gene mouse B6T not expressed in cells
An NC # 10 clone gene fragment was obtained.
【００３０】（２）全長マウスB6TNC#10 cDNAの同定 単離したマウスB6TNC#10 cDNA断片をもとに遺伝子解析
プログラムBLAST(インターネット・アドレス http://ww
w.ncbi.nlm.gov/BLAST)で検索し、ヒトDiGeorge症候群
遺伝子座に相当するマウスゲノムDNA配列（アクセッシ
ョン ナンバー AC000096）の一部と相同性を示した。こ
のマウスゲノムDNA配列をもとに以下のプライマーを合
成した。 B6RACE 5'-CTGTCTGTGGATCG-3' (配列番号４) B6K36 5'-CCTCGTTTTCTGAGCACGTGGAATTGCCTTCG-3' (配列番号５) B6K311 5'-AGCCAGAGCAGCAGCAGCAGTC-3' (配列番号６) B6K56 5'-TGCGCGACAAGACTCGCAGC-3' (配列番号７) B6N10-51 5'-AAGGCATTTCATTGGCCCCCAA-3' (配列番号８) B6K58 5'-ACTCCGCTTCCGGCCGCCCTTG-3' (配列番号９) B6N10-33 5'-AGCTTTGGCCTGCTATGAGGA-3' (配列番号１０) また、マウスB6TNC#10遺伝子の5'RACE、3'RACEに必要な
プライマーの配列を示す。 3'RACE Adapter Primer （3'RACE AP） 5'-GGCCACGCGTCGACTAGTAC(T)17-3' (配列番号１１) Abridged Universal Amplification Primer (AUAP) 5'-GGCCACGCGTCGACTAGTAC-3' (配列番号１２)(2) Identification of full-length mouse B6TNC # 10 cDNA Gene analysis program BLAST (Internet address http: // ww
w.ncbi.nlm.gov/BLAST) and showed homology to a part of the mouse genomic DNA sequence corresponding to the human DiGeorge syndrome locus (accession number AC000096). The following primers were synthesized based on the mouse genomic DNA sequence. B6RACE 5'-CTGTCTGTGGATCG-3 '(SEQ ID NO: 4) B6K36 5'-CCTCGTTTTCTGAGCACGTGGAATTGCCTTCG-3' (SEQ ID NO: 5) B6K311 5'-AGCCAGAGCAGCAGCAGCAGTC-3 '(SEQ ID NO: 6) B6K56 5'-TGCGCGACAAGACTCGCAGC-3' 7) B6N10-51 5'-AAGGCATTTCATTGGCCCCCAA-3 '(SEQ ID NO: 8) B6K58 5'-ACTCCGCTTCCGGCCGCCCTTG-3' (SEQ ID NO: 9) B6N10-33 5'-AGCTTTGGCCTGCTATGAGGA-3 '(SEQ ID NO: 10) In addition, mouse B6TNC # The primer sequences required for 5'RACE and 3'RACE of 10 genes are shown. 3'RACE Adapter Primer (3'RACE AP) 5'-GGCCACGCGTCGACTAGTAC (T) 17 -3 '(SEQ ID NO: 11) Abridged Universal Amplification Primer (AUAP) 5'-GGCCACGCGTCGACTAGTAC-3' (SEQ ID NO: 12)
【００３１】全長マウスB6TNC#10 cDNAを単離するため
に、まず、B6TNC細胞mRNAを調製した。マウス細胞株B6T
NC細胞5X 106個当たり１mlのTRIzolTM（LIFE TECHNOLOG
IES,INC.社製）を加え、細胞を溶解した。クロロホルム
0.2 ml添加し、攪拌後、12,000rpm 10分間遠心した。上
清を回収し、0.5 mlのイソプロパノールを添加し攪拌
後、12,000 rpm 10分間遠心し、75%エタノール洗浄後、
風乾し、沈殿を注射用水（扶桑薬品工業社製）で溶解
し、 B6TNC細胞total RNAサンフ゜ルとした。B6TNC細胞total
RNAよりmRNA Purification Kit （ファルマシア社製）
を用いてB6TNC細胞mRNAを精製した。To isolate full-length mouse B6TNC # 10 cDNA, B6TNC cell mRNA was first prepared. Mouse cell line B6T
NC cells 5X 10 6 per 1ml TRIzol TM (LIFE TECHNOLOG
(IES, INC.) Was added to lyse the cells. Chloroform
After adding 0.2 ml and stirring, the mixture was centrifuged at 12,000 rpm for 10 minutes. Collect the supernatant, add 0.5 ml of isopropanol, stir, centrifuge at 12,000 rpm for 10 minutes, wash with 75% ethanol,
The mixture was air-dried, and the precipitate was dissolved in water for injection (Fuso Pharmaceutical Co., Ltd.) to obtain a B6TNC cell total RNA sample. B6TNC cell total
RNA to mRNA Purification Kit (Pharmacia)
Was used to purify B6TNC cell mRNA.
【００３２】次に、マウスB6TNC#10 cDNAの5'RACEをお
こなった。genomic DNAを除去するために、Deoxyribonu
clease I, Amplification Grade（LIFE TECHNOLOGIES,I
NC.社製）を用いた。 B6TNC細胞mRNA 1.5μg（1.5μl）
、10X DNase I Buffer１μl、RNase free DNase I (1
U/μl) 1μl、D.D.W. 6.5μlで室温15分間 インキュベ
ートした。25 mM EDTA (pH 8.0)を1μl添加し、65 ℃、
15分間インキュベート後、氷上に5分間、放置した。B6T
NC細胞cDNAの合成するために、５’RACE System for Ra
pid Amplification of cDNA Ends，Version 2.0 (LIFE
TECHNOLOGIES,INC.社製）を用いた。DNase I処理したB6
TNC細胞cDNA 0.5μg(5 μl) にD.D.W. 15μl、1μM B6R
ACE primer（配列番号４） 5μlを添加し、70 ℃、10分
間インキュベートし、50℃に保温する（溶液Ａ）。一
方、10 X PCR buffer 5μl、25 mMMgCl2 5μl、10mM d
NTPs 2.5μl、 0.1 M DTT 5μl、D.D.W. 6.5μlを50℃
で保温する（溶液Ｂ）。溶液Ａと溶液ＢとSUPERSCRIPT
TM II (200 units/μl) 1μl混ぜ合わせ50℃、50分間
インキュベートした。70℃、15分間処理後、氷上に5分
間放置した。RNase MIX 1 μl添加し37℃、30分間イン
キュベートした。225μlの6M NaIを添加し、GLASSMAX D
NA Isolation Spin Cartridge Systemを用い、cDNAを50
μlのD.D.W.で溶出して精製した。精製したcDNA 10μl
に、D.D.W. 4μl、5X Tailing Buffer 5μl、1 mM dATP
5μlを添加し、94℃、2分間処理後、氷上に1分間放置
した。terminal deoxynucleotidyl transferaseを1μl
添加し、37℃、10分間インキュベートした。65℃、10分
間処理後、氷上に放置し、これを5' RACE用の鋳型cDNA
とした。Next, 5 ′ RACE of mouse B6TNC # 10 cDNA was performed. Deoxyribonu to remove genomic DNA
clease I, Amplification Grade (LIFE TECHNOLOGIES, I
NC.) Was used. B6TNC cell mRNA 1.5μg (1.5μl)
, 10X DNase I Buffer 1μl, RNase free DNase I (1
(U / μl) 1 μl and 6.5 μl of DDW were incubated at room temperature for 15 minutes. Add 1 μl of 25 mM EDTA (pH 8.0),
After incubation for 15 minutes, the plate was left on ice for 5 minutes. B6T
5'RACE System for Ra for synthesis of NC cell cDNA
pid Amplification of cDNA Ends, Version 2.0 (LIFE
TECHNOLOGIES, INC.). B6 treated with DNase I
0.5 μg (5 μl) of TNC cell cDNA to 15 μl of DDW, 1 μM B6R
5 μl of ACE primer (SEQ ID NO: 4) is added, incubated at 70 ° C. for 10 minutes, and kept at 50 ° C. (solution A). On the other hand, 5 μl of 10X PCR buffer, 5 μl of 25 mM MgCl 2 , 10 mM d
2.5 μl of NTPs, 5 μl of 0.1 M DTT, 6.5 μl of DDW at 50 ° C
(Solution B). Solution A, Solution B and SUPERCRIPT
1 μl of TM II (200 units / μl) was mixed and incubated at 50 ° C. for 50 minutes. After treatment at 70 ° C. for 15 minutes, the mixture was left on ice for 5 minutes. 1 μl of RNase MIX was added, and the mixture was incubated at 37 ° C. for 30 minutes. Add 225 μl of 6 M NaI and add GLASSMAX D
Use the NA Isolation Spin Cartridge System to transfer 50
Purified by elution with μl DDW. 10 μl of purified cDNA
Into, 4 μl of DDW, 5 μl of 5X Tailing Buffer, 1 mM dATP
5 μl was added, the mixture was treated at 94 ° C. for 2 minutes, and then left on ice for 1 minute. 1 μl of terminal deoxynucleotidyl transferase
Was added and incubated at 37 ° C. for 10 minutes. After treatment at 65 ° C for 10 minutes, leave on ice, and use this as the template cDNA for 5 'RACE.
And
【００３３】Polymerase Chain Reaction（PCR）はTaKa
Ra LA TaqTM with GC Buffer（宝酒造社製）を用いて
おこなった。上記の鋳型cDNA 2.5μl、2X GC buffer 1
2.5μl、2.5 mM dNTPs 4μl、10μM 3'RACE-AP primer
(配列番号１１) 1μl、10 μMB6K36 primer (配列番号
５) 1μl、TaKaRa LA Taq (5 U/μl) 0.25μl、D.D.W.
3.75μlを混ぜた溶液を94℃、2分間を1回、94℃、1分
間、55℃、1分間、72℃、2分間を30回、72℃、2分間を1
回で1回目のPCRをおこなった。1回目のPCR反応液を50倍
希釈したものを2.5μl、2X GC buffer 12.5μl、2.5 mM
dNTPs 4μl、10μM AUAP primer (配列番号１２) 1μ
l、10μM B6K311 primer (配列番号６) 1μl、TaKaRa L
A Taq (5 U/μl) 0.25μl、D.D.W. 3.75μlを混ぜて、9
4℃、2分間を1回、94℃、1分間、55℃、1分間、72℃、2
分間を20回、72℃、2分間を1回で2回目のPCRをおこなっ
た。2回目のPCR反応液をフェノール／クロロホルム抽
出、エタノール沈澱後、3％ 低融点アガルース電気泳動
により確認した約230 bpのDNA断片をWizard TM PCR Pre
ps DNA Purification System (Promega社製) を用いて
回収した。このDNA断片をプラスミドベクター pGEM-T-E
asy （Promega社製）に挿入し、塩基配列の決定をABI P
RISMTM dRhodamine Terminator Cycle Sequencing Read
y Reaction Kit （Applied Biosystems社製）とABI PRI
SM TM 310 ジェネティックアナライザー （Applied Bio
systems社製）を用いておこなった。Polymerase Chain Reaction (PCR) is performed by TaKa
This was performed using Ra LA Taq ™ with GC Buffer (Takara Shuzo). 2.5 μl of the above template cDNA, 2X GC buffer 1
2.5 μl, 2.5 mM dNTPs 4 μl, 10 μM 3'RACE-AP primer
(SEQ ID NO: 11) 1 μl, 10 μMB6K36 primer (SEQ ID NO: 5) 1 μl, TaKaRa LA Taq (5 U / μl) 0.25 μl, DDW
3.75 μl of the mixed solution was once at 94 ° C for 2 minutes, 94 ° C for 1 minute, 55 ° C for 1 minute, 72 ° C for 2 minutes 30 times, and 72 ° C for 2 minutes at 1 minute.
The first PCR was performed once. 2.5 μl of a 50-fold dilution of the first PCR reaction solution, 12.5 μl of 2X GC buffer, 2.5 mM
dNTPs 4μl, 10μM AUAP primer (SEQ ID NO: 12) 1μ
l, 10 μM B6K311 primer (SEQ ID NO: 6) 1 μl, TaKaRa L
Mix A Taq (5 U / μl) 0.25 μl and DDW 3.75 μl, and add 9
4 ° C, 2 minutes once, 94 ° C, 1 minute, 55 ° C, 1 minute, 72 ° C, 2 minutes
The second PCR was performed 20 times for 20 minutes and once at 72 ° C. for 2 minutes. After extracting the second PCR reaction solution with phenol / chloroform and precipitating with ethanol, a DNA fragment of about 230 bp confirmed by 3% low-melting point agarose electrophoresis was used for Wizard ™ PCR Pretreatment.
The DNA was recovered using a ps DNA Purification System (Promega). This DNA fragment was converted into a plasmid vector pGEM-TE
asy (Promega), and the base sequence was determined by ABI P
RISM TM dRhodamine Terminator Cycle Sequencing Read
y Reaction Kit (Applied Biosystems) and ABI PRI
SM TM 310 Genetic Analyzer (Applied Bio
systems).
【００３４】次に、マウスB6TNC#10 cDNAの3'RACEをお
こなった。genomic DNAを除去するために、Deoxyribonu
clease I, Amplification Grade（LIFE TECHNOLOGIES,I
NC.社製）を用いた。 B6TNC細胞mRNA 1.5μg（1.5μl）
、10X DNase I Buffer１μl、RNase free DNase I (1
U/μl) 1μl、D.D.W. 6.5μlで室温15分間 インキュベ
ートした。25 mM EDTA (pH 8.0)を1μl添加し、65 ℃、
15分間インキュベート後、氷上に5分間、放置した。B6T
NC細胞cDNAの合成するために、５’RACE System for Ra
pid Amplification of cDNA Ends，Version 2.0 (LIFE
TECHNOLOGIES,INC.社製）と新たに合成した3’RACE AP
プライマー(配列番号１１)を用いた。DNase I処理したB
6TNC細胞cDNA 0.5 μg(5 μl) にD.D.W. 19 μl、10 μ
M 3’RACEAPプライマー(配列番号１１) 1μlを添加し、
70 ℃、10分間インキュベートし、50℃に保温する（溶
液Ｃ）。一方、10X PCR buffer 5μl、25 mM MgCl2 5
μl、10mM dNTPs 2.5 μl、 0.1 M DTT 5μl、D.D.W.
6.5μlを50℃で保温する（溶液Ｄ）。溶液Ｃと溶液Ｄと
SUPERSCRIPTTM II (200 units/μl) 1μl混ぜ合わせ50
℃、50分間インキュベートした。70℃、15分間処理後、
氷上に5分間放置した。RNase MIX 1μl添加し37℃、30
分間インキュベートした。これを3’RACE用の鋳型cDNA
とした。Next, 3 ′ RACE of mouse B6TNC # 10 cDNA was performed. Deoxyribonu to remove genomic DNA
clease I, Amplification Grade (LIFE TECHNOLOGIES, I
NC.) Was used. B6TNC cell mRNA 1.5μg (1.5μl)
, 10X DNase I Buffer 1μl, RNase free DNase I (1
(U / μl) 1 μl and 6.5 μl of DDW were incubated at room temperature for 15 minutes. Add 1 μl of 25 mM EDTA (pH 8.0),
After incubation for 15 minutes, the plate was left on ice for 5 minutes. B6T
5'RACE System for Ra for synthesis of NC cell cDNA
pid Amplification of cDNA Ends, Version 2.0 (LIFE
TECHNOLOGIES, INC.) And newly synthesized 3'RACE AP
A primer (SEQ ID NO: 11) was used. B treated with DNase I
6 TNC cell cDNA 0.5 μg (5 μl) to DDW 19 μl, 10 μl
1 μl of M 3 ′ RACEAP primer (SEQ ID NO: 11) was added,
Incubate at 70 ° C for 10 minutes and keep at 50 ° C (Solution C). On the other hand, 10X PCR buffer 5μl, 25 mM MgCl 2 5
μl, 10 mM dNTPs 2.5 μl, 0.1 M DTT 5 μl, DDW
Incubate 6.5 μl at 50 ° C. (solution D). Solution C and Solution D
SUPERSCRIPT TM II (200 units / μl ) 50 was 1μl mixed
Incubated at 50 ° C for 50 minutes. After treatment at 70 ° C for 15 minutes,
Left on ice for 5 minutes. Add 1μl of RNase MIX, 37 ℃, 30
Incubated for minutes. This is the template cDNA for 3'RACE
And
【００３５】Polymerase Chain Reaction（PCR）はTaKa
Ra LA TaqTM with GC Buffer（宝酒造社製）を用いて
おこなった。上記の鋳型cDNA 2.5μl、2X GC buffer 1
2.5μl、2.5 mM dNTPs 4μl、10μM AUAPプライマー(配
列番号１２) 1μl、10μM B6K56プライマー(配列番号
７) 1μl、TaKaRa LA Taq (5 U/μl) 0.25μl、D.D.W.
3.75μlを混ぜた溶液を94℃、2分間を1回、94℃、1分
間、55℃、1分間、72℃、2分間を30回、72℃、5分間を1
回で1回目のPCRをおこなった。1回目のPCR反応液を50倍
希釈したものを2.5μl、2X GC buffer 12.5μl、2.5 mM
dNTPs 4 μl、10μM AUAPプライマー (配列番号１２)
1μl、10μM B6N10-51プライマー(配列番号８) 1μl、T
aKaRa LA Taq (5 U/μl) 0.25μl、D.D.W. 3.75μlを混
ぜて、94℃、2分間を1回、94℃、1分間、55℃、1分間、
72℃、2分間を20回、72℃、5分間を1回で2回目のPCRを
おこなった。2回目のPCR反応液をフェノール／クロロホ
ルム抽出、エタノール沈澱後、3％ 低融点アガロース電
気泳動により確認した約600 bpのDNA断片をWizard TM P
CR Preps DNA Purification System (Promega社製)を用
いて回収した。このDNA断片をプラスミドベクター pGEM
-T-Easy （Promega社製）に挿入し、塩基配列の決定をA
BI PRISMTM dRhodamine Terminator CycleSequencing R
eady Reaction Kit （Applied Biosystems社製）とABI
PRISM TM 310 ジェネティックアナライザー（Applied B
iosystems社製）を用いておこなった。Polymerase Chain Reaction (PCR) is performed by TaKa
This was performed using Ra LA Taq ™ with GC Buffer (Takara Shuzo). 2.5 μl of the above template cDNA, 2X GC buffer 1
2.5 μl, 2.5 mM dNTPs 4 μl, 10 μM AUAP primer (SEQ ID NO: 12) 1 μl, 10 μM B6K56 primer (SEQ ID NO: 7) 1 μl, TaKaRa LA Taq (5 U / μl) 0.25 μl, DDW
3.75 μl of the mixed solution was once at 94 ° C for 2 minutes, 94 ° C for 1 minute, 55 ° C for 1 minute, 72 ° C for 2 minutes 30 times, and 72 ° C for 5 minutes for 1 minute.
The first PCR was performed once. 2.5 μl of a 50-fold dilution of the first PCR reaction solution, 12.5 μl of 2X GC buffer, 2.5 mM
dNTPs 4 μl, 10 μM AUAP primer (SEQ ID NO: 12)
1 μl, 10 μM B6N10-51 primer (SEQ ID NO: 8) 1 μl, T
aKaRa LA Taq (5 U / μl) 0.25 μl, mix 3.75 μl of DDW, 94 ° C, 2 minutes once, 94 ° C, 1 minute, 55 ° C, 1 minute,
A second PCR was performed at 72 ° C. for 2 minutes 20 times and at 72 ° C. for 5 minutes once. After the second PCR reaction solution was extracted with phenol / chloroform and precipitated with ethanol, a DNA fragment of about 600 bp confirmed by 3% low-melting-point agarose electrophoresis was used for Wizard ™ P
It was recovered using CR Preps DNA Purification System (Promega). This DNA fragment was converted into a plasmid vector pGEM.
-T-Easy (Promega).
BI PRISM TM dRhodamine Terminator CycleSequencing R
eady Reaction Kit (Applied Biosystems) and ABI
PRISM TM 310 Genetic Analyzer (Applied B
iosystems).
【００３６】全長マウスB6TNC#10 cDNAの塩基配列の決
定するために、5’RACEと3’RACEで同定していないマウ
スB6TNC#10 cDNAの領域を同定した。genomic DNAを除去
するために、Deoxyribonuclease I, Amplification Gra
de（LIFE TECHNOLOGIES,INC.社製）を用いた。 B6TNC細
胞mRNA 1μg（1μl） 、10X DNase I Buffer１μl、RNa
se free DNase I (1 U/μl) 1μl、D.D.W. 7μlで室温1
5分間 インキュベートした。25 mM EDTA (pH 8.0)を1μ
l添加し、65 ℃、15分間インキュベート後、氷上に5分
間、放置した。B6TNC細胞cDNAの合成するために、SUPER
SCRIPTTM Preamplification System for First Strand
cDNA Synthesis (LIFE TECHNOLOGIES,INC.社製）を用い
た。DNase I処理したB6TNC細胞cDNA 0.5μg(5μl) にD.
D.W. 19μl、Oligo（dT）12-18 primer（0.5μg/μl）1
μlを添加し、70 ℃、10分間インキュベートし、50℃に
保温する（溶液Ｅ）。一方、10X PCR buffer 5μl、25
mMMgCl2 5μl、10mM dNTPs 2.5μl、 0.1 M DTT 5μ
l、D.D.W. 6.5μlを50℃で保温する（溶液Ｆ）。溶液Ｅ
と溶液ＦとSUPERSCRIPTTM II (200 units/μl) 1μl混
ぜ合わせ50℃、50分間インキュベートした。70℃、15分
間処理後、氷上に5分間放置した。RNase MIX 1μl添加
し37℃、30分間インキュベートし、これを鋳型DNAとし
た。鋳型DNA 1μl、2X GC buffer 25μl、2.5 mM dNTPs
8μl、100μM B6K58プライマー(配列番号９) 0.25μ
l、100μM B6N10-33プライマー(配列番号１０) 0.25μ
l、TaKaRa LA Taq (5 U/μl) 0.5μl、D.D.W. 15μlを
混ぜて、94℃、2分間を1回、94℃、1分間、60℃、1分
間、72℃、4分30秒間を35回、72℃、2分間を1回でPCRを
おこなった。PCR反応液をフェノール／クロロホルム抽
出、エタノール沈澱後、1％ 低融点アガロース電気泳動
により確認した約３kbpのPCR増幅DNA断片をWizard TM P
CR Preps DNA Purification System (Promega社製) を
用いて回収した。このDNA断片をプラスミドベクター pG
EM-T-Easy （Promega社製）に挿入し、塩基配列の決定
をABI PRISMTM dRhodamine Terminator Cycle Sequenci
ng Ready Reaction Kit （Applied Biosystems社製）と
ABI PRISM TM 310ジェネティックアナライザー（Applie
d Biosystems社製）を用いておこなった。以上、マウス
B6TNC#10遺伝子の5'RACEと3'RACEのPCR産物、ならびにB
6K58プライマーとB6N10-33プライマーにより得られたPC
R産物の塩基配列をもとに全長マウスB6TNC#10 cDNAの塩
基配列（配列番号１）を確定した。その結果、マウスB6
TNC#10 cDNAは全長3,274 bpからなることを同定した。In order to determine the nucleotide sequence of the full-length mouse B6TNC # 10 cDNA, a region of the mouse B6TNC # 10 cDNA not identified by 5′RACE and 3′RACE was identified. Deoxyribonuclease I, Amplification Grade to remove genomic DNA
de (LIFE TECHNOLOGIES, INC.) was used. B6TNC cell mRNA 1μg (1μl), 10X DNase I Buffer 1μl, RNa
se free DNase I (1 U / μl) 1 μl, DDW 7 μl at room temperature 1
Incubated for 5 minutes. 1 μm of 25 mM EDTA (pH 8.0)
l, and incubated at 65 ° C for 15 minutes, and then left on ice for 5 minutes. SUPER to synthesize B6TNC cell cDNA
SCRIPT TM Preamplification System for First Strand
cDNA Synthesis (LIFE TECHNOLOGIES, INC.) was used. Add 0.5 μg (5 μl) of B6TNC cell cDNA treated with DNase I to D.
DW 19μl, Oligo (dT) 12-18 primer (0.5μg / μl) 1
Add μl, incubate at 70 ° C for 10 minutes, and keep at 50 ° C (Solution E). On the other hand, 5 μl of 10X PCR buffer, 25
mM MgCl 2 5 μl, 10 mM dNTPs 2.5 μl, 0.1 M DTT 5 μ
l, 6.5 µl of DDW is kept at 50 ° C (solution F). Solution E
, Solution F and 1 µl of SUPERSCRIPT ™ II (200 units / µl) were mixed and incubated at 50 ° C for 50 minutes. After treatment at 70 ° C. for 15 minutes, the mixture was left on ice for 5 minutes. 1 μl of RNase MIX was added and incubated at 37 ° C. for 30 minutes, and this was used as a template DNA. 1 μl of template DNA, 25 μl of 2X GC buffer, 2.5 mM dNTPs
8 μl, 100 μM B6K58 primer (SEQ ID NO: 9) 0.25 μ
l, 100 μM B6N10-33 primer (SEQ ID NO: 10) 0.25 μ
l, TaKaRa LA Taq (5 U / μl) 0.5 μl, DDW 15 μl, mix 94 ° C, 2 minutes once, 94 ° C, 1 minute, 60 ° C, 1 minute, 72 ° C, 4 minutes 30 seconds 35 PCR was performed once at 72 ° C. for 2 minutes. After extracting the PCR reaction solution with phenol / chloroform and precipitating with ethanol, a PCR-amplified DNA fragment of about 3 kbp, which was confirmed by 1% low-melting-point agarose electrophoresis, was used in Wizard TM P
It was recovered using CR Preps DNA Purification System (Promega). This DNA fragment was converted into a plasmid vector pG.
Insert into EM-T-Easy (Promega) and determine the nucleotide sequence by ABI PRISM ™ dRhodamine Terminator Cycle Sequenci
ng Ready Reaction Kit (Applied Biosystems)
ABI PRISM TM 310 Genetic Analyzer (Applie
d Biosystems). The mouse
PCR products of 5'RACE and 3'RACE of B6TNC # 10 gene, and B
PC obtained with 6K58 primer and B6N10-33 primer
Based on the nucleotide sequence of the R product, the nucleotide sequence of the full-length mouse B6TNC # 10 cDNA (SEQ ID NO: 1) was determined. As a result, mouse B6
TNC # 10 cDNA was identified to be 3,274 bp in length.
【００３７】実施例２ マウスB6TNC#10の推定アミノ酸配列解析 確定したマウスB6TNC#10 cDNAの塩基配列および内部に
終始コドンを持たないopen reading frame (ORF)のアミ
ノ酸配列を図１（図１Ａ及び図１Ｂ）に示す。マウスB6
TNC#10 cDNAは全長3,274 bpからなり、3' 非翻訳領域に
ポリＡ付加シグナル（二重下線）を確認できた。この遺
伝子は833個のアミノ酸配列よりなるORFを有し、2箇所
に疎水性の強いアミノ酸（下線）を有する遺伝子である
ことが明らかになり、膜タンパク質、もしくは膜に存在
するレセプタータンパク質であることが推定される。こ
の833個のアミノ酸からなるタンパク質の分子量は、計
算によると87,772であった。 Example 2 Predicted Amino Acid Sequence Analysis of Mouse B6TNC # 10 The nucleotide sequence of the determined mouse B6TNC # 10 cDNA and the amino acid sequence of an open reading frame (ORF) having no internal termination codon are shown in FIG. 1B). Mouse B6
TNC # 10 cDNA was 3,274 bp in total length, and a poly-A addition signal (double underline) was confirmed in the 3 ′ untranslated region. This gene has an ORF consisting of 833 amino acid sequences, and has been found to be a gene with two highly hydrophobic amino acids (underlined) at two positions, and is a membrane protein or a receptor protein present on the membrane Is estimated. The molecular weight of the protein consisting of 833 amino acids was calculated to be 87,772.
【００３８】アミノ酸配列の類似性解析は遺伝子解析ソ
フトGENETYX-SV/RC Ver.3.2.0（ソフトウェアー開発社
製）を用いておこなった。マウスB6TNC#10と最も相同性
が高かったヒトアセチルLDLレセプター（Adachi, H., T
sujimoto, M., Arai, H. & Inoue, K. (1997) J. Biol.
Chem. 272, 31217-31220）との結果を図２（図２Ａ及
び図２Ｂ）に示す。保存されているアミノ酸を＊で示し
た。マウスB6TNC#10とヒトアセチルLDLレセプターとの
相同性は39％で、特に、細胞外領域と考えられる部分の
相同性が高かった。このことからマウスB6TNC#10はスカ
ベンジャー受容体ファミリーの一つであることが予想さ
れる。The amino acid sequence similarity analysis was performed using gene analysis software GENETYX-SV / RC Ver. 3.2.0 (manufactured by Software Development Corporation). Human acetyl LDL receptor with the highest homology to mouse B6TNC # 10 (Adachi, H., T
sujimoto, M., Arai, H. & Inoue, K. (1997) J. Biol.
Chem. 272, 31217-31220) are shown in FIG. 2 (FIGS. 2A and 2B). Conserved amino acids are indicated by *. The homology between mouse B6TNC # 10 and the human acetyl LDL receptor was 39%, and the homology was particularly high in the portion considered to be the extracellular region. This suggests that mouse B6TNC # 10 is a member of the scavenger receptor family.
【００３９】図３、４および５にマウスB6TNC#10の蛋白
質の推定される構造を示す。マウスB6TNC#10とヒトアセ
チルLDLレセプターで保存されているアミノ酸の繰り返
し配列のアミノ酸配列を示した。マウスB6TNC#10の細胞
外領域と考えられる部分でシステイン残基とグリシン残
基が保存された10個の繰り返し配列がヒトアセチルLDL
レセプター同様存在した（図３）。また、アミノ酸の繰
り返し配列中にEGF様リピートが保存されており、タン
パク質間の結合、またはリガンドの結合に必要な領域で
あることが推定される（図４、図５）。2箇所に疎水性
の強いアミノ酸（図５細下線）で示した。マウスB6TNC#
10の細胞外領域にはヒトアセチルLDLレセプター同様、E
GF様リピート（図５太下線）が保存されており、タンパ
ク質間の結合、またはリガンドの結合に必要な領域であ
ることが推定される。また、細胞内領域はセリン／プロ
リンに富んでおり、リン酸化を受けることが予想され、
マウスB6TNC#10はシグナルを細胞内に伝えることができ
る分子であることが推定される。特に、波線で示した領
域はチロシン残基がリン酸化を受けた時、SH２ドメイン
を持つタンパク質の結合部位になることが予想される。
また、二重下線のプロリン残基が富んだ領域はSH３ドメ
インを持つタンパク質の結合部位になることが予想され
る。FIGS. 3, 4 and 5 show the putative structure of the protein of mouse B6TNC # 10. The amino acid sequence of the repeated amino acid sequence conserved between mouse B6TNC # 10 and human acetyl LDL receptor is shown. Conserved cysteine and glycine residues in the putative extracellular domain of mouse B6TNC # 10 are 10 repeats of human acetyl LDL
It was present as well as the receptor (FIG. 3). In addition, EGF-like repeats are conserved in the amino acid repeat sequence, which is presumed to be a region necessary for protein-protein binding or ligand-binding (FIGS. 4 and 5). Two hydrophobic amino acids (underlined in FIG. 5) are shown. Mouse B6TNC #
As in the human acetyl LDL receptor, E
The GF-like repeat (Fig. 5, thick underline) is conserved, and is presumed to be a region necessary for protein-protein binding or ligand binding. In addition, the intracellular region is rich in serine / proline and is expected to undergo phosphorylation,
It is presumed that mouse B6TNC # 10 is a molecule that can transmit signals into cells. In particular, the region shown by the dashed line is expected to become a binding site for a protein having an SH2 domain when a tyrosine residue is phosphorylated.
In addition, the region underlined with proline residues, which is double underlined, is expected to be a binding site for a protein having an SH3 domain.
【００４０】実施例３ ノーザンブロット法解析によるマウスB6TNC#10 mRNAの
発現解析 マウスB6TNC#10 mRNAの発現を調べるためにマウス細胞
株B6TNC（Nanno, M. etal. (1995) J. Immunol. 155,29
18）、IT-79 MTNC3 (Itoh, T. et al.(1998) Eur. J. I
mmunol. 18,821)、Doi Nurse（Iwagami, S. et al. (19
94) J. Immunol. 153,2927）、C3H10T1/2 clone8 (ATCC
No.CCL-226)、L929 (ATCC No.CCL-1)、IT76-M712（Sav
ino, W. et al. (1989) Eur. J. Immunol. 19,1727）、
NIH3T3 (ATCC No.CRL-1658)からTRIzolTM（LIFE TECHNO
LOGIES,INC.社製）を用いてtotalRNAを調製した。ま
た、マウスの組織におけるマウスB6TNC#10 mRNAの発現
を調べるためにBalb/cマウスの脳、胸腺、心臓、肺、脾
臓、リンパ節、胃、肝臓、腎臓、小腸、膵臓を摘出しTR
IzolTM（LIFE TECHNOLOGIES,INC.社製）を用いてtotal
RNAを調製した。調製したマウス細胞株のtotal RNA 10
μg、マウスの組織のtotal RNA 20 μgをホルムアルデ
ヒドを含む1％アガロースゲルで電気泳動し、ナイロン
膜HybondTM-N+ （アマシャム社製）に転写した。 Example 3 Mouse B6TNC # 10 mRNA by Northern Blot Analysis
Expression analysis To examine the expression of mouse B6TNC # 10 mRNA, a mouse cell line B6TNC (Nanno, M. et al. (1995) J. Immunol. 155, 29
18), IT-79 MTNC3 (Itoh, T. et al. (1998) Eur. J. I
mmunol. 18,821), Doi Nurse (Iwagami, S. et al. (19
94) J. Immunol. 153,2927), C3H10T 1/2 clone8 (ATCC
No.CCL-226), L929 (ATCC No.CCL-1), IT76-M712 (Sav
ino, W. et al. (1989) Eur. J. Immunol. 19, 1727),
From NIH3T3 (ATCC No. CRL-1658) to TRIzol TM (LIFE TECHNO
LOGIES, INC.) To prepare total RNA. In addition, in order to examine the expression of mouse B6TNC # 10 mRNA in mouse tissues, the brain, thymus, heart, lung, spleen, lymph nodes, stomach, liver, kidney, small intestine, and pancreas of Balb / c mice were extracted and TR
Total using Izol TM (LIFE TECHNOLOGIES, INC.)
RNA was prepared. Total RNA 10 of the prepared mouse cell line
μg and 20 μg of total RNA from mouse tissues were electrophoresed on a 1% agarose gel containing formaldehyde, and transferred to a nylon membrane Hybond ™ -N + (manufactured by Amersham).
【００４１】マウスB6TNC#10のプローブを作製した。B6
K58プライマー（配列番号９）とB6N10-33プライマー
（配列番号１０）により得られたPCR産物をプラスミド
ベクターpGEM-T-Easy （Promega社製）に挿入したもの
を鋳型としてB6N10-51プライマー（配列番号８）とB6N1
0-33プライマー（配列番号１０）でPCRをおこなった。P
CR産物をフェノール／クロロホルム抽出、エタノール沈
澱後、3％ 低融点アガロース電気泳動により確認した約
600 bpのPCR増幅DNA断片をWizard TM PCR Preps DNA Pu
rification System (Promega社製) を用いて回収し、マ
ウスB6TNC#10のプローブとした。マウスB6TNC#10のプロ
ーブをPrime-It II Random Primer LabelingKits （STR
ATAGENE社製）を用いて32P標識をおこない、NICKTM Col
umn （ファルマシア社製）で精製した。A probe for mouse B6TNC # 10 was prepared. B6
The PCR product obtained by the K58 primer (SEQ ID NO: 9) and the B6N10-33 primer (SEQ ID NO: 10) was inserted into a plasmid vector pGEM-T-Easy (Promega) and the B6N10-51 primer (SEQ ID NO: 8) and B6N1
PCR was performed with the 0-33 primer (SEQ ID NO: 10). P
After the CR product was extracted with phenol / chloroform and precipitated with ethanol, it was confirmed by 3% low-melting-point agarose electrophoresis.
600 bp PCR amplified DNA fragment of Wizard TM PCR Preps DNA Pu
Using a rification System (Promega), it was collected and used as a probe for mouse B6TNC # 10. The mouse B6TNC # 10 probe was used for the Prime-It II Random Primer Labeling Kits (STR
Perform 32 P-labeled using a ATAGENE Co., Ltd.), NICK TM Col
Purified by umn (Pharmacia).
【００４２】転写したナイロン膜をハイフ゛リタ゛イセ゛ーション ハ゛ッ
ファー（5X SSPE、10X デンハルト溶液、2％ SDS、50％ ホ
ルムアミド、100μg/mlサケ精子DNA）中で42℃、2時間
処理し、32P標識したマウスB6TNC#10プローブを加え、4
2℃、一晩インキュベートした。ナイロン膜を取り出
し、2X SSC、0.1％ SDS溶液で室温15分間２回、2X SS
C、0.1％ SDS溶液で６５℃、15分間、０.５ XSSC、0.1
％ SDS溶液で６５℃、15分間、０.１X SSC、0.1％ SDS
溶液で６５℃、15分間洗浄した。洗浄したナイロン膜を
３日間、-８０℃でＸ線フィルム（コダック社製）に感
光させた。マウスの臓器では特に肺で強い発現が見ら
れ、その他の組織で弱い発現が見られた。この結果、ナ
ース細胞は、既に報告されている組織以外にも存在する
ことが推定される。また、B6TNC、IT-79 MTNC3、Doi Nu
rse、C3H10T1/2clone8、NIH3T3で約３kbのバンドを検出
した。ナース細胞であるB6TNC、IT-79 MTNC3、Doi Nurs
e、C3H10T1/2clone8で発現がマウスB6TNC#10が確認でき
たことからマウスB6TNC#10がナース細胞の機能に関るこ
とが推定される。[0042] Hythe transcription nylon membrane Bu Rita Bu Ise Bu Shon Ha Bu Ffa (5X SSPE, 10X Denhardt's solution, 2% SDS, 50% formamide, 100 [mu] g / ml salmon sperm DNA) 42 ° C. in, for 2 hours, 32 P-labeled mouse B6TNC Add # 10 probe, 4
Incubated overnight at 2 ° C. Take out the nylon membrane and use 2X SSC, 0.1% SDS solution twice at room temperature for 15 minutes, 2X SS
C, 0.1% SDS solution at 65 ° C for 15 minutes, 0.5 XSSC, 0.1
0.1X SSC, 0.1% SDS at 65 ° C for 15 minutes
The solution was washed at 65 ° C. for 15 minutes. The washed nylon membrane was exposed to an X-ray film (manufactured by Kodak) at −80 ° C. for 3 days. In mouse organs, strong expression was observed particularly in the lung, and weak expression was observed in other tissues. As a result, it is presumed that the nurse cells exist in addition to the tissues already reported. Also, B6TNC, IT-79 MTNC3, Doi Nu
rse, it was detected a band of about 3kb in C3H10T 1/2 clone8, NIH3T3. Nurse cells B6TNC, IT-79 MTNC3, Doi Nurs
e, mouse B6TNC # 10 since it expressed in C3H10T 1/2 clone8 was confirmed mice B6TNC # 10 is estimated to be Sekiru the function of nurse cells.
【００４３】[0043]
【発明の効果】本発明によれば、マウスナース細胞レセ
プター；本発明のポリペプチドをコードするDNA；本発
明の塩基配列中の連続した少なくとも１４個の塩基を含
み、該塩基配列と特異的に結合するDNA；本発明のポリ
ペプチドを特異的に認識する抗体；本発明の抗体を産生
するハイブリドーマ；本発明のDNAを含む発現ベクタ
ー；本発明の発現ベクターより得られる形質転換体；組
換えマウスナース細胞レセプターの製造方法；本発明の
マウスナース細胞レセプターに特異的に結合するリガン
ドのスクリーニング方法；本発明のマウスナース細胞レ
セプターとリガンドとの結合を阻害する化合物のスクリ
ーニング方法；本発明のスクリーニング方法により得ら
れる医薬；本発明プライマーを含むディジョージ症候群
を検出するためのキット；本発明プライマーを含む自己
免疫疾患を検出するためのキットが提供される。According to the present invention, a mouse nurse cell receptor; a DNA encoding the polypeptide of the present invention; at least 14 contiguous bases in the base sequence of the present invention, and specifically An antibody that specifically recognizes the polypeptide of the present invention; a hybridoma producing the antibody of the present invention; an expression vector containing the DNA of the present invention; a transformant obtained from the expression vector of the present invention; A method for producing a nurse cell receptor; a method for screening a ligand that specifically binds to a mouse nurse cell receptor of the present invention; a method for screening a compound that inhibits binding between a mouse nurse cell receptor and a ligand according to the present invention; A kit for detecting DiGeorge syndrome comprising the primer of the present invention; Kits for detecting autoimmune diseases, including invention primers are provided.
【００４４】本発明のDNAの一部をプライマーとして用
いることにより、ディジョージ症候群の検出が可能とな
る。更に、本レセプターが欠損した場合には、ナース細
胞によるT細胞の成熟・分化が正常におこなわれない可
能性がある。従って、本発明のDNAの一部をプライマー
として用いることにより、本レセプターの欠損に起因す
る自己免疫疾患の検出が可能となる。更に、本発明のレ
セプターは、レセプターに対するアゴニスト及びアンタ
ゴニストのスクリーニングに有用である。前述のとお
り、本レセプターは、スカベンジャーレセプターとして
機能し、動脈硬化に関与することが予想される。従っ
て、本レセプターの阻害物質は、動脈硬化の治療に有用
であると考えられる。By using part of the DNA of the present invention as a primer, DiGeorge syndrome can be detected. Furthermore, when the present receptor is deficient, the maturation and differentiation of T cells by nurse cells may not be performed normally. Therefore, by using a part of the DNA of the present invention as a primer, it becomes possible to detect an autoimmune disease caused by the deficiency of the present receptor. Further, the receptor of the present invention is useful for screening for agonists and antagonists for the receptor. As described above, this receptor functions as a scavenger receptor and is expected to be involved in arteriosclerosis. Therefore, inhibitors of this receptor are considered useful for treating arteriosclerosis.
【００４５】また、前述のとおり、ナース細胞は、胸
腺、皮膚組織、骨髄、リンパ節、肝臓、脳、リウマチ患
者の滑膜、癌の原発巣及び転移巣に存在することが確認
されている。ナース細胞は、血球系幹細胞の増殖と自己
再生能の維持及びリンパ球の正及び負の選択に関与し、
正常な免疫系の発生とメモリー細胞の維持に関与してい
ると考えられる。よって、ナース細胞膜表面に発現する
本レセプターの機能異常が免疫系の機能異常と自己免疫
疾患の発症に関わることが予想される。そのため、本発
明のスクリーニングにより得られるアゴニストおよびア
ンタゴニストは、自己免疫疾患と腫瘍に対する治療に有
用であることが考えられる。As described above, it has been confirmed that nurse cells are present in the thymus, skin tissue, bone marrow, lymph node, liver, brain, synovium of rheumatic patients, and primary and metastatic lesions of cancer. Nurse cells are involved in the proliferation of blood cell stem cells, maintenance of self-renewal ability, and positive and negative selection of lymphocytes.
It is thought to be involved in the development of a normal immune system and the maintenance of memory cells. Therefore, it is expected that the dysfunction of the present receptor expressed on the surface of the nurse cell membrane will contribute to the dysfunction of the immune system and the development of autoimmune diseases. Therefore, the agonists and antagonists obtained by the screening of the present invention are considered to be useful for treating autoimmune diseases and tumors.
【００４６】[0046]
【配列表】 SEQUENCE LISTING <110> Shionogi & Co.,Ltd. <120> A Gene Encoding Mouse Nures Cell Receptor <130> A005977 <140> <141> <160> 12 <170> PatentIn Ver. 2.0 <210> 1 <211> 3274 <212> DNA <213> Mus musculus <220> <221> CDS <222> (65)..(2563) <400> 1 actccgcttc cggccgccct tgccgcggcc gcacccgcgc ccacccgcgc ctgccccgcg 60 cctc atg gag ggc gca ggg tcc cgg ggg gcc ggg ccg gcg cgg cgc cag 109 Met Glu Gly Ala Gly Ser Arg Gly Ala Gly Pro Ala Arg Arg Gln 1 5 10 15 gga gcc cga ggg ctg gga ctg ctg ctg ctg ctc tgg ctg ctg ccc ggt 157 Gly Ala Arg Gly Leu Gly Leu Leu Leu Leu Leu Trp Leu Leu Pro Gly 20 25 30 ctc gcg gcg ccc cag gac ttg aac ccg cga ggc cgc aac gtg tgc cgc 205 Leu Ala Ala Pro Gln Asp Leu Asn Pro Arg Gly Arg Asn Val Cys Arg 35 40 45 acg ccc ggt tcc cag gtg ctc acg tgt tgc gct ggc tgg agg cag ctg 253 Thr Pro Gly Ser Gln Val Leu Thr Cys Cys Ala Gly Trp Arg Gln Leu 50 55 60 ggg gat gag tgt ggg ata gcg gtg tgc gaa ggc aat tcc acg tgc tca 301 Gly Asp Glu Cys Gly Ile Ala Val Cys Glu Gly Asn Ser Thr Cys Ser 65 70 75 gaa aac gag gtg tgc gtg cgg cca ggc gaa tgc cgc tgc cga cat ggc 349 Glu Asn Glu Val Cys Val Arg Pro Gly Glu Cys Arg Cys Arg His Gly 80 85 90 95 tac ttt ggt gcc aac tgc gac aca aag tgc ccg cgc cag ttc tgg ggc 397 Tyr Phe Gly Ala Asn Cys Asp Thr Lys Cys Pro Arg Gln Phe Trp Gly 100 105 110 cct gac tgc aag gag agg tgc agt tgc cac ccg cac gga cag tgc gag 445 Pro Asp Cys Lys Glu Arg Cys Ser Cys His Pro His Gly Gln Cys Glu 115 120 125 gac gtg acc gga cag tgt acg tgt cac gcg cgc cgc tgg ggt gcg cgc 493 Asp Val Thr Gly Gln Cys Thr Cys His Ala Arg Arg Trp Gly Ala Arg 130 135 140 tgc gag cat gct tgc caa tgc cag cat ggc acg tgc cac ccg cgg agc 541 Cys Glu His Ala Cys Gln Cys Gln His Gly Thr Cys His Pro Arg Ser 145 150 155 ggc gcg tgc cgg tgc gag ccg ggc tgg tgg ggt gcg caa tgc gct agc 589 Gly Ala Cys Arg Cys Glu Pro Gly Trp Trp Gly Ala Gln Cys Ala Ser 160 165 170 175 gct tgc tat tgc agc gct act tcc cgg tgc gat cca cag aca ggc gcc 637 Ala Cys Tyr Cys Ser Ala Thr Ser Arg Cys Asp Pro Gln Thr Gly Ala 180 185 190 tgc ctg tgc cac gta ggc tgg tgg ggc cgc agc tgt aac aac cag tgc 685 Cys Leu Cys His Val Gly Trp Trp Gly Arg Ser Cys Asn Asn Gln Cys 195 200 205 gcc tgc aac tcg tcg ccc tgc gag cag cag agt ggc cgc tgc cag tgt 733 Ala Cys Asn Ser Ser Pro Cys Glu Gln Gln Ser Gly Arg Cys Gln Cys 210 215 220 cgc gag cgc atg ttt ggc gcc cgc tgt gat cgc tat tgc cag tgc tct 781 Arg Glu Arg Met Phe Gly Ala Arg Cys Asp Arg Tyr Cys Gln Cys Ser 225 230 235 cac ggt cgc tgc cac ccg gtg gac ggc acg tgt gcc tgc gat cct ggc 829 His Gly Arg Cys His Pro Val Asp Gly Thr Cys Ala Cys Asp Pro Gly 240 245 250 255 tac cgg ggc aag tat tgt cgc gag cca tgc ccc gct gga ttc tat ggc 877 Tyr Arg Gly Lys Tyr Cys Arg Glu Pro Cys Pro Ala Gly Phe Tyr Gly 260 265 270 ccg ggc tgt cgc cgt cgg tgt ggc caa tgc aaa ggc cag cag ccg tgc 925 Pro Gly Cys Arg Arg Arg Cys Gly Gln Cys Lys Gly Gln Gln Pro Cys 275 280 285 acg gta gtc gaa ggc cgc tgt ctg aca tgc gag ccc ggc tgg aac gga 973 Thr Val Val Glu Gly Arg Cys Leu Thr Cys Glu Pro Gly Trp Asn Gly 290 295 300 acc aaa tgt gac caa ccc tgc gcc acc ggt ttc tac ggc gaa ggt tgt 1021 Thr Lys Cys Asp Gln Pro Cys Ala Thr Gly Phe Tyr Gly Glu Gly Cys 305 310 315 ggc cac cgc tgc cca ccc tgc cgc gac ggg cat gcc tgc aac cat gtc 1069 Gly His Arg Cys Pro Pro Cys Arg Asp Gly His Ala Cys Asn His Val 320 325 330 335 acc ggc aag tgt acg cac tgc aat gcg ggc tgg atc ggc gac cgg tgc 1117 Thr Gly Lys Cys Thr His Cys Asn Ala Gly Trp Ile Gly Asp Arg Cys 340 345 350 gag act aag tgc agt aat ggc act tac ggt gag gac tgt gcc ttc gtg 1165 Glu Thr Lys Cys Ser Asn Gly Thr Tyr Gly Glu Asp Cys Ala Phe Val 355 360 365 tgc tct gat tgc ggc agc ggc cac tgt gac ttc cag tcc ggg cgc tgc 1213 Cys Ser Asp Cys Gly Ser Gly His Cys Asp Phe Gln Ser Gly Arg Cys 370 375 380 ctt tgc agc cct ggt gtt cac gga cct cac tgt aat gta act tgc ccg 1261 Leu Cys Ser Pro Gly Val His Gly Pro His Cys Asn Val Thr Cys Pro 385 390 395 gcc ggg ctc cac ggc gtg gac tgc gcc cag gcc tgc agc tgt cac gag 1309 Ala Gly Leu His Gly Val Asp Cys Ala Gln Ala Cys Ser Cys His Glu 400 405 410 415 gaa tca tgc gac ccg gtc acc ggt gcc tgc cac ctg gag acc aat cag 1357 Glu Ser Cys Asp Pro Val Thr Gly Ala Cys His Leu Glu Thr Asn Gln 420 425 430 cgc aaa ggt gtg atg ggc gcg ggc gct ctg ctc acg ctg ctc ctc ggc 1405 Arg Lys Gly Val Met Gly Ala Gly Ala Leu Leu Thr Leu Leu Leu Gly 435 440 445 ctg ctg ctc tcg ctg ctc ggt tgt tgc tgc gcc tgc cgg ggc aag gac 1453 Leu Leu Leu Ser Leu Leu Gly Cys Cys Cys Ala Cys Arg Gly Lys Asp 450 455 460 tcg gcg cgc cgg gag ctc acc ctt gga agg aag aag gcg cct caa cgt 1501 Ser Ala Arg Arg Glu Leu Thr Leu Gly Arg Lys Lys Ala Pro Gln Arg 465 470 475 ttt tgt gga agc ttc agc cgc atc agc atg aag ctg ccc cga atc ccg 1549 Phe Cys Gly Ser Phe Ser Arg Ile Ser Met Lys Leu Pro Arg Ile Pro 480 485 490 495 ctt cgc agg cag aag ctg ccc aaa gtc gta gtg gcc cat cat gac cta 1597 Leu Arg Arg Gln Lys Leu Pro Lys Val Val Val Ala His His Asp Leu 500 505 510 gac aac aca ctc aac tgc agt ttt ctg gac cca ccc tca ggg ctg gag 1645 Asp Asn Thr Leu Asn Cys Ser Phe Leu Asp Pro Pro Ser Gly Leu Glu 515 520 525 cag ccc tct cca tca tgg tcc tcc agg gcc tcc ttc tca tca ttc gac 1693 Gln Pro Ser Pro Ser Trp Ser Ser Arg Ala Ser Phe Ser Ser Phe Asp 530 535 540 acc aca gat gaa ggc cct gtg tac tgt gtg ccc cac gag gaa gcg act 1741 Thr Thr Asp Glu Gly Pro Val Tyr Cys Val Pro His Glu Glu Ala Thr 545 550 555 gcc gac agc cga gac ctg gaa gcg act gcc gct ctc act gag gtg gcc 1789 Ala Asp Ser Arg Asp Leu Glu Ala Thr Ala Ala Leu Thr Glu Val Ala 560 565 570 575 gct gtg tcc tta gag ccc acg ggc acc tcg acg ccc ggg gag gag gca 1837 Ala Val Ser Leu Glu Pro Thr Gly Thr Ser Thr Pro Gly Glu Glu Ala 580 585 590 gcg gtc ctc cct gca tcc tca gac agc gag cgc tcc gca tca agc gtg 1885 Ala Val Leu Pro Ala Ser Ser Asp Ser Glu Arg Ser Ala Ser Ser Val 595 600 605 gag ggg ccg agc ggg gcg ctg tac gcg cgt gtg gcc cgg cgc gag gcc 1933 Glu Gly Pro Ser Gly Ala Leu Tyr Ala Arg Val Ala Arg Arg Glu Ala 610 615 620 cgg ccg gcc cgg acc cga aat gag gct ggg ggc ttg tca ctg tcc cca 1981 Arg Pro Ala Arg Thr Arg Asn Glu Ala Gly Gly Leu Ser Leu Ser Pro 625 630 635 tcg ccc gag cgc agg aag ccg cca cca cca gac cct gcc acc aag cct 2029 Ser Pro Glu Arg Arg Lys Pro Pro Pro Pro Asp Pro Ala Thr Lys Pro 640 645 650 655 aag gtg tcc tgg atc cac ggc aag cac agc gcc gct gcc gct gca ccg 2077 Lys Val Ser Trp Ile His Gly Lys His Ser Ala Ala Ala Ala Ala Pro 660 665 670 tcg cct ccg cct gca ggc cgc aag gct gcg ccg agc cct agc ggg agg 2125 Ser Pro Pro Pro Ala Gly Arg Lys Ala Ala Pro Ser Pro Ser Gly Arg 675 680 685 aaa cgg acc ccc agc aac tcg tcg gtg cag ccc ccc gga ctg acc gag 2173 Lys Arg Thr Pro Ser Asn Ser Ser Val Gln Pro Pro Gly Leu Thr Glu 690 695 700 gag gcc ccc ggc ccg gct tca ccc acg cca ccc cgc gcc cga gcg cgc 2221 Glu Ala Pro Gly Pro Ala Ser Pro Thr Pro Pro Arg Ala Arg Ala Arg 705 710 715 ggc cgc ggc ctg ggg ctc tcg gag cca acg gac gcg gga ggt ccc ccg 2269 Gly Arg Gly Leu Gly Leu Ser Glu Pro Thr Asp Ala Gly Gly Pro Pro 720 725 730 735 cgc agc gcg ccc gag gcc gcc tct atg ctg gca gct gag ctg cgc gac 2317 Arg Ser Ala Pro Glu Ala Ala Ser Met Leu Ala Ala Glu Leu Arg Asp 740 745 750 aag act cgc agc tta ggc cgc gcc gag aag ccg ccg ccg ccg cag aag 2365 Lys Thr Arg Ser Leu Gly Arg Ala Glu Lys Pro Pro Pro Pro Gln Lys 755 760 765 gcc aag cgc tcc gtg ctc ccc gcc gcg acg gtc cgc aca gcc tcg gcg 2413 Ala Lys Arg Ser Val Leu Pro Ala Ala Thr Val Arg Thr Ala Ser Ala 770 775 780 tcc gag gcc tcg ggg tca gag aag gcg gcg gcc agc gca cct gcg ccc 2461 Ser Glu Ala Ser Gly Ser Glu Lys Ala Ala Ala Ser Ala Pro Ala Pro 785 790 795 gag acc cct cgg aag aaa acc ccc atc cag aaa ccg cct cgg aag aag 2509 Glu Thr Pro Arg Lys Lys Thr Pro Ile Gln Lys Pro Pro Arg Lys Lys 800 805 810 815 agc agg gag gca gcg ggg gag ccg agt agg gcg ggc acg gcc ccc gga 2557 Ser Arg Glu Ala Ala Gly Glu Pro Ser Arg Ala Gly Thr Ala Pro Gly 820 825 830 gct tcc taagctcgca gccccaggag gctttctcac caccatttcc ccgcgcggcc 2613 Ala Ser gcagcgaagg catttcattg gcccccaaag cccagcgccc gcccaagcct gcgtctggtt 2673 ggcctaggct caagcagccg cggcctggtt ggatctgctc tcgggcctcg cagacactta 2733 gctggctacc cgctcccact agcaaagttg tggagctttt ctagtaatct ctgtctcgtt 2793 ggccatggct tggagagcct acagacttct tactggccaa gaagagtgtt cttggcaggg 2853 ctaccttgtc actggccgat gccagcagcg cttctgcctc ttggctgcct ctcatttgcc 2913 aaggcctggt gcctatggct gaagggtctt tttctctgaa gacaaaaaga ggttgcgtcc 2973 ataaactggg ctccagagta tctggttggc ccgaacctgg ggagaagagc tggtctcttc 3033 ttcgcagggg gctcagccca tgttggcttg tccccttccc acgcacgcca gccctggtct 3093 ctcagccatc aagctggttt tgatggcctc ctatcacccc acgagggaac cccagggcct 3153 actctggtgg ctttagatgt atttataggc cctgggcagg gcttctctca tcccatctgg 3213 gaccttctgg atgggctcct catagcaggc caaagctttc tttaataaaa tgcttctccc 3273 c 3274 <210> 2 <211> 833 <212> PRT <213> Mus musculus <400> 2 Met Glu Gly Ala Gly Ser Arg Gly Ala Gly Pro Ala Arg Arg Gln Gly 1 5 10 15 Ala Arg Gly Leu Gly Leu Leu Leu Leu Leu Trp Leu Leu Pro Gly Leu 20 25 30 Ala Ala Pro Gln Asp Leu Asn Pro Arg Gly Arg Asn Val Cys Arg Thr 35 40 45 Pro Gly Ser Gln Val Leu Thr Cys Cys Ala Gly Trp Arg Gln Leu Gly 50 55 60 Asp Glu Cys Gly Ile Ala Val Cys Glu Gly Asn Ser Thr Cys Ser Glu 65 70 75 80 Asn Glu Val Cys Val Arg Pro Gly Glu Cys Arg Cys Arg His Gly Tyr 85 90 95 Phe Gly Ala Asn Cys Asp Thr Lys Cys Pro Arg Gln Phe Trp Gly Pro 100 105 110 Asp Cys Lys Glu Arg Cys Ser Cys His Pro His Gly Gln Cys Glu Asp 115 120 125 Val Thr Gly Gln Cys Thr Cys His Ala Arg Arg Trp Gly Ala Arg Cys 130 135 140 Glu His Ala Cys Gln Cys Gln His Gly Thr Cys His Pro Arg Ser Gly 145 150 155 160 Ala Cys Arg Cys Glu Pro Gly Trp Trp Gly Ala Gln Cys Ala Ser Ala 165 170 175 Cys Tyr Cys Ser Ala Thr Ser Arg Cys Asp Pro Gln Thr Gly Ala Cys 180 185 190 Leu Cys His Val Gly Trp Trp Gly Arg Ser Cys Asn Asn Gln Cys Ala 195 200 205 Cys Asn Ser Ser Pro Cys Glu Gln Gln Ser Gly Arg Cys Gln Cys Arg 210 215 220 Glu Arg Met Phe Gly Ala Arg Cys Asp Arg Tyr Cys Gln Cys Ser His 225 230 235 240 Gly Arg Cys His Pro Val Asp Gly Thr Cys Ala Cys Asp Pro Gly Tyr 245 250 255 Arg Gly Lys Tyr Cys Arg Glu Pro Cys Pro Ala Gly Phe Tyr Gly Pro 260 265 270 Gly Cys Arg Arg Arg Cys Gly Gln Cys Lys Gly Gln Gln Pro Cys Thr 275 280 285 Val Val Glu Gly Arg Cys Leu Thr Cys Glu Pro Gly Trp Asn Gly Thr 290 295 300 Lys Cys Asp Gln Pro Cys Ala Thr Gly Phe Tyr Gly Glu Gly Cys Gly 305 310 315 320 His Arg Cys Pro Pro Cys Arg Asp Gly His Ala Cys Asn His Val Thr 325 330 335 Gly Lys Cys Thr His Cys Asn Ala Gly Trp Ile Gly Asp Arg Cys Glu 340 345 350 Thr Lys Cys Ser Asn Gly Thr Tyr Gly Glu Asp Cys Ala Phe Val Cys 355 360 365 Ser Asp Cys Gly Ser Gly His Cys Asp Phe Gln Ser Gly Arg Cys Leu 370 375 380 Cys Ser Pro Gly Val His Gly Pro His Cys Asn Val Thr Cys Pro Ala 385 390 395 400 Gly Leu His Gly Val Asp Cys Ala Gln Ala Cys Ser Cys His Glu Glu 405 410 415 Ser Cys Asp Pro Val Thr Gly Ala Cys His Leu Glu Thr Asn Gln Arg 420 425 430 Lys Gly Val Met Gly Ala Gly Ala Leu Leu Thr Leu Leu Leu Gly Leu 435 440 445 Leu Leu Ser Leu Leu Gly Cys Cys Cys Ala Cys Arg Gly Lys Asp Ser 450 455 460 Ala Arg Arg Glu Leu Thr Leu Gly Arg Lys Lys Ala Pro Gln Arg Phe 465 470 475 480 Cys Gly Ser Phe Ser Arg Ile Ser Met Lys Leu Pro Arg Ile Pro Leu 485 490 495 Arg Arg Gln Lys Leu Pro Lys Val Val Val Ala His His Asp Leu Asp 500 505 510 Asn Thr Leu Asn Cys Ser Phe Leu Asp Pro Pro Ser Gly Leu Glu Gln 515 520 525 Pro Ser Pro Ser Trp Ser Ser Arg Ala Ser Phe Ser Ser Phe Asp Thr 530 535 540 Thr Asp Glu Gly Pro Val Tyr Cys Val Pro His Glu Glu Ala Thr Ala 545 550 555 560 Asp Ser Arg Asp Leu Glu Ala Thr Ala Ala Leu Thr Glu Val Ala Ala 565 570 575 Val Ser Leu Glu Pro Thr Gly Thr Ser Thr Pro Gly Glu Glu Ala Ala 580 585 590 Val Leu Pro Ala Ser Ser Asp Ser Glu Arg Ser Ala Ser Ser Val Glu 595 600 605 Gly Pro Ser Gly Ala Leu Tyr Ala Arg Val Ala Arg Arg Glu Ala Arg 610 615 620 Pro Ala Arg Thr Arg Asn Glu Ala Gly Gly Leu Ser Leu Ser Pro Ser 625 630 635 640 Pro Glu Arg Arg Lys Pro Pro Pro Pro Asp Pro Ala Thr Lys Pro Lys 645 650 655 Val Ser Trp Ile His Gly Lys His Ser Ala Ala Ala Ala Ala Pro Ser 660 665 670 Pro Pro Pro Ala Gly Arg Lys Ala Ala Pro Ser Pro Ser Gly Arg Lys 675 680 685 Arg Thr Pro Ser Asn Ser Ser Val Gln Pro Pro Gly Leu Thr Glu Glu 690 695 700 Ala Pro Gly Pro Ala Ser Pro Thr Pro Pro Arg Ala Arg Ala Arg Gly 705 710 715 720 Arg Gly Leu Gly Leu Ser Glu Pro Thr Asp Ala Gly Gly Pro Pro Arg 725 730 735 Ser Ala Pro Glu Ala Ala Ser Met Leu Ala Ala Glu Leu Arg Asp Lys 740 745 750 Thr Arg Ser Leu Gly Arg Ala Glu Lys Pro Pro Pro Pro Gln Lys Ala 755 760 765 Lys Arg Ser Val Leu Pro Ala Ala Thr Val Arg Thr Ala Ser Ala Ser 770 775 780 Glu Ala Ser Gly Ser Glu Lys Ala Ala Ala Ser Ala Pro Ala Pro Glu 785 790 795 800 Thr Pro Arg Lys Lys Thr Pro Ile Gln Lys Pro Pro Arg Lys Lys Ser 805 810 815 Arg Glu Ala Ala Gly Glu Pro Ser Arg Ala Gly Thr Ala Pro Gly Ala 820 825 830 Ser <210> 3 <211> 44 <212> DNA <213> Artificial Sequence <400> 3 gactagttct agatcgcgag cggccgccct tttttttttt tttt 44 <210> 4 <211> 14 <212> DNA <213> Artificial Sequence <400> 4 ctgtctgtgg atcg 14 <210> 5 <211> 32 <212> DNA <213> Artificial Sequence <400> 5 cctcgttttc tgagcacgtg gaattgcctt cg 32 <210> 6 <211> 22 <212> DNA <213> Artificial Sequence <400> 6 agccagagca gcagcagcag tc 22 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <400> 7 tgcgcgacaa gactcgcagc 20 <210> 8 <211> 22 <212> DNA <213> Artificial Sequence <400> 8 aaggcatttc attggccccc aa 22 <210> 9 <211> 22 <212> DNA <213> Artificial Sequence <400> 9 actccgcttc cggccgccct tg 22 <210> 10 <211> 21 <212> DNA <213> Artificial Sequence <400> 10 agctttggcc tgctatgagg a 21 <210> 11 <211> 37 <212> DNA <213> Artificial Sequence <400> 11 ggccacgcgt cgactagtac tttttttttt ttttttt 37 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <400> 12 ggccacgcgt cgactagtac 20[Sequence List] SEQUENCE LISTING <110> Shionogi & Co., Ltd. <120> A Gene Encoding Mouse Nures Cell Receptor <130> A005977 <140> <141> <160> 12 <170> PatentIn Ver. 2.0 <210> 1 <211> 3274 <212> DNA <213> Mus musculus <220> <221> CDS <222> (65) .. (2563) <400> 1 actccgcttc cggccgccct tgccgcggcc gcacccgcgc ccacccgcgc ctgccccgcg 60 cctc atg gag gcc gca cgg ggg gcc ggg ccg gcg cgg cgc cag 109 Met Glu Gly Ala Gly Ser Arg Gly Ala Gly Pro Ala Arg Arg Gln 1 5 10 15 gga gcc cga ggg ctg gga ctg ctg ctg ctg ctg ctc tgg ctg ctg ccc ggt Gly 157 Gly Leu Gly Leu Leu Leu Leu Leu Trp Leu Leu Pro Gly 20 25 30 ctc gcg gcg ccc cag gac ttg aac ccg cga ggc cgc aac gtg tgc cgc 205 Leu Ala Ala Pro Gln Asp Leu Asn Pro Arg Gly Arg Asn Valsg Cyg 45 acg ccc ggt tcc cag gtg ctc acg tgt tgc gct ggc tgg agg cag ctg 253 Thr Pro Gly Ser Gln Val Leu Thr Cys Cys Ala Gly Trp Arg Gln Leu 50 55 60 ggg gat gag tgt ggg ata gcg gtg tgc atagacc acg tgc tca 301 Gly Asp Glu Cys Gly Ile Ala Val Cys Glu Gly Asn Ser Thr Cys Ser 65 70 75 gaa aac gag gtg tgc gtg cgg cca ggc gaa tgc cgc tgc cga cat ggc 349 Glu Asn Glu Val Cys Val Arg Pro Gly Glu Cys Arg Cys Arg His Gly 80 85 90 95 tac ttt ggt gcc aac tgc gac aca aag tgc ccg cgc cag ttc tgg ggc 397 Tyr Phe Gly Ala Asn Cys Asp Thr Lys Cys Pro Arg Gln Phe Trp Gly 100 105 110 cct gac tgc aag gag agg tgc agt tgc cac ccg cac gga cag tc Cys Lys Glu Arg Cys Ser Cys His Pro His Gly Gln Cys Glu 115 120 125 gac gtg acc gga cag tgt acg tgt cac gcg cgc cgc tgg ggt gcg cgc 493 Asp Val Thr Gly Gln Cys Thr Cys His Ala Arg Arg Trp Gly Ala Arg 130 135 140 tgc gag cat gct tgc caa tgc cag cat ggc acg tgc cac ccg cgg agc 541 Cys Glu His Ala Cys Gln Cys Gln His Gly Thr Cys His Pro Arg Ser 145 150 155 ggc gcg tgc cgg tgc gag ccg ggc tgg gcg caa tgc gct agc 589 Gly Ala Cys Arg Cys Glu Pro Gly Trp Trp Gly Ala Gln Cys Ala Ser 160 165 170 175 gct tgc tat tgc agc gct act tcc cgg tgc gat cca cag aca ggc gcc 637 Ala Cys Tyr Cy Ser Ser Ar g Cys Asp Pro Gln Thr Gly Ala 180 185 190 tgc ctg tgc cac gta ggc tgg tgg ggc cgc agc tgt aac aac cag tgc 685 Cys Leu Cys His Val Gly Trp Trp Gly Arg Ser Cys Asn Asn Gln Cys 195 200 205 gcc tgc tcg tcg ccc tgc gag cag cag agt ggc cgc tgc cag tgt 733 Ala Cys Asn Ser Ser Pro Cys Glu Gln Gln Ser Gly Arg Cys Gln Cys 210 215 220 cgc gag cgc atg ttt ggc gcc cgc tgt gat cgc tat tg Arg Glu Arg Met Phe Gly Ala Arg Cys Asp Arg Tyr Cys Gln Cys Ser 225 230 235 cac ggt cgc tgc cac ccg gtg gac ggc acg tgt gcc tgc gat cct ggc 829 His Gly Arg Cys His Pro Val Asp Gly Thr Cys Ala Cys Pro Gly 240 245 250 255 tac cgg ggc aag tat tgt cgc gag cca tgc ccc gct gga ttc tat ggc 877 Tyr Arg Gly Lys Tyr Cys Arg Glu Pro Cys Pro Ala Gly Phe Tyr Gly 260 265 270 cc ggg ggc tgt cgc cgt cgg caa tgc aaa ggc cag cag ccg tgc 925 Pro Gly Cys Arg Arg Arg Cys Gly Gln Cys Lys Gly Gln Gln Pro Cys 275 280 285 acg gta gtc gaa ggc cgc tgt ctg aca tgc gag ccc ggc Tgg Valac g 97 A rg Cys Leu Thr Cys Glu Pro Gly Trp Asn Gly 290 295 300 acc aaa tgt gac caa ccc tgc gcc acc ggt ttc tac ggc gaa ggt tgt 1021 Thr Lys Cys Asp Gln Pro Cys Ala Thr Gly Phe Tyr Gly Glu Gly Cys 305 310 315 ggc cac cgc tgc cca ccc tgc cgc gac ggg cat gcc tgc aac cat gtc 1069 Gly His Arg Cys Pro Pro Cys Arg Asp Gly His Ala Cys Asn His Val 320 325 330 335 acc ggc aag tgt acg cac tgc aat gcg ggc atg atg gac cgg tgc 1117 Thr Gly Lys Cys Thr His Cys Asn Ala Gly Trp Ile Gly Asp Arg Cys 340 345 350 gag act aag tgc agt aat ggc act tac ggt gag gac tgt gcc ttc gtg 1165 Glu Thr Lys Cys Ser Asn Gly Thr Tyr Gly Glu Asp Cys Ala Phe Val 355 360 365 tgc tct gat tgc ggc agc ggc cac tgt gac ttc cag tcc ggg cgc tgc 1213 Cys Ser Asp Cys Gly Ser Gly His Cys Asp Phe Gln Ser Gly Arg Cys 370 375 380 ctt cct gc gtt cac gga cct cac tgt aat gta act tgc ccg 1261 Leu Cys Ser Pro Gly Val His Gly Pro His Cys Asn Val Thr Cys Pro 385 390 395 gcc ggg ctc cac ggc gtg gac tgc gcc cag gcc tgc agc tgt cac gag 1309 A la Gly Leu His Gly Val Asp Cys Ala Gln Ala Cys Ser Cys His Glu 400 405 410 415 gaa tca tgc gac ccg gtc acc ggt gcc tgc cac ctg gag acc aat cag 1357 Glu Ser Cys Asp Pro Val Thr Gly Ala Cys His Leu Glu Thr Asn Gln 420 425 430 cgc aaa ggt gtg atg ggc gcg ggc gct ctg ctc acg ctg ctc ctc ggc 1405 Arg Lys Gly Val Met Gly Ala Gly Ala Leu Leu Thr Leu Leu Leu Gly 435 440 445 ctg ct gt g ct ct g ct ct ct g ct gt g ct ct gt g tgc tgc gcc tgc cgg ggc aag gac 1453 Leu Leu Leu Ser Leu Leu Gly Cys Cys Cys Ala Cys Arg Gly Lys Asp 450 455 460 tcg gcg cgc cgg gag ctc acc ctt gga agg aag aag gcg cct caa cgt Arg A1 G Leu Thr Leu Gly Arg Lys Lys Ala Pro Gln Arg 465 470 475 ttt tgt gga agc ttc agc cgc atc agc atg aag ctg ccc cga atc ccg 1549 Phe Cys Gly Ser Phe Ser Arg Ile Ser Met Lys Leu Pro Arg Ile Pro 480 485 495 ctt cgc agg cag aag ctg ccc aaa gtc gta gtg gcc cat cat gac cta 1597 Leu Arg Arg Gln Lys Leu Pro Lys Val Val Val Ala His His Asp Leu 500 505 510 gac aac aca ctc aac tgc agt ttt ctg gac cca ccc tca ggg ctg gag 1645 Asp Asn Thr Leu Asn Cys Ser Phe Leu Asp Pro Pro Ser Gly Leu Glu 515 520 525 cag ccc tct cca tca tgg tcc tcc agg gcc tcc ttc tca tca ttc gac 1693 Gln Pro Ser Pro Ser Trp Ser Ser Arg Ala Ser Phe Ser Ser Phe Asp 530 535 540 acc aca gat gaa ggc cct gtg tac tgt gtg ccc cac gag gaa gcg act 1741 Thr Thr Asp Glu Gly Pro Val Tyr Cys Val Pro His Glu Glu Ala Thr 545 550 555 555 gcc gac agc cga gac ctg gaa gcg act gcc gct ctc act gag gtg gcc 1789 Ala Asp Ser Arg Asp Leu Glu Ala Thr Ala Ala Leu Thr Glu Val Ala 560 565 570 570 575 gct gtg tcc tta gag ccc acg ggc acc tcg acg ccc ggg gag gag Ala Val Ser Leu Glu Pro Thr Gly Thr Ser Thr Pro Gly Glu Glu Ala 580 585 590 gcg gtc ctc cct gca tcc tca gac agc gag cgc tcc gca tca agc gtg 1885 Ala Val Leu Pro Ala Ser Ser Asp Ser Glu Arg Ser Ala Ser Ser Val 595 600 605 gag ggg ccg agc ggg gcg ctg tac gcg cgt gtg gcc cgg cgc gag gcc 1933 Glu Gly Pro Ser Gly Ala Leu Tyr Ala Arg Val Ala Arg Arg Glu Ala 610 615 620 cgg ccg gcc cgg accgaat gag gct ggg ggc ttg tca ctg tcc cca 1981 Arg Pro Ala Arg Thr Arg Asn Glu Ala Gly Gly Leu Ser Leu Ser Pro 625 630 635 tcg ccc gag cgc agg aag ccg cca cca cca gac cct gcc acc aag cct 2029 Ser Pro Glug Arg Lys Pro Pro Pro Pro Asp Pro Ala Thr Lys Pro 640 645 650 655 aag gtg tcc tgg atc cac ggc aag cac agc gcc gct gcc gct gca ccg 2077 Lys Val Ser Trp Ile His Gly Lys His Ser Ala Ala Ala Ala Ala Pro 660 665 670 tcg cct ccg cct gca ggc cgc aag gct gcg ccg agc cct agc ggg agg 2125 Ser Pro Pro Pro Ala Gly Arg Lys Ala Ala Pro Ser Pro Ser Gly Arg 675 680 685 aaa cgg acc ccc agc aac tcg tcg gtg cag gga ctg acc gag 2173 Lys Arg Thr Pro Ser Asn Ser Ser Val Gln Pro Pro Gly Leu Thr Glu 690 695 700 gag gcc ccc ggc ccg gct tca ccc acg cca ccc cgc gcc cga gcg cgc 2221 Glu Ala Pro Gly Pro Ala Ser Pro Thr Pro Pro Arg Ala Arg Ala Arg 705 710 715 ggc cgc ggc ctg ggg ctc tcg gag cca acg gac gcg gga ggt ccc ccg 2269 Gly Arg Gly Leu Gly Leu Ser Glu Pro Thr Asp Ala Gly Gly Pro Pro 720 725 730 735 cgc agc gcg ccc gag gcc gcc tct atg ctg gca gct gag ctg cgc gac 2317 Arg Ser Ala Pro Glu Ala Ala Ser Met Leu Ala Ala Glu Leu Arg Asp 740 745 750 aag act cgc agc tta ggc cgc gcc gag agcc gag gag agcc aag 2365 Lys Thr Arg Ser Leu Gly Arg Ala Glu Lys Pro Pro Pro Pro Gln Lys 755 760 765 gcc aag cgc tcc gtg ctc ccc gcc gcg acg gtc cgc aca gcc tcg gcg 2413 Ala Lys Arg Ser Val Leu Pro Ala Ala Thr Val Arg Thr Ala Ser Ala 770 775 780 tcc gag gcc tcg ggg tca gag aag gcg gcg gcc agc gca cct gcg ccc 2461 Ser Glu Ala Ser Gly Ser Glu Lys Ala Ala Ala Ser Ala Pro Ala Pro 785 790 795 gag acc cct cgg aag aaa acc ccc atc cag aaa ccg cct cgg aag aag 2509 Glu Thr Pro Arg Lys Lys Thr Pro Ile Gln Lys Pro Pro Arg Lys Lys 800 805 810 815 agc agg gag gca gcg ggg gag ccg agt agg gcg ggc acg gcc ccc gga 2557 Ser Arg Ala Ala Gly Glu Pro Ser Arg Ala Gly Thr Ala Pro Gly 820 825 830 gct tcc taagctcgca gccccaggag gctttctcc caccatttcc ccgcgcggcc 2613 Ala Ser gcagcgaagg catttcattg gcccccaaag cccagcgcccc gccagcc t gcgtctggtt 2673 ggcctaggct caagcagccg cggcctggtt ggatctgctc tcgggcctcg cagacactta 2733 gctggctacc cgctcccact agcaaagttg tggagctttt ctagtaatct ctgtctcgtt 2793 ggccatggct tggagagcct acagacttct tactggccaa gaagagtgtt cttggcaggg 2853 ctaccttgtc actggccgat gccagcagcg cttctgcctc ttggctgcct ctcatttgcc 2913 aaggcctggt gcctatggct gaagggtctt tttctctgaa gacaaaaaga ggttgcgtcc 2973 ataaactggg ctccagagta tctggttggc ccgaacctgg ggagaagagc tggtctcttc 3033 ttcgcagggg gctcagccca tgttggcttg tccccttccc acgcacgcca gccctggtct 3093 ctcagccatc aagctggttt tgatggcctc ctatcacccc acgagggaac cccagggcct 3153 actctggtgg ctttagatgt atttataggc cctgggcagg gcttctctca tcccatctgg 3213 gaccttctgg atgggctcct catagcaggc caaagctttc tttaataaaa tgcttctccc 3273 c 3274 <210> 2 <211> 833 <212> PRT <213> Mus musculus <400> 2 Met Glu Gly Ala Gly Ser Arg Gly Ala Gly Pro Ala Arg Arg Gln Gly 1 5 10 15 Ala Arg Gly Leu Gly Leu Leu Leu Leu Leu Trp Leu Leu Pro Gly Leu 20 25 30 Ala Ala Pro Gln Asp Leu Asn Pro Arg Gly Arg Asn Val Cys Arg Th r 35 40 45 Pro Gly Ser Gln Val Leu Thr Cys Cys Ala Gly Trp Arg Gln Leu Gly 50 55 60 Asp Glu Cys Gly Ile Ala Val Cys Glu Gly Asn Ser Thr Cys Ser Glu 65 70 75 80 Asn Glu Val Cys Val Arg Pro Gly Glu Cys Arg Cys Arg His Gly Tyr 85 90 95 Phe Gly Ala Asn Cys Asp Thr Lys Cys Pro Arg Gln Phe Trp Gly Pro 100 105 110 Asp Cys Lys Glu Arg Cys Ser Cys His Pro His Gly Gln Cys Glu Asp 115 120 125 Val Thr Gly Gln Cys Thr Cys His Ala Arg Arg Trp Gly Ala Arg Cys 130 135 140 Glu His Ala Cys Gln Cys Gln His Gly Thr Cys His Pro Arg Ser Gly 145 150 155 160 Ala Cys Arg Cys Glu Pro Gly Trp Trp Gly Ala Gln Cys Ala Ser Ala 165 170 175 Cys Tyr Cys Ser Ala Thr Ser Arg Cys Asp Pro Gln Thr Gly Ala Cys 180 185 190 Leu Cys His Val Gly Trp Trp Gly Arg Ser Cys Asn Asn Gln Cys Ala 195 200 205 Cys Asn Ser Ser Pro Cys Glu Gln Gln Ser Gly Arg Cys Gln Cys Arg 210 215 220 Glu Arg Met Phe Gly Ala Arg Cys Asp Arg Tyr Cys Gln Cys Ser His 225 230 235 240 Gly Arg Cys His Pro Val Asp Gly Thr Cys Ala Cys Asp Pro Gly Tyr 245 250 25 5 Arg Gly Lys Tyr Cys Arg Glu Pro Cys Pro Ala Gly Phe Tyr Gly Pro 260 265 270 Gly Cys Arg Arg Arg Cys Gly Gln Cys Lys Gly Gln Gln Pro Cys Thr 275 280 285 Val Val Glu Gly Arg Cys Leu Thr Cys Glu Pro Gly Trp Asn Gly Thr 290 295 300 Lys Cys Asp Gln Pro Cys Ala Thr Gly Phe Tyr Gly Glu Gly Cys Gly 305 310 315 320 His Arg Cys Pro Pro Cys Arg Asp Gly His Ala Cys Asn His Val Thr 325 330 335 Gly Lys Cys Thr His Cys Asn Ala Gly Trp Ile Gly Asp Arg Cys Glu 340 345 350 Thr Lys Cys Ser Asn Gly Thr Tyr Gly Glu Asp Cys Ala Phe Val Cys 355 360 365 Ser Asp Cys Gly Ser Gly His Cys Asp Phe Gln Ser Gly Arg Cys Leu 370 375 380 380 Cys Ser Pro Gly Val His Gly Pro His Cys Asn Val Thr Cys Pro Ala 385 390 395 400 Gly Leu His Gly Val Asp Cys Ala Gln Ala Cys Ser Cys His Glu Glu 405 410 415 Ser Cys Asp Pro Val Thr Gly Ala Cys His Leu Glu Thr Asn Gln Arg 420 425 430 Lys Gly Val Met Gly Ala Gly Ala Leu Leu Thr Leu Leu Leu Gly Leu 435 440 445 445 Leu Leu Ser Leu Leu Gly Cys Cys Cys Ala Cys Arg Gly Lys Asp Ser 450 455 460 Al a Arg Arg Glu Leu Thr Leu Gly Arg Lys Lys Ala Pro Gln Arg Phe 465 470 475 480 Cys Gly Ser Phe Ser Arg Ile Ser Met Lys Leu Pro Arg Ile Pro Leu 485 490 495 Arg Arg Gln Lys Leu Pro Lys Val Val Val Ala His His Asp Leu Asp 500 505 510 Asn Thr Leu Asn Cys Ser Phe Leu Asp Pro Pro Ser Gly Leu Glu Gln 515 520 525 Pro Ser Pro Ser Trp Ser Ser Arg Ala Ser Phe Ser Ser Phe Asp Thr 530 535 540 Thr Asp Glu Gly Pro Val Tyr Cys Val Pro His Glu Glu Ala Thr Ala 545 550 555 560 Asp Ser Arg Asp Leu Glu Ala Thr Ala Ala Leu Thr Glu Val Ala Ala 565 570 575 Val Ser Leu Glu Pro Thr Gly Thr Ser Thr Pro Gly Glu Glu Ala Ala 580 585 590 Val Leu Pro Ala Ser Ser Asp Ser Glu Arg Ser Ala Ser Ser Val Glu 595 600 605 Gly Pro Ser Gly Ala Leu Tyr Ala Arg Val Ala Arg Arg Glu Ala Arg 610 615 620 Pro Ala Arg Thr Arg Asn Glu Ala Gly Gly Leu Ser Leu Ser Pro Ser 625 630 635 640 640 Pro Glu Arg Arg Lys Pro Pro Pro Pro Asp Pro Ala Thr Lys Pro Lys 645 650 655 Val Ser Trp Ile His Gly Lys His Ser Ala Ala Ala Ala Ala Pro Ser 660 665 670 P ro Pro Pro Ala Gly Arg Lys Ala Ala Pro Ser Pro Ser Gly Arg Lys 675 680 685 Arg Thr Pro Ser Asn Ser Ser Val Gln Pro Pro Gly Leu Thr Glu Glu 690 695 700 Ala Pro Gly Pro Ala Ser Pro Thr Pro Pro Arg Ala Arg Ala Arg Gly 705 710 715 715 720 Arg Gly Leu Gly Leu Ser Glu Pro Thr Asp Ala Gly Gly Pro Pro Arg 725 730 735 Ser Ala Pro Glu Ala Ala Ser Met Leu Ala Ala Glu Leu Arg Asp Lys 740 745 750 Thr Arg Ser Leu Gly Arg Ala Glu Lys Pro Pro Pro Pro Gln Lys Ala 755 760 765 Lys Arg Ser Val Leu Pro Ala Ala Thr Val Arg Thr Ala Ser Ala Ser 770 775 780 Glu Ala Ser Gly Ser Glu Lys Ala Ala Ala Ser Ala Pro Ala Pro Glu 785 790 795 800 Thr Pro Arg Lys Lys Thr Pro Ile Gln Lys Pro Pro Arg Lys Lys Ser 805 810 815 Arg Glu Ala Ala Gly Glu Pro Ser Arg Ala Gly Thr Ala Pro Gly Ala 820 825 830 Ser <210> 3 <211> 44 <212> DNA <213> Artificial Sequence <400> 3 gactagttct agatcgcgag cggccgccct tttttttttt tttt 44 <210> 4 <211> 14 <212> DNA <213> Artificial Sequence <400> 4 ctgtctgtgg atcg 14 <210> 5 <211 > 32 <212> DNA <213> Ar tificial Sequence <400> 5 cctcgttttc tgagcacgtg gaattgcctt cg 32 <210> 6 <211> 22 <212> DNA <213> Artificial Sequence <400> 6 agccagagca gcagcagcag tc 22 <210> 7 <211> 20 <212> DNA <213 > Artificial Sequence <400> 7 tgcgcgacaa gactcgcagc 20 <210> 8 <211> 22 <212> DNA <213> Artificial Sequence <400> 8 aaggcatttc attggccccc aa 22 <210> 9 <211> 22 <212> DNA <213> Artificial Sequence <400> 9 actccgcttc cggccgccct tg 22 <210> 10 <211> 21 <212> DNA <213> Artificial Sequence <400> 10 agctttggcc tgctatgagg a 21 <210> 11 <211> 37 <212> DNA <213> Artificial Sequence <400> 11 ggccacgcgt cgactagtac tttttttttt ttttttt 37 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <400> 12 ggccacgcgt cgactagtac 20
【図１Ａ、図１Ｂ】 マウスナース細胞レセプターcDNA
（mB6TNC#10）の塩基配列およびアミノ酸を示す図であ
る。FIGS. 1A and 1B: Mouse nurse cell receptor cDNA
It is a figure which shows the base sequence and amino acid of (mB6TNC # 10).
【図２Ａ、図２Ｂ】 マウスナース細胞レセプターのア
ミノ酸配列（mB6TNC#10）とヒトアセチルLDLレセプター
のアミノ酸配列（hAcLDLR）の相同性を示す図である。2A and 2B are diagrams showing the homology between the amino acid sequence of mouse nurse cell receptor (mB6TNC # 10) and the amino acid sequence of human acetyl LDL receptor (hAcLDLR).
【図３】マウスナース細胞レセプター（mB6TNC#10）と
ヒトアセチルLDLレセプター（hAc-LDLR）で保存されて
いる１０個のシステイン残基とグリシン残基の繰り返し
配列を示す図である。FIG. 3 is a diagram showing a repeated sequence of ten cysteine residues and glycine residues conserved in a mouse nurse cell receptor (mB6TNC # 10) and a human acetyl LDL receptor (hAc-LDLR).
【図４】マウスナース細胞レセプター（mB6TNC#10）と
ヒトアセチルLDLレセプター（hAc-LDLR）で保存されて
いるEGF様リピートを示す図である。FIG. 4 shows EGF-like repeats conserved by a mouse nurse cell receptor (mB6TNC # 10) and a human acetyl LDL receptor (hAc-LDLR).
【図５】マウスナース細胞レセプターのアミノ酸配列中
の、疎水性アミノ酸部位、EGF様リピート部位、SH２ド
メインを持つタンパク質の結合部位、SH３ドメインを持
つタンパク質の結合部位を示す図である。FIG. 5 is a diagram showing a hydrophobic amino acid site, an EGF-like repeat site, a binding site of a protein having an SH2 domain, and a binding site of a protein having an SH3 domain in the amino acid sequence of a mouse nurse cell receptor.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ｃ０７Ｋ 14/705 Ｃ０７Ｋ 14/705 16/28 16/28 Ｃ１２Ｎ 15/02 Ｃ１２Ｐ 21/08 Ｃ１２Ｐ 21/08 Ｇ０１Ｎ 33/15 Ｚ Ｇ０１Ｎ 33/15 33/50 Ｔ 33/50 Ｐ 33/566 33/566 Ｇ０１Ｎ 33/577 Ｂ // Ｇ０１Ｎ 33/577 Ｃ１２Ｎ 15/00 Ｃ (Ｃ１２Ｎ 15/09 ＺＮＡ Ｃ１２Ｒ 1:91） Ｆターム(参考） 2G045 AA25 AA34 AA35 BB20 CB01 CB21 DA12 DA13 DA14 DA36 FB03 4B024 AA01 AA11 BA43 BA63 CA04 CA12 DA06 EA04 GA11 HA01 HA15 4B064 AG20 AG27 CA02 CA19 CC24 DA01 DA13 4C084 AA17 ZB072 4H045 AA10 AA11 BA10 CA40 DA50 DA86 EA20 EA50 FA74 ──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme coat ゛ (Reference) C07K 14/705 C07K 14/705 16/28 16/28 C12N 15/02 C12P 21/08 C12P 21/08 G01N 33/15 Z G01N 33/15 33/50 T 33/50 P 33/566 33/566 G01N 33/577 B // G01N 33/577 C12N 15/00 C (C12N 15/09 ZNA C12R 1:91) F Term (reference) 2G045 AA25 AA34 AA35 BB20 CB01 CB21 DA12 DA13 DA14 DA36 FB03 4B024 AA01 AA11 BA43 BA63 CA04 CA12 DA06 EA04 GA11 HA01 HA15 4B064 AG20 AG27 CA02 CA19 CC24 DA01 DA13 4C084 AA11 ZB072A DA0
Claims (20)
までのアミノ酸配列を含むポリペプチド。(1) Ser from position 1 to position 833 of SEQ ID NO: 2
A polypeptide comprising the amino acid sequence of
もしくは数個のアミノ酸が置換、欠失、挿入または付加
されたアミノ酸配列を含み、かつマウスナース細胞レセ
プターであるポリペプチド。2. The amino acid sequence according to claim 1, wherein
Alternatively, a polypeptide comprising an amino acid sequence in which several amino acids have been substituted, deleted, inserted or added, and which is a mouse nurse cell receptor.
スナース細胞レセプター。3. A mouse nurse cell receptor comprising the polypeptide according to claim 1.
コードするDNA。(4) a DNA encoding the polypeptide of (1) or (2);
までの塩基配列を含む請求項４記載のDNA。5. An amino acid sequence of SEQ ID NO: 1 from A at position 65 to C at position 2563.
The DNA according to claim 4, which comprises a nucleotide sequence up to:
ジェントな条件でハイブリダイズし、かつマウスナース
細胞レセプターであるポリペプチドをコードするDNA。6. A DNA that hybridizes with the DNA of claim 4 or 5 under stringent conditions and encodes a polypeptide that is a mouse nurse cell receptor.
DNAからなるマウスナース細胞レセプター遺伝子。7. The method according to claim 4, 5 or 6, wherein
Mouse nurse cell receptor gene consisting of DNA.
少なくとも１４個の塩基を含み、該塩基配列と特異的に
結合するDNA。8. A DNA comprising at least 14 consecutive bases in the base sequence of SEQ ID NO: 1 and specifically binding to the base sequence.
基配列中の連続した少なくとも１４個の塩基を含む請求
項８に記載のDNA。9. The DNA according to claim 8, comprising at least 14 consecutive bases in the base sequence of any of SEQ ID NOs: 4 to 10.
を特異的に認識する抗体。10. An antibody that specifically recognizes the polypeptide according to claim 1 or 2.
に記載の抗体。11. The method according to claim 10, which is a monoclonal antibody.
The antibody according to 1.
を産生するハイブリドーマ。A hybridoma that produces the monoclonal antibody according to claim 11.
を有する発現ベクター。13. The DNA according to any one of claims 4 to 6
An expression vector having
導入して得られる形質転換体。A transformant obtained by introducing the expression vector according to claim 13 into a host.
る工程、および生産された組換えタンパク質を培養培地
から回収する工程を包含する、組換えマウスナース細胞
レセプターの製造方法。15. A method for producing a recombinant mouse nurse cell receptor, comprising a step of culturing the transformant according to claim 14, and a step of recovering the produced recombinant protein from a culture medium.
項１５に記載の製造方法より得られたマウスナース細胞
レセプターを用いた、マウスナース細胞レセプターに特
異的に結合するリガンドのスクリーニング方法。16. A method for screening a ligand that specifically binds to a mouse nurse cell receptor, using the transformant according to claim 14 or the mouse nurse cell receptor obtained by the production method according to claim 15.
項１５に記載の製造方法より得られたマウスナース細胞
レセプターと請求項１６に記載のスクリーニング方法よ
り得られるリガンドとの結合を阻害する化合物のスクリ
ーニング方法。[17] a compound which inhibits the binding of the transformant according to [14] or the mouse nurse cell receptor obtained by the method according to [15] to the ligand obtained by the screening method according to [16]; Screening method.
より得られる医薬。[18] a medicine obtained by the screening method according to [17];
ディジョージ症候群を検出するためのキット。(19) A DNA comprising the DNA according to (8) or (9),
Kit for detecting DiGeorge syndrome.
自己免疫疾患を検出するためのキット。20. A DNA comprising the DNA according to claim 8 or 9;
Kit for detecting autoimmune diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11046603A JP2000236882A (en) | 1999-02-24 | 1999-02-24 | Mouse nurse cell receptor gene |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11046603A JP2000236882A (en) | 1999-02-24 | 1999-02-24 | Mouse nurse cell receptor gene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000236882A true JP2000236882A (en) | 2000-09-05 |
Family
ID=12751888
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11046603A Pending JP2000236882A (en) | 1999-02-24 | 1999-02-24 | Mouse nurse cell receptor gene |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2000236882A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012513747A (en) * | 2008-12-24 | 2012-06-21 | アールエスアール リミテッド | Human anti-TSHR antibody |
-
1999
- 1999-02-24 JP JP11046603A patent/JP2000236882A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012513747A (en) * | 2008-12-24 | 2012-06-21 | アールエスアール リミテッド | Human anti-TSHR antibody |
| JP2016034934A (en) * | 2008-12-24 | 2016-03-17 | アールエスアール リミテッド | Human anti tshr antibody |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101446626B1 (en) | Composition and method for diagnosing kidney cancer and for predicting prognosis for kidney cancer patient | |
| EP1270724A2 (en) | Guanosine triphosphate-binding protein coupled receptors | |
| KR100566839B1 (en) | Oncology compositions and methods | |
| JP2002518048A (en) | Prostate cancer-related genes | |
| JPWO2002028894A1 (en) | Drug resistance-related genes and uses thereof | |
| US20030235833A1 (en) | Guanosine triphosphate-binding protein coupled receptors | |
| JP2003235573A (en) | Diabetic nephropathy marker and its use | |
| JP2003510053A (en) | Heparanase-2, a member of the heparanase protein family | |
| EP1711635A1 (en) | Genes associated with canine osteoarthritis and related methods and compositions | |
| US20040086913A1 (en) | Human genes and gene expression products XVI | |
| JP2000236882A (en) | Mouse nurse cell receptor gene | |
| EP1854881B1 (en) | METHODS FOR IDENTIFYING PURKINJE CELLS USING THE Corl2 GENE AS A TARGET | |
| US7105315B2 (en) | Transmembrane protein differentially expressed in cancer | |
| US20020102551A1 (en) | Nope polypeptides, encoding nucleic acids and methods of use | |
| US6586579B1 (en) | PR-domain containing nucleic acids, polypeptides, antibodies and methods | |
| JP2002541850A (en) | Genes and expression products from hematopoietic cells | |
| JP2000308492A (en) | Human nurse cell receptor gene | |
| US20030186241A1 (en) | Human choline/ethanolamine kinase (HCEK)-related gene variant associated with lung cancers | |
| CN101300348A (en) | Composition and method for kidney cancer diagnosis and prognosis prediction of kidney cancer patients | |
| JPH11332579A (en) | Tsc501 gene | |
| KR20220062881A (en) | Compositions, kits and methods for diagnosing cancer resistant to palbociclib, fulvestrant or combination thereof | |
| US20030186242A1 (en) | Human megakaryocyte-associated tyrosine kinase (MATK)-related gene variant associated with lung cancers | |
| JP2003274981A (en) | Protein overexpressed in cancer cells and gene encoding the same | |
| CA2493263A1 (en) | Novel gene associated with rheumatoid arthritis | |
| JP2002112787A (en) | HUMAN Lhx4 GENE |