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 18-JUN-2025, entry version 244. DE RecName: Full=Complement C2 {ECO:0000305}; DE AltName: Full=C3/C5 convertase; DE Contains: DE RecName: Full=Complement C2a; DE Contains: DE RecName: Full=Serine protease complement C2b; DE EC=3.4.21.43 {ECO:0000269|PubMed:14561755, ECO:0000269|PubMed:17027507}; DE Flags: Precursor; GN Name=C2 {ECO:0000303|PubMed:2949737, ECO:0000312|HGNC:HGNC:1248}; 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 PROTEIN SEQUENCE OF N-TERMINUS, AND PROTEOLYTIC CLEAVAGE. RX PubMed=6282646; DOI=10.1016/0014-5793(82)80006-9; RA Thielens N.M., Villiers M.B., Reboul A., Villiers C.L., Colomb M.G.; RT "Human complement subcomponent C2: purification and proteolytic cleavage in RT fluid phase by C1s, C1r2-C1s2 and C1."; RL FEBS Lett. 141:19-24(1982). RN [17] RP PROTEOLYTIC CLEAVAGE. RX PubMed=70787; DOI=10.1073/pnas.74.7.2998; RA Nagasawa S., Stroud R.M.; RT "Cleavage of C2 by C1s into the antigenically distinct fragments C2a and RT C2b: demonstration of binding of C2b to C4b."; RL Proc. Natl. Acad. Sci. U.S.A. 74:2998-3001(1977). RN [18] RP PROTEOLYTIC CLEAVAGE. RX PubMed=417728; DOI=10.1042/bj1710099; RA Kerr M.A., Porter R.R.; RT "The purification and properties of the second component of human RT complement."; RL Biochem. J. 171:99-107(1978). RN [19] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND PROTEOLYTIC CLEAVAGE. RX PubMed=6906228; DOI=10.1042/bj1890173; RA Kerr M.A.; RT "The human complement system: assembly of the classical pathway C3 RT convertase."; RL Biochem. J. 189:173-181(1980). RN [20] RP SUBCELLULAR LOCATION. RX PubMed=6602833; RA Brown E.J., Ramsey J., Hammer C.H., Frank M.M.; RT "Surface modulation of classical pathway activation: C2 and C3 convertase RT formation and regulation on sheep, guinea pig, and human erythrocytes."; RL J. Immunol. 131:403-408(1983). RN [21] RP FUNCTION, AND SUBUNIT. RX PubMed=6611150; DOI=10.1042/bj2190391; RA Kerr M.A., Parkes C.; RT "The effects of iodine and thiol-blocking reagents on complement component RT C2 and on the assembly of the classical-pathway C3 convertase."; RL Biochem. J. 219:391-399(1984). RN [22] RP PROTEOLYTIC CLEAVAGE. RX PubMed=6319179; DOI=10.1016/0014-5793(84)80025-3; RA Thielens N.M., Villiers C.L., Villiers M.B., Colomb M.G.; RT "Comparative study of the fluid-phase proteolytic cleavage of human RT complement subcomponents C4 and C2 by C1s and C1r2-C1s2."; RL FEBS Lett. 165:111-116(1984). RN [23] RP SUBUNIT. RX PubMed=3874204; DOI=10.1093/oxfordjournals.jbchem.a135083; RA Nagasawa S., Kobayashi C., Maki-Suzuki T., Yamashita N., Koyama J.; RT "Purification and characterization of the C3 convertase of the classical RT pathway of human complement system by size exclusion high-performance RT liquid chromatography."; RL J. Biochem. 97:493-499(1985). RN [24] RP PROTEOLYTIC CLEAVAGE. RX PubMed=9422791; DOI=10.1074/jbc.273.2.1232; RA Rossi V., Bally I., Thielens N.M., Esser A.F., Arlaud G.J.; RT "Baculovirus-mediated expression of truncated modular fragments from the RT catalytic region of human complement serine protease C1s. Evidence for the RT involvement of both complement control protein modules in the recognition RT of the C4 protein substrate."; RL J. Biol. Chem. 273:1232-1239(1998). RN [25] RP PROTEOLYTIC CLEAVAGE. RX PubMed=11527969; DOI=10.1074/jbc.m105934200; RA Rossi V., Cseh S., Bally I., Thielens N.M., Jensenius J.C., Arlaud G.J.; RT "Substrate specificities of recombinant mannan-binding lectin-associated RT serine proteases-1 and -2."; RL J. Biol. Chem. 276:40880-40887(2001). RN [26] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=12878586; DOI=10.1074/jbc.m307017200; RA Rawal N., Pangburn M.K.; RT "Formation of high affinity C5 convertase of the classical pathway of RT complement."; RL J. Biol. Chem. 278:38476-38483(2003). RN [27] RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF ASN-344; TYR-347 AND LEU-348. RX PubMed=14561755; DOI=10.1074/jbc.m304620200; RA Kuttner-Kondo L.A., Dybvig M.P., Mitchell L.M., Muqim N., Atkinson J.P., RA Medof M.E., Hourcade D.E.; RT "A corresponding tyrosine residue in the C2/factor B type A domain is a hot RT spot in the decay acceleration of the complement C3 convertases."; RL J. Biol. Chem. 278:52386-52391(2003). RN [28] RP PROTEOLYTIC CLEAVAGE. RX PubMed=16169853; DOI=10.1074/jbc.m506131200; RA Kerr F.K., O'Brien G., Quinsey N.S., Whisstock J.C., Boyd S., RA de la Banda M.G., Kaiserman D., Matthews A.Y., Bird P.I., Pike R.N.; RT "Elucidation of the substrate specificity of the C1s protease of the RT classical complement pathway."; RL J. Biol. Chem. 280:39510-39514(2005). RN [29] 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 [30] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=18204047; DOI=10.1074/jbc.m707591200; RA Rawal N., Rajagopalan R., Salvi V.P.; RT "Activation of complement component C5: comparison of C5 convertases of the RT lectin pathway and the classical pathway of complement."; RL J. Biol. Chem. 283:7853-7863(2008). RN [31] 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 [32] 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 [33] RP SUBUNIT, AND MUTAGENESIS OF CYS-261 AND GLN-263. RX PubMed=27252379; DOI=10.1074/jbc.m116.722017; RA Mortensen S., Jensen J.K., Andersen G.R.; RT "Solution Structures of Complement C2 and Its C4 Complexes Propose Pathway- RT specific mechanisms for control and activation of the complement RT proconvertases."; RL J. Biol. Chem. 291:16494-16507(2016). RN [34] RP FUNCTION, AND PROTEOLYTIC CLEAVAGE. RX PubMed=39914456; DOI=10.1038/s41586-025-08713-9; RG Accelerating Medicines Partnership RA/SLE Network; RA Donado C.A., Theisen E., Zhang F., Nathan A., Fairfield M.L., Rupani K.V., RA Jones D., Johannes K.P., Raychaudhuri S., Dwyer D.F., Jonsson A.H., RA Brenner M.B.; RT "Granzyme K activates the entire complement cascade."; RL Nature 0:0-0(2025). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 244-752, GLYCOSYLATION AT ASN-333; RP ASN-467 AND ASN-621, FUNCTION, CATALYTIC ACTIVITY, MIDAS-LIKE MOTIF, RP COFACTOR, METAL-BINDING SITES, ACTIVE SITE, 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 [36] {ECO:0007744|PDB:2ODQ} RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 244-752, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-651. RX PubMed=17234210; DOI=10.1016/j.jmb.2006.12.039; RA Krishnan V., Xu Y., Macon K., Volanakis J.E., Narayana S.V.; RT "The crystal structure of C2a, the catalytic fragment of classical pathway RT C3 and C5 convertase of human complement."; RL J. Mol. Biol. 367:224-233(2007). RN [37] 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 [38] RP VARIANTS C2D PHE-209 AND ARG-464, AND SUBCELLULAR LOCATION. 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 [39] 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 [40] 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: Precursor of the catalytic component of the C3 and C5 CC convertase complexes, which are part of the complement pathway, a CC cascade of proteins that leads to phagocytosis and breakdown of CC pathogens and signaling that strengthens the adaptive immune system CC (PubMed:12878586, PubMed:17027507, PubMed:18204047, PubMed:39914456). CC Component C2 is part of the classical, lectin and GZMK complement CC systems (PubMed:12878586, PubMed:17027507, PubMed:18204047, CC PubMed:39914456). {ECO:0000269|PubMed:12878586, CC ECO:0000269|PubMed:17027507, ECO:0000269|PubMed:18204047, CC ECO:0000269|PubMed:39914456}. CC -!- FUNCTION: [Serine protease complement C2b]: Catalytic component of the CC complement C3 and C5 convertase complexes (PubMed:12878586, CC PubMed:17027507, PubMed:18204047, PubMed:6906228). Following complement CC activation, recruited to the surface of pathogens by complement C4b CC opsonin to form the C3 convertase, or C3b and C4b opsonins to form the CC C5 convertase (PubMed:6611150, PubMed:6906228). As part of the C3 CC convertase, cleaves and activate C3 into C3a anaphylatoxin and C3b CC opsonin, the next components of the complement pathways CC (PubMed:14561755, PubMed:17027507). As part of the C5 convertase, CC cleaves and activate C5 into C5a anaphylatoxin and C5b component of the CC membrane attack complex (PubMed:12878586, PubMed:17027507, CC PubMed:18204047). {ECO:0000269|PubMed:12878586, CC ECO:0000269|PubMed:14561755, ECO:0000269|PubMed:17027507, CC ECO:0000269|PubMed:18204047, ECO:0000269|PubMed:6611150, CC ECO:0000269|PubMed:6906228}. CC -!- CATALYTIC ACTIVITY: [Serine protease complement C2b]: 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 Evidence={ECO:0000269|PubMed:12878586, ECO:0000269|PubMed:14561755, CC ECO:0000269|PubMed:17027507, ECO:0000269|PubMed:18204047, CC ECO:0000269|PubMed:6906228}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:17234210}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:17027507}; CC -!- SUBUNIT: [Serine protease complement C2b]: Serine protease component of CC the C3 convertase, also named C4bC2b, composed of the serine protease CC complement C2b and complement C4b (PubMed:14561755, PubMed:27252379, CC PubMed:3874204, PubMed:6611150, PubMed:6906228). Serine protease CC component of the C5 convertase, also named C4bC2bC3b, composed of the CC serine protease complement C2b, complement C3b, as well as complement CC C4b (PubMed:12878586, PubMed:18204047). {ECO:0000269|PubMed:12878586, CC ECO:0000269|PubMed:14561755, ECO:0000269|PubMed:18204047, CC ECO:0000269|PubMed:27252379, ECO:0000269|PubMed:3874204, CC ECO:0000269|PubMed:6611150, ECO:0000269|PubMed:6906228}. CC -!- SUBUNIT: [Serine protease complement C2b]: (Microbial infection) CC 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 {ECO:0000269|PubMed:8621452}. Cell CC surface {ECO:0000269|PubMed:6602833}. Note=Recruited to the surface of CC pathogens by complement C3b and complement C4b opsonins. CC {ECO:0000269|PubMed:6602833}. 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. {ECO:0000269|PubMed:17027507}. CC -!- PTM: Cleaved and activated by different proteases depending on the CC complement pathway to generate complement C2a and serine protease CC complement C2b chains (PubMed:6282646, PubMed:6319179, PubMed:6906228, CC PubMed:70787). Cleaved and activated by C1S following activation by the CC classical complement system (PubMed:11527969, PubMed:16169853, CC PubMed:417728, PubMed:6282646, PubMed:6319179, PubMed:6906228, CC PubMed:70787, PubMed:9422791). Cleaved and activated by MASP2 following CC activation by the lectin complement system (PubMed:11527969). Cleaved CC and activated by GZMK following activation by the GZMK complement CC system (PubMed:39914456). {ECO:0000269|PubMed:11527969, CC ECO:0000269|PubMed:16169853, ECO:0000269|PubMed:39914456, CC ECO:0000269|PubMed:417728, ECO:0000269|PubMed:6282646, CC ECO:0000269|PubMed:6319179, ECO:0000269|PubMed:6906228, CC ECO:0000269|PubMed:70787, ECO:0000269|PubMed:9422791}. 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 analyzes 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 -!- CAUTION: Historically, the serine protease complement C2b, which CC constitutes the larger catalytic fragment, was named C2a. It was later CC renamed C2b, a nomenclature widely accepted now. {ECO:0000305}. CC -!- WEB RESOURCE: Name=C2base; Note=C2 mutation db; CC URL="https://databases.lovd.nl/shared/genes/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_001145903.3. [P06681-3] DR RefSeq; NP_001171534.1; NM_001178063.3. [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 PDB; 8ACF; X-ray; 1.80 A; A=21-217. DR PDB; 8ACI; X-ray; 1.85 A; A=21-217. DR PDBsum; 2I6Q; -. DR PDBsum; 2I6S; -. DR PDBsum; 2ODP; -. DR PDBsum; 2ODQ; -. DR PDBsum; 3ERB; -. DR PDBsum; 8ACF; -. DR PDBsum; 8ACI; -. 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 FunCoup; P06681; 236. 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; 12 sites, 54 N-linked glycans (8 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 PaxDb; 9606-ENSP00000299367; -. DR PeptideAtlas; P06681; -. DR ProteomicsDB; 20143; -. DR ProteomicsDB; 51908; -. [P06681-1] DR ProteomicsDB; 51909; -. [P06681-2] DR Antibodypedia; 7528; 552 antibodies from 34 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; YTKPWHV; -. DR OrthoDB; 6127264at2759; -. DR PAN-GO; P06681; 3 GO annotations based on evolutionary models. 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: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 FunFam; 3.40.50.410:FF:000065; Complement C2; 1. DR FunFam; 2.40.10.10:FF:000051; complement C2 isoform X1; 1. DR FunFam; 2.10.70.10:FF:000052; Complement factor B; 1. DR FunFam; 2.10.70.10:FF:000019; Complement factor b,-like; 2. DR FunFam; 2.40.10.10:FF:000046; Complement factor b,-like; 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. 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; Proteomics identification; Reference proteome; KW Repeat; Secreted; 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 C2a" FT /evidence="ECO:0000305|PubMed:6282646" FT /id="PRO_0000027611" FT CHAIN 244..752 FT /note="Serine protease complement C2b" FT /evidence="ECO:0000305|PubMed:6282646" 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 /evidence="ECO:0000269|PubMed:17027507" 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="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:17234210, FT ECO:0007744|PDB:2ODP" FT BINDING 262 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:17027507, FT ECO:0007744|PDB:2I6Q" FT BINDING 264 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:17234210, FT ECO:0007744|PDB:2ODP" FT BINDING 264 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:17027507, FT ECO:0007744|PDB:2I6Q" FT BINDING 337 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:17234210, FT ECO:0007744|PDB:2ODP" FT BINDING 337 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:17027507, FT ECO:0007744|PDB:2I6Q" FT SITE 243..244 FT /note="Cleavage; by C1S, MASP2 and GZMK" FT /evidence="ECO:0000269|PubMed:6282646" 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 ECO:0000269|PubMed:17234210, ECO:0007744|PDB:2ODQ" FT DISULFID 24..64 FT /evidence="ECO:0000269|PubMed:19237749" FT DISULFID 51..84 FT /evidence="ECO:0000269|PubMed:19237749" FT DISULFID 89..131 FT /evidence="ECO:0000269|PubMed:19237749" FT DISULFID 117..144 FT /evidence="ECO:0000269|PubMed:19237749" FT DISULFID 151..191 FT /evidence="ECO:0000269|PubMed:19237749" FT DISULFID 177..204 FT /evidence="ECO:0000269|PubMed:19237749" FT DISULFID 463..581 FT /evidence="ECO:0000269|PubMed:17027507, FT ECO:0000269|PubMed:17234210, ECO:0007744|PDB:2I6Q, FT ECO:0007744|PDB:2ODQ" FT DISULFID 492..508 FT /evidence="ECO:0000269|PubMed:17027507, FT ECO:0000269|PubMed:17234210, ECO:0007744|PDB:2I6Q, FT ECO:0007744|PDB:2ODQ" FT DISULFID 584..600 FT /evidence="ECO:0000269|PubMed:17027507, FT ECO:0000269|PubMed:17234210, ECO:0007744|PDB:2I6Q, FT ECO:0007744|PDB:2ODQ" FT DISULFID 638..665 FT /evidence="ECO:0000269|PubMed:17027507, FT ECO:0000269|PubMed:17234210, ECO:0007744|PDB:2I6Q, FT ECO:0007744|PDB:2ODQ" FT DISULFID 675..705 FT /evidence="ECO:0000269|PubMed:17027507, FT ECO:0000269|PubMed:17234210, ECO:0007744|PDB:2I6Q, FT ECO:0007744|PDB:2ODQ" 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 MUTAGEN 261 FT /note="C->A: Prolonged activity and half-life." FT /evidence="ECO:0000269|PubMed:27252379" FT MUTAGEN 263 FT /note="Q->K: Prolonged activity and half-life." FT /evidence="ECO:0000269|PubMed:27252379" FT MUTAGEN 344 FT /note="N->A: Promotes partial resistance to degradation, FT slightly increasing half-life of the protein." FT /evidence="ECO:0000269|PubMed:14561755" FT MUTAGEN 347 FT /note="Y->A: Promotes resistance to degradation, increasing FT half-life of the protein." FT /evidence="ECO:0000269|PubMed:14561755" FT MUTAGEN 348 FT /note="L->A: Promotes partial resistance to degradation, FT slightly increasing half-life of the protein." FT /evidence="ECO:0000269|PubMed:14561755" 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 //