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 27-MAR-2024, entry version 264. 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 745-754, AND CLEAVAGE BY N.MENINGITIDIS NALP (MICROBIAL RP INFECTION). RX PubMed=24367091; DOI=10.1073/pnas.1321556111; RA Del Tordello E., Vacca I., Ram S., Rappuoli R., Serruto D.; RT "Neisseria meningitidis NalP cleaves human complement C3, facilitating RT degradation of C3b and survival in human serum."; RL Proc. Natl. Acad. Sci. U.S.A. 111:427-432(2014). RN [8] 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 [9] 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 [10] 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 [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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 [29] 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 [30] 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 [31] RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION). RX PubMed=18160402; DOI=10.1074/jbc.m704821200; RA Terao Y., Mori Y., Yamaguchi M., Shimizu Y., Ooe K., Hamada S., RA Kawabata S.; RT "Group A streptococcal cysteine protease degrades C3 (C3b) and contributes RT to evasion of innate immunity."; RL J. Biol. Chem. 283:6253-6260(2008). RN [32] 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 [33] 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 [34] 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 [35] 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 [36] 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 [37] 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 [38] 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 [39] 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 [40] 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 [41] 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 [42] 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 [43] 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 [44] 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 [45] 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 [46] 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 [47] 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 [48] 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 [49] 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 [50] 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 [51] 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 [52] 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 [53] {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 [54] {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 [55] 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 [56] 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 [57] 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 [58] 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 [59] 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 [60] 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 [61] 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 [62] 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 [63] 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 [64] 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 [65] 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 [66] 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; PRO_0000005911 [P01024]: C3; NbExp=9; IntAct=EBI-6863145, EBI-12735725; CC PRO_0000005908; P08603: CFH; NbExp=4; IntAct=EBI-6863145, EBI-1223708; 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: Phosphorylated by FAM20C in the extracellular medium. CC {ECO:0000269|PubMed:26091039}. 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: (Microbial infection) Complement C3 beta chain is cleaved and CC inactivated by S.pyogenes SpeB. {ECO:0000269|PubMed:18160402}. CC -!- PTM: (Microbial infection) Cleaved by N.meningitidis NalP between Leu- CC 744 and Gly-754, generating a slightly shorter C3 alpha form and a CC slightly longer C3 beta form. The C3b-like fragment is degraded in the CC presence of the complement regulators CFH and CFI, preventing its CC deposition on the bacterial surface. {ECO:0000269|PubMed:24367091}. 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]: CC An 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/"; 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; 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; 7NOZ; X-ray; 3.90 A; A=23-667, B=752-1663. DR PDB; 7PI6; X-ray; 2.60 A; B/D=996-1287. 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 PDB; 7UE9; X-ray; 1.75 A; C=994-1303. DR PDB; 7ZGK; EM; 3.59 A; A=23-667, B=749-1663. DR PDB; 8ENU; EM; 3.22 A; G=23-667, H=749-1663. DR PDB; 8EOK; EM; 3.53 A; G=23-667, H=749-1663. DR PDB; 8HK2; EM; 2.90 A; D=672-748. DR PDB; 8I9L; EM; 3.18 A; D=672-748. 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; 7NOZ; -. DR PDBsum; 7PI6; -. DR PDBsum; 7QIV; -. DR PDBsum; 7TV9; -. DR PDBsum; 7UE9; -. DR PDBsum; 7ZGK; -. DR PDBsum; 8ENU; -. DR PDBsum; 8EOK; -. DR PDBsum; 8HK2; -. DR PDBsum; 8I9L; -. DR AlphaFoldDB; P01024; -. DR EMDB; EMD-14707; -. DR EMDB; EMD-14708; -. DR EMDB; EMD-2403; -. DR EMDB; EMD-28279; -. DR EMDB; EMD-28378; -. DR EMDB; EMD-34842; -. DR EMDB; EMD-35275; -. DR SMR; P01024; -. DR BioGRID; 107179; 152. 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; 58. 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 GlyCosmos; P01024; 4 sites, 51 glycans. DR GlyGen; P01024; 5 sites, 50 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 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; 9606-ENSP00000245907; -. DR PeptideAtlas; P01024; -. DR PRIDE; P01024; -. DR ProteomicsDB; 51308; -. DR Pumba; P01024; -. DR ABCD; P01024; 22 sequenced antibodies. DR Antibodypedia; 692; 2194 antibodies from 44 providers. DR DNASU; 718; -. DR Ensembl; ENST00000245907.11; ENSP00000245907.4; ENSG00000125730.18. DR GeneID; 718; -. DR KEGG; hsa:718; -. DR MANE-Select; ENST00000245907.11; ENSP00000245907.4; NM_000064.4; NP_000055.2. DR AGR; HGNC:1318; -. 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; 4033541at2759; -. 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 1163 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 200 other cell types or tissues. DR ExpressionAtlas; P01024; baseline and differential. 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:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. 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:0006956; P:complement activation; IMP:BHF-UCL. 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:0002430; P:complement receptor mediated signaling pathway; IEA:Ensembl. 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: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: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:0010884; P:positive regulation of lipid storage; IDA:UniProtKB. 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: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; cd02896; complement_C3_C4_C5; 1. DR CDD; cd03583; NTR_complement_C3; 1. DR Gene3D; 1.50.10.20; -; 1. DR Gene3D; 2.20.130.20; -; 1. DR Gene3D; 2.40.50.120; -; 1. DR Gene3D; 2.60.120.1540; -; 1. DR Gene3D; 2.60.40.1930; -; 3. DR Gene3D; 2.60.40.1940; -; 1. DR Gene3D; 6.20.50.160; -; 1. DR Gene3D; 2.60.40.690; Alpha-macroglobulin, receptor-binding domain; 1. DR Gene3D; 1.20.91.20; Anaphylotoxins (complement system); 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR InterPro; IPR009048; A-macroglobulin_rcpt-bd. DR InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf. DR InterPro; IPR011625; A2M_N_BRD. DR InterPro; IPR047565; Alpha-macroglob_thiol-ester_cl. 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; IPR049466; C3_CUB1. DR InterPro; IPR048848; C3_CUB2. 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; COMPLEMENT C3; 1. DR PANTHER; PTHR11412; MACROGLOBULIN / COMPLEMENT; 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; PF21406; C3_CUB1; 1. DR Pfam; PF21308; C3_CUB2; 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 SFLD; SFLDG01179; Complement_C3/C4_Like; 1. 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 SMART; SM01419; Thiol-ester_cl; 1. DR SUPFAM; SSF49410; Alpha-macroglobulin receptor domain; 1. DR SUPFAM; SSF47686; Anaphylotoxins (complement system); 1. DR SUPFAM; SSF48239; Terpenoid cyclases/Protein prenyltransferases; 1. DR SUPFAM; SSF50242; TIMP-like; 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. DR SWISS-2DPAGE; P01024; -. DR Genevisible; P01024; HS. 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 541..542 FT /note="Cleavage; by S.pyogenes SpeB" FT /evidence="ECO:0000269|PubMed:18160402" 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; risk factor for ARMD9; FT results in decreased binding affinity for regulator factor FT H; results in reduced sensitivity to cleavage by factor I; FT 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. 9; 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 366..368 FT /evidence="ECO:0007829|PDB:7TV9" 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 TURN 702..705 FT /evidence="ECO:0007829|PDB:8HK2" 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 STRAND 992..994 FT /evidence="ECO:0007829|PDB:7AKK" 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 STRAND 1134..1138 FT /evidence="ECO:0007829|PDB:7TV9" 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 HELIX 1377..1379 FT /evidence="ECO:0007829|PDB:7AKK" 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 //