ID CO2_HUMAN STANDARD; PRT; 752 AA. AC P06681; O19694; Q13904; DT 01-JAN-1988 (Rel. 06, Created) DT 15-DEC-1998 (Rel. 37, Last sequence update) DT 25-JAN-2005 (Rel. 46, Last annotation update) DE Complement C2 precursor (EC 3.4.21.43) (C3/C5 convertase). GN Name=C2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE. RC TISSUE=Liver; RX MEDLINE=87127920; PubMed=2949737; RA Bentley D.R.; RT "Primary structure of human complement component C2. Homology to two RT unrelated protein families."; RL Biochem. J. 239:339-345(1986). RN [2] RP NUCLEOTIDE SEQUENCE. RC TISSUE=Liver; RX PubMed=2493504; RA Horiuchi T., Macon K.J., Kidd V.J., Volanakis J.E.; RT "cDNA cloning and expression of human complement component C2."; RL J. Immunol. 142:2105-2111(1989). RN [3] RP NUCLEOTIDE SEQUENCE. RX MEDLINE=93315833; PubMed=8326124; RA Ishii Y., Zhu Z.B., Macon K.J., Volanakis J.E.; RT "Structure of the human C2 gene."; RL J. Immunol. 151:170-174(1993). RN [4] RP NUCLEOTIDE SEQUENCE. RA Rowen L., Dankers C., Baskin D., Faust J., Loretz C., Ahearn M.E., RA Banta A., Swartzell S., Smith T.M., Spies T., Hood L.; RT "Sequence determination of 300 kilobases of the human class III MHC RT locus."; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE, AND VARIANTS ASP-318 AND CYS-734. RA Rieder M.J., Carrington D.P., da Ponte S.H., Hastings N.C., RA Ahearn M.O., Kuldanek S.A., Rajkumar N., Toth E.J., Yi Q., RA Nickerson D.A.; RT "SeattleSNPs. NHLBI HL66682 program for genomic applications, UW- RT FHCRC, Seattle, WA (URL: http://pga.gs.washington.edu)."; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE. RC TISSUE=Brain; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [7] RP PROTEIN SEQUENCE OF 21-46 AND 244-256. RX PubMed=6922702; RA Kerr M.A., Gagnon J.; RT "The purification and properties of the second component of guinea-pig RT complement."; RL Biochem. J. 205:59-67(1982). RN [8] RP NUCLEOTIDE SEQUENCE OF 21-46. RX MEDLINE=86032058; PubMed=2997031; RA Bentley D.R., Campbell R.D., Cross S.J.; RT "DNA polymorphism of the C2 locus."; RL Immunogenetics 22:377-390(1985). RN [9] RP PROTEIN SEQUENCE OF 137-171; 454-466 AND 574-717. RX MEDLINE=85038851; PubMed=6149575; RA Gagnon J.; RT "Structure and activation of complement components C2 and factor B."; RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 306:301-309(1984). RN [10] RP PROTEIN SEQUENCE OF 244-269. RX MEDLINE=83308518; PubMed=6555044; RA Parkes C., Gagnon J., Kerr M.A.; RT "The reaction of iodine and thiol-blocking reagents with human RT complement components C2 and factor B. Purification and N-terminal RT amino acid sequence of a peptide from C2a containing a free thiol RT group."; RL Biochem. J. 213:201-209(1983). RN [11] RP NUCLEOTIDE SEQUENCE OF 588-717. RX MEDLINE=84144868; PubMed=6199794; RA Bentley D.R., Porter R.R.; RT "Isolation of cDNA clones for human complement component C2."; RL Proc. Natl. Acad. Sci. U.S.A. 81:1212-1215(1984). RN [12] RP NUCLEOTIDE SEQUENCE OF 694-752. RX MEDLINE=87102880; PubMed=3643061; DOI=10.1016/0092-8674(87)90436-3; RA Wu L., Morley B.J., Campbell R.D.; RT "Cell-specific expression of the human complement protein factor B RT gene: evidence for the role of two distinct 5'-flanking elements."; RL Cell 48:331-342(1987). RN [13] RP VARIANTS C2D PHE-209 AND ARG-464. RX MEDLINE=96215049; PubMed=8621452; DOI=10.1074/jbc.271.10.5824; RA Wetsel R.A., Kulics J., Lokki M.L., Kiepiela P., Akama H., RA Johnson C.A., Densen P., Colten H.R.; RT "Type II human complement C2 deficiency. Allele-specific amino acid RT substitutions (Ser189 --> Phe; Gly444 --> Arg) cause impaired C2 RT secretion."; RL J. Biol. Chem. 271:5824-5831(1996). RN [14] RP VARIANT C2D TYR-131. RX MEDLINE=98334005; PubMed=9670930; RA Zhu Z.B., Atkinson T.P., Volanakis J.E.; RT "A novel type II complement C2 deficiency allele in an African- RT American family."; RL J. Immunol. 161:578-584(1998). CC -!- FUNCTION: Component C2 which is part of the classical pathway of CC the complement system is cleaved by activated factor C1 into two CC fragments: C2b and C2a. C2a, a serine protease, then combines with CC complement factor 4b to generate the C3 or C5 convertase. CC -!- CATALYTIC ACTIVITY: Selective cleavage of Arg-|-Ser bond in CC complement component C3 alpha-chain to form C3a and C3b, and CC Arg-|-Xaa bond in complement component C5 alpha-chain to form C5a CC and C5b. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- DISEASE: Defects in C2 are the cause of C2 deficiency (CD2D) CC [MIM:217000]. CD2D is an autosomal recesive disease. Deficient CC individuals have an increased incidence of SLE and SLE-like CC syndromes, glomerulonephritis, vasculitis and pyogenic infections. CC Type I C2D is characterized by complete loss of the protein while CC type II C2D is characterized by a selective block in C2 secretion. CC -!- MISCELLANEOUS: C2 is a major histocompatibility complex class-III CC protein. CC -!- SIMILARITY: Belongs to the peptidase S1 family. CC -!- SIMILARITY: Contains 3 Sushi (CCP/SCR) domains. CC -!- SIMILARITY: Contains 1 VWFA domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X04481; CAA28169.1; -. DR EMBL; M26301; AAA35614.1; -. DR EMBL; L09708; AAB97607.1; -. DR EMBL; L09706; AAB97607.1; JOINED. DR EMBL; L09707; AAB97607.1; JOINED. DR EMBL; AF019413; AAB67975.1; -. DR EMBL; AY349611; AAQ15273.1; -. DR EMBL; BC043484; AAH43484.1; -. DR EMBL; M15549; AAA59649.1; -. DR EMBL; M15082; AAA59624.1; -. DR PIR; A25971; C2HU. DR HSSP; P10998; 1VVD. DR MEROPS; S01.194; -. DR Genew; HGNC:1248; C2. DR MIM; 217000; -. DR GO; GO:0005603; C:complement component C2 complex; TAS. DR GO; GO:0006958; P:complement activation, classical pathway; TAS. DR InterPro; IPR009003; Pept_Ser_Cys. DR InterPro; IPR001254; Peptidase_S1. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR000436; Sushi_SCR_CCP. DR InterPro; IPR002035; VWF_A. DR Pfam; PF00084; Sushi; 3. DR Pfam; PF00089; Trypsin; 2. DR Pfam; PF00092; VWA; 1. DR PIRSF; PIRSF001154; Compl_C2_B; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR PRINTS; PR00453; VWFADOMAIN. DR SMART; SM00032; CCP; 3. DR SMART; SM00020; Tryp_SPc; 1. DR SMART; SM00327; VWA; 1. DR PROSITE; PS50923; SUSHI; 3. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. DR PROSITE; PS50234; VWFA; 1. KW Complement pathway; Direct protein sequencing; Disease mutation; KW Glycoprotein; Hydrolase; Plasma; Polymorphism; Repeat; KW Serine protease; Signal; Sushi. FT SIGNAL 1 20 FT CHAIN 21 752 Complement C2. FT CHAIN 21 243 Complement C2b fragment. FT CHAIN 244 752 Complement C2a fragment. FT DOMAIN 22 86 Sushi 1. FT DOMAIN 87 146 Sushi 2. FT DOMAIN 149 206 Sushi 3. FT DOMAIN 254 452 VWFA. FT DOMAIN 466 752 Serine protease. FT ACT_SITE 507 507 Charge relay system (By similarity). FT ACT_SITE 561 561 Charge relay system (By similarity). FT ACT_SITE 679 679 Charge relay system (By similarity). FT DISULFID 24 64 By similarity. FT DISULFID 51 84 By similarity. FT DISULFID 89 131 By similarity. FT DISULFID 117 144 By similarity. FT DISULFID 151 191 By similarity. FT DISULFID 177 204 By similarity. FT CARBOHYD 29 29 N-linked (GlcNAc...) (Potential). FT CARBOHYD 112 112 N-linked (GlcNAc...) (Potential). FT CARBOHYD 290 290 N-linked (GlcNAc...) (Potential). FT CARBOHYD 333 333 N-linked (GlcNAc...) (Potential). FT CARBOHYD 467 467 N-linked (GlcNAc...) (Potential). FT CARBOHYD 471 471 N-linked (GlcNAc...) (Potential). FT CARBOHYD 621 621 N-linked (GlcNAc...). FT CARBOHYD 651 651 N-linked (GlcNAc...). FT VARIANT 131 131 C -> Y (in C2D; type II). FT /FTId=VAR_008544. FT VARIANT 209 209 S -> F (in C2D; type II). FT /FTId=VAR_008545. FT VARIANT 318 318 E -> D (in dbSNP:9332739). FT /FTId=VAR_019158. FT VARIANT 464 464 G -> R (in C2D; type II). FT /FTId=VAR_008546. FT VARIANT 533 533 F -> L (in dbSNP:1042664). FT /FTId=VAR_011772. FT VARIANT 734 734 R -> C (in dbSNP:4151648). FT /FTId=VAR_019159. FT CONFLICT 30 30 I -> L (in Ref. 7). FT CONFLICT 34 34 T -> S (in Ref. 7). FT CONFLICT 249 249 R -> S (in Ref. 7). FT CONFLICT 253 253 L -> K (in Ref. 7). SQ SEQUENCE 752 AA; 83268 MW; 5A96A13E700CF444 CRC64; MGPLMVLFCL LFLYPGLADS APSCPQNVNI SGGTFTLSHG WAPGSLLTYS CPQGLYPSPA SRLCKSSGQW QTPGATRSLS KAVCKPVRCP APVSFENGIY TPRLGSYPVG GNVSFECEDG FILRGSPVRQ CRPNGMWDGE TAVCDNGAGH CPNPGISLGA VRTGFRFGHG DKVRYRCSSN LVLTGSSERE CQGNGVWSGT EPICRQPYSY DFPEDVAPAL GTSFSHMLGA TNPTQKTKES LGRKIQIQRS GHLNLYLLLD CSQSVSENDF LIFKESASLM VDRIFSFEIN VSVAIITFAS EPKVLMSVLN DNSRDMTEVI SSLENANYKD HENGTGTNTY AALNSVYLMM NNQMRLLGME TMAWQEIRHA IILLTDGKSN MGGSPKTAVD HIREILNINQ KRNDYLDIYA IGVGKLDVDW RELNELGSKK DGERHAFILQ DTKALHQVFE HMLDVSKLTD TICGVGNMSA NASDQERTPW HVTIKPKSQE TCRGALISDQ WVLTAAHCFR DGNDHSLWRV NVGDPKSQWG KEFLIEKAVI SPGFDVFAKK NQGILEFYGD DIALLKLAQK VKMSTHARPI CLPCTMEANL ALRRPQGSTC RDHENELLNK QSVPAHFVAL NGSKLNINLK MGVEWTSCAE VVSQEKTMFP NLTDVREVVT DQFLCSGTQE DESPCKGESG GAVFLERRFR FFQVGLVSWG LYNPCLGSAD KNSRKRAPRS KVPPPRDFHI NLFRMQPWLR QHLGDVLNFL PL //