CO3_HUMAN
ID CO3_HUMAN Reviewed; 1663 AA.
AC P01024; A7E236;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 03-AUG-2022, entry version 255.
DE RecName: Full=Complement C3;
DE AltName: Full=C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1;
DE Contains:
DE RecName: Full=Complement C3 beta chain;
DE Contains:
DE RecName: Full=C3-beta-c;
DE Short=C3bc;
DE Contains:
DE RecName: Full=Complement C3 alpha chain;
DE Contains:
DE RecName: Full=C3a anaphylatoxin;
DE Contains:
DE RecName: Full=Acylation stimulating protein;
DE Short=ASP;
DE AltName: Full=C3adesArg;
DE Contains:
DE RecName: Full=Complement C3b alpha' chain;
DE Contains:
DE RecName: Full=Complement C3c alpha' chain fragment 1;
DE Contains:
DE RecName: Full=Complement C3dg fragment;
DE Contains:
DE RecName: Full=Complement C3g fragment;
DE Contains:
DE RecName: Full=Complement C3d fragment;
DE Contains:
DE RecName: Full=Complement C3f fragment;
DE Contains:
DE RecName: Full=Complement C3c alpha' chain fragment 2;
DE Flags: Precursor;
GN Name=C3; Synonyms=CPAMD1;
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], AND VARIANT LEU-314.
RX PubMed=2579379; DOI=10.1073/pnas.82.3.708;
RA de Bruijn M.H.L., Fey G.H.;
RT "Human complement component C3: cDNA coding sequence and derived primary
RT structure.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:708-712(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-102; LEU-314; LYS-863;
RP ASP-1224 AND THR-1367.
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP PROTEIN SEQUENCE OF N-TERMINUS, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP FUNCTION.
RX PubMed=8376604; DOI=10.1172/jci116733;
RA Baldo A., Sniderman A.D., St-Luce S., Avramoglu R.K., Maslowska M.,
RA Hoang B., Monge J.C., Bell A., Mulay S., Cianflone K.;
RT "The adipsin-acylation stimulating protein system and regulation of
RT intracellular triglyceride synthesis.";
RL J. Clin. Invest. 92:1543-1547(1993).
RN [6]
RP PROTEIN SEQUENCE OF 672-748.
RX PubMed=1238393; DOI=10.1016/s0021-9258(19)40758-8;
RA Hugli T.E.;
RT "Human anaphylatoxin (C3a) from the third component of complement. Primary
RT structure.";
RL J. Biol. Chem. 250:8293-8301(1975).
RN [7]
RP PROTEIN SEQUENCE OF 955-966, AND SUBUNIT.
RC TISSUE=Serum;
RX PubMed=7539791; DOI=10.1074/jbc.270.23.13645;
RA Oxvig C., Haaning J., Kristensen L., Wagner J.M., Rubin I., Stigbrand T.,
RA Gleich G.J., Sottrup-Jensen L.;
RT "Identification of angiotensinogen and complement C3dg as novel proteins
RT binding the proform of eosinophil major basic protein in human pregnancy
RT serum and plasma.";
RL J. Biol. Chem. 270:13645-13651(1995).
RN [8]
RP PROTEIN SEQUENCE OF 988-1036.
RX PubMed=6175959; DOI=10.1073/pnas.79.4.1054;
RA Thomas M.L., Janatova J., Gray W.R., Tack B.F.;
RT "Third component of human complement: localization of the internal
RT thiolester bond.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:1054-1058(1982).
RN [9]
RP INTERACTION WITH CR1.
RX PubMed=2972794; DOI=10.1084/jem.168.5.1699;
RA Klickstein L.B., Bartow T.J., Miletic V., Rabson L.D., Smith J.A.,
RA Fearon D.T.;
RT "Identification of distinct C3b and C4b recognition sites in the human
RT C3b/C4b receptor (CR1, CD35) by deletion mutagenesis.";
RL J. Exp. Med. 168:1699-1717(1988).
RN [10]
RP PROTEIN SEQUENCE OF 1409-1563.
RX PubMed=3279119;
RA Daoudaki M.E., Becherer J.D., Lambris J.D.;
RT "A 34-amino acid peptide of the third component of complement mediates
RT properdin binding.";
RL J. Immunol. 140:1577-1580(1988).
RN [11]
RP INTERACTION WITH HERPES SIMPLEX VIRUS HHV-1 AND HHV-2 GYCOPROTEIN C
RP (MICROBIAL INFECTION).
RX PubMed=2849025; DOI=10.1016/0882-4010(87)90012-x;
RA Eisenberg R.J., Ponce de Leon M., Friedman H.M., Fries L.F., Frank M.M.,
RA Hastings J.C., Cohen G.H.;
RT "Complement component C3b binds directly to purified glycoprotein C of
RT herpes simplex virus types 1 and 2.";
RL Microb. Pathog. 3:423-435(1987).
RN [12]
RP FUNCTION.
RX PubMed=2909530; DOI=10.1016/s0021-9258(17)31275-9;
RA Cianflone K.M., Sniderman A.D., Walsh M.J., Vu H.T., Gagnon J.,
RA Rodriguez M.A.;
RT "Purification and characterization of acylation stimulating protein.";
RL J. Biol. Chem. 264:426-430(1989).
RN [13]
RP MUTAGENESIS OF THE THIOESTER BOND REGION.
RX PubMed=1577777; DOI=10.1016/s0021-9258(19)50200-9;
RA Isaac L., Isenman D.E.;
RT "Structural requirements for thioester bond formation in human complement
RT component C3. Reassessment of the role of thioester bond integrity on the
RT conformation of C3.";
RL J. Biol. Chem. 267:10062-10069(1992).
RN [14]
RP DISULFIDE BONDS.
RX PubMed=8416818; DOI=10.1016/0014-5793(93)81139-q;
RA Dolmer K., Sottrup-Jensen L.;
RT "Disulfide bridges in human complement component C3b.";
RL FEBS Lett. 315:85-90(1993).
RN [15]
RP INTERACTION WITH CR1.
RX PubMed=8175757; DOI=10.1016/s0021-9258(17)36829-1;
RA Krych M., Clemenza L., Howdeshell D., Hauhart R., Hourcade D.,
RA Atkinson J.P.;
RT "Analysis of the functional domains of complement receptor type 1 (C3b/C4b
RT receptor; CD35) by substitution mutagenesis.";
RL J. Biol. Chem. 269:13273-13278(1994).
RN [16]
RP FUNCTION.
RX PubMed=9059512; DOI=10.1016/s0005-2760(96)00144-0;
RA Tao Y., Cianflone K., Sniderman A.D., Colby-Germinario S.P.,
RA Germinario R.J.;
RT "Acylation-stimulating protein (ASP) regulates glucose transport in the rat
RT L6 muscle cell line.";
RL Biochim. Biophys. Acta 1344:221-229(1997).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=9555951;
RA Saleh J., Summers L.K., Cianflone K., Fielding B.A., Sniderman A.D.,
RA Frayn K.N.;
RT "Coordinated release of acylation stimulating protein (ASP) and
RT triacylglycerol clearance by human adipose tissue in vivo in the
RT postprandial period.";
RL J. Lipid Res. 39:884-891(1998).
RN [18]
RP FUNCTION.
RX PubMed=10432298; DOI=10.1042/bj3420041;
RA Murray I., Kohl J., Cianflone K.;
RT "Acylation-stimulating protein (ASP): structure-function determinants of
RT cell surface binding and triacylglycerol synthetic activity.";
RL Biochem. J. 342:41-48(1999).
RN [19]
RP INTERACTION WITH C5AR2.
RX PubMed=11773063; DOI=10.1074/jbc.c100714200;
RA Cain S.A., Monk P.N.;
RT "The orphan receptor C5L2 has high affinity binding sites for complement
RT fragments C5a and C5a des Arg(74).";
RL J. Biol. Chem. 277:7165-7169(2002).
RN [20]
RP INTERACTION WITH C5AR2.
RX PubMed=12540846; DOI=10.1074/jbc.m206169200;
RA Kalant D., Cain S.A., Maslowska M., Sniderman A.D., Cianflone K.,
RA Monk P.N.;
RT "The chemoattractant receptor-like protein C5L2 binds the C3a des-
RT Arg77/acylation-stimulating protein.";
RL J. Biol. Chem. 278:11123-11129(2003).
RN [21]
RP GLYCOSYLATION AT ASN-85.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [22]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-939.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [23]
RP EFFECTS OF EXERCISE.
RX PubMed=15809665; DOI=10.1038/sj.ijo.0802949;
RA Schrauwen P., Hesselink M.K., Jain M., Cianflone K.;
RT "Acylation-stimulating protein: effect of acute exercise and endurance
RT training.";
RL Int. J. Obes. Relat. Metab. Disord. 29:632-638(2005).
RN [24]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15833747; DOI=10.1074/jbc.m406921200;
RA Kalant D., MacLaren R., Cui W., Samanta R., Monk P.N., Laporte S.A.,
RA Cianflone K.;
RT "C5L2 is a functional receptor for acylation-stimulating protein.";
RL J. Biol. Chem. 280:23936-23944(2005).
RN [25]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-85; ASN-939 AND ASN-1617.
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 [26]
RP ASSOCIATION WITH TYPE 2 DIABETES.
RX PubMed=16302015; DOI=10.1038/sj.ijo.0803173;
RA Yang Y., Lu H.L., Zhang J., Yu H.Y., Wang H.W., Zhang M.X., Cianflone K.;
RT "Relationships among acylation stimulating protein, adiponectin and
RT complement C3 in lean vs obese type 2 diabetes.";
RL Int. J. Obes. Relat. Metab. Disord. 30:439-446(2006).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND FUNCTION.
RX PubMed=16333141; DOI=10.1194/jlr.m500500-jlr200;
RA Maslowska M., Legakis H., Assadi F., Cianflone K.;
RT "Targeting the signaling pathway of acylation stimulating protein.";
RL J. Lipid Res. 47:643-652(2006).
RN [28]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-85.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [29]
RP ASSOCIATION WITH OBESITY.
RX PubMed=18805911; DOI=10.1530/eje-08-0467;
RA Wamba P.C., Mi J., Zhao X.Y., Zhang M.X., Wen Y., Cheng H., Hou D.Q.,
RA Cianflone K.;
RT "Acylation stimulating protein but not complement C3 associates with
RT metabolic syndrome components in Chinese children and adolescents.";
RL Eur. J. Endocrinol. 159:781-790(2008).
RN [30]
RP INTERACTION WITH STAPHYLOCOCCUS AUREUS PROTEIN SBI (MICROBIAL INFECTION).
RX PubMed=19112495; DOI=10.1371/journal.ppat.1000250;
RA Haupt K., Reuter M., van den Elsen J., Burman J., Haelbich S., Richter J.,
RA Skerka C., Zipfel P.F.;
RT "The Staphylococcus aureus protein Sbi acts as a complement inhibitor and
RT forms a tripartite complex with host complement Factor H and C3b.";
RL PLoS Pathog. 4:E1000250-E1000250(2008).
RN [31]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-85.
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 FUNCTION.
RX PubMed=19615750; DOI=10.1016/j.molimm.2009.06.007;
RA Cui W., Simaan M., Laporte S., Lodge R., Cianflone K.;
RT "C5a- and ASP-mediated C5L2 activation, endocytosis and recycling are lost
RT in S323I-C5L2 mutation.";
RL Mol. Immunol. 46:3086-3098(2009).
RN [33]
RP MUTAGENESIS OF ASP-1029; GLU-1030; GLU-1032; GLU-1035; ARG-1042; ASP-1140;
RP GLU-1153; ASP-1156; GLU-1159; GLU-1160; ASN-1163 AND LYS-1284, AND
RP INTERACTION WITH CR2 AND S.AUREUS SBI (MICROBIAL INFECTION).
RX PubMed=20083651; DOI=10.4049/jimmunol.0902919;
RA Isenman D.E., Leung E., Mackay J.D., Bagby S., van den Elsen J.M.;
RT "Mutational analyses reveal that the staphylococcal immune evasion molecule
RT Sbi and complement receptor 2 (CR2) share overlapping contact residues on
RT C3d: implications for the controversy regarding the CR2/C3d cocrystal
RT structure.";
RL J. Immunol. 184:1946-1955(2010).
RN [34]
RP MUTAGENESIS OF ASP-1029; GLU-1030; GLU-1032; GLU-1110; ASP-1115; ASP-1121;
RP ASP-1140; GLU-1153; ASP-1156; GLU-1159; GLU-1160 AND ASN-1163, AND
RP INTERACTION WITH CR2.
RX PubMed=20951140; DOI=10.1016/j.jmb.2010.10.005;
RA Shaw C.D., Storek M.J., Young K.A., Kovacs J.M., Thurman J.M., Holers V.M.,
RA Hannan J.P.;
RT "Delineation of the complement receptor type 2-C3d complex by site-directed
RT mutagenesis and molecular docking.";
RL J. Mol. Biol. 404:697-710(2010).
RN [35]
RP ASSOCIATION WITH CORONARY HEART DISEASE.
RX PubMed=19913840; DOI=10.1016/j.metabol.2009.09.006;
RA Onat A., Hergenc G., Can G., Kaya Z., Yuksel H.;
RT "Serum complement C3: a determinant of cardiometabolic risk, additive to
RT the metabolic syndrome, in middle-aged population.";
RL Metabolism 59:628-634(2010).
RN [36]
RP CLEAVAGE BY STAPHYLOCOCCUS AUREUS PROTEIN AUREOLYSIN (MICROBIAL INFECTION).
RX PubMed=21502375; DOI=10.4049/jimmunol.1002948;
RA Laarman A.J., Ruyken M., Malone C.L., van Strijp J.A., Horswill A.R.,
RA Rooijakkers S.H.;
RT "Staphylococcus aureus metalloprotease aureolysin cleaves complement C3 to
RT mediate immune evasion.";
RL J. Immunol. 186:6445-6453(2011).
RN [37]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [38]
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 [39]
RP PHOSPHORYLATION AT SER-38; SER-70; SER-297; SER-303; SER-672; SER-968;
RP SER-1321 AND SER-1573.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [40]
RP STRUCTURE BY NMR OF C3A.
RX PubMed=3260670; DOI=10.1073/pnas.85.14.5036;
RA Nettesheim D.G., Edalji R.P., Mollison K.W., Greer J., Zuiderweg E.R.P.;
RT "Secondary structure of complement component C3a anaphylatoxin in solution
RT as determined by NMR spectroscopy: differences between crystal and solution
RT conformations.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:5036-5040(1988).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF C3D.
RX PubMed=9596584; DOI=10.1126/science.280.5367.1277;
RA Nagar B., Jones R.G., Diefenbach R.J., Isenman D.E., Rini J.M.;
RT "X-ray crystal structure of C3d: a C3 fragment and ligand for complement
RT receptor 2.";
RL Science 280:1277-1281(1998).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF C3D IN COMPLEX WITH CR2, AND
RP MUTAGENESIS OF 1108-ILE-LEU-1109 AND ASN-1163.
RX PubMed=11387479; DOI=10.1126/science.1059118;
RA Szakonyi G., Guthridge J.M., Li D., Young K., Holers V.M., Chen X.S.;
RT "Structure of complement receptor 2 in complex with its C3d ligand.";
RL Science 292:1725-1728(2001).
RN [43]
RP X-RAY SCATTERING SOLUTION STRUCTURE OF C3D IN COMPLEX WITH CR2.
RX PubMed=15713468; DOI=10.1016/j.jmb.2004.12.006;
RA Gilbert H.E., Eaton J.T., Hannan J.P., Holers V.M., Perkins S.J.;
RT "Solution structure of the complex between CR2 SCR 1-2 and C3d of human
RT complement: an X-ray scattering and sedimentation modelling study.";
RL J. Mol. Biol. 346:859-873(2005).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF C3C, AND X-RAY CRYSTALLOGRAPHY
RP (3.3 ANGSTROMS) OF C3.
RX PubMed=16177781; DOI=10.1038/nature04005;
RA Janssen B.J.C., Huizinga E.G., Raaijmakers H.C.A., Roos A., Daha M.R.,
RA Nilsson-Ekdahl K., Nilsson B., Gros P.;
RT "Structures of complement component C3 provide insights into the function
RT and evolution of immunity.";
RL Nature 437:505-511(2005).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF C3B.
RX PubMed=17051160; DOI=10.1038/nature05172;
RA Janssen B.J.C., Christodoulidou A., McCarthy A., Lambris J.D., Gros P.;
RT "Structure of C3b reveals conformational changes that underlie complement
RT activity.";
RL Nature 444:213-216(2006).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF C3C IN COMPLEX WITH VSIG4, X-RAY
RP CRYSTALLOGRAPHY (4.1 ANGSTROMS) OF C3B IN COMPLEX WITH VSIG4, AND
RP GLYCOSYLATION AT ASN-85 AND ASN-939.
RX PubMed=17051150; DOI=10.1038/nature05263;
RA Wiesmann C., Katschke K.J., Yin J., Helmy K.Y., Steffek M.,
RA Fairbrother W.J., McCallum S.A., Embuscado L., DeForge L., Hass P.E.,
RA van Lookeren Campagne M.;
RT "Structure of C3b in complex with CRIg gives insights into regulation of
RT complement activation.";
RL Nature 444:217-220(2006).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 23-936 AND 1321-1663 IN COMPLEX
RP WITH INHIBITOR COMPSTATIN, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-85.
RX PubMed=17684013; DOI=10.1074/jbc.m704587200;
RA Janssen B.J., Halff E.F., Lambris J.D., Gros P.;
RT "Structure of compstatin in complex with complement component C3c reveals a
RT new mechanism of complement inhibition.";
RL J. Biol. Chem. 282:29241-29247(2007).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 996-1287 IN COMPLEX WITH
RP STAPHYLOCOCCUS AUREUS PROTEIN FIB (MICROBIAL INFECTION).
RX PubMed=17351618; DOI=10.1038/ni1450;
RA Hammel M., Sfyroera G., Ricklin D., Magotti P., Lambris J.D.,
RA Geisbrecht B.V.;
RT "A structural basis for complement inhibition by Staphylococcus aureus.";
RL Nat. Immunol. 8:430-437(2007).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 996-1303 IN COMPLEX WITH
RP STAPHYLOCOCCUS AUREUS SBI (MICROBIAL INFECTION), AND SUBUNIT.
RX PubMed=21055811; DOI=10.1016/j.molimm.2010.09.017;
RA Clark E.A., Crennell S., Upadhyay A., Zozulya A.V., Mackay J.D.,
RA Svergun D.I., Bagby S., van den Elsen J.M.;
RT "A structural basis for Staphylococcal complement subversion: X-ray
RT structure of the complement-binding domain of Staphylococcus aureus protein
RT Sbi in complex with ligand C3d.";
RL Mol. Immunol. 48:452-462(2011).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (3.16 ANGSTROMS) OF 996-1303 IN COMPLEX WITH CR2, AND
RP INTERACTION WITH CR2.
RX PubMed=21527715; DOI=10.1126/science.1201954;
RA van den Elsen J.M., Isenman D.E.;
RT "A crystal structure of the complex between human complement receptor 2 and
RT its ligand C3d.";
RL Science 332:608-611(2011).
RN [51] {ECO:0007744|PDB:6RUR}
RP X-RAY CRYSTALLOGRAPHY (6.0 ANGSTROMS) OF 23-667 AND 749-1663 IN COMPLEX
RP WITH CFP; COMPLEMENT FACTOR B BB FRAGMENT AND STAPHYLOCOCCUS AUREUS PROTEIN
RP SCN, AND INTERACTION WITH COMPLEMENT FACTOR B BB FRAGMENT AND CFP.
RX PubMed=28264884; DOI=10.15252/embj.201696173;
RA Pedersen D.V., Roumenina L., Jensen R.K., Gadeberg T.A., Marinozzi C.,
RA Picard C., Rybkine T., Thiel S., Soerensen U.B., Stover C.,
RA Fremeaux-Bacchi V., Andersen G.R.;
RT "Functional and structural insight into properdin control of complement
RT alternative pathway amplification.";
RL EMBO J. 36:1084-1099(2017).
RN [52] {ECO:0007744|PDB:6RUV}
RP X-RAY CRYSTALLOGRAPHY (6.15 ANGSTROMS) OF 23-667 AND 749-1663 IN COMPLEX
RP WITH COMPLEMENT FACTOR B BB FRAGMENT; CFP AND STAPHYLOCOCCUS AUREUS PROTEIN
RP SCN, AND INTERACTION WITH COMPLEMENT FACTOR B BB FRAGMENT AND CFP.
RX PubMed=31507604; DOI=10.3389/fimmu.2019.02007;
RA Pedersen D.V., Gadeberg T.A.F., Thomas C., Wang Y., Joram N., Jensen R.K.,
RA Mazarakis S.M.M., Revel M., El Sissy C., Petersen S.V., Lindorff-Larsen K.,
RA Thiel S., Laursen N.S., Fremeaux-Bacchi V., Andersen G.R.;
RT "Structural Basis for Properdin Oligomerization and Convertase Stimulation
RT in the Human Complement System.";
RL Front. Immunol. 10:2007-2007(2019).
RN [53]
RP RETRACTED PAPER.
RX PubMed=2473125;
RA Poznansky M.C., Clissold P.M., Lachmann P.J.;
RT "The difference between human C3F and C3S results from a single amino acid
RT change from an asparagine to an aspartate residue at position 1216 on the
RT alpha-chain of the complement component, C3.";
RL J. Immunol. 143:1254-1258(1989).
RN [54]
RP RETRACTION NOTICE OF PUBMED:2473125.
RX PubMed=2584723;
RA Poznansky M.C., Clissold P.M., Lachmann P.J.;
RL J. Immunol. 143:3860-3862(1989).
RN [55]
RP VARIANTS GLY-102 AND LEU-314.
RX PubMed=1976733; DOI=10.1084/jem.172.4.1011;
RA Botto M., Yong Fong K., So A.K., Koch C., Walport M.J.;
RT "Molecular basis of polymorphisms of human complement component C3.";
RL J. Exp. Med. 172:1011-1017(1990).
RN [56]
RP VARIANT C3D ASN-549.
RX PubMed=7961791; DOI=10.1016/s0021-9258(18)46954-2;
RA Singer L., Whitehead W.T., Akama H., Katz Y., Fishelson Z., Wetsel R.A.;
RT "Inherited human complement C3 deficiency. An amino acid substitution in
RT the beta-chain (Asp549 to Asn) impairs C3 secretion.";
RL J. Biol. Chem. 269:28494-28499(1994).
RN [57]
RP ASSOCIATION OF VARIANT GLY-102 WITH ARMD9.
RX PubMed=17634448; DOI=10.1056/nejmoa072618;
RA Yates J.R.W., Sepp T., Matharu B.K., Khan J.C., Thurlby D.A., Shahid H.,
RA Clayton D.G., Hayward C., Morgan J., Wright A.F., Armbrecht A.M.,
RA Dhillon B., Deary I.J., Redmond E., Bird A.C., Moore A.T.;
RT "Complement C3 variant and the risk of age-related macular degeneration.";
RL N. Engl. J. Med. 357:553-561(2007).
RN [58]
RP VARIANTS AHUS5 GLN-592; TRP-592; TRP-735; VAL-1094; ASN-1115; TRP-1158;
RP LYS-1161 AND ASP-1464, AND CHARACTERIZATION OF VARIANTS AHUS5 GLN-592;
RP TRP-592; VAL-1094; ASN-1115 AND LYS-1161.
RX PubMed=18796626; DOI=10.1182/blood-2008-01-133702;
RA Fremeaux-Bacchi V., Miller E.C., Liszewski M.K., Strain L., Blouin J.,
RA Brown A.L., Moghal N., Kaplan B.S., Weiss R.A., Lhotta K., Kapur G.,
RA Mattoo T., Nivet H., Wong W., Gie S., Hurault de Ligny B., Fischbach M.,
RA Gupta R., Hauhart R., Meunier V., Loirat C., Dragon-Durey M.A.,
RA Fridman W.H., Janssen B.J., Goodship T.H., Atkinson J.P.;
RT "Mutations in complement C3 predispose to development of atypical hemolytic
RT uremic syndrome.";
RL Blood 112:4948-4952(2008).
RN [59]
RP VARIANTS AHUS5 VAL-603 AND LEU-1042.
RX PubMed=20513133; DOI=10.1002/humu.21256;
RA Maga T.K., Nishimura C.J., Weaver A.E., Frees K.L., Smith R.J.H.;
RT "Mutations in alternative pathway complement proteins in American patients
RT with atypical hemolytic uremic syndrome.";
RL Hum. Mutat. 31:E1445-E1460(2010).
RN [60]
RP VARIANT ASN-549, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22028381; DOI=10.1093/jmcb/mjr024;
RA Su Z.D., Sun L., Yu D.X., Li R.X., Li H.X., Yu Z.J., Sheng Q.H., Lin X.,
RA Zeng R., Wu J.R.;
RT "Quantitative detection of single amino acid polymorphisms by targeted
RT proteomics.";
RL J. Mol. Cell Biol. 3:309-315(2011).
RN [61]
RP CHARACTERIZATION OF VARIANT GLY-102.
RX PubMed=21555552; DOI=10.1073/pnas.1019338108;
RA Heurich M., Martinez-Barricarte R., Francis N.J., Roberts D.L.,
RA Rodriguez de Cordoba S., Morgan B.P., Harris C.L.;
RT "Common polymorphisms in C3, factor B, and factor H collaborate to
RT determine systemic complement activity and disease risk.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:8761-8766(2011).
RN [62]
RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 996-1287, AND INTERACTION WITH
RP CFH.
RX PubMed=21285368; DOI=10.1073/pnas.1017087108;
RA Kajander T., Lehtinen M.J., Hyvaerinen S., Bhattacharjee A., Leung E.,
RA Isenman D.E., Meri S., Goldman A., Jokiranta T.S.;
RT "Dual interaction of factor H with C3d and glycosaminoglycans in host-
RT nonhost discrimination by complement.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:2897-2902(2011).
RN [63]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 996-1303, AND INTERACTION WITH
RP CFH.
RX PubMed=21317894; DOI=10.1038/nsmb.2018;
RA Morgan H.P., Schmidt C.Q., Guariento M., Blaum B.S., Gillespie D.,
RA Herbert A.P., Kavanagh D., Mertens H.D., Svergun D.I., Johansson C.M.,
RA Uhrin D., Barlow P.N., Hannan J.P.;
RT "Structural basis for engagement by complement factor H of C3b on a self
RT surface.";
RL Nat. Struct. Mol. Biol. 18:463-470(2011).
RN [64]
RP VARIANT ARMD9 GLN-155, AND CHARACTERIZATION OF VARIANT ARMD9 GLN-155.
RX PubMed=24036952; DOI=10.1038/ng.2741;
RA Seddon J.M., Yu Y., Miller E.C., Reynolds R., Tan P.L., Gowrisankar S.,
RA Goldstein J.I., Triebwasser M., Anderson H.E., Zerbib J., Kavanagh D.,
RA Souied E., Katsanis N., Daly M.J., Atkinson J.P., Raychaudhuri S.;
RT "Rare variants in CFI, C3 and C9 are associated with high risk of advanced
RT age-related macular degeneration.";
RL Nat. Genet. 45:1366-1370(2013).
CC -!- FUNCTION: C3 plays a central role in the activation of the complement
CC system. Its processing by C3 convertase is the central reaction in both
CC classical and alternative complement pathways. After activation C3b can
CC bind covalently, via its reactive thioester, to cell surface
CC carbohydrates or immune aggregates.
CC -!- FUNCTION: Derived from proteolytic degradation of complement C3, C3a
CC anaphylatoxin is a mediator of local inflammatory process. In chronic
CC inflammation, acts as a chemoattractant for neutrophils (By
CC similarity). It induces the contraction of smooth muscle, increases
CC vascular permeability and causes histamine release from mast cells and
CC basophilic leukocytes. {ECO:0000250}.
CC -!- FUNCTION: [C3-beta-c]: Acts as a chemoattractant for neutrophils in
CC chronic inflammation. {ECO:0000250}.
CC -!- FUNCTION: [Acylation stimulating protein]: Adipogenic hormone that
CC stimulates triglyceride (TG) synthesis and glucose transport in
CC adipocytes, regulating fat storage and playing a role in postprandial
CC TG clearance. Appears to stimulate TG synthesis via activation of the
CC PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes the
CC phosphorylation, ARRB2-mediated internalization and recycling of C5AR2
CC (PubMed:8376604, PubMed:2909530, PubMed:9059512, PubMed:10432298,
CC PubMed:15833747, PubMed:16333141, PubMed:19615750).
CC {ECO:0000269|PubMed:10432298, ECO:0000269|PubMed:15833747,
CC ECO:0000269|PubMed:16333141, ECO:0000269|PubMed:19615750,
CC ECO:0000269|PubMed:2909530, ECO:0000269|PubMed:8376604,
CC ECO:0000269|PubMed:9059512}.
CC -!- SUBUNIT: C3 precursor is first processed by the removal of 4 Arg
CC residues, forming two chains, beta and alpha, linked by a disulfide
CC bond. C3 convertase activates C3 by cleaving the alpha chain, releasing
CC C3a anaphylatoxin and generating C3b (beta chain + alpha' chain). Forms
CC the pro-C3-convertase enzyme complex by interacting with Complement
CC factor B Bb fragment (Bb), which is then stabilized by binding CFP,
CC allowing the complex to become active (PubMed:28264884,
CC PubMed:31507604). The interaction with Bb is dependent on Mg2+
CC (PubMed:31507604). C3b interacts with CR1 (via Sushi 8 and Sushi 9
CC domains) (PubMed:8175757, PubMed:2972794). C3b interacts with CFH
CC (PubMed:21285368). C3d interacts with CFH (PubMed:21285368,
CC PubMed:21317894). C3dg interacts with CR2 (via the N-terminal Sushi
CC domains 1 and 2). During pregnancy, C3dg exists as a complex (probably
CC a 2:2:2 heterohexamer) with AGT and the proform of PRG2. Interacts with
CC VSIG4. Interacts (both C3a and ASP) with C5AR2; the interaction occurs
CC with higher affinity for ASP, enhancing the phosphorylation and
CC activation of C5AR2, recruitment of ARRB2 to the cell surface and
CC endocytosis of GRP77. {ECO:0000269|PubMed:11387479,
CC ECO:0000269|PubMed:11773063, ECO:0000269|PubMed:12540846,
CC ECO:0000269|PubMed:17051150, ECO:0000269|PubMed:17684013,
CC ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140,
CC ECO:0000269|PubMed:21285368, ECO:0000269|PubMed:21317894,
CC ECO:0000269|PubMed:21527715, ECO:0000269|PubMed:28264884,
CC ECO:0000269|PubMed:2849025, ECO:0000269|PubMed:2972794,
CC ECO:0000269|PubMed:31507604, ECO:0000269|PubMed:7539791,
CC ECO:0000269|PubMed:8175757}.
CC -!- SUBUNIT: (Microbial infection) C3b interacts with herpes simplex virus
CC 1 (HHV-1) and herpes simplex virus 2 (HHV-2) envelope glycoprotein C;
CC this interaction inhibits the activation of the complement system.
CC {ECO:0000269|PubMed:2849025}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus
CC immunoglobulin-binding protein Sbi; this interaction prevents the
CC association between C3dg and CR2. {ECO:0000269|PubMed:19112495,
CC ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:21055811}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus
CC protein Fib. {ECO:0000269|PubMed:17351618}.
CC -!- INTERACTION:
CC P01024; O95994: AGR2; NbExp=3; IntAct=EBI-905851, EBI-712648;
CC P01024; P15529: CD46; NbExp=2; IntAct=EBI-905851, EBI-2623451;
CC P01024; P00751: CFB; NbExp=3; IntAct=EBI-905851, EBI-1223668;
CC P01024; P08603: CFH; NbExp=6; IntAct=EBI-905851, EBI-1223708;
CC P01024; PRO_0000005896 [Q03591]: CFHR1; NbExp=2; IntAct=EBI-905851, EBI-22118464;
CC P01024; Q92496-1: CFHR4; NbExp=5; IntAct=EBI-905851, EBI-22033617;
CC P01024; P20023: CR2; NbExp=4; IntAct=EBI-905851, EBI-2872467;
CC P01024; O95967: EFEMP2; NbExp=3; IntAct=EBI-905851, EBI-743414;
CC P01024; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-905851, EBI-5916454;
CC P01024; Q15323: KRT31; NbExp=3; IntAct=EBI-905851, EBI-948001;
CC P01024; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-905851, EBI-10171774;
CC P01024; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-905851, EBI-742388;
CC P01024; Q9Y279-1: VSIG4; NbExp=5; IntAct=EBI-905851, EBI-903144;
CC P01024; Q9Y279-2: VSIG4; NbExp=2; IntAct=EBI-905851, EBI-903148;
CC PRO_0000005908; P08603: CFH; NbExp=4; IntAct=EBI-6863145, EBI-1223708;
CC PRO_0000005911; PRO_0000005908 [P01024]: C3; NbExp=9; IntAct=EBI-12735725, EBI-6863145;
CC PRO_0000005911; Q92496-3: CFHR4; NbExp=3; IntAct=EBI-12735725, EBI-22033638;
CC PRO_0000005913; PRO_0000005897 [P36980]: CFHR2; NbExp=2; IntAct=EBI-21988425, EBI-21988278;
CC PRO_0000005915; P08603: CFH; NbExp=2; IntAct=EBI-6863106, EBI-1223708;
CC PRO_0000005915; PRO_0000005897 [P36980]: CFHR2; NbExp=3; IntAct=EBI-6863106, EBI-21988278;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Plasma. The acylation stimulating protein (ASP) is
CC expressed in adipocytes and released into the plasma during both the
CC fasting and postprandial periods. {ECO:0000269|PubMed:15833747,
CC ECO:0000269|PubMed:9555951}.
CC -!- PTM: C3b is rapidly split in two positions by factor I and a cofactor
CC to form iC3b (inactivated C3b) and C3f which is released. Then iC3b is
CC slowly cleaved (possibly by factor I) to form C3c (beta chain + alpha'
CC chain fragment 1 + alpha' chain fragment 2), C3dg and C3f. Other
CC proteases produce other fragments such as C3d or C3g. C3a is further
CC processed by carboxypeptidases to release the C-terminal arginine
CC residue generating the acylation stimulating protein (ASP). Levels of
CC ASP are increased in adipocytes in the postprandial period and by
CC insulin and dietary chylomicrons.
CC -!- PTM: (Microbial infection) C3 is cleaved by Staphylococcus aureus
CC aureolysin; this cleavage renders C3a and C3b inactive. C3b is rapidly
CC degraded by host factors CFH and CFI preventing its deposition on the
CC bacterial surface while C3a is further inactivated by aureolysin.
CC {ECO:0000269|PubMed:21502375}.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000269|PubMed:26091039}.
CC -!- POLYMORPHISM: There are two alleles: C3S (C3 slow), the most common
CC allele in all races and C3F (C3 fast), relatively frequent in
CC Caucasians, less common in Black Americans, extremely rare in
CC Orientals.
CC -!- DISEASE: Complement component 3 deficiency (C3D) [MIM:613779]: A rare
CC defect of the complement classical pathway. Patients develop recurrent,
CC severe, pyogenic infections because of ineffective opsonization of
CC pathogens. Some patients may also develop autoimmune disorders, such as
CC arthralgia and vasculitic rashes, lupus-like syndrome and
CC membranoproliferative glomerulonephritis. {ECO:0000269|PubMed:7961791}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Macular degeneration, age-related, 9 (ARMD9) [MIM:611378]: 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:17634448,
CC ECO:0000269|PubMed:24036952}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Hemolytic uremic syndrome atypical 5 (AHUS5) [MIM:612925]: An
CC atypical form of hemolytic uremic syndrome. It is a complex genetic
CC disease characterized by microangiopathic hemolytic anemia,
CC thrombocytopenia, renal failure and absence of episodes of
CC enterocolitis and diarrhea. In contrast to typical hemolytic uremic
CC syndrome, atypical forms have a poorer prognosis, with higher death
CC rates and frequent progression to end-stage renal disease.
CC {ECO:0000269|PubMed:18796626, ECO:0000269|PubMed:20513133}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry. Other genes may play a role in
CC modifying the phenotype.
CC -!- DISEASE: Note=Increased levels of C3 and its cleavage product ASP, are
CC associated with obesity, diabetes and coronary heart disease. Short-
CC term endurance training reduces baseline ASP levels and subsequently
CC fat storage.
CC -!- CAUTION: An article reported the interaction surface between C3 and CR2
CC (PubMed:11387479). According to a another paper, it is however an
CC artifact and can be ascribed to the presence of zinc acetate in the
CC buffer (PubMed:21527715). {ECO:0000269|PubMed:11387479,
CC ECO:0000269|PubMed:21527715}.
CC -!- CAUTION: The difference between allele C3S (C3 slow) and allele C3F (C3
CC fast) was reported to be caused by a an Asn at position 1216 instead of
CC an Asp (PubMed:2473125). The paper was however retracted
CC (PubMed:2584723). {ECO:0000269|PubMed:2473125,
CC ECO:0000269|PubMed:2584723}.
CC -!- WEB RESOURCE: Name=C3base; Note=C3 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/C3base/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Complement C3 entry;
CC URL="https://en.wikipedia.org/wiki/Complement_c3";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/c3/";
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DR EMBL; K02765; AAA85332.1; -; mRNA.
DR EMBL; AY513239; AAR89906.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69071.1; -; Genomic_DNA.
DR EMBL; BC150179; AAI50180.1; -; mRNA.
DR EMBL; BC150200; AAI50201.1; -; mRNA.
DR CCDS; CCDS32883.1; -.
DR PIR; A94065; C3HU.
DR RefSeq; NP_000055.2; NM_000064.3.
DR PDB; 1C3D; X-ray; 1.80 A; A=996-1287.
DR PDB; 1GHQ; X-ray; 2.04 A; A=996-1300.
DR PDB; 1W2S; X-ray; -; A=996-1299.
DR PDB; 2A73; X-ray; 3.30 A; A=23-665, B=673-1663.
DR PDB; 2A74; X-ray; 2.40 A; A/D=23-665, B/E=749-936, C/F=1321-1663.
DR PDB; 2GOX; X-ray; 2.20 A; A/C=996-1287.
DR PDB; 2I07; X-ray; 4.00 A; A=23-667, B=749-1663.
DR PDB; 2ICE; X-ray; 3.10 A; A/D=23-664, B/E=749-954, C/F=1321-1663.
DR PDB; 2ICF; X-ray; 4.10 A; A=23-664, B=749-1663.
DR PDB; 2NOJ; X-ray; 2.70 A; A/C/E/G=996-1287.
DR PDB; 2QKI; X-ray; 2.40 A; A/D=23-665, B/E=749-936, C/F=1321-1663.
DR PDB; 2WII; X-ray; 2.70 A; A=23-667, B=749-1663.
DR PDB; 2WIN; X-ray; 3.90 A; A/C/E/G=23-667, B/D/F/H=749-1663.
DR PDB; 2WY7; X-ray; 1.70 A; A=996-1303.
DR PDB; 2WY8; X-ray; 1.70 A; A=996-1303.
DR PDB; 2XQW; X-ray; 2.31 A; A/B=996-1287.
DR PDB; 2XWB; X-ray; 3.49 A; A/C=23-664, B/D=752-1663.
DR PDB; 2XWJ; X-ray; 4.00 A; A/C/E/G=23-667, B/D/F/H=749-1663.
DR PDB; 3D5R; X-ray; 2.10 A; A/B=996-1287.
DR PDB; 3D5S; X-ray; 2.30 A; A/B=996-1287.
DR PDB; 3G6J; X-ray; 3.10 A; A/C=23-666, B/D=749-1663.
DR PDB; 3L3O; X-ray; 3.40 A; A/D=23-667, B/E=749-954, C/F=1321-1663.
DR PDB; 3L5N; X-ray; 7.54 A; A=23-667, B=749-1663.
DR PDB; 3NMS; X-ray; 4.10 A; A=23-667, B=749-954, C=1321-1663.
DR PDB; 3OED; X-ray; 3.16 A; A/B=996-1303.
DR PDB; 3OHX; X-ray; 3.50 A; A/D=23-667, B/E=749-954, C/F=1321-1663.
DR PDB; 3OXU; X-ray; 2.10 A; A/B/C=996-1303.
DR PDB; 3RJ3; X-ray; 2.35 A; A/B/C=996-1303.
DR PDB; 3T4A; X-ray; 3.40 A; A/D=23-667, B/E=749-954, C/F=1321-1663.
DR PDB; 4HW5; X-ray; 2.25 A; A/B=672-748.
DR PDB; 4HWJ; X-ray; 2.60 A; A=672-747.
DR PDB; 4I6O; X-ray; 2.14 A; A=672-748.
DR PDB; 4M76; X-ray; 2.80 A; A=994-1288.
DR PDB; 4ONT; X-ray; 2.15 A; A/B/C=996-1303.
DR PDB; 4ZH1; X-ray; 2.24 A; A/B/C=996-1303.
DR PDB; 5FO7; X-ray; 2.80 A; A=23-667, B=749-1663.
DR PDB; 5FO8; X-ray; 2.40 A; A=23-667, B=749-1663.
DR PDB; 5FO9; X-ray; 3.30 A; A/D=23-667, B/E=749-1663.
DR PDB; 5FOA; X-ray; 4.19 A; A/C=23-667, B/D=749-1663.
DR PDB; 5FOB; X-ray; 2.60 A; A=23-667, B=749-1663.
DR PDB; 5NBQ; X-ray; 3.18 A; A/B/C=994-1287.
DR PDB; 5O32; X-ray; 4.21 A; A/E=23-667, B/F=749-1663.
DR PDB; 5O35; X-ray; 4.20 A; A=23-667, B=749-1663.
DR PDB; 6EHG; X-ray; 2.65 A; A=23-665, B=749-1663.
DR PDB; 6RMT; X-ray; 2.00 A; A/B=996-1303.
DR PDB; 6RMU; X-ray; 2.40 A; A/B=996-1303.
DR PDB; 6RUR; X-ray; 6.00 A; A/G=23-667, B/H=749-1663.
DR PDB; 6RUV; X-ray; 6.15 A; A/G=23-667, B/H=749-1663.
DR PDB; 6S0B; X-ray; 2.31 A; C=1517-1663.
DR PDB; 6YO6; X-ray; 6.00 A; A=23-667, B=749-1663.
DR PDB; 7AKK; X-ray; 3.40 A; A/E=749-1663, B/C=23-667.
DR PDB; 7BAG; X-ray; 2.00 A; A=23-667, B=749-1663.
DR PDB; 7QIV; X-ray; 2.80 A; A=23-667, B=749-1663.
DR PDB; 7TV9; X-ray; 3.40 A; A=23-667, B=749-1663.
DR PDBsum; 1C3D; -.
DR PDBsum; 1GHQ; -.
DR PDBsum; 1W2S; -.
DR PDBsum; 2A73; -.
DR PDBsum; 2A74; -.
DR PDBsum; 2GOX; -.
DR PDBsum; 2I07; -.
DR PDBsum; 2ICE; -.
DR PDBsum; 2ICF; -.
DR PDBsum; 2NOJ; -.
DR PDBsum; 2QKI; -.
DR PDBsum; 2WII; -.
DR PDBsum; 2WIN; -.
DR PDBsum; 2WY7; -.
DR PDBsum; 2WY8; -.
DR PDBsum; 2XQW; -.
DR PDBsum; 2XWB; -.
DR PDBsum; 2XWJ; -.
DR PDBsum; 3D5R; -.
DR PDBsum; 3D5S; -.
DR PDBsum; 3G6J; -.
DR PDBsum; 3L3O; -.
DR PDBsum; 3L5N; -.
DR PDBsum; 3NMS; -.
DR PDBsum; 3OED; -.
DR PDBsum; 3OHX; -.
DR PDBsum; 3OXU; -.
DR PDBsum; 3RJ3; -.
DR PDBsum; 3T4A; -.
DR PDBsum; 4HW5; -.
DR PDBsum; 4HWJ; -.
DR PDBsum; 4I6O; -.
DR PDBsum; 4M76; -.
DR PDBsum; 4ONT; -.
DR PDBsum; 4ZH1; -.
DR PDBsum; 5FO7; -.
DR PDBsum; 5FO8; -.
DR PDBsum; 5FO9; -.
DR PDBsum; 5FOA; -.
DR PDBsum; 5FOB; -.
DR PDBsum; 5NBQ; -.
DR PDBsum; 5O32; -.
DR PDBsum; 5O35; -.
DR PDBsum; 6EHG; -.
DR PDBsum; 6RMT; -.
DR PDBsum; 6RMU; -.
DR PDBsum; 6RUR; -.
DR PDBsum; 6RUV; -.
DR PDBsum; 6S0B; -.
DR PDBsum; 6YO6; -.
DR PDBsum; 7AKK; -.
DR PDBsum; 7BAG; -.
DR PDBsum; 7QIV; -.
DR PDBsum; 7TV9; -.
DR AlphaFoldDB; P01024; -.
DR SMR; P01024; -.
DR BioGRID; 107179; 138.
DR ComplexPortal; CPX-5381; Alternative pathway fluid-phase C3 convertase complex C3(H2O)Bb.
DR ComplexPortal; CPX-973; Complement C3b complex.
DR CORUM; P01024; -.
DR DIP; DIP-35180N; -.
DR IntAct; P01024; 56.
DR MINT; P01024; -.
DR STRING; 9606.ENSP00000245907; -.
DR BindingDB; P01024; -.
DR ChEMBL; CHEMBL4917; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB00028; Human immunoglobulin G.
DR DrugBank; DB06492; Mirococept.
DR DrugBank; DB16694; Pegcetacoplan.
DR DrugBank; DB01915; S-Hydroxycysteine.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR MEROPS; I39.950; -.
DR CarbonylDB; P01024; -.
DR GlyConnect; 110; 35 N-Linked glycans (3 sites), 1 O-Linked glycan (1 site).
DR GlyGen; P01024; 5 sites, 48 N-linked glycans (4 sites), 2 O-linked glycans (2 sites).
DR iPTMnet; P01024; -.
DR MetOSite; P01024; -.
DR PhosphoSitePlus; P01024; -.
DR BioMuta; C3; -.
DR DMDM; 119370332; -.
DR DOSAC-COBS-2DPAGE; P01024; -.
DR SWISS-2DPAGE; P01024; -.
DR CPTAC; CPTAC-1239; -.
DR CPTAC; non-CPTAC-1105; -.
DR CPTAC; non-CPTAC-1106; -.
DR CPTAC; non-CPTAC-2653; -.
DR EPD; P01024; -.
DR jPOST; P01024; -.
DR MassIVE; P01024; -.
DR PaxDb; P01024; -.
DR PeptideAtlas; P01024; -.
DR PRIDE; P01024; -.
DR ProteomicsDB; 51308; -.
DR ABCD; P01024; 22 sequenced antibodies.
DR Antibodypedia; 692; 1924 antibodies from 44 providers.
DR DNASU; 718; -.
DR Ensembl; ENST00000245907.11; ENSP00000245907.4; ENSG00000125730.17.
DR GeneID; 718; -.
DR KEGG; hsa:718; -.
DR MANE-Select; ENST00000245907.11; ENSP00000245907.4; NM_000064.4; NP_000055.2.
DR CTD; 718; -.
DR DisGeNET; 718; -.
DR GeneCards; C3; -.
DR GeneReviews; C3; -.
DR HGNC; HGNC:1318; C3.
DR HPA; ENSG00000125730; Tissue enriched (liver).
DR MalaCards; C3; -.
DR MIM; 120700; gene.
DR MIM; 611378; phenotype.
DR MIM; 612925; phenotype.
DR MIM; 613779; phenotype.
DR neXtProt; NX_P01024; -.
DR OpenTargets; ENSG00000125730; -.
DR Orphanet; 544472; Atypical hemolytic uremic syndrome with complement gene abnormality.
DR Orphanet; 280133; Complement component 3 deficiency.
DR Orphanet; 279; NON RARE IN EUROPE: Age-related macular degeneration.
DR PharmGKB; PA25897; -.
DR VEuPathDB; HostDB:ENSG00000125730; -.
DR eggNOG; KOG1366; Eukaryota.
DR GeneTree; ENSGT00940000154063; -.
DR HOGENOM; CLU_001634_4_0_1; -.
DR InParanoid; P01024; -.
DR OMA; QATNTMQ; -.
DR OrthoDB; 23785at2759; -.
DR PhylomeDB; P01024; -.
DR TreeFam; TF313285; -.
DR BRENDA; 3.4.21.47; 2681.
DR PathwayCommons; P01024; -.
DR Reactome; R-HSA-173736; Alternative complement activation.
DR Reactome; R-HSA-174577; Activation of C3 and C5.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SABIO-RK; P01024; -.
DR SignaLink; P01024; -.
DR SIGNOR; P01024; -.
DR BioGRID-ORCS; 718; 11 hits in 1074 CRISPR screens.
DR ChiTaRS; C3; human.
DR EvolutionaryTrace; P01024; -.
DR GeneWiki; Complement_component_3; -.
DR GenomeRNAi; 718; -.
DR Pharos; P01024; Tclin.
DR PRO; PR:P01024; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P01024; protein.
DR Bgee; ENSG00000125730; Expressed in parietal pleura and 198 other tissues.
DR ExpressionAtlas; P01024; baseline and differential.
DR Genevisible; P01024; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
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; IDA:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IPI:ComplexPortal.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:1905370; C:serine-type endopeptidase complex; IPI:ComplexPortal.
DR GO; GO:0031715; F:C5L2 anaphylatoxin chemotactic receptor binding; IDA:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IEA:InterPro.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0097242; P:amyloid-beta clearance; ISS:ARUK-UCL.
DR GO; GO:1905114; P:cell surface receptor signaling pathway involved in cell-cell signaling; IEA:Ensembl.
DR GO; GO:0006956; P:complement activation; IDA:ComplexPortal.
DR GO; GO:0006957; P:complement activation, alternative pathway; IEA:UniProtKB-KW.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0097278; P:complement-dependent cytotoxicity; IEA:Ensembl.
DR GO; GO:0150062; P:complement-mediated synapse pruning; ISS:ARUK-UCL.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0016322; P:neuron remodeling; ISS:ARUK-UCL.
DR GO; GO:0008228; P:opsonization; IDA:ComplexPortal.
DR GO; GO:0035846; P:oviduct epithelium development; IEA:Ensembl.
DR GO; GO:0001970; P:positive regulation of activation of membrane attack complex; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:2000427; P:positive regulation of apoptotic cell clearance; IMP:BHF-UCL.
DR GO; GO:0044533; P:positive regulation of apoptotic process in another organism; IC:ComplexPortal.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0010828; P:positive regulation of glucose transmembrane transport; IDA:UniProtKB.
DR GO; GO:0050778; P:positive regulation of immune response; IC:ComplexPortal.
DR GO; GO:0010884; P:positive regulation of lipid storage; IDA:UniProtKB.
DR GO; GO:1903028; P:positive regulation of opsonization; IDA:ComplexPortal.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IC:ComplexPortal.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; ISS:ARUK-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISS:ARUK-UCL.
DR GO; GO:0001798; P:positive regulation of type IIa hypersensitivity; IEA:Ensembl.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IDA:BHF-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:ComplexPortal.
DR GO; GO:0030449; P:regulation of complement activation; IDA:ComplexPortal.
DR GO; GO:0030451; P:regulation of complement activation, alternative pathway; IDA:ComplexPortal.
DR GO; GO:0010866; P:regulation of triglyceride biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0150064; P:vertebrate eye-specific patterning; ISS:ARUK-UCL.
DR CDD; cd00017; ANATO; 1.
DR CDD; cd03583; NTR_complement_C3; 1.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 2.60.40.690; -; 1.
DR InterPro; IPR009048; A-macroglobulin_rcpt-bd.
DR InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf.
DR InterPro; IPR011625; A2M_N_BRD.
DR InterPro; IPR011626; Alpha-macroglobulin_TED.
DR InterPro; IPR000020; Anaphylatoxin/fibulin.
DR InterPro; IPR018081; Anaphylatoxin_comp_syst.
DR InterPro; IPR001840; Anaphylatoxn_comp_syst_dom.
DR InterPro; IPR041425; C3/4/5_MG1.
DR InterPro; IPR035711; Complement_C3-like.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR001599; Macroglobln_a2.
DR InterPro; IPR019742; MacrogloblnA2_CS.
DR InterPro; IPR002890; MG2.
DR InterPro; IPR041555; MG3.
DR InterPro; IPR040839; MG4.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR018933; Netrin_module_non-TIMP.
DR InterPro; IPR035815; NTR_complement_C3.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR PANTHER; PTHR11412:SF81; PTHR11412:SF81; 1.
DR Pfam; PF00207; A2M; 1.
DR Pfam; PF07703; A2M_BRD; 1.
DR Pfam; PF07677; A2M_recep; 1.
DR Pfam; PF01821; ANATO; 1.
DR Pfam; PF17790; MG1; 1.
DR Pfam; PF01835; MG2; 1.
DR Pfam; PF17791; MG3; 1.
DR Pfam; PF17789; MG4; 1.
DR Pfam; PF01759; NTR; 1.
DR Pfam; PF07678; TED_complement; 1.
DR PRINTS; PR00004; ANAPHYLATOXN.
DR SMART; SM01360; A2M; 1.
DR SMART; SM01359; A2M_N_2; 1.
DR SMART; SM01361; A2M_recep; 1.
DR SMART; SM00104; ANATO; 1.
DR SMART; SM00643; C345C; 1.
DR SUPFAM; SSF47686; SSF47686; 1.
DR SUPFAM; SSF48239; SSF48239; 1.
DR SUPFAM; SSF49410; SSF49410; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1.
DR PROSITE; PS01177; ANAPHYLATOXIN_1; 1.
DR PROSITE; PS01178; ANAPHYLATOXIN_2; 1.
DR PROSITE; PS50189; NTR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Age-related macular degeneration;
KW Cleavage on pair of basic residues; Complement alternate pathway;
KW Complement pathway; Direct protein sequencing; Disease variant;
KW Disulfide bond; Fatty acid metabolism; Glycoprotein;
KW Hemolytic uremic syndrome; Immunity; Inflammatory response;
KW Innate immunity; Lipid metabolism; Phosphoprotein; Reference proteome;
KW Secreted; Signal; Thioester bond.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:8376604"
FT CHAIN 23..1663
FT /note="Complement C3"
FT /id="PRO_0000005907"
FT CHAIN 23..667
FT /note="Complement C3 beta chain"
FT /id="PRO_0000005908"
FT CHAIN 569..667
FT /note="C3-beta-c"
FT /evidence="ECO:0000250"
FT /id="PRO_0000430430"
FT CHAIN 672..1663
FT /note="Complement C3 alpha chain"
FT /id="PRO_0000005909"
FT CHAIN 672..748
FT /note="C3a anaphylatoxin"
FT /id="PRO_0000005910"
FT CHAIN 672..747
FT /note="Acylation stimulating protein"
FT /id="PRO_0000419935"
FT CHAIN 749..1663
FT /note="Complement C3b alpha' chain"
FT /id="PRO_0000005911"
FT CHAIN 749..954
FT /note="Complement C3c alpha' chain fragment 1"
FT /id="PRO_0000005912"
FT CHAIN 955..1303
FT /note="Complement C3dg fragment"
FT /id="PRO_0000005913"
FT CHAIN 955..1001
FT /note="Complement C3g fragment"
FT /id="PRO_0000005914"
FT CHAIN 1002..1303
FT /note="Complement C3d fragment"
FT /id="PRO_0000005915"
FT PEPTIDE 1304..1320
FT /note="Complement C3f fragment"
FT /evidence="ECO:0000269|PubMed:8376604"
FT /id="PRO_0000005916"
FT CHAIN 1321..1663
FT /note="Complement C3c alpha' chain fragment 2"
FT /id="PRO_0000273948"
FT DOMAIN 693..728
FT /note="Anaphylatoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022"
FT DOMAIN 1518..1661
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 954..973
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1634..1659
FT /note="Interaction with CFP/properdin"
FT /evidence="ECO:0000269|PubMed:28264884,
FT ECO:0000269|PubMed:31507604"
FT SITE 747..748
FT /note="Cleavage; by carboxypeptidases"
FT SITE 748..749
FT /note="Cleavage; by C3 convertase"
FT SITE 954..955
FT /note="Cleavage; by factor I"
FT /evidence="ECO:0000255"
FT SITE 1303..1304
FT /note="Cleavage; by factor I"
FT SITE 1320..1321
FT /note="Cleavage; by factor I"
FT SITE 1663
FT /note="Coordinates Mg2+ for interaction with Complement
FT factor B Bb fragment"
FT /evidence="ECO:0000269|PubMed:28264884,
FT ECO:0000269|PubMed:31507604"
FT MOD_RES 38
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 70
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 297
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 303
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 672
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 968
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 1321
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 1573
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 85
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:17051150, ECO:0000269|PubMed:17684013,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:2579379"
FT CARBOHYD 939
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:17051150"
FT CARBOHYD 1617
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT DISULFID 559..816
FT /note="Interchain (between beta and alpha chains)"
FT DISULFID 627..662
FT DISULFID 693..720
FT /evidence="ECO:0000269|PubMed:8416818"
FT DISULFID 694..727
FT DISULFID 707..728
FT DISULFID 873..1513
FT DISULFID 1101..1158
FT DISULFID 1358..1489
FT DISULFID 1389..1458
FT DISULFID 1506..1511
FT DISULFID 1518..1590
FT DISULFID 1537..1661
FT DISULFID 1637..1646
FT CROSSLNK 1010..1013
FT /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT VARIANT 102
FT /note="R -> G (in allele C3F; associated with
FT susceptibility to ARMD9; results in decreased binding
FT affinity for regulator factor H; results in reduced
FT sensitivity to cleavage by factor I; dbSNP:rs2230199)"
FT /evidence="ECO:0000269|PubMed:1976733,
FT ECO:0000269|PubMed:21555552, ECO:0000269|Ref.2"
FT /id="VAR_001983"
FT VARIANT 155
FT /note="K -> Q (in ARMD9; results in resistance to
FT proteolytic inactivation by CFH and CFI;
FT dbSNP:rs147859257)"
FT /evidence="ECO:0000269|PubMed:24036952"
FT /id="VAR_070941"
FT VARIANT 314
FT /note="P -> L (in dbSNP:rs1047286)"
FT /evidence="ECO:0000269|PubMed:1976733,
FT ECO:0000269|PubMed:2579379, ECO:0000269|Ref.2"
FT /id="VAR_001984"
FT VARIANT 469
FT /note="E -> D (in dbSNP:rs11569422)"
FT /id="VAR_020262"
FT VARIANT 549
FT /note="D -> N (in C3D; impairs secretion; variant confirmed
FT at protein level; dbSNP:rs1449441916)"
FT /evidence="ECO:0000269|PubMed:22028381,
FT ECO:0000269|PubMed:7961791"
FT /id="VAR_001985"
FT VARIANT 592
FT /note="R -> Q (in AHUS5; leads to impaired binding to the
FT regulator CD46/MCP and resistance to cleavage by factor I;
FT dbSNP:rs121909583)"
FT /evidence="ECO:0000269|PubMed:18796626"
FT /id="VAR_063213"
FT VARIANT 592
FT /note="R -> W (in AHUS5; leads to impaired binding to the
FT regulator CD46/MCP and resistance to cleavage by factor I;
FT dbSNP:rs771353792)"
FT /evidence="ECO:0000269|PubMed:18796626"
FT /id="VAR_063214"
FT VARIANT 603
FT /note="F -> V (in AHUS5)"
FT /evidence="ECO:0000269|PubMed:20513133"
FT /id="VAR_063654"
FT VARIANT 735
FT /note="R -> W (in AHUS5; dbSNP:rs117793540)"
FT /evidence="ECO:0000269|PubMed:18796626"
FT /id="VAR_063215"
FT VARIANT 863
FT /note="R -> K (in dbSNP:rs11569472)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019206"
FT VARIANT 1042
FT /note="R -> L (in AHUS5)"
FT /evidence="ECO:0000269|PubMed:20513133"
FT /id="VAR_063655"
FT VARIANT 1094
FT /note="A -> V (in AHUS5; leads to impaired binding to the
FT regulator CD46/MCP and resistance to cleavage by factor I;
FT dbSNP:rs121909584)"
FT /evidence="ECO:0000269|PubMed:18796626"
FT /id="VAR_063216"
FT VARIANT 1115
FT /note="D -> N (in AHUS5; leads to impaired binding to the
FT regulator CD46/MCP and resistance to cleavage by factor I;
FT dbSNP:rs121909585)"
FT /evidence="ECO:0000269|PubMed:18796626"
FT /id="VAR_063217"
FT VARIANT 1158
FT /note="C -> W (in AHUS5)"
FT /evidence="ECO:0000269|PubMed:18796626"
FT /id="VAR_063218"
FT VARIANT 1161
FT /note="Q -> K (in AHUS5; leads to impaired binding to the
FT regulator CD46/MCP and resistance to cleavage by factor I)"
FT /evidence="ECO:0000269|PubMed:18796626"
FT /id="VAR_063219"
FT VARIANT 1224
FT /note="G -> D (in dbSNP:rs11569534)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019207"
FT VARIANT 1367
FT /note="I -> T (in dbSNP:rs11569541)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019208"
FT VARIANT 1464
FT /note="H -> D (in AHUS5)"
FT /evidence="ECO:0000269|PubMed:18796626"
FT /id="VAR_063220"
FT VARIANT 1521
FT /note="Q -> R (in dbSNP:rs7256789)"
FT /id="VAR_029792"
FT VARIANT 1601
FT /note="H -> N (in dbSNP:rs1803225)"
FT /id="VAR_029793"
FT VARIANT 1619
FT /note="S -> R (in dbSNP:rs2230210)"
FT /id="VAR_029326"
FT MUTAGEN 1029
FT /note="D->A: Minor effect on binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651,
FT ECO:0000269|PubMed:20951140"
FT MUTAGEN 1030
FT /note="E->A: Impaired binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651,
FT ECO:0000269|PubMed:20951140"
FT MUTAGEN 1032
FT /note="E->A: Impaired binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651,
FT ECO:0000269|PubMed:20951140"
FT MUTAGEN 1035
FT /note="E->A: No effect on binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651"
FT MUTAGEN 1042
FT /note="R->M: Impaired binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651"
FT MUTAGEN 1108..1109
FT /note="IL->RR: Impaired binding of C3d to CR2; when
FT associated with A-1163."
FT /evidence="ECO:0000269|PubMed:11387479"
FT MUTAGEN 1110
FT /note="E->A: No effect on binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20951140"
FT MUTAGEN 1115
FT /note="D->A: No effect on binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20951140"
FT MUTAGEN 1121
FT /note="D->A: No effect on binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20951140"
FT MUTAGEN 1140
FT /note="D->A: No effect on binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651,
FT ECO:0000269|PubMed:20951140"
FT MUTAGEN 1153
FT /note="E->A: Impaired binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651,
FT ECO:0000269|PubMed:20951140"
FT MUTAGEN 1156
FT /note="D->A: Impaired binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651,
FT ECO:0000269|PubMed:20951140"
FT MUTAGEN 1159
FT /note="E->A: Impaired binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651,
FT ECO:0000269|PubMed:20951140"
FT MUTAGEN 1160
FT /note="E->A: Minor effect on binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651,
FT ECO:0000269|PubMed:20951140"
FT MUTAGEN 1163
FT /note="N->A: No effect on binding of C3d to CR2. Impaired
FT binding of C3d to CR2; when associated with 1108-R-R-1109."
FT /evidence="ECO:0000269|PubMed:11387479,
FT ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"
FT MUTAGEN 1163
FT /note="N->R: Impaired binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:11387479,
FT ECO:0000269|PubMed:20083651, ECO:0000269|PubMed:20951140"
FT MUTAGEN 1284
FT /note="K->A: Impaired binding of C3d to CR2."
FT /evidence="ECO:0000269|PubMed:20083651"
FT CONFLICT 681
FT /note="D -> N (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 700
FT /note="E -> Q (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1026
FT /note="H -> S (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 25..35
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 53..61
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 67..76
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 78..82
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:2ICE"
FT STRAND 104..112
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 115..124
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 129..135
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 144..152
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 162..168
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 174..181
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 183..187
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 202..210
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:2XWB"
FT STRAND 218..224
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 231..244
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 251..259
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 267..277
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 289..294
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 297..302
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 304..309
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 316..319
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 323..332
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 338..352
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 358..360
FT /evidence="ECO:0007829|PDB:2A73"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 370..377
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:3T4A"
FT STRAND 388..393
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 395..397
FT /evidence="ECO:0007829|PDB:2QKI"
FT STRAND 398..400
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 405..411
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:5FO8"
FT STRAND 420..426
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 429..431
FT /evidence="ECO:0007829|PDB:2A74"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 438..445
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 449..451
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 455..459
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 470..478
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 481..483
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 484..486
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 489..496
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 499..507
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 513..520
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 523..525
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 527..538
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 540..542
FT /evidence="ECO:0007829|PDB:2QKI"
FT STRAND 544..554
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 563..569
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 571..573
FT /evidence="ECO:0007829|PDB:3G6J"
FT STRAND 580..588
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 592..599
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 600..605
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 613..622
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 628..630
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 635..641
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 644..648
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 675..684
FT /evidence="ECO:0007829|PDB:4HW5"
FT HELIX 688..697
FT /evidence="ECO:0007829|PDB:4I6O"
FT HELIX 707..710
FT /evidence="ECO:0007829|PDB:4I6O"
FT TURN 712..714
FT /evidence="ECO:0007829|PDB:4HW5"
FT HELIX 718..743
FT /evidence="ECO:0007829|PDB:4I6O"
FT STRAND 753..755
FT /evidence="ECO:0007829|PDB:3L3O"
FT HELIX 758..760
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 769..771
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 775..777
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 783..794
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 800..810
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 811..813
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 814..817
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 821..825
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 828..834
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 837..840
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 845..853
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 860..866
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 872..875
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 878..880
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 882..888
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 892..902
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 906..916
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 917..920
FT /evidence="ECO:0007829|PDB:3G6J"
FT STRAND 922..932
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 934..947
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 949..951
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 954..956
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 957..962
FT /evidence="ECO:0007829|PDB:5FO8"
FT STRAND 968..970
FT /evidence="ECO:0007829|PDB:5FOB"
FT STRAND 977..985
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 988..990
FT /evidence="ECO:0007829|PDB:3G6J"
FT HELIX 997..999
FT /evidence="ECO:0007829|PDB:2WY8"
FT HELIX 1001..1003
FT /evidence="ECO:0007829|PDB:2WY7"
FT STRAND 1009..1012
FT /evidence="ECO:0007829|PDB:3G6J"
FT HELIX 1013..1031
FT /evidence="ECO:0007829|PDB:2WY7"
FT HELIX 1034..1037
FT /evidence="ECO:0007829|PDB:2WY7"
FT HELIX 1041..1057
FT /evidence="ECO:0007829|PDB:2WY7"
FT TURN 1062..1064
FT /evidence="ECO:0007829|PDB:5FO7"
FT STRAND 1068..1072
FT /evidence="ECO:0007829|PDB:5FOB"
FT HELIX 1076..1089
FT /evidence="ECO:0007829|PDB:2WY7"
FT TURN 1090..1092
FT /evidence="ECO:0007829|PDB:2WY7"
FT HELIX 1097..1111
FT /evidence="ECO:0007829|PDB:2WY7"
FT TURN 1114..1116
FT /evidence="ECO:0007829|PDB:2NOJ"
FT HELIX 1127..1133
FT /evidence="ECO:0007829|PDB:2WY7"
FT HELIX 1139..1158
FT /evidence="ECO:0007829|PDB:2WY7"
FT TURN 1159..1161
FT /evidence="ECO:0007829|PDB:2WY7"
FT HELIX 1165..1179
FT /evidence="ECO:0007829|PDB:2WY7"
FT HELIX 1180..1182
FT /evidence="ECO:0007829|PDB:2WY7"
FT HELIX 1186..1198
FT /evidence="ECO:0007829|PDB:2WY7"
FT HELIX 1204..1213
FT /evidence="ECO:0007829|PDB:2WY7"
FT TURN 1216..1218
FT /evidence="ECO:0007829|PDB:2WY7"
FT STRAND 1223..1225
FT /evidence="ECO:0007829|PDB:1GHQ"
FT HELIX 1226..1243
FT /evidence="ECO:0007829|PDB:2WY7"
FT TURN 1246..1248
FT /evidence="ECO:0007829|PDB:2WY7"
FT HELIX 1249..1258
FT /evidence="ECO:0007829|PDB:2WY7"
FT STRAND 1265..1267
FT /evidence="ECO:0007829|PDB:3G6J"
FT HELIX 1269..1285
FT /evidence="ECO:0007829|PDB:2WY7"
FT HELIX 1286..1288
FT /evidence="ECO:0007829|PDB:6RMU"
FT TURN 1297..1299
FT /evidence="ECO:0007829|PDB:3OXU"
FT STRAND 1303..1305
FT /evidence="ECO:0007829|PDB:2WII"
FT STRAND 1307..1310
FT /evidence="ECO:0007829|PDB:3G6J"
FT TURN 1312..1315
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1320..1326
FT /evidence="ECO:0007829|PDB:5FO8"
FT STRAND 1331..1333
FT /evidence="ECO:0007829|PDB:3G6J"
FT STRAND 1336..1350
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1356..1369
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1383..1392
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1394..1396
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1400..1406
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1411..1413
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 1415..1422
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1424..1428
FT /evidence="ECO:0007829|PDB:6EHG"
FT HELIX 1431..1434
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1438..1440
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1443..1449
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1453..1455
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1457..1465
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1469..1471
FT /evidence="ECO:0007829|PDB:2A73"
FT STRAND 1475..1481
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1485..1493
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1495..1497
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 1498..1500
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1504..1507
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1510..1516
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1518..1520
FT /evidence="ECO:0007829|PDB:2A74"
FT STRAND 1524..1526
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 1529..1536
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1537..1540
FT /evidence="ECO:0007829|PDB:2ICE"
FT STRAND 1541..1553
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1556..1570
FT /evidence="ECO:0007829|PDB:7BAG"
FT TURN 1577..1579
FT /evidence="ECO:0007829|PDB:5FOB"
FT STRAND 1581..1587
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 1588..1593
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1601..1607
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 1608..1610
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1611..1613
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 1615..1617
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1619..1621
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1627..1631
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 1634..1636
FT /evidence="ECO:0007829|PDB:7BAG"
FT STRAND 1637..1639
FT /evidence="ECO:0007829|PDB:2A74"
FT HELIX 1640..1642
FT /evidence="ECO:0007829|PDB:7BAG"
FT HELIX 1643..1658
FT /evidence="ECO:0007829|PDB:7BAG"
SQ SEQUENCE 1663 AA; 187148 MW; 30C2832A9E75FFC4 CRC64;
MGPTSGPSLL LLLLTHLPLA LGSPMYSIIT PNILRLESEE TMVLEAHDAQ GDVPVTVTVH
DFPGKKLVLS SEKTVLTPAT NHMGNVTFTI PANREFKSEK GRNKFVTVQA TFGTQVVEKV
VLVSLQSGYL FIQTDKTIYT PGSTVLYRIF TVNHKLLPVG RTVMVNIENP EGIPVKQDSL
SSQNQLGVLP LSWDIPELVN MGQWKIRAYY ENSPQQVFST EFEVKEYVLP SFEVIVEPTE
KFYYIYNEKG LEVTITARFL YGKKVEGTAF VIFGIQDGEQ RISLPESLKR IPIEDGSGEV
VLSRKVLLDG VQNPRAEDLV GKSLYVSATV ILHSGSDMVQ AERSGIPIVT SPYQIHFTKT
PKYFKPGMPF DLMVFVTNPD GSPAYRVPVA VQGEDTVQSL TQGDGVAKLS INTHPSQKPL
SITVRTKKQE LSEAEQATRT MQALPYSTVG NSNNYLHLSV LRTELRPGET LNVNFLLRMD
RAHEAKIRYY TYLIMNKGRL LKAGRQVREP GQDLVVLPLS ITTDFIPSFR LVAYYTLIGA
SGQREVVADS VWVDVKDSCV GSLVVKSGQS EDRQPVPGQQ MTLKIEGDHG ARVVLVAVDK
GVFVLNKKNK LTQSKIWDVV EKADIGCTPG SGKDYAGVFS DAGLTFTSSS GQQTAQRAEL
QCPQPAARRR RSVQLTEKRM DKVGKYPKEL RKCCEDGMRE NPMRFSCQRR TRFISLGEAC
KKVFLDCCNY ITELRRQHAR ASHLGLARSN LDEDIIAEEN IVSRSEFPES WLWNVEDLKE
PPKNGISTKL MNIFLKDSIT TWEILAVSMS DKKGICVADP FEVTVMQDFF IDLRLPYSVV
RNEQVEIRAV LYNYRQNQEL KVRVELLHNP AFCSLATTKR RHQQTVTIPP KSSLSVPYVI
VPLKTGLQEV EVKAAVYHHF ISDGVRKSLK VVPEGIRMNK TVAVRTLDPE RLGREGVQKE
DIPPADLSDQ VPDTESETRI LLQGTPVAQM TEDAVDAERL KHLIVTPSGC GEQNMIGMTP
TVIAVHYLDE TEQWEKFGLE KRQGALELIK KGYTQQLAFR QPSSAFAAFV KRAPSTWLTA
YVVKVFSLAV NLIAIDSQVL CGAVKWLILE KQKPDGVFQE DAPVIHQEMI GGLRNNNEKD
MALTAFVLIS LQEAKDICEE QVNSLPGSIT KAGDFLEANY MNLQRSYTVA IAGYALAQMG
RLKGPLLNKF LTTAKDKNRW EDPGKQLYNV EATSYALLAL LQLKDFDFVP PVVRWLNEQR
YYGGGYGSTQ ATFMVFQALA QYQKDAPDHQ ELNLDVSLQL PSRSSKITHR IHWESASLLR
SEETKENEGF TVTAEGKGQG TLSVVTMYHA KAKDQLTCNK FDLKVTIKPA PETEKRPQDA
KNTMILEICT RYRGDQDATM SILDISMMTG FAPDTDDLKQ LANGVDRYIS KYELDKAFSD
RNTLIIYLDK VSHSEDDCLA FKVHQYFNVE LIQPGAVKVY AYYNLEESCT RFYHPEKEDG
KLNKLCRDEL CRCAEENCFI QKSDDKVTLE ERLDKACEPG VDYVYKTRLV KVQLSNDFDE
YIMAIEQTIK SGSDEVQVGQ QRTFISPIKC REALKLEEKK HYLMWGLSSD FWGEKPNLSY
IIGKDTWVEH WPEEDECQDE ENQKQCQDLG AFTESMVVFG CPN
