CO2_HUMAN
ID CO2_HUMAN Reviewed; 752 AA.
AC P06681; B4DPF3; B4DV20; E9PFN7; O19694; Q13904;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Complement C2;
DE EC=3.4.21.43;
DE AltName: Full=C3/C5 convertase;
DE Contains:
DE RecName: Full=Complement C2b fragment;
DE Contains:
DE RecName: Full=Complement C2a fragment;
DE Flags: Precursor;
GN Name=C2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=2949737; DOI=10.1042/bj2390339;
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 [MRNA] (ISOFORM 1).
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 [GENOMIC DNA].
RX 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 [GENOMIC DNA].
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 [GENOMIC DNA], AND VARIANTS ASP-318 AND CYS-734.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Kidney, and Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 21-46 AND 244-256.
RX PubMed=6922702; DOI=10.1042/bj2050059;
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 [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 21-46.
RX PubMed=2997031; DOI=10.1007/bf00430921;
RA Bentley D.R., Campbell R.D., Cross S.J.;
RT "DNA polymorphism of the C2 locus.";
RL Immunogenetics 22:377-390(1985).
RN [11]
RP PROTEIN SEQUENCE OF 21-28, AND INTERACTION WITH SCHISTOSOMA HAEMATOBIUM
RP TOR.
RX PubMed=10734221; DOI=10.1016/s0014-5793(00)01304-1;
RA Inal J.M., Sim R.B.;
RT "A Schistosoma protein, Sh-TOR, is a novel inhibitor of complement which
RT binds human C2.";
RL FEBS Lett. 470:131-134(2000).
RN [12]
RP PROTEIN SEQUENCE OF 137-171; 454-466 AND 574-717.
RX PubMed=6149575; DOI=10.1098/rstb.1984.0091;
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 [13]
RP PROTEIN SEQUENCE OF 244-269.
RX PubMed=6555044; DOI=10.1042/bj2130201;
RA Parkes C., Gagnon J., Kerr M.A.;
RT "The reaction of iodine and thiol-blocking reagents with human complement
RT components C2 and factor B. Purification and N-terminal amino acid sequence
RT of a peptide from C2a containing a free thiol group.";
RL Biochem. J. 213:201-209(1983).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 588-717 (ISOFORM 1).
RX PubMed=6199794; DOI=10.1073/pnas.81.4.1212;
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 [15]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 694-752.
RX PubMed=3643061; DOI=10.1016/0092-8674(87)90436-3;
RA Wu L.C., Morley B.J., Campbell R.D.;
RT "Cell-specific expression of the human complement protein factor B gene:
RT evidence for the role of two distinct 5'-flanking elements.";
RL Cell 48:331-342(1987).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-112; ASN-333; ASN-467; ASN-471;
RP ASN-621 AND ASN-651.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-112 AND ASN-333.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 244-752, GLYCOSYLATION AT ASN-333;
RP ASN-467 AND ASN-621, MIDAS-LIKE MOTIF, METAL-BINDING SITES, ACTIVE SITE,
RP AND DISULFIDE BONDS.
RX PubMed=17027507; DOI=10.1016/j.str.2006.08.008;
RA Milder F.J., Raaijmakers H.C., Vandeputte M.D., Schouten A., Huizinga E.G.,
RA Romijn R.A., Hemrika W., Roos A., Daha M.R., Gros P.;
RT "Structure of complement component C2A: implications for convertase
RT formation and substrate binding.";
RL Structure 14:1587-1597(2006).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 21-243, AND DISULFIDE BONDS.
RX PubMed=19237749; DOI=10.1107/s0907444909000389;
RA Krishnan V., Xu Y., Macon K., Volanakis J.E., Narayana S.V.;
RT "The structure of C2b, a fragment of complement component C2 produced
RT during C3 convertase formation.";
RL Acta Crystallogr. D 65:266-274(2009).
RN [21]
RP VARIANTS C2D PHE-209 AND ARG-464.
RX PubMed=8621452; DOI=10.1074/jbc.271.10.5824;
RA Wetsel R.A., Kulics J., Lokki M.L., Kiepiela P., Akama H., Johnson C.A.,
RA 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 [22]
RP VARIANT C2D TYR-131.
RX PubMed=9670930;
RA Zhu Z.B., Atkinson T.P., Volanakis J.E.;
RT "A novel type II complement C2 deficiency allele in an African-American
RT family.";
RL J. Immunol. 161:578-584(1998).
RN [23]
RP VARIANT ASP-318, AND INVOLVEMENT IN ARMD14.
RX PubMed=16518403; DOI=10.1038/ng1750;
RA Gold B., Merriam J.E., Zernant J., Hancox L.S., Taiber A.J., Gehrs K.,
RA Cramer K., Neel J., Bergeron J., Barile G.R., Smith R.T., Hageman G.S.,
RA Dean M., Allikmets R.;
RT "Variation in factor B (BF) and complement component 2 (C2) genes is
RT associated with age-related macular degeneration.";
RL Nat. Genet. 38:458-462(2006).
CC -!- FUNCTION: Component C2 which is part of the classical pathway of the
CC complement system is cleaved by activated factor C1 into two fragments:
CC C2b and C2a. C2a, a serine protease, then combines with complement
CC factor C4b to generate the C3 or C5 convertase.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective cleavage of Arg-|-Ser bond in complement component
CC C3 alpha-chain to form C3a and C3b, and Arg-|-Xaa bond in complement
CC component C5 alpha-chain to form C5a and C5b.; EC=3.4.21.43;
CC -!- SUBUNIT: C2a interacts with Schistosoma haematobium TOR (via N-terminal
CC extracellular domain). This results in inhibition of the classical and
CC lectin pathway of complement activation, probably due to interference
CC with binding of C2a to C4b such that C3 convertase cannot be formed.
CC This infers resistance to complement-mediated cell lysis, allowing
CC parasite survival and infection. {ECO:0000269|PubMed:10734221}.
CC -!- INTERACTION:
CC P06681; P09871: C1S; NbExp=3; IntAct=EBI-2835920, EBI-2810045;
CC P06681; O43889-2: CREB3; NbExp=3; IntAct=EBI-2835920, EBI-625022;
CC P06681; Q15125: EBP; NbExp=3; IntAct=EBI-2835920, EBI-3915253;
CC P06681; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-2835920, EBI-781551;
CC P06681; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-2835920, EBI-18304435;
CC P06681; P15941-11: MUC1; NbExp=3; IntAct=EBI-2835920, EBI-17263240;
CC P06681; Q9BY50: SEC11C; NbExp=5; IntAct=EBI-2835920, EBI-2855401;
CC P06681; Q14973: SLC10A1; NbExp=3; IntAct=EBI-2835920, EBI-3923031;
CC P06681; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-2835920, EBI-17295964;
CC P06681; P27105: STOM; NbExp=3; IntAct=EBI-2835920, EBI-1211440;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P06681-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P06681-2; Sequence=VSP_043038, VSP_043039;
CC Name=3;
CC IsoId=P06681-3; Sequence=VSP_046103;
CC -!- DOMAIN: The MIDAS-like motif in the VWFA domain binds divalent metal
CC cations.
CC -!- DISEASE: Macular degeneration, age-related, 14 (ARMD14) [MIM:615489]: A
CC form of age-related macular degeneration, a multifactorial eye disease
CC and the most common cause of irreversible vision loss in the developed
CC world. In most patients, the disease is manifest as ophthalmoscopically
CC visible yellowish accumulations of protein and lipid that lie beneath
CC the retinal pigment epithelium and within an elastin-containing
CC structure known as Bruch membrane. {ECO:0000269|PubMed:16518403}.
CC Note=Disease susceptibility may be associated with variants affecting
CC the gene represented in this entry. Haplotype analyses have identified
CC a statistically significant common risk haplotype and two protective
CC haplotypes. CFB variant His-9 and C2 variant Asp-318, as well as CFB
CC variant Gln-32 and a variant in intron 10 of C2, confer a significantly
CC reduced risk of AMD. {ECO:0000269|PubMed:16518403}.
CC -!- DISEASE: Complement component 2 deficiency (C2D) [MIM:217000]: A rare
CC defect of the complement classical pathway associated with the
CC development of autoimmune disorders, mainly systemic lupus
CC erythematosus. Skin and joint manifestations are common and renal
CC disease is relatively rare. Patients with complement component 2
CC deficiency are also reported to have recurrent invasive infections.
CC {ECO:0000269|PubMed:8621452, ECO:0000269|PubMed:9670930}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: C2 is a major histocompatibility complex class-III
CC protein.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- WEB RESOURCE: Name=C2base; Note=C2 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/C2base/";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/c2/";
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DR EMBL; X04481; CAA28169.1; -; mRNA.
DR EMBL; M26301; AAA35614.1; -; mRNA.
DR EMBL; L09708; AAB97607.1; -; Genomic_DNA.
DR EMBL; L09706; AAB97607.1; JOINED; Genomic_DNA.
DR EMBL; L09707; AAB97607.1; JOINED; Genomic_DNA.
DR EMBL; AF019413; AAB67975.1; -; Genomic_DNA.
DR EMBL; AY349611; AAQ15273.1; -; Genomic_DNA.
DR EMBL; AK298311; BAG60565.1; -; mRNA.
DR EMBL; AK300892; BAG62532.1; -; mRNA.
DR EMBL; AL645922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL671762; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL844853; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX005143; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR388219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR759782; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR759784; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR933857; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043484; AAH43484.1; -; mRNA.
DR EMBL; M15549; AAA59649.1; -; Genomic_DNA.
DR EMBL; M15082; AAA59624.1; -; Genomic_DNA.
DR CCDS; CCDS4728.1; -. [P06681-1]
DR CCDS; CCDS54991.1; -. [P06681-3]
DR CCDS; CCDS56416.1; -. [P06681-2]
DR PIR; A25971; C2HU.
DR RefSeq; NP_000054.2; NM_000063.5. [P06681-1]
DR RefSeq; NP_001139375.1; NM_001145903.2. [P06681-3]
DR RefSeq; NP_001171534.1; NM_001178063.2. [P06681-2]
DR PDB; 2I6Q; X-ray; 2.10 A; A=244-752.
DR PDB; 2I6S; X-ray; 2.70 A; A=244-752.
DR PDB; 2ODP; X-ray; 1.90 A; A=244-752.
DR PDB; 2ODQ; X-ray; 2.30 A; A=244-752.
DR PDB; 3ERB; X-ray; 1.80 A; A=21-243.
DR PDBsum; 2I6Q; -.
DR PDBsum; 2I6S; -.
DR PDBsum; 2ODP; -.
DR PDBsum; 2ODQ; -.
DR PDBsum; 3ERB; -.
DR AlphaFoldDB; P06681; -.
DR SMR; P06681; -.
DR BioGRID; 107178; 12.
DR ComplexPortal; CPX-5675; Classical and lectin pathway C3 convertase complex C4b2a-A.
DR ComplexPortal; CPX-6156; Classical and lectin pathway C3 convertase complex C4b2a-B.
DR IntAct; P06681; 13.
DR STRING; 9606.ENSP00000299367; -.
DR BindingDB; P06681; -.
DR ChEMBL; CHEMBL4295701; -.
DR MEROPS; S01.194; -.
DR GlyConnect; 1145; 17 N-Linked glycans (6 sites).
DR GlyGen; P06681; 9 sites, 20 N-linked glycans (7 sites).
DR iPTMnet; P06681; -.
DR PhosphoSitePlus; P06681; -.
DR BioMuta; C2; -.
DR DMDM; 3915642; -.
DR CPTAC; non-CPTAC-1104; -.
DR jPOST; P06681; -.
DR MassIVE; P06681; -.
DR MaxQB; P06681; -.
DR PaxDb; P06681; -.
DR PeptideAtlas; P06681; -.
DR PRIDE; P06681; -.
DR ProteomicsDB; 20143; -.
DR ProteomicsDB; 51908; -. [P06681-1]
DR ProteomicsDB; 51909; -. [P06681-2]
DR Antibodypedia; 7528; 509 antibodies from 32 providers.
DR DNASU; 717; -.
DR Ensembl; ENST00000299367.10; ENSP00000299367.5; ENSG00000166278.15. [P06681-1]
DR Ensembl; ENST00000375510.8; ENSP00000364660.4; ENSG00000204364.10. [P06681-1]
DR Ensembl; ENST00000383362.8; ENSP00000372853.4; ENSG00000206372.11. [P06681-1]
DR Ensembl; ENST00000411803.6; ENSP00000402278.2; ENSG00000235696.8. [P06681-1]
DR Ensembl; ENST00000413548.6; ENSP00000407961.2; ENSG00000231543.9. [P06681-1]
DR Ensembl; ENST00000416252.6; ENSP00000405800.2; ENSG00000235017.9. [P06681-1]
DR Ensembl; ENST00000442278.6; ENSP00000395683.2; ENSG00000166278.15. [P06681-3]
DR Ensembl; ENST00000448206.6; ENSP00000392835.2; ENSG00000226560.10. [P06681-1]
DR Ensembl; ENST00000452323.6; ENSP00000392322.2; ENSG00000166278.15. [P06681-2]
DR Ensembl; ENST00000548973.5; ENSP00000446728.1; ENSG00000206372.11. [P06681-3]
DR Ensembl; ENST00000548995.3; ENSP00000449286.1; ENSG00000204364.10. [P06681-3]
DR Ensembl; ENST00000549972.3; ENSP00000447632.1; ENSG00000235696.8. [P06681-3]
DR Ensembl; ENST00000550682.5; ENSP00000446639.1; ENSG00000231543.9. [P06681-3]
DR Ensembl; ENST00000551081.4; ENSP00000450387.1; ENSG00000235017.9. [P06681-3]
DR Ensembl; ENST00000551648.5; ENSP00000449715.1; ENSG00000226560.10. [P06681-3]
DR Ensembl; ENST00000612228.1; ENSP00000482616.1; ENSG00000231543.9. [P06681-2]
DR Ensembl; ENST00000615380.4; ENSP00000481651.1; ENSG00000226560.10. [P06681-2]
DR Ensembl; ENST00000618254.4; ENSP00000483231.1; ENSG00000235017.9. [P06681-2]
DR Ensembl; ENST00000621558.4; ENSP00000480739.1; ENSG00000206372.11. [P06681-2]
DR GeneID; 717; -.
DR KEGG; hsa:717; -.
DR MANE-Select; ENST00000299367.10; ENSP00000299367.5; NM_000063.6; NP_000054.2.
DR UCSC; uc010jtk.5; human. [P06681-1]
DR CTD; 717; -.
DR DisGeNET; 717; -.
DR GeneCards; C2; -.
DR HGNC; HGNC:1248; C2.
DR HPA; ENSG00000166278; Tissue enriched (liver).
DR MalaCards; C2; -.
DR MIM; 217000; phenotype.
DR MIM; 613927; gene.
DR MIM; 615489; phenotype.
DR neXtProt; NX_P06681; -.
DR OpenTargets; ENSG00000166278; -.
DR Orphanet; 169147; Immunodeficiency due to a classical component pathway complement deficiency.
DR PharmGKB; PA25637; -.
DR VEuPathDB; HostDB:ENSG00000166278; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000162934; -.
DR HOGENOM; CLU_022004_0_0_1; -.
DR InParanoid; P06681; -.
DR OMA; PRSILWI; -.
DR PhylomeDB; P06681; -.
DR TreeFam; TF330194; -.
DR PathwayCommons; P06681; -.
DR Reactome; R-HSA-166663; Initial triggering of complement.
DR Reactome; R-HSA-174577; Activation of C3 and C5.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SABIO-RK; P06681; -.
DR SignaLink; P06681; -.
DR SIGNOR; P06681; -.
DR BioGRID-ORCS; 717; 11 hits in 1065 CRISPR screens.
DR ChiTaRS; C2; human.
DR EvolutionaryTrace; P06681; -.
DR GeneWiki; Complement_component_2; -.
DR GenomeRNAi; 717; -.
DR Pharos; P06681; Tchem.
DR PRO; PR:P06681; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P06681; protein.
DR Bgee; ENSG00000166278; Expressed in liver and 99 other tissues.
DR ExpressionAtlas; P06681; baseline and differential.
DR Genevisible; P06681; HS.
DR GO; GO:0005601; C:classical-complement-pathway C3/C5 convertase complex; IPI:ComplexPortal.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0006956; P:complement activation; IDA:ComplexPortal.
DR GO; GO:0006958; P:complement activation, classical pathway; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:2000427; P:positive regulation of apoptotic cell clearance; IMP:BHF-UCL.
DR GO; GO:0050778; P:positive regulation of immune response; IC:ComplexPortal.
DR GO; GO:1903028; P:positive regulation of opsonization; IC:ComplexPortal.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0009617; P:response to bacterium; IBA:GO_Central.
DR CDD; cd00033; CCP; 3.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR011360; Compl_C2_B.
DR InterPro; IPR037568; Complement_C2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR PANTHER; PTHR46393; PTHR46393; 1.
DR PANTHER; PTHR46393:SF2; PTHR46393:SF2; 1.
DR Pfam; PF00084; Sushi; 2.
DR Pfam; PF00089; Trypsin; 1.
DR Pfam; PF00092; VWA; 1.
DR PIRSF; PIRSF001154; Compl_C2_B; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00032; CCP; 3.
DR SMART; SM00020; Tryp_SPc; 1.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF53300; SSF53300; 1.
DR SUPFAM; SSF57535; SSF57535; 3.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Age-related macular degeneration; Alternative splicing;
KW Complement pathway; Direct protein sequencing; Disease variant;
KW Disulfide bond; Glycoprotein; Hydrolase; Immunity; Innate immunity;
KW Metal-binding; Protease; Reference proteome; Repeat; Secreted;
KW Serine protease; Signal; Sushi.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:10734221,
FT ECO:0000269|PubMed:6922702"
FT CHAIN 21..752
FT /note="Complement C2"
FT /id="PRO_0000027610"
FT CHAIN 21..243
FT /note="Complement C2b fragment"
FT /id="PRO_0000027611"
FT CHAIN 244..752
FT /note="Complement C2a fragment"
FT /id="PRO_0000027612"
FT DOMAIN 22..86
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 87..146
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 149..206
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 254..452
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 464..744
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT MOTIF 260..264
FT /note="MIDAS-like motif"
FT ACT_SITE 507
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:17027507"
FT ACT_SITE 561
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:17027507"
FT ACT_SITE 679
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:17027507"
FT BINDING 262
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT BINDING 264
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT BINDING 337
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:17027507, ECO:0000269|PubMed:19159218"
FT CARBOHYD 467
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:17027507"
FT CARBOHYD 471
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 621
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:17027507"
FT CARBOHYD 651
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT DISULFID 24..64
FT DISULFID 51..84
FT DISULFID 89..131
FT DISULFID 117..144
FT DISULFID 151..191
FT DISULFID 177..204
FT DISULFID 492..508
FT /evidence="ECO:0000250"
FT DISULFID 675..705
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..147
FT /note="MGPLMVLFCLLFLYPGLADSAPSCPQNVNISGGTFTLSHGWAPGSLLTYSCP
FT QGLYPSPASRLCKSSGQWQTPGATRSLSKAVCKPVRCPAPVSFENGIYTPRLGSYPVGG
FT NVSFECEDGFILRGSPVRQCRPNGMWDGETAVCDNG -> MRALCIRETCSSELGFSRN
FT WSRRK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043038"
FT VAR_SEQ 16..147
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046103"
FT VAR_SEQ 238..328
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043039"
FT VARIANT 131
FT /note="C -> Y (in C2D; dbSNP:rs760744400)"
FT /evidence="ECO:0000269|PubMed:9670930"
FT /id="VAR_008544"
FT VARIANT 209
FT /note="S -> F (in C2D; dbSNP:rs28934590)"
FT /evidence="ECO:0000269|PubMed:8621452"
FT /id="VAR_008545"
FT VARIANT 318
FT /note="E -> D (may be associated with a reduced risk for
FT age-related macular degeneration; dbSNP:rs9332739)"
FT /evidence="ECO:0000269|PubMed:16518403, ECO:0000269|Ref.5"
FT /id="VAR_019158"
FT VARIANT 464
FT /note="G -> R (in C2D; dbSNP:rs151340617)"
FT /evidence="ECO:0000269|PubMed:8621452"
FT /id="VAR_008546"
FT VARIANT 533
FT /note="F -> L (in dbSNP:rs1042664)"
FT /id="VAR_011772"
FT VARIANT 734
FT /note="R -> C (in dbSNP:rs4151648)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_019159"
FT CONFLICT 30
FT /note="I -> L (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 34
FT /note="T -> S (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="D -> G (in Ref. 6; BAG62532)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="R -> S (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 253
FT /note="L -> K (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 46..50
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 98..102
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 105..108
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 122..125
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 127..131
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 160..163
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:3ERB"
FT HELIX 207..211
FT /evidence="ECO:0007829|PDB:3ERB"
FT STRAND 249..260
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 267..284
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 291..306
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 311..314
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 316..325
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 328..331
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 339..357
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:2I6S"
FT HELIX 362..365
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 367..375
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 385..396
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 401..405
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 406..415
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 420..426
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 436..441
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 442..452
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 474..477
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 481..485
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 492..504
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 506..508
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 515..517
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 519..522
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 531..533
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 535..540
FT /evidence="ECO:0007829|PDB:2I6Q"
FT TURN 546..549
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 550..552
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 563..569
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 574..576
FT /evidence="ECO:0007829|PDB:2I6S"
FT HELIX 586..591
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 600..607
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 610..618
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 624..630
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 633..639
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 640..644
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 646..648
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 655..657
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 663..666
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 676..678
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 681..687
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 690..701
FT /evidence="ECO:0007829|PDB:2I6Q"
FT TURN 704..707
FT /evidence="ECO:0007829|PDB:2I6S"
FT STRAND 720..723
FT /evidence="ECO:0007829|PDB:2I6Q"
FT STRAND 727..731
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 732..734
FT /evidence="ECO:0007829|PDB:2I6Q"
FT HELIX 736..743
FT /evidence="ECO:0007829|PDB:2I6Q"
FT TURN 744..746
FT /evidence="ECO:0007829|PDB:2I6Q"
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
