Showing drug card for Etanercept (DB00005)

• BIOD00052
• BTD00052

• Approved
• Biotech
• Investigational

1. CD120b
2. TNF-R2
3. Tumor necrosis factor receptor 2
4. Tumor necrosis factor receptor superfamily member 1B precursor
5. Tumor necrosis factor receptor type II
6. etanercept
7. p75
8. p80 TNF-alpha receptor

1. Enbrel
2. Enbrel (Immunex Corp)

LPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPGQHAKVFCTKTSDTVCDSCEDST
YTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTCRPGWYCALSKQEGCRLCAPLRK
CRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICRPHQICNVVAIPGNASMDAVCTS
TSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTSFLLPMGPSPPAEGSTGDEPKSC
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPQVKFNWYVD
GVQVHNAKTKPREQQYNSTYRVVSVLTVLHQNWLDGKEYKCKVSNKALPAPIEKTISKAK
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

• Antirheumatic Agents
• Immunomodulatory Agents

• L04AA11

• 92:00.00

1. Drugs.com
2. Wikipedia
3. RxList

• Humans and other mammals

1. Tumor necrosis factor
2. High affinity immunoglobulin gamma Fc receptor I
3. Low affinity immunoglobulin gamma Fc region receptor III-B
4. Tumor necrosis factor receptor superfamily member 1B
5. Lymphotoxin-alpha
6. Complement C1s subcomponent
7. Complement C1r subcomponent
8. Complement C1q subcomponent subunit A
9. Complement C1q subcomponent subunit B
10. Complement C1q subcomponent subunit C
11. Low affinity immunoglobulin gamma Fc region receptor III-A
12. Low affinity immunoglobulin gamma Fc region receptor II-a
13. Low affinity immunoglobulin gamma Fc region receptor II-b
14. Low affinity immunoglobulin gamma Fc region receptor II-c

1. Cachectin
2. TNF-a
3. TNF-alpha
4. Tumor necrosis factor ligand superfamily member 2
5. Tumor necrosis factor precursor

MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL

• TNF (PF00229 )

• None

• 36-56

• Cell membrane
• single-pass type II membrane protein. Processed form:Secreted protein. Also exists as

ATGAGCACTGAAAGCATGATCCGGGACGTGGAGCTGGCCGAGGAGGCGCTCCCCAAGAAG
ACAGGGGGGCCCCAGGGCTCCAGGCGGTGCTTGTTCCTCAGCCTCTTCTCCTTCCTGATC
GTGGCAGGCGCCACCACGCTCTTCTGCCTGCTGCACTTTGGAGTGATCGGCCCCCAGAGG
GAAGAGTTCCCCAGGGACCTCTCTCTAATCAGCCCTCTGGCCCAGGCAGTCAGATCATCT
TCTCGAACCCCGAGTGACAAGCCTGTAGCCCATGTTGTAGCAAACCCTCAAGCTGAGGGG
CAGCTCCAGTGGCTGAACCGCCGGGCCAATGCCCTCCTGGCCAATGGCGTGGAGCTGAGA
GATAACCAGCTGGTGGTGCCATCAGAGGGCCTGTACCTCATCTACTCCCAGGTCCTCTTC
AAGGGCCAAGGCTGCCCCTCCACCCATGTGCTCCTCACCCACACCATCAGCCGCATCGCC
GTCTCCTACCAGACCAAGGTCAACCTCCTCTCTGCCATCAAGAGCCCCTGCCAGAGGGAG
ACCCCAGAGGGGGCTGAGGCCAAGCCCTGGTATGAGCCCATCTATCTGGGAGGGGTCTTC
CAGCTGGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGACTATCTCGACTTT
GCCGAGTCTGGGCAGGTCTACTTTGGGATCATTGCCCTGTGA

1. Neville MJ, Campbell RD: A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. J Immunol. 1999 Apr 15;162(8):4745-54. [PubMed ]
2. Watts AD, Hunt NH, Wanigasekara Y, Bloomfield G, Wallach D, Roufogalis BD, Chaudhri G: A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'. EMBO J. 1999 Apr 15;18(8):2119-26. [PubMed ]
3. Stevenson FT, Bursten SL, Locksley RM, Lovett DH: Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues. J Exp Med. 1992 Oct 1;176(4):1053-62. [PubMed ]
4. Jones EY, Stuart DI, Walker NP: The structure of tumour necrosis factor--implications for biological function. J Cell Sci Suppl. 1990;13:11-8. [PubMed ]
5. Van Ostade X, Tavernier J, Prange T, Fiers W: Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis. EMBO J. 1991 Apr;10(4):827-36. [PubMed ]
6. Eck MJ, Sprang SR: The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding. J Biol Chem. 1989 Oct 15;264(29):17595-605. [PubMed ]
7. Jones EY, Stuart DI, Walker NP: Structure of tumour necrosis factor. Nature. 1989 Mar 16;338(6212):225-8. [PubMed ]
8. Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, Goeddel DV, Gray PW: Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucleic Acids Res. 1985 Sep 11;13(17):6361-73. [PubMed ]
9. Nedospasov SA, Shakhov AN, Turetskaya RL, Mett VA, Azizov MM, Georgiev GP, Korobko VG, Dobrynin VN, Filippov SA, Bystrov NS, et al.: Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:611-24. [PubMed ]
10. Wang AM, Creasey AA, Ladner MB, Lin LS, Strickler J, Van Arsdell JN, Yamamoto R, Mark DF: Molecular cloning of the complementary DNA for human tumor necrosis factor. Science. 1985 Apr 12;228(4696):149-54. [PubMed ]
11. 3883195 Shirai T, Yamaguchi H, Ito H, Todd CW, Wallace RB: Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor. Nature. 1985 Feb 28-Mar 6;313(6005):803-6.
12. 3932069 Marmenout A, Fransen L, Tavernier J, Van der Heyden J, Tizard R, Kawashima E, Shaw A, Johnson MJ, Semon D, Muller R, et al.: Molecular cloning and expression of human tumor necrosis factor and comparison with mouse tumor necrosis factor. Eur J Biochem. 1985 Nov 4;152(3):515-22.
13. 6392892 Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV: Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20-1985 Jan 2;312(5996):724-9.
14. 8499947 Iris FJ, Bougueleret L, Prieur S, Caterina D, Primas G, Perrot V, Jurka J, Rodriguez-Tome P, Claverie JM, Dausset J, et al.: Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment. Nat Genet. 1993 Feb;3(2):137-45.
15. 8597870 Pocsik E, Duda E, Wallach D: Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells. J Inflamm. 1995;45(3):152-60.
16. 9034191 Moss ML, Jin SL, Milla ME, Bickett DM, Burkhart W, Carter HL, Chen WJ, Clay WC, Didsbury JR, Hassler D, Hoffman CR, Kost TA, Lambert MH, Leesnitzer MA, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su JL, Becherer JD, et al.: Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997 Feb 20;385(6618):733-6.
17. 9442056 Cha SS, Kim JS, Cho HS, Shin NK, Jeong W, Shin HC, Kim YJ, Hahn JH, Oh BH: High resolution crystal structure of a human tumor necrosis factor-alpha mutant with low systemic toxicity. J Biol Chem. 1998 Jan 23;273(4):2153-60.
18. 9488135 Reed C, Fu ZQ, Wu J, Xue YN, Harrison RW, Chen MJ, Weber IT: Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2. Protein Eng. 1997 Oct;10(10):1101-7.

1. Park YC, Burkitt V, Villa AR, Tong L, Wu H: Structural basis for self-association and receptor recognition of human TRAF2. Nature. 1999 Apr 8;398(6727):533-8. [PubMed ]
2. Sandborn WJ, Hanauer SB: Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharmacology, clinical results, and safety. Inflamm Bowel Dis. 1999 May;5(2):119-33. [PubMed ]
3. Grell M, Zimmermann G, Gottfried E, Chen CM, Grunwald U, Huang DC, Wu Lee YH, Durkop H, Engelmann H, Scheurich P, Wajant H, Strasser A: Induction of cell death by tumour necrosis factor (TNF) receptor 2, CD40 and CD30: a role for TNF-R1 activation by endogenous membrane-anchored TNF. EMBO J. 1999 Jun 1;18(11):3034-43. [PubMed ]
4. Moreland LW: Inhibitors of tumor necrosis factor: new treatment options for rheumatoid arthritis. Cleve Clin J Med. 1999 Jun;66(6):367-74. [PubMed ]
5. Calabrese LH: Rheumatoid arthritis and primary care: the case for early diagnosis and treatment. J Am Osteopath Assoc. 1999 Jun;99(6):313-21. [PubMed ]
6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed ]

1. CD64 antigen
2. Fc-gamma RI
3. FcRI
4. High affinity immunoglobulin gamma Fc receptor I precursor
5. IgG Fc receptor I

MWFLTTLLLWVPVDGQVDTTKAVITLQPPWVSVFQEETVTLHCEVLHLPGSSSTQWFLNG
TATQTSTPSYRITSASVNDSGEYRCQRGLSGRSDPIQLEIHRGWLLLQVSSRVFTEGEPL
ALRCHAWKDKLVYNVLYYRNGKAFKFFHWNSNLTILKTNISHNGTYHCSGMGKHRYTSAG
ISVTVKELFPAPVLNASVTSPLLEGNLVTLSCETKLLLQRPGLQLYFSFYMGSKTLRGRN
TSSEYQILTARREDSGLYWCEAATEDGNVLKRSPELELQVLGLQLPTPVWFHVLFYLAVG
IMFLVNTVLWVTIRKELKRKKKWDLEISLDSGHEKKVISSLQEDRHLEEELKCQEQKEEQ
LQEGVHRKEPQGAT

• ig (PF00047 )

• 1-15

• 293-313

• Membrane
• single-pass type I membrane protein

ATGTGGTTCTTGACAACTCTGCTCCTTTGGGTTCCAGTTGATGGGCAAGTGGACACCACA
AAGGCAGTGATCTCTTTGCAGCCTCCATGGGTCAGCGTGTTCCAAGAGGAAACCGTAACC
TTGCACTGTGAGGTGCTCCATCTGCCTGGGAGCAGCTCTACACAGTGGTTTCTCAATGGC
ACAGCCACTCAGACCTCGACCCCCAGCTACAGAATCACCTCTGCCAGTGTCAATGACAGT
GGTGAATACAGGTGCCAGAGAGGTCTCTCAGGGCGAAGTGACCCCATACAGCTGGAAATC
CACAGAGGCTGGCTACTACTGCAGGTCTCCAGCAGAGTCTTCACGGAAGGAGAACCTCTG
GCCTTGAGGTGTCATGCGTGGAAGGATAAGCTGGTGTACAATGTGCTTTACTATCGAAAT
GGCAAAGCCTTTAAGTTTTTCCACTGGAATTCTAACCTCACCATTCTGAAAACCAACATA
AGTCACAATGGCACCTACCATTGCTCAGGCATGGGAAAGCATCGCTACACATCAGCAGGA
ATATCTGTCACTGTGAAAGAGCTATTTCCAGCTCCAGTGCTGAATGCATCTGTGACATCC
CCACTCCTGGAGGGGAATCTGGTCACCCTGAGCTGTGAAACAAAGTTGCTCTTGCAGAGG
CCTGGTTTGCAGCTTTACTTCTCCTTCTACATGGGCAGCAAGACCCTGCGAGGCAGGAAC
ACATCCTCTGAATACCAAATACTAACTGCTAGAAGAGAAGACTCTGGGTTATACTGGTGC
GAGGCTGCCACAGAGGATGGAAATGTCCTTAAGCGCAGCCCTGAGTTGGAGCTTCAAGTG
CTTGGCCTCCAGTTACCAACTCCTGTCTGGTTTCATGTCCTTTTCTATCTGGCAGTGGGA
ATAATGTTTTTAGTGAACACTGTTCTCTGGGTGACAATACGTAAAGAACTGAAAAGAAAG
AAAAAGTGGGATTTAGAAATCTCTTTGGATTCTGGTCATGAGAAGAAGGTAACTTCCAGC
CTTCAAGAAGACAGACATTTAGAAGAAGAGCTGAAATGTCAGGAACAAAAAGAAGAACAG
CTGCAGGAAGGGGTGCACCGGAAGGAGCCCCAGGGGGCCACGTAG

1. Ernst LK, van de Winkel JG, Chiu IM, Anderson CL: Three genes for the human high affinity Fc receptor for IgG (Fc gamma RI) encode four distinct transcription products. J Biol Chem. 1992 Aug 5;267(22):15692-700. [PubMed ]
2. Benech PD, Sastry K, Iyer RR, Eichbaum QG, Raveh DP, Ezekowitz RA: Definition of interferon gamma-response elements in a novel human Fc gamma receptor gene (Fc gamma RIb) and characterization of the gene structure. J Exp Med. 1992 Oct 1;176(4):1115-23. [PubMed ]
3. Porges AJ, Redecha PB, Doebele R, Pan LC, Salmon JE, Kimberly RP: Novel Fc gamma receptor I family gene products in human mononuclear cells. J Clin Invest. 1992 Nov;90(5):2102-9. [PubMed ]
4. Allen JM, Seed B: Isolation and expression of functional high-affinity Fc receptor complementary DNAs. Science. 1989 Jan 20;243(4889):378-81. [PubMed ]
5. Allen JM, Seed B: Nucleotide sequence of three cDNAs for the human high affinity Fc receptor (FcRI). Nucleic Acids Res. 1988 Dec 23;16(24):11824. [PubMed ]

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. CD16b antigen
2. Fc-gamma RIII
3. Fc-gamma RIII-beta
4. Fc-gamma RIIIb
5. FcR-10
6. FcRIII
7. FcRIIIb
8. IgG Fc receptor III-1
9. Low affinity immunoglobulin gamma Fc region receptor III-B precursor

MWQLLLPTALLLLVSAGMRTEDLPKAVVFLEPQWYSVLEKDSVTLKCQGAYSPEDNSTQW
FHNESLISSQASSYFIDAATVNDSGEYRCQTNLSTLSDPVQLEVHIGWLLLQAPRWVFKE
EDPIHLRCHSWKNTALHKVTYLQNGKDRKYFHHNSDFHIPKATLKDSGSYFCRGLVGSKN
VSSETVNITITQGLAVSTISSFSPPGYQVSFCLVMVLLFAVDTGLYFSVKTNI

• ig (PF00047 )

• 1-16

• None

• Cell membrane
• GPI-anchor. Secreted protein. Note=Secreted after cleavage
• lipid-anchor

ATGTGGCAGCTGCTCCTCCCAACTGCTCTGCTACTTCTAGTTTCAGCTGGCATGCGGACT
GAAGATCTCCCAAAGGCTGTGGTGTTCCTGGAGCCTCAATGGTACAGCGTGCTTGAGAAG
GACAGTGTGACTCTGAAGTGCCAGGGAGCCTACTCCCCTGAGGACAATTCCACACAGTGG
TTTCACAATGAGAGCCTCATCTCAAGCCAGGCCTCGAGCTACTTCATTGACGCTGCCACA
GTCAACGACAGTGGAGAGTACAGGTGCCAGACAAACCTCTCCACCCTCAGTGACCCGGTG
CAGCTAGAAGTCCATATCGGCTGGCTGTTGCTCCAGGCCCCTCGGTGGGTGTTCAAGGAG
GAAGACCCTATTCACCTGAGGTGTCACAGCTGGAAGAACACTGCTCTGCATAAGGTCACA
TATTTACAGAATGGCAAAGACAGGAAGTATTTTCATCATAATTCTGACTTCCACATTCCA
AAAGCCACACTCAAAGATAGCGGCTCCTACTTCTGCAGGGGGCTTGTTGGGAGTAAAAAT
GTGTCTTCAGAGACTGTGAACATCACCATCACTCAAGGTTTGGCAGTGTCAACCATCTCA
TCATTCTCTCCACCTGGGTACCAAGTCTCTTTCTGCTTGGTGATGGTACTCCTTTTTGCA
GTGGACACAGGACTATATTTCTCTGTGAAGACAAACATTTGA

1. Sondermann P, Huber R, Oosthuizen V, Jacob U: The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex. Nature. 2000 Jul 20;406(6793):267-73. [PubMed ]
2. Zhang Y, Boesen CC, Radaev S, Brooks AG, Fridman WH, Sautes-Fridman C, Sun PD: Crystal structure of the extracellular domain of a human Fc gamma RIII. Immunity. 2000 Sep;13(3):387-95. [PubMed ]
3. Peltz GA, Grundy HO, Lebo RV, Yssel H, Barsh GS, Moore KW: Human Fc gamma RIII: cloning, expression, and identification of the chromosomal locus of two Fc receptors for IgG. Proc Natl Acad Sci U S A. 1989 Feb;86(3):1013-7. [PubMed ]
4. Scallon BJ, Scigliano E, Freedman VH, Miedel MC, Pan YC, Unkeless JC, Kochan JP: A human immunoglobulin G receptor exists in both polypeptide-anchored and phosphatidylinositol-glycan-anchored forms. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5079-83. [PubMed ]
5. Ravetch JV, Perussia B: Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions. J Exp Med. 1989 Aug 1;170(2):481-97. [PubMed ]
6. Simmons D, Seed B: The Fc gamma receptor of natural killer cells is a phospholipid-linked membrane protein. Nature. 1988 Jun 9;333(6173):568-70. [PubMed ]
7. Gessner JE, Grussenmeyer T, Kolanus W, Schmidt RE: The human low affinity immunoglobulin G Fc receptor III-A and III-B genes. Molecular characterization of the promoter regions. J Biol Chem. 1995 Jan 20;270(3):1350-61. [PubMed ]
8. Bux J, Stein EL, Bierling P, Fromont P, Clay M, Stroncek D, Santoso S: Characterization of a new alloantigen (SH) on the human neutrophil Fc gamma receptor IIIb. Blood. 1997 Feb 1;89(3):1027-34. [PubMed ]

1. Hart SP, Ross JA, Ross K, Haslett C, Dransfield I: Molecular characterization of the surface of apoptotic neutrophils: implications for functional downregulation and recognition by phagocytes. Cell Death Differ. 2000 May;7(5):493-503. [PubMed ]
2. Criswell LA, Lum RF, Turner KN, Woehl B, Zhu Y, Wang J, Tiwari HK, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL Jr: The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis Rheum. 2004 Sep;50(9):2750-6. [PubMed ]
3. Hughes LB, Criswell LA, Beasley TM, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL: Genetic risk factors for infection in patients with early rheumatoid arthritis. Genes Immun. 2004 Dec;5(8):641-7. [PubMed ]
4. Ozgocmen S, Godekmerdan A, Ozkurt-Zengin F: Acute-phase response, clinical measures and disease activity in ankylosing spondylitis. Joint Bone Spine. 2007 May;74(3):249-53. Epub 2007 Mar 5. [PubMed ]

1. CD120b antigen
2. Etanercept
3. TNF-R2
4. Tumor necrosis factor receptor 2
5. Tumor necrosis factor receptor superfamily member 1B precursor
6. Tumor necrosis factor receptor type II
7. p75
8. p80 TNF-alpha receptor

MAPVAVWAALAVGLELWAAAHALPAQVAFTPYAPEPGSTCRLREYYDQTAQMCCSKCSPG
QHAKVFCTKTSDTVCDSCEDSTYTQLWNWVPECLSCGSRCSSDQVETQACTREQNRICTC
RPGWYCALSKQEGCRLCAPLRKCRPGFGVARPGTETSDVVCKPCAPGTFSNTTSSTDICR
PHQICNVVAIPGNASMDAVCTSTSPTRSMAPGAVHLPQPVSTRSQHTQPTPEPSTAPSTS
FLLPMGPSPPAEGSTGDFALPVGLIVGVTALGLLIIGVVNCVIMTQVKKKPLCLQREAKV
PHLPADKARGTQGPEQQHLLITAPSSSSSSLESSASALDRRAPTRNQPQAPGVEASGAGE
ARASTGSSDSSPGGHGTQVNVTCIVNVCSSSDHSSQCSSQASSTMGDTDSSPSESPKDEQ
VPFSKEECAFRSQLETPETLLGSTEEKPLPLGVPDAGMKPS

• TNFR_c6 (PF00020 )

• 1-22

• 258-287

• Isoform 1:Cell membrane
• single-pass type I membrane protein. Isoform 2:Secreted protein. TBP-II:Sec

ATGGCGCCCGTCGCCGTCTGGGCCGCGCTGGCCGTCGGACTGGAGCTCTGGGCTGCGGCG
CACGCCTTGCCCGCCCAGGTGGCATTTACACCCTACGCCCCGGAGCCCGGGAGCACATGC
CGGCTCAGAGAATACTATGACCAGACAGCTCAGATGTGCTGCAGCAAATGCTCGCCGGGC
CAACATGCAAAAGTCTTCTGTACCAAGACCTCGGACACCGTGTGTGACTCCTGTGAGGAC
AGCACATACACCCAGCTCTGGAACTGGGTTCCCGAGTGCTTGAGCTGTGGCTCCCGCTGT
AGCTCTGACCAGGTGGAAACTCAAGCCTGCACTCGGGAACAGAACCGCATCTGCACCTGC
AGGCCCGGCTGGTACTGCGCGCTGAGCAAGCAGGAGGGGTGCCGGCTGTGCGCGCCGCTG
CGCAAGTGCCGCCCGGGCTTCGGCGTGGCCAGACCAGGAACTGAAACATCAGACGTGGTG
TGCAAGCCCTGTGCCCCGGGGACGTTCTCCAACACGACTTCATCCACGGATATTTGCAGG
CCCCACCAGATCTGTAACGTGGTGGCCATCCCTGGGAATGCAAGCATGGATGCAGTCTGC
ACGTCCACGTCCCCCACCCGGAGTATGGCCCCAGGGGCAGTACACTTACCCCAGCCAGTG
TCCACACGATCCCAACACACGCAGCCAACTCCAGAACCCAGCACTGCTCCAAGCACCTCC
TTCCTGCTCCCAATGGGCCCCAGCCCCCCAGCTGAAGGGAGCACTGGCGACTTCGCTCTT
CCAGTTGGACTGATTGTGGGTGTGACAGCCTTGGGTCTACTAATAATAGGAGTGGTGAAC
TGTGTCATCATGACCCAGGTGAAAAAGAAGCCCTTGTGCCTGCAGAGAGAAGCCAAGGTG
CCTCACTTGCCTGCCGATAAGGCCCGGGGTACACAGGGCCCCGAGCAGCAGCACCTGCTG
ATCACAGCGCCGAGCTCCAGCAGCAGCTCCCTGGAGAGCTCGGCCAGTGCGTTGGACAGA
AGGGCGCCCACTCGGAACCAGCCACAGGCACCAGGCGTGGAGGCCAGTGGGGCCGGGGAG
GCCCGGGCCAGCACCGGGAGCTCAGATTCTTCCCCTGGTGGCCATGGGACCCAGGTCAAT
GTCACCTGCATCGTGAACGTCTGTAGCAGCTCTGACCACAGCTCACAGTGCTCCTCCCAA
GCCAGCTCCACAATGGGAGACACAGATTCCAGCCCCTCGGAGTCCCCGAAGGACGAGCAG
GTCCCCTTCTCCAAGGAGGAATGTGCCTTTCGGTCACAGCTGGAGACGCCAGAGACCCTG
CTGGGGAGCACCGAAGAGAAGCCCCTGCCCCTTGGAGTGCCTGATGCTGGGATGAAGCCC
AGTTAA

1. Park YC, Burkitt V, Villa AR, Tong L, Wu H: Structural basis for self-association and receptor recognition of human TRAF2. Nature. 1999 Apr 8;398(6727):533-8. [PubMed ]
2. Tsuchiya N, Komata T, Matsushita M, Ohashi J, Tokunaga K: New single nucleotide polymorphisms in the coding region of human TNFR2: association with systemic lupus erythematosus. Genes Immun. 2000 Dec;1(8):501-3. [PubMed ]
3. Morita C, Horiuchi T, Tsukamoto H, Hatta N, Kikuchi Y, Arinobu Y, Otsuka T, Sawabe T, Harashima S, Nagasawa K, Niho Y: Association of tumor necrosis factor receptor type II polymorphism 196R with Systemic lupus erythematosus in the Japanese: molecular and functional analysis. Arthritis Rheum. 2001 Dec;44(12):2819-27. [PubMed ]
4. Peral B, San Millan JL, Castello R, Moghetti P, Escobar-Morreale HF: Comment: the methionine 196 arginine polymorphism in exon 6 of the TNF receptor 2 gene (TNFRSF1B) is associated with the polycystic ovary syndrome and hyperandrogenism. J Clin Endocrinol Metab. 2002 Aug;87(8):3977-83. [PubMed ]
5. Pennica D, Lam VT, Mize NK, Weber RF, Lewis M, Fendly BM, Lipari MT, Goeddel DV: Biochemical properties of the 75-kDa tumor necrosis factor receptor. Characterization of ligand binding, internalization, and receptor phosphorylation. J Biol Chem. 1992 Oct 15;267(29):21172-8. [PubMed ]
6. Dembic Z, Loetscher H, Gubler U, Pan YC, Lahm HW, Gentz R, Brockhaus M, Lesslauer W: Two human TNF receptors have similar extracellular, but distinct intracellular, domain sequences. Cytokine. 1990 Jul;2(4):231-7. [PubMed ]
7. Engelmann H, Novick D, Wallach D: Two tumor necrosis factor-binding proteins purified from human urine. Evidence for immunological cross-reactivity with cell surface tumor necrosis factor receptors. J Biol Chem. 1990 Jan 25;265(3):1531-6. [PubMed ]
8. Smith CA, Davis T, Anderson D, Solam L, Beckmann MP, Jerzy R, Dower SK, Cosman D, Goodwin RG: A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science. 1990 May 25;248(4958):1019-23. [PubMed ]
9. Heller RA, Song K, Onasch MA, Fischer WH, Chang D, Ringold GM: Complementary DNA cloning of a receptor for tumor necrosis factor and demonstration of a shed form of the receptor. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6151-5. [PubMed ]
10. Kohno T, Brewer MT, Baker SL, Schwartz PE, King MW, Hale KK, Squires CH, Thompson RC, Vannice JL: A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8331-5. [PubMed ]
11. 2173696 Loetscher H, Schlaeger EJ, Lahm HW, Pan YC, Lesslauer W, Brockhaus M: Purification and partial amino acid sequence analysis of two distinct tumor necrosis factor receptors from HL60 cells. J Biol Chem. 1990 Nov 25;265(33):20131-8.
12. 8069916 Rothe M, Wong SC, Henzel WJ, Goeddel DV: A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell. 1994 Aug 26;78(4):681-92.
13. 8661109 Beltinger CP, White PS, Maris JM, Sulman EP, Jensen SJ, LePaslier D, Stallard BJ, Goeddel DV, de Sauvage FJ, Brodeur GM: Physical mapping and genomic structure of the human TNFR2 gene. Genomics. 1996 Jul 1;35(1):94-100.

1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed ]

1. LT-alpha
2. Lymphotoxin-alpha precursor
3. TNF-beta
4. Tumor necrosis factor ligand superfamily member 1

MTPPERLFLPRVCGTTLHLLLLGLLLVLLPGAQGLPGVGLTPSAAQTARQHPKMHLAHST
LKPAAHLIGDPSKQNSLLWRANTDRAFLQDGFSLSNNSLLVPTSGIYFVYSQVVFSGKAY
SPKATSSPLYLAHEVQLFSSQYPFHVPLLSSQKMVYPGLQEPWLHSMYHGAAFQLTQGDQ
LSTHTDGIPHLVLSPSTVFFGAFAL

• TNF (PF00229 )

• 1-34

• None

• Homotrimer:Secreted protein. Heterotrimer:Membrane

ATGACACCACCTGAACGTCTCTTCCTCCCAAGGGTGTGTGGCACCACCCTACACCTCCTC
CTTCTGGGGCTGCTGCTGGTTCTGCTGCCTGGGGCCCAGGGGCTCCCTGGTGTTGGCCTC
ACACCTTCAGCTGCCCAGACTGCCCGTCAGCACCCCAAGATGCATCTTGCCCACAGCACC
CTCAAACCTGCTGCTCACCTCATTGGAGACCCCAGCAAGCAGAACTCACTGCTCTGGAGA
GCAAACACGGACCGTGCCTTCCTCCAGGATGGTTTCTCCTTGAGCAACAATTCTCTCCTG
GTCCCCACCAGTGGCATCTACTTCGTCTACTCCCAGGTGGTCTTCTCTGGGAAAGCCTAC
TCTCCCAAGGCCACCTCCTCCCCACTCTACCTGGCCCATGAGGTCCAGCTCTTCTCCTCC
CAGTACCCCTTCCATGTGCCTCTCCTCAGCTCCCAGAAGATGGTGTATCCAGGGCTGCAG
GAACCCTGGCTGCACTCGATGTACCACGGGGCTGCGTTCCAGCTCACCCAGGGAGACCAG
CTATCCACCCACACAGATGGCATCCCCCACCTAGTCCTCAGCCCTAGTACTGTCTTCTTT
GGAGCCTTCGCTCTGTAG

1. Neville MJ, Campbell RD: A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. J Immunol. 1999 Apr 15;162(8):4745-54. [PubMed ]
2. Matsuyama N, Okawa N, Tsukii Y, Endo T, Kaji A: Nucleotide sequence of a cDNA encoding human tumor necrosis factor beta from B lymphoblastoid cell RPMI 1788. FEBS Lett. 1992 May 11;302(2):141-4. [PubMed ]
3. Voigt CG, Maurer-Fogy I, Adolf GR: Natural human tumor necrosis factor beta (lymphotoxin). Variable O-glycosylation at Thr7, proteolytic processing, and allelic variation. FEBS Lett. 1992 Dec 7;314(1):85-8. [PubMed ]
4. Messer G, Spengler U, Jung MC, Honold G, Blomer K, Pape GR, Riethmuller G, Weiss EH: Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production. J Exp Med. 1991 Jan 1;173(1):209-19. [PubMed ]
5. Abraham LJ, Du DC, Zahedi K, Dawkins RL, Whitehead AS: Haplotypic polymorphisms of the TNFB gene. Immunogenetics. 1991;33(1):50-3. [PubMed ]
6. Eck MJ, Ultsch M, Rinderknecht E, de Vos AM, Sprang SR: The structure of human lymphotoxin (tumor necrosis factor-beta) at 1.9-A resolution. J Biol Chem. 1992 Feb 5;267(4):2119-22. [PubMed ]
7. Nedwin GE, Jarrett-Nedwin J, Smith DH, Naylor SL, Sakaguchi AY, Goeddel DV, Gray PW: Structure and chromosomal localization of the human lymphotoxin gene. J Cell Biochem. 1985;29(3):171-81. [PubMed ]
8. Kobayashi Y, Miyamoto D, Asada M, Obinata M, Osawa T: Cloning and expression of human lymphotoxin mRNA derived from a human T cell hybridoma. J Biochem (Tokyo). 1986 Sep;100(3):727-33. [PubMed ]
9. Nedospasov SA, Shakhov AN, Turetskaya RL, Mett VA, Azizov MM, Georgiev GP, Korobko VG, Dobrynin VN, Filippov SA, Bystrov NS, et al.: Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:611-24. [PubMed ]
10. Gray PW, Aggarwal BB, Benton CV, Bringman TS, Henzel WJ, Jarrett JA, Leung DW, Moffat B, Ng P, Svedersky LP, et al.: Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature. 1984 Dec 20-1985 Jan 2;312(5996):721-4. [PubMed ]
11. 8387891 Banner DW, D'Arcy A, Janes W, Gentz R, Schoenfeld HJ, Broger C, Loetscher H, Lesslauer W: Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell. 1993 May 7;73(3):431-45.
12. 8499947 Iris FJ, Bougueleret L, Prieur S, Caterina D, Primas G, Perrot V, Jurka J, Rodriguez-Tome P, Claverie JM, Dausset J, et al.: Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment. Nat Genet. 1993 Feb;3(2):137-45.

1. Johnson CJ, Reilly KM, Murray KM: Etanercept in juvenile rheumatoid arthritis. Ann Pharmacother. 2001 Apr;35(4):464-71. [PubMed ]
2. Pennica D, Lam VT, Mize NK, Weber RF, Lewis M, Fendly BM, Lipari MT, Goeddel DV: Biochemical properties of the 75-kDa tumor necrosis factor receptor. Characterization of ligand binding, internalization, and receptor phosphorylation. J Biol Chem. 1992 Oct 15;267(29):21172-8. [PubMed ]
3. Gudbrandsdottir S, Larsen R, Sorensen LK, Nielsen S, Hansen MB, Svenson M, Bendtzen K, Muller K: TNF and LT binding capacities in the plasma of arthritis patients: effect of etanercept treatment in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2004 Jan-Feb;22(1):118-24. [PubMed ]
4. Buch MH, Conaghan PG, Quinn MA, Bingham SJ, Veale D, Emery P: True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin alpha? Ann Rheum Dis. 2004 Oct;63(10):1344-6. Epub 2004 Mar 19. [PubMed ]
5. Kang CP, Lee KW, Yoo DH, Kang C, Bae SC: The influence of a polymorphism at position -857 of the tumour necrosis factor alpha gene on clinical response to etanercept therapy in rheumatoid arthritis. Rheumatology (Oxford). 2005 Apr;44(4):547-52. Epub 2005 Feb 3. [PubMed ]

1. C1 esterase
2. Complement C1s subcomponent precursor
3. EC 3.4.21.42

MWCIVLFSLLAWVYAEPTMYGEILSPNYPQAYPSEVEKSWDIEVPEGYGIHLYFTHLDIE
LSENCAYDSVQIISGDTEEGRLCGQRSSNNPHSPIVEEFQVPYNKLQVIFKSDFSNEERF
TGFAAYYVATDINECTDFVDVPCSHFCNNFIGGYFCSCPPEYFLHDDMKNCGVNCSGDVF
TALIGEIASPNYPKPYPENSRCEYQIRLEKGFQVVVTLRREDFDVEAADSAGNCLDSLVF
VAGDRQFGPYCGHGFPGPLNIETKSNALDIIFQTDLTGQKKGWKLRYHGDPMPCPKEDTP
NSVWEPAKAKYVFRDVVQITCLDGFEVVEGRVGATSFYSTCQSNGKWSNSKLKCQPVDCG
IPESIENGKVEDPESTLFGSVIRYTCEEPYYYMENGGGGEYHCAGNGSWVNEVLGPELPK
CVPVCGVPREPFEEKQRIIGGSDADIKNFPWQVFFDNPWAGGALINEYWVLTAAHVVEGN
REPTMYVGSTSVQTSRLAKSKMLTPEHVFIHPGWKLLEVPEGRTNFDNDIALVRLKDPVK
MGPTVSPICLPGTSSDYNLMDGDLGLISGWGRTEKRDRAVRLKAARLPVAPLRKCKEVKV
EKPTADAEAYVFTPNMICAGGEKGMDSCKGDSGGAFAVQDPNDKTKFYAAGLVSWGPQCG
TYGLYTRVKNYVDWIMKTMQENSTPRED

• Cleavage of Arg!Ala bond in complement component C4 to form C4a and C4b, and Lys(or Arg)!Lys bond in complement component C2 to form C2a and C2b: the "classical" pathway C3 convertase

• EGF (PF00008 )
• Sushi (PF00084 )
• Trypsin (PF00089 )
• CUB (PF00431 )

• 1-15

• None

• Cytoplasmic

ATGTGGTGCATTGTCCTGTTTTCACTTTTGGCATGGGTTTATGCTGAGCCTACCATGTAT
GGGGAGATCCTGTCCCCTAACTATCCTCAGGCATATCCCAGTGAGGTAGAGAAATCTTGG
GACATAGAAGTTCCTGAAGGGTATGGGATTCACCTCTACTTCACCCATCTGGACATTGAG
CTGTCAGAGAACTGTGCGTATGACTCAGTGCAGATAATCTCAGGAGACACTGAAGAAGGG
AGGCTCTGTGGACAGAGGAGCAGTAACAATCCCCACTCTCCAATTGTGGAAGAGTTCCAA
GTCCCATACAACAAACTCCAGGTGATCTTTAAGTCAGACTTTTCCAATGAAGAGCGTTTT
ACGGGGTTTGCTGCATACTATGTTGCCACAGACATAAATGAATGCACAGATTTTGTAGAT
GTCCCTTGTAGCCACTTCTGCAACAATTTCATTGGTGGTTACTTCTGCTCCTGCCCCCCG
GAATATTTCCTCCATGATGACATGAAGAATTGCGGAGTTAATTGCAGTGGGGATGTATTC
ACTGCACTGATTGGGGAGATTGCAAGTCCCAATTATCCCAAACCATATCCAGAGAACTCA
AGGTGTGAATACCAGATCCGGTTGGAGAAAGGGTTCCAAGTGGTGGTGACCTTGCGGAGA
GAAGATTTTGATGTGGAAGCAGCTGACTCAGCGGGAAACTGCCTTGACAGTTTAGTTTTT
GTTGCAGGAGATCGGCAATTTGGTCCTTACTGTGGTCATGGATTCCCTGGGCCTCTAAAT
ATTGAAACCAAGAGTAATGCTCTTGATATCATCTTCCAAACTGATCTAACAGGGCAAAAA
AAGGGCTGGAAACTTCGCTATCATGGAGATCCAATGCCCTGCCCTAAGGAAGACACTCCC
AATTCTGTTTGGGAGCCTGCGAAGGCAAAATATGTCTTTAGAGATGTGGTGCAGATAACC
TGTCTGGATGGGTTTGAAGTTGTGGAGGGACGTGTTGGTGCAACATCTTTCTATTCGACT
TGTCAAAGCAATGGAAAGTGGAGTAATTCCAAACTGAAATGTCAACCTGTGGACTGTGGC
ATTCCTGAATCCATTGAGAATGGTAAAGTTGAAGACCCAGAGAGCACTTTGTTTGGTTCT
GTCATCCGCTACACTTGTGAGGAGCCATATTACTACATGGAAAATGGAGGAGGTGGGGAG
TATCACTGTGCTGGTAACGGGAGCTGGGTGAATGAGGTGCTGGGCCCGGAGCTGCCGAAA
TGTGTTCCAGTCTGTGGAGTCCCCAGAGAACCCTTTGAAGAAAAACAGAGGATAATTGGA
GGATCCGATGCAGATATTAAAAACTTCCCCTGGCAAGTCTTCTTTGACAACCCATGGGCT
GGTGGAGCGCTCATTAATGAGTACTGGGTGCTGACGGCTGCTCATGTTGTGGAGGGAAAC
AGGGAGCCAACAATGTATGTTGGGTCCACCTCAGTGCAGACCTCACGGCTGGCAAAATCC
AAGATGCTCACTCCTGAGCATGTGTTTATTCATCCGGGATGGAAGCTGCTGGAAGTCCCA
GAAGGACGAACCAATTTTGATAATGACATTGCACTGGTGCGGCTGAAAGACCCAGTGAAA
ATGGGACCCACCGTCTCTCCCATCTGCCTACCAGGCACCTCTTCCGACTACAACCTCATG
GATGGGGACCTGGGACTGATCTCAGGCTGGGGCCGAACAGAGAAGAGAGATCGTGCTGTT
CGCCTCAAGGCGGCAAGGTTACCTGTAGCTCCTTTAAGAAAATGCAAAGAAGTGAAAGTG
GAGAAACCCACAGCAGATGCAGAGGCCTATGTTTTCACTCCTAACATGATCTGTGCTGGA
GGAGAGAAGGGCATGGATAGCTGTAAAGGGGACAGTGGTGGGGCCTTTGCTGTACAGGAT
CCCAATGACAAGACCAAATTCTACGCAGCTGGCCTGGTGTCCTGGGGGCCCCAGTGTGGG
ACCTATGGGCTCTACACACGGGTAAAGAACTATGTTGACTGGATAATGAAGACTATGCAG
GAAAATAGCACCCCCCGTGAGGACTAA

1. Dragon-Durey MA, Quartier P, Fremeaux-Bacchi V, Blouin J, de Barace C, Prieur AM, Weiss L, Fridman WH: Molecular basis of a selective C1s deficiency associated with early onset multiple autoimmune diseases. J Immunol. 2001 Jun 15;166(12):7612-6. [PubMed ]
2. Illy C, Thielens NM, Gagnon J, Arlaud GJ: Effect of lactoperoxidase-catalyzed iodination on the Ca(2+)-dependent interactions of human C1s. Location of the iodination sites. Biochemistry. 1991 Jul 23;30(29):7135-41. [PubMed ]
3. Hess D, Schaller J, Rickli EE: Identification of the disulfide bonds of human complement C1s. Biochemistry. 1991 Mar 19;30(11):2827-33. [PubMed ]
4. Kusumoto H, Hirosawa S, Salier JP, Hagen FS, Kurachi K: Human genes for complement components C1r and C1s in a close tail-to-tail arrangement. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7307-11. [PubMed ]
5. Tosi M, Duponchel C, Meo T, Couture-Tosi E: Complement genes C1r and C1s feature an intronless serine protease domain closely related to haptoglobin. J Mol Biol. 1989 Aug 20;208(4):709-14. [PubMed ]
6. Tosi M, Duponchel C, Meo T, Julier C: Complete cDNA sequence of human complement Cls and close physical linkage of the homologous genes Cls and Clr. Biochemistry. 1987 Dec 29;26(26):8516-24. [PubMed ]
7. Spycher SE, Nick H, Rickli EE: Human complement component C1s. Partial sequence determination of the heavy chain and identification of the peptide bond cleaved during activation. Eur J Biochem. 1986 Apr 1;156(1):49-57. [PubMed ]
8. Mackinnon CM, Carter PE, Smyth SJ, Dunbar B, Fothergill JE: Molecular cloning of cDNA for human complement component C1s. The complete amino acid sequence. Eur J Biochem. 1987 Dec 15;169(3):547-53. [PubMed ]
9. Carter PE, Dunbar B, Fothergill JE: The serine proteinase chain of human complement component C1s. Cyanogen bromide cleavage and N-terminal sequences of the fragments. Biochem J. 1983 Dec 1;215(3):565-71. [PubMed ]
10. Rossi V, Gaboriaud C, Lacroix M, Ulrich J, Fontecilla-Camps JC, Gagnon J, Arlaud GJ: Structure of the catalytic region of human complement protease C1s: study by chemical cross-linking and three-dimensional homology modeling. Biochemistry. 1995 Jun 6;34(22):7311-21. [PubMed ]
11. 9794427 Endo Y, Takahashi M, Nakao M, Saiga H, Sekine H, Matsushita M, Nonaka M, Fujita T: Two lineages of mannose-binding lectin-associated serine protease (MASP) in vertebrates. J Immunol. 1998 Nov 1;161(9):4924-30.

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. Complement C1r subcomponent precursor
2. Complement component 1, r subcomponent
3. EC 3.4.21.41

MWLLYLLVPALFCRAGGSIPIPQKLFGEVTSPLFPKPYPNNFETTTVITVPTGYRVKLVF
QQFDLEPSEGCFYDYVKISADKKSLGRFCGQLGSPLGNPPGKKEFMSQGNKMLLTFHTDF
SNEENGTIMFYKGFLAYYQAVDLDECASRSKSGEEDPQPQCQHLCHNYVGGYFCSCRPGY
ELQEDRHSCQAECSSELYTEASGYISSLEYPRSYPPDLRCNYSIRVERGLTLHLKFLEPF
DIDDHQQVHCPYDQLQIYANGKNIGEFCGKQRPPDLDTSSNAVDLLFFTDESGDSRGWKL
RYTTEIIKCPQPKTLDEFTIIQNLQPQYQFRDYFIATCKQGYQLIEGNQVLHSFTAVCQD
DGTWHRAMPRCKIKDCGQPRNLPNGDFRYTTTMGVNTYKARIQYYCHEPYYKMQTRAGSR
ESEQGVYTCTAQGIWKNEQKGEKIPRCLPVCGKPVNPVEQRQRIIGGQKAKMGNFPWQVF
TNIHGRGGGALLGDRWILTAAHTLYPKEHEAQSNASLDVFLGHTNVEELMKLGNHPIRRV
SVHPDYRQDESYNFEGDIALLELENSVTLGPNLLPICLPDNDTFYDLGLMGYVSGFGVME
EKIAHDLRFVRLPVANPQACENWLRGKNRMDVFSQNMFCAGHPSLKQDACQGDSGGVFAV
RDPNTDRWVATGIVSWGIGCSRGYGFYTKVLNYVDWIKKEMEEED

• Selective cleavage of Lys(or Arg)!Ile bond in complement subcomponent C1s to form C_overbar_1s_ (internal_xref(ec_num(3,4,21,42)))

• Sushi (PF00084 )
• Trypsin (PF00089 )
• CUB (PF00431 )
• EGF_CA (PF07645 )

• 1-17

• None

• Cytoplasmic

ATGTGGCTCTTGTACCTCCTGGTGCCGGCCCTGTTCTGCAGGGCAGGAGGCTCCATTCCC
ATCCCTCAGAAGTTATTTGGGGAGGTGACTTCCCCTCTGTTCCCCAAGCCTTACCCCAAC
AACTTTGAAACAACCACTGTGATCACAGTCCCCACGGGATACAGGGTGAAGCTCGTCTTC
CAGCAGTTTGACCTGGAGCCTTCTGAAGGCTGCTTCTATGATTATGTCAAGATCTCTGCT
GATAAGAAAAGCCTGGGGAGGTTCTGTGGGCAACTGGGTTCTCCACTGGGCAACCCCCCG
GGAAAGAAGGAATTTATGTCCCAAGGGAACAAGATGCTGCTGACCTTCCACACAGACTTC
TCCAACGAGGAGAATGGGACCATCATGTTCTACAAGGGCTTCCTGGCCTACTACCAAGCT
GTGGACCTTGATGAATGTGCTTCCCGGAGCAAATTAGGGGAGGAGGATCCCCAGCCCCAG
TGCCAGCACCTGTGTCACAACTACGTTGGAGGCTACTTCTGTTCCTGCCGTCCAGGCTAT
GAGCTTCAGGAAGACAGGCATTCCTGCCAGGCTGAGTGCAGCAGCGAGCTGTACACGGAG
GCATCAGGCTACATCTCCAGCCTGGAGTACCCTCGGTCCTACCCCCCTGACCTGCGCTGC
AACTACAGCATCCGGGTGGAGCGGGGCCTCACCCTGCACCTCAAGTTCCTGGAGCCTTTT
GATATTGATGACCACCAGCAAGTACACTGCCCCTATGACCAGCTACAGATCTATGCCAAC
GGGAAGAACATTGGCGAGTTCTGTGGGAAGCAAAGGCCCCCCGACCTCGACACCAGCAGC
AATGCTGTGGATCTGCTGTTCTTCACAGATGAGTCGGGGGACAGCCGGGGCTGGAAGCTG
CGCTACACCACCGAGATCATCAAGTGCCCCCAGCCCAAGACCCTAGACGAGTTCACCATC
ATCCAGAACCTGCAGCCTCAGTACCAGTTCCGTGACTACTTCATTGCTACCTGCAAGCAA
GGCTACCAGCTCATAGAGGGGAACCAGGTGCTGCATTCCTTCACAGCTGTCTGCCAGGAT
GATGGCACGTGGCATCGTGCCATGCCCAGATGCAAGATCAAGGACTGTGGGCAGCCCCGA
AACCTGCCTAATGGTGACTTCCGTTACACCACCACAATGGGAGTGAACACCTACAAGGCC
CGTATCCAGTACTACTGCCATGAGCCATATTACAAGATGCAGACCAGAGCTGGCAGCAGG
GAGTCTGAGCAAGGGGTGTACACCTGCACAGCACAGGGCATTTGGAAGAATGAACAGAAG
GGAGAGAAGATTCCTCGGTGCTTGCCAGTGTGTGGGAAGCCCGTGAACCCCGTGGAACAG
AGGCAGCGCATCATCGGAGGGCAAAAAGCCAAGATGGGCAACTTCCCCTGGCAGGTGTTC
ACCAACATCCACGGGCGCGGGGGCGGGGCCCTGCTGGGCGACCGCTGGATCCTCACAGCT
GCCCACACCCTGTATCCCAAGGAACACGAAGCGCAAAGCAACGCCTCTTTGGATGTGTTC
CTGGGCCACACAAATGTGGAAGAGCTCATGAAGCTAGGAAATCACCCCATCCGCAGGGTC
AGCGTCCACCCGGACTACCGTCAGGATGAGTCCTACAATTTTGAGGGGGACATCGCCCTG
CTGGAGCTGGAAAATAGTGTCACCCTGGGTCCCAACCTCCTCCCCATCTGCCTCCCTGAC
AACGATACCTTCTACGACCTGGGCTTGATGGGCTATGTCAGTGGCTTCGGGGTCATGGAG
GAGAAGATTGCTCATGACCTCAGGTTTGTCCGTCTGCCCGTAGCTAATCCACAGGCCTGT
GAGAACTGGCTCCGGGGAAAGAATAGGATGGATGTGTTCTCTCAAAACATGTTCTGTGCT
GGACACCCATCTCTAAAGCAGGACGCCTGCCAGGGGGATAGTGGGGGCGTTTTTGCAGTA
AGGGACCCGAACACTGATCGCTGGGTGGCCACGGGCATCGTGTCCTGGGGCATCGGGTGC
AGCAGGGGCTATGGCTTCTACACCAAAGTGCTCAACTACGTGGACTGGATCAAGAAAGAG
ATGGAGGAGGAGGACTGA

1. Arlaud GJ, Van Dorsselaer A, Bell A, Mancini M, Aude C, Gagnon J: Identification of erythro-beta-hydroxyasparagine in the EGF-like domain of human C1r. FEBS Lett. 1987 Sep 28;222(1):129-34. [PubMed ]
2. Leytus SP, Kurachi K, Sakariassen KS, Davie EW: Nucleotide sequence of the cDNA coding for human complement C1r. Biochemistry. 1986 Aug 26;25(17):4855-63. [PubMed ]
3. Journet A, Tosi M: Cloning and sequencing of full-length cDNA encoding the precursor of human complement component C1r. Biochem J. 1986 Dec 15;240(3):783-7. [PubMed ]
4. Arlaud GJ, Willis AC, Gagnon J: Complete amino acid sequence of the A chain of human complement-classical-pathway enzyme C1r. Biochem J. 1987 Feb 1;241(3):711-20. [PubMed ]
5. Arlaud GJ, Gagnon J: Complete amino acid sequence of the catalytic chain of human complement subcomponent C1-r. Biochemistry. 1983 Apr 12;22(8):1758-64. [PubMed ]
6. Pelloux S, Thielens NM, Hudry-Clergeon G, Petillot Y, Filhol O, Arlaud GJ: Identification of a cryptic protein kinase CK2 phosphorylation site in human complement protease Clr, and its use to probe intramolecular interaction. FEBS Lett. 1996 May 13;386(1):15-20. [PubMed ]
7. Bersch B, Hernandez JF, Marion D, Arlaud GJ: Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family. Biochemistry. 1998 Feb 3;37(5):1204-14. [PubMed ]

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. Complement C1q subcomponent subunit A precursor

MEGPRGWLVLCVLAISLASMVTEDLCRAPDGKKGEAGRPGRRGRPGLKGEQGEPGAPGIR
TGIQGLKGDQGEPGPSGNPGKVGYPGPSGPLGARGIPGIKGTKGSPGNIKDQPRPAFSAI
RRNPPMGGNVVIFDTVITNQEEPYQNHSGRFVCTVPGYYYFTFQVLSQWEICLSIVSSSR
GQVRRSLGFCDTTNKGLFQVVSGGMVLQLQQGDQVWVEKDPKKGHIYQGSEADSVFSGFL
IFPSA

• C1q (PF00386 )
• Collagen (PF01391 )

• 1-22

• None

• Secreted protein

ATGGAGGGTCCCCGGGGATGGCTGGTGCTCTGTGTGCTGGCCATATCGCTGGCCTCTATG
GTGACCGAGGACTTGTGCCGAGCACCAGACGGGAAGAAAGGGGAGGCAGGAAGACCTGGC
AGACGGGGGCGGCCAGGCCTCAAGGGGGAGCAAGGGGAGCCGGGGGCCCCTGGCATCCGG
ACAGGCATCCAAGGCCTTAAAGGAGACCAGGGGGAACCTGGGCCCTCTGGAAACCCCGGC
AAGGTGGGCTACCCAGGGCCCAGCGGCCCCCTCGGGGCCCGTGGCATCCCGGGAATTAAA
GGCACCAAGGGCAGCCCAGGAAACATCAAGGACCAGCCGAGGCCAGCCTTCTCCGCCATT
CGGCGGAACCCCCCAATGGGGGGCAACGTGGTCATCTTCGACACGGTCATCACCAACCAG
GAAGAACCGTACCAGAACCACTCCGGCCGATTCGTCTGCACTGTACCCGGCTACTACTAC
TTCACCTTCCAGGTGCTGTCCCAGTGGGAAATCTGCCTGTCCATCGTCTCCTCCTCAAGG
GGCCAGGTCCGACGCTCCCTGGGCTTCTGTGACACCACCAACAAGGGGCTCTTCCAGGTG
GTGTCAGGGGGCATGGTGCTTCAGCTGCAGCAGGGTGACCAGGTCTGGGTTGAAAAAGAC
CCCAAAAAGGGTCACATTTACCAGGGCTCTGAGGCCGACAGCGTCTTCAGCGGCTTCCTC
ATCTTCCCATCTGCCTGA

1. Gaboriaud C, Juanhuix J, Gruez A, Lacroix M, Darnault C, Pignol D, Verger D, Fontecilla-Camps JC, Arlaud GJ: The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J Biol Chem. 2003 Nov 21;278(47):46974-82. Epub 2003 Sep 5. [PubMed ]
2. Sellar GC, Blake DJ, Reid KB: Characterization and organization of the genes encoding the A-, B- and C-chains of human complement subcomponent C1q. The complete derived amino acid sequence of human C1q. Biochem J. 1991 Mar 1;274 ( Pt 2):481-90. [PubMed ]
3. Reid KB: Complete amino acid sequences of the three collagen-like regions present in subcomponent C1q of the first component of human complement. Biochem J. 1979 May 1;179(2):367-71. [PubMed ]
4. Reid KB, Gagnon J, Frampton J: Completion of the amino acid sequences of the A and B chains of subcomponent C1q of the first component of human complement. Biochem J. 1982 Jun 1;203(3):559-69. [PubMed ]
5. Petry F: Molecular basis of hereditary C1q deficiency. Immunobiology. 1998 Aug;199(2):286-94. [PubMed ]

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. Complement C1q subcomponent subunit B precursor

MKIPWGSIPVLMLLLLLGLIDISQAQLSCTGPPAIPGIPGIPGTPGPDGQPGTPGIKGEK
GLPGLAGDHGEFGEKGDPGIPGNPGKVGPKGPMGPKGGPGAPGAPGPKGESGDYKATQKI
AFSATRTINVPLRRDQTIRFDHVITNMNNNYEPRSGKFTCKVPGLYYFTYHASSRGNLCV
NLMRGRERAQKVVTFCDYAYNTFQVTTGGMVLKLEQGENVFLQATDKNSLLGMEGANSIF
SGFLLFPDMEA

• C1q (PF00386 )
• Collagen (PF01391 )

• 1-25

• None

• Secreted protein

CCAGGCCCAGCTCAGCTGCACCGGGCCCCCAGCCATCCCTGGCATCCCGGGTATCCCTGG
GACACCTGGCCCCGATGGCCAACCTGGGACCCCAGGGATAAAAGGAGAGAAAGGGCTTCC
AGGGCTGGCTGGAGACCATGGTGAGTTCGGAGAGAAGGGAGACCCAGGGATTCCTGGGAA
TCCAGGAAAAGTCGGCCCCAAGGGCCCCATGGGCCCTAAAGGTGGCCCAGGGGCCCCTGG
AGCCCCAGGCCCCAAAGGTGAATCGGGAGACTACAAGGCCACCCAGAAAATCGCCTTCTC
TGCCACAAGAACCATCAACGTCCCCCTGCGCCGGGACCAGACCATCCGCTTCGACCACGT
GATCACCAACATGAACAACAATTATGAGCCCCGCAGTGGCAAGTTCACCTGCAAGGTGCC
CGGTCTCTACTACTTCACCTACCACGCCAGCTCTCGAGGGAACCTGTGCGTGAACCTCAT
GCGTGGCCGGGAGCGTGCACAGAAGGTGGTCACCTTCTGTGACTATGCCTACAACACCTT
CCAGGTCACCACCGGTGGCATGGTCCTCAAGCTGGAGCAGGGGGAGAACGTCTTCCTGCA
GGCCACCGACAAGAACTCACTACTGGGCATGGAGGGTGCCAACAGCATCTTTTCCGGGTT
CCTGCTCTTTCCAGATATGGAGGCCTGA

1. Gaboriaud C, Juanhuix J, Gruez A, Lacroix M, Darnault C, Pignol D, Verger D, Fontecilla-Camps JC, Arlaud GJ: The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J Biol Chem. 2003 Nov 21;278(47):46974-82. Epub 2003 Sep 5. [PubMed ]
2. Reid KB: Molecular cloning and characterization of the complementary DNA and gene coding for the B-chain of subcomponent C1q of the human complement system. Biochem J. 1985 Nov 1;231(3):729-35. [PubMed ]
3. Reid KB: Complete amino acid sequences of the three collagen-like regions present in subcomponent C1q of the first component of human complement. Biochem J. 1979 May 1;179(2):367-71. [PubMed ]
4. Reid KB, Bentley DR, Wood KJ: Cloning and characterization of the complementary DNA for the B chain of normal human serum C1q. Philos Trans R Soc Lond B Biol Sci. 1984 Sep 6;306(1129):345-54. [PubMed ]
5. Reid KB, Gagnon J, Frampton J: Completion of the amino acid sequences of the A and B chains of subcomponent C1q of the first component of human complement. Biochem J. 1982 Jun 1;203(3):559-69. [PubMed ]
6. Reid KB, Thompson EO: Amino acid sequence of the N-terminal 108 amino acid residues of the B chain of subcomponent C1q of the first component of human complement. Biochem J. 1978 Sep 1;173(3):863-8. [PubMed ]
7. Petry F: Molecular basis of hereditary C1q deficiency. Immunobiology. 1998 Aug;199(2):286-94. [PubMed ]

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. Complement C1q subcomponent subunit C precursor

MDVGPSSLPHLGLKLLLLLLLLPLRGQANTGCYGIPGMPGLPGAPGKDGYDGLPGPKGEP
GIPAIPGIRGPKGQKGEPGLPGHPGKNGPMGPPGMPGVPGPMGIPGEPGEEGRYKQKFQS
VFTVTRQTHQPPAPNSLIRFNAVLTNPQGDYDTSTGKFTCKVPGLYYFVYHASHTANLCV
LLYRSGVKVVTFCGHTSKTNQVNSGGVLLRLQVGEEVWLAVNDYYDMVGIQGSDSVFSGF
LLFPD

• C1q (PF00386 )
• Collagen (PF01391 )

• 1-28

• None

• Secreted protein

ATGGACGTGGGGCCCAGCTCCCTGCCCCACCTTGGGCTGAAGCTGCTGCTGCTCCTGCTG
CTGCTGCCCCTCAGGGCCAAAGCCAACACAGGCTGCTACGGGATCCCAGGGATGCCCGGC
CTGCCCGGGGCACCAGGGAAGGATGGGTACGACGGACTGCCGGGGCCCAAGGGGGAGCCA
GGAATCCCAGCCATTCCCGGGATCCGAGGACCCAAAGGGCAGAAGGGAGAACCCGGCTTA
CCCGGCCATCCTGGGAAAAATGGCCCCATGGGACCCCCTGGGATGCCAGGGGTGCCCGGC
CCCATGGGATTCCCTGGAGAGCCAGGTGAGGAGGGCAGATACAAGCAGAAATTCCAGTCA
GTGTTCACGGTCACTCGGCAGACCCACCAGCCCCCTGCACCCAACAGCCTGATCAGATTC
AACGCGGTCCTCACCAACCCGCAGGAGGATTATGACACGAGCACTGGCAAGTTCACCTGC
AAAGTCCCCGGCCTCTACTACTTTGTCTACCACGCGTCGCATACAGCCAACCTGTGCGTG
CTGCTGTACCGCAGCGGCGTCAAAGTGGTCACCTTCTGTGGCCACACGTCCAAAACCAAT
CAGGTCAACTCGGGCGGTGTGCTGCTGAGGTTGCAGGTGGGCGAGGAGGTGTGGCTGGCT
GTCAATGACTACTACGACATGGTGGGCATCCAGGGCTCTGACAGCGTCTTCTCCGGCTTC
CTGCTCTTCCCCGACTAG

1. Gaboriaud C, Juanhuix J, Gruez A, Lacroix M, Darnault C, Pignol D, Verger D, Fontecilla-Camps JC, Arlaud GJ: The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J Biol Chem. 2003 Nov 21;278(47):46974-82. Epub 2003 Sep 5. [PubMed ]
2. Sellar GC, Blake DJ, Reid KB: Characterization and organization of the genes encoding the A-, B- and C-chains of human complement subcomponent C1q. The complete derived amino acid sequence of human C1q. Biochem J. 1991 Mar 1;274 ( Pt 2):481-90. [PubMed ]
3. Reid KB: Complete amino acid sequences of the three collagen-like regions present in subcomponent C1q of the first component of human complement. Biochem J. 1979 May 1;179(2):367-71. [PubMed ]
4. Petry F: Molecular basis of hereditary C1q deficiency. Immunobiology. 1998 Aug;199(2):286-94. [PubMed ]

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. CD16a antigen
2. Fc-gamma RIII
3. Fc-gamma RIII-alpha
4. Fc-gamma RIIIa
5. FcR-10
6. FcRIII
7. FcRIIIa
8. IgG Fc receptor III-2
9. Low affinity immunoglobulin gamma Fc region receptor III-A precursor

MWQLLLPTALLLLVSAGMRTEDLPKAVVFLEPQWYRVLEKDSVTLKCQGAYSPEDNSTQW
FHNESLISSQASSYFIDAATVDDSGEYRCQTNLSTLSDPVQLEVHIGWLLLQAPRWVFKE
EDPIHLRCHSWKNTALHKVTYLQNGKGRKYFHHNSDFYIPKATLKDSGSYFCRGLFGSKN
VSSETVNITITQGLAVSTISSFFPPGYQVSFCLVMVLLFAVDTGLYFSVKTNIRSSTRDW
KDHKFKWRKDPQDK

• ig (PF00047 )

• 1-16

• 209-229

• Cell membrane

ATGTGGCAGCTGCTCCTCCCAACTGCTCTGCTACTTCTAGTTTCAGCTGGCATGCGGACT
GAAGATCTCCCAAAGGCTGTGGTGTTCCTGGAGCCTCAATGGTACAGGGTGCTCGAGAAG
GACAGTGTGACTCTGAAGTGCCAGGGAGCCTACTCCCCTGAGGACAATTCCACACAGTGG
TTTCACAATGAGAGCCTCATCTCAAGCCAGGCCTCGAGCTACTTCATTGACGCTGCCACA
GTCGACGACAGTGGAGAGTACAGGTGCCAGACAAACCTCTCCACCCTCAGTGACCCGGTG
CAGCTAGAAGTCCATATCGGCTGGCTGTTGCTCCAGGCCCCTCGGTGGGTGTTCAAGGAG
GAAGACCCTATTCACCTGAGGTGTCACAGCTGGAAGAACACTGCTCTGCATAAGGTCACA
TATTTACAGAATGGCAAAGGCAGGAAGTATTTTCATCATAATTCTGACTTCTACATTCCA
AAAGCCACACTCAAAGACAGCGGCTCCTACTTCTGCAGGGGGCTTTTTGGGAGTAAAAAT
GTGTCTTCAGAGACTGTGAACATCACCATCACTCAAGGTTTGGCAGTGTCAACCATCTCA
TCATTCTTTCCACCTGGGTACCAAGTCTCTTTCTGCTTGGTGATGGTACTCCTTTTTGCA
GTGGACACAGGACTATATTTCTCTGTGAAGACAAACATTCGAAGCTCAACAAGAGACTGG
AAGGACCATAAATTTAAATGGAGAAAGGACCCTCAAGACAAATGA

1. Ravetch JV, Perussia B: Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions. J Exp Med. 1989 Aug 1;170(2):481-97. [PubMed ]
2. Gessner JE, Grussenmeyer T, Kolanus W, Schmidt RE: The human low affinity immunoglobulin G Fc receptor III-A and III-B genes. Molecular characterization of the promoter regions. J Biol Chem. 1995 Jan 20;270(3):1350-61. [PubMed ]
3. de Haas M, Koene HR, Kleijer M, de Vries E, Simsek S, van Tol MJ, Roos D, von dem Borne AE: A triallelic Fc gamma receptor type IIIA polymorphism influences the binding of human IgG by NK cell Fc gamma RIIIa. J Immunol. 1996 Apr 15;156(8):3948-55. [PubMed ]
4. Koene HR, Kleijer M, Algra J, Roos D, von dem Borne AE, de Haas M: Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Blood. 1997 Aug 1;90(3):1109-14. [PubMed ]
5. Wu J, Edberg JC, Redecha PB, Bansal V, Guyre PM, Coleman K, Salmon JE, Kimberly RP: A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. J Clin Invest. 1997 Sep 1;100(5):1059-70. [PubMed ]

1. Criswell LA, Lum RF, Turner KN, Woehl B, Zhu Y, Wang J, Tiwari HK, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL Jr: The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis Rheum. 2004 Sep;50(9):2750-6. [PubMed ]
2. Hughes LB, Criswell LA, Beasley TM, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL: Genetic risk factors for infection in patients with early rheumatoid arthritis. Genes Immun. 2004 Dec;5(8):641-7. [PubMed ]

1. CD32 antigen
2. CDw32
3. Fc-gamma RII-a
4. Fc-gamma-RIIa
5. FcRII-a
6. IgG Fc receptor II-a
7. Low affinity immunoglobulin gamma Fc region receptor II-a precursor

MAMETQMSQNVCPRNLWLLQPLTVLLLLASADSQAAAPPKAVLKLEPPWINVLQEDSVTL
TCQGARSPESDSIQWFHNGNLIPTHTQPSYRFKANNNDSGEYTCQTGQTSLSDPVHLTVL
SEWLVLQTPHLEFQEGETIMLRCHSWKDKPLVKVTFFQNGKSQKFSRLDPTFSIPQANHS
HSGDYHCTGNIGYTLFSSKPVTITVQVPSMGSSSPMGIIVAVVIATAVAAIVAAVVALIY
CRKKRISANSTDPVKAAQFEPPGRQMIAIRKRQLEETNNDYETADGGYMTLNPRAPTDDD
KNIYLTLPPNDHVNSNN

• ig (PF00047 )

• 1-33

• 218-240

• Membrane

ATGGCTATGGAGACCCAAATGTCTCAGAATGTATGTCCCAGAAACCTGTGGCTGCTTCAA
CCATTGACAGTTTTGCTGCTGCTGGCTTCTGCAGACAGTCAAGCTGCAGCTCCCCCAAAG
GCTGTGCTGAAACTTGAGCCCCCGTGGATCAACGTGCTCCAGGAGGACTCTGTGACTCTG
ACATGCCAGGGGGCTCGCAGCCCTGAGAGCGACTCCATTCAGTGGTTCCACAATGGGAAT
CTCATTCCCACCCACACGCAGCCCAGCTACAGGTTCAAGGCCAACAACAATGACAGCGGG
GAGTACACGTGCCAGACTGGCCAGACCAGCCTCAGCGACCCTGTGCATCTGACTGTGCTT
TCCGAATGGCTGGTGCTCCAGACCCCTCACCTGGAGTTCCAGGAGGGAGAAACCATCATG
CTGAGGTGCCACAGCTGGAAGGACAAGCCTCTGGTCAAGGTCACATTCTTCCAGAATGGA
AAATCCCAGAAATTCTCCCGTTTGGATCCCACCTTCTCCATCCCACAAGCAAACCACAGT
CACAGTGGTGATTACCACTGCACAGGAAACATAGGCTACACGCTGTTCTCATCCAAGCCT
GTGACCATCACTGTCCAAGTGCCCAGCATGGGCAGCTCTTCACCAATGGGGATCATTGTG
GCTGTGGTCATTGCGACTGCTGTAGCAGCCATTGTTGCTGCTGTAGTGGCCTTGATCTAC
TGCAGGAAAAAGCGGATTTCAGCCAATTCCACTGATCCTGTGAAGGCTGCCCAATTTGAG
CCACCTGGACGTCAAATGATTGCCATCAGAAAGAGACAACTTGAAGAAACCAACAATGAC
TATGAAACAGCTGACGGCGGCTACATGACTCTGAACCCCAGGGCACCTACTGACGATGAT
AAAAACATCTACCTGACTCTTCCTCCCAACGACCATGTCAACAGTAATAACTAA

1. Maxwell KF, Powell MS, Hulett MD, Barton PA, McKenzie IF, Garrett TP, Hogarth PM: Crystal structure of the human leukocyte Fc receptor, Fc gammaRIIa. Nat Struct Biol. 1999 May;6(5):437-42. [PubMed ]
2. Powell MS, Barton PA, Emmanouilidis D, Wines BD, Neumann GM, Peitersz GA, Maxwell KF, Garrett TP, Hogarth PM: Biochemical analysis and crystallisation of Fc gamma RIIa, the low affinity receptor for IgG. Immunol Lett. 1999 May 3;68(1):17-23. [PubMed ]
3. Seki T: Identification of multiple isoforms of the low-affinity human IgG Fc receptor. Immunogenetics. 1989;30(1):5-12. [PubMed ]
4. Brooks DG, Qiu WQ, Luster AD, Ravetch JV: Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes. J Exp Med. 1989 Oct 1;170(4):1369-85. [PubMed ]
5. Stuart SG, Trounstine ML, Vaux DJ, Koch T, Martens CL, Mellman I, Moore KW: Isolation and expression of cDNA clones encoding a human receptor for IgG (Fc gamma RII). J Exp Med. 1987 Dec 1;166(6):1668-84. [PubMed ]
6. Hibbs ML, Bonadonna L, Scott BM, McKenzie IF, Hogarth PM: Molecular cloning of a human immunoglobulin G Fc receptor. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2240-4. [PubMed ]
7. Stengelin S, Stamenkovic I, Seed B: Isolation of cDNAs for two distinct human Fc receptors by ligand affinity cloning. EMBO J. 1988 Apr;7(4):1053-9. [PubMed ]
8. Salmon JE, Millard S, Schachter LA, Arnett FC, Ginzler EM, Gourley MF, Ramsey-Goldman R, Peterson MG, Kimberly RP: Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans. J Clin Invest. 1996 Mar 1;97(5):1348-54. [PubMed ]

1. Criswell LA, Lum RF, Turner KN, Woehl B, Zhu Y, Wang J, Tiwari HK, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL Jr: The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis Rheum. 2004 Sep;50(9):2750-6. [PubMed ]
2. Hughes LB, Criswell LA, Beasley TM, Edberg JC, Kimberly RP, Moreland LW, Seldin MF, Bridges SL: Genetic risk factors for infection in patients with early rheumatoid arthritis. Genes Immun. 2004 Dec;5(8):641-7. [PubMed ]

1. CD32 antigen
2. CDw32
3. Fc-gamma RII-b
4. Fc-gamma-RIIb
5. FcRII-b
6. IgG Fc receptor II-b
7. Low affinity immunoglobulin gamma Fc region receptor II-b precursor

MGILSFLPVLATESDWADCKSPQPWGHMLLWTAVLFLAPVAGTPAAPPKAVLKLEPQWIN
VLQEDSVTLTCRGTHSPESDSIQWFHNGNLIPTHTQPSYRFKANNNDSGEYTCQTGQTSL
SDPVHLTVLSEWLVLQTPHLEFQEGETIVLRCHSWKDKPLVKVTFFQNGKSKKFSRSDPN
FSIPQANHSHSGDYHCTGNIGYTLYSSKPVTITVQAPSSSPMGIIVAVVTGIAVAAIVAA
VVALIYCRKKRISALPGYPECREMGETLPEKPANPTNPDEADKVGAENTITYSLLMHPDA
LEEPDDQNRI

• ig (PF00047 )

• 1-42

• 218-240

• Membrane

ATGGGAATCCTGTCATTCTTACCTGTCCTTGCCACTGAGAGTGACTGGGCTGACTGCAAG
TCCCCCCAGCCTTGGGGTCATATGCTTCTGTGGACAGCTGTGCTATTCCTGGCTCCTGTT
GCTGGGACACCTGCAGCTCCCCCAAAGGCTGTGCTGAAACTCGAGCCCCAGTGGATCAAC
GTGCTCCAGGAGGACTCTGTGACTCTGACATGCCGGGGGACTCACAGCCCTGAGAGCGAC
TCCATTCAGTGGTTCCACAATGGGAATCTCATTCCCACCCACACGCAGCCCAGCTACAGG
TTCAAGGCCAACAACAATGACAGCGGGGAGTACACGTGCCAGACTGGCCAGACCAGCCTC
AGCGACCCTGTGCATCTGACTGTGCTTTCTGAGTGGCTGGTGCTCCAGACCCCTCACCTG
GAGTTCCAGGAGGGAGAAACCATCGTGCTGAGGTGCCACAGCTGGAAGGACAAGCCTCTG
GTCAAGGTCACATTCTTCCAGAATGGAAAATCCAAGAAATTTTCCCGTTCGGATCCCAAC
TTCTCCATCCCACAAGCAAACCACAGTCACAGTGGTGATTACCACTGCACAGGAAACATA
GGCTACACGCTGTACTCATCCAAGCCTGTGACCATCACTGTCCAAGCTCCCAGCTCTTCA
CCGATGGGGATCATTGTGGCTGTGGTCACTGGGATTGCTGTAGCGGCCATTGTTGCTGCT
GTAGTGGCCTTGATCTACTGCAGGAAAAAGCGGATTTCAGCTCTCCCAGGATACCCTGAG
TGCAGGGAAATGGGAGAGACCCTCCCTGAGAAACCAGCCAATCCCACTAATCCTGATGAG
GCTGACAAAGTTGGGGCTGAGAACACAATCACCTATTCACTTCTCATGCACCCGGATGCT
CTGGAAGAGCCTGATGACCAGAACCGTATT

1. Kyogoku C, Dijstelbloem HM, Tsuchiya N, Hatta Y, Kato H, Yamaguchi A, Fukazawa T, Jansen MD, Hashimoto H, van de Winkel JG, Kallenberg CG, Tokunaga K: Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility. Arthritis Rheum. 2002 May;46(5):1242-54. [PubMed ]
2. Engelhardt W, Geerds C, Frey J: Distribution, inducibility and biological function of the cloned and expressed human beta Fc receptor II. Eur J Immunol. 1990 Jun;20(6):1367-77. [PubMed ]
3. Brooks DG, Qiu WQ, Luster AD, Ravetch JV: Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes. J Exp Med. 1989 Oct 1;170(4):1369-85. [PubMed ]
4. Stuart SG, Simister NE, Clarkson SB, Kacinski BM, Shapiro M, Mellman I: Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium. EMBO J. 1989 Dec 1;8(12):3657-66. [PubMed ]

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed ]

1. CD32 antigen
2. CDw32
3. Fc-gamma RII-c
4. Fc-gamma-RIIc
5. FcRII-c
6. IgG Fc receptor II-c
7. Low affinity immunoglobulin gamma Fc region receptor II-c precursor

MGILSFLPVLATESDWADCKSPQPWGHMLLWTAVLFLAPVAGTPAAPPKAVLKLEPQWIN
VLQEDSVTLTCRGTHSPESDSIQWFHNGNLIPTHTQPSYRFKANNNDSGEYTCQTGQTSL
SDPVHLTVLSEWLVLQTPHLEFQEGETIVLRCHSWKDKPLVKVTFFQNGKSKKFSRSDPN
FSIPQANHSHSGDYHCTGNIGYTLYSSKPVTITVQAPSSSPMGIIVAVVTGIAVAAIVAA
VVALIYCRKKRISANSTDPVKAAQFEPPGRQMIAIRKRQPEETNNDYETADGGYMTLNPR
APTDDDKNIYLTLPPNDHVNSNN

• ig (PF00047 )

• 1-42

• 224-246

• Cell membrane

ATGGGAATCCTGTCATTTTTACCTGTCCTTGCCACTGAGAGTGACTGGGCTGACTGCAAG
TCCCCCCAGCCTTGGGGTCATATGCTTCTGTGGACAGCTGTGCTATTCCTGGCTCCTGTT
GCTGGGACACCTGCAGCTCCCCCAAAGGCTGTGCTGAAACTCGAGCCCCAGTGGATCAAC
GTGCTCCAGGAGGACTCTGTGACTCTGACATGCCGGGGGACTCACAGCCCTGAGAGCGAC
TCCATTCAGTGGTTCCACAATGGGAATCTCATTCCCACCCACACGCAGCCCAGCTACAGG
TTCAAGGCCAACAACAATGACAGCGGGGAGTACACGTGCCAGACTGGCCAGACCAGCCTC
AGCGACCCTGTGCATCTGACAGTGCTTTCTGAGTGGCTGGTGCTCCAGACCCCTCACCTG
GAGTTCCAGGAGGGAGAAACCATCGTGCTGAGGTGCCACAGCTGGAAGGACAAGCCTCTG
GTCAAGGTCACATTCTTCCAGAATGGAAAATCCAAGAAATTTTCCCGTTCGGATCCCAAC
TTCTCCATCCCACAAGCAAACCACAGTCACAGTGGTGATTACCATTGCACAGGAAACATA
GGCTACACGCTGTACTCATCCAAGCCTGTGACCATCACTGTCCAAGCTCCCAGCTCTTCA
CCGATGGGGATCATTGTGGCTGTGGTCACTGGGATTGCTGTAGCTGCCATTGTTGCTGCT
GTAGTGGCCTTGATCTACTGCAGGAAAAAGCGGATTTCAGCCAATTCCACTGATCCTGTG
AAGGCTGCCCAATTTGAGCCACCTGGACGTCAAATGATTGCCATCAGAAAGAGACAACCT
GAAGAAACCAACAATGACTATGAAACAGCTGACGGCGGCTACATGACTCTGAACCCCAGG
GCACCTACTGACGATGATAAAAACATCTACTTGACTCTTCCTCCCAACGACCATGTCAAC
AGTAATAACTAA

1. Stuart SG, Simister NE, Clarkson SB, Kacinski BM, Shapiro M, Mellman I: Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium. EMBO J. 1989 Dec 1;8(12):3657-66. [PubMed ]
2. Metes D, Ernst LK, Chambers WH, Sulica A, Herberman RB, Morel PA: Expression of functional CD32 molecules on human NK cells is determined by an allelic polymorphism of the FcgammaRIIC gene. Blood. 1998 Apr 1;91(7):2369-80. [PubMed ]

1. Hart SP, Ross JA, Ross K, Haslett C, Dransfield I: Molecular characterization of the surface of apoptotic neutrophils: implications for functional downregulation and recognition by phagocytes. Cell Death Differ. 2000 May;7(5):493-503. [PubMed ]
2. Ranheim EA, Kipps TJ: Tumor necrosis factor-alpha facilitates induction of CD80 (B7-1) and CD54 on human B cells by activated T cells: complex regulation by IL-4, IL-10, and CD40L. Cell Immunol. 1995 Apr 1;161(2):226-35. [PubMed ]