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 24-JAN-2024, entry version 237. 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/"; 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; -; 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 GlyCosmos; P06681; 9 sites, 18 glycans. 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; 9606-ENSP00000299367; -. DR PeptideAtlas; P06681; -. DR ProteomicsDB; 20143; -. DR ProteomicsDB; 51908; -. [P06681-1] DR ProteomicsDB; 51909; -. [P06681-2] DR Antibodypedia; 7528; 591 antibodies from 32 providers. DR DNASU; 717; -. DR Ensembl; ENST00000299367.10; ENSP00000299367.5; ENSG00000166278.16. [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; ENSG00000166278.16. [P06681-3] DR Ensembl; ENST00000448206.6; ENSP00000392835.2; ENSG00000226560.10. [P06681-1] DR Ensembl; ENST00000452323.7; ENSP00000392322.2; ENSG00000166278.16. [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 AGR; HGNC:1248; -. 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 OrthoDB; 3594820at2759; -. 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; 13 hits in 1148 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 cell types or tissues. DR ExpressionAtlas; P06681; baseline and differential. DR GO; GO:0005601; C:classical-complement-pathway C3/C5 convertase complex; IBA:GO_Central. 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: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; IMP:BHF-UCL. 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:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0009617; P:response to bacterium; IBA:GO_Central. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR GO; GO:0097066; P:response to thyroid hormone; IEA:Ensembl. DR CDD; cd00033; CCP; 2. DR CDD; cd00190; Tryp_SPc; 1. DR CDD; cd01470; vWA_complement_factors; 1. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 3. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1. DR InterPro; IPR011360; Compl_C2_B. 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:SF2; COMPLEMENT C2; 1. DR PANTHER; PTHR46393; SUSHI DOMAIN-CONTAINING PROTEIN; 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; SSF57535; Complement control module/SCR domain; 3. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR SUPFAM; SSF53300; vWA-like; 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. DR Genevisible; P06681; HS. 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 //