ID CFAH_HUMAN Reviewed; 1231 AA. AC P08603; A5PL14; P78435; Q14570; Q2TAZ5; Q38G77; Q5TFM3; Q8N708; Q9NU86; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 11-SEP-2007, sequence version 4. DT 04-NOV-2026, entry version 262. DE RecName: Full=Complement factor H; DE AltName: Full=H factor 1; DE Flags: Precursor; GN Name=CFH; Synonyms=HF, HF1, HF2; 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] (ISOFORMS 1 AND 2), GLYCOSYLATION AT ASN-529, RP AND VARIANTS HIS-402 AND ARG-493. RC TISSUE=Liver; RX PubMed=2963625; DOI=10.1042/bj2490593; RA Ripoche J., Day A.J., Harris T.J.R., Sim R.B.; RT "The complete amino acid sequence of human complement factor H."; RL Biochem. J. 249:593-602(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-62; THR-551; ILE-890; RP ASP-936; ILE-1007; ILE-1017; TYR-1050 AND THR-1059. RG SeattleSNPs variation discovery resource; RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT HIS-402. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP ILE-62. RC TISSUE=Testis, and Urinary bladder; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 53-445. RX PubMed=2946589; DOI=10.1002/eji.1830161107; RA Schulz T.F., Schwaeble W., Stanley K.K., Weiss E., Dierich M.P.; RT "Human complement factor H: isolation of cDNA clones and partial cDNA RT sequence of the 38-kDa tryptic fragment containing the binding site for RT C3b."; RL Eur. J. Immunol. 16:1351-1355(1986). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 226-449, AND PROTEIN SEQUENCE OF 205-216; RP 237-246; 320-331; 425-435; 508-518; 645-662; 667-717; 858-885; 907-972; RP 1163-1182 AND 1193-1203. RX PubMed=2937845; DOI=10.4049/jimmunol.136.9.3407; RA Kristensen T., Wetsel R.A., Tack B.F.; RT "Structural analysis of human complement protein H: homology with C4b RT binding protein, beta 2-glycoprotein I, and the Ba fragment of B2."; RL J. Immunol. 136:3407-3411(1986). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1047-1231. RX PubMed=1826708; DOI=10.5282/ubm/epub.3049; RA Estaller C., Koistinen V., Schwaeble W., Dierich M.P., Weiss E.H.; RT "Cloning of the 1.4-kb mRNA species of human complement factor H reveals a RT novel member of the short consensus repeat family related to the carboxy RT terminal of the classical 150-kDa molecule."; RL J. Immunol. 146:3190-3196(1991). RN [8] RP PROTEIN SEQUENCE OF 19-35. RX PubMed=6215918; DOI=10.1042/bj2050285; RA Sim R.B., Discipio R.G.; RT "Purification and structural studies on the complement-system control RT protein beta 1H (Factor H)."; RL Biochem. J. 205:285-293(1982). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-19. RA Vik D.P., Williams S.A.; RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9. RA Dominguez O.; RL Thesis (1993), Hospital Trias I Pujol, Spain. RN [11] RP TISSUE SPECIFICITY. RX PubMed=6444659; DOI=10.1084/jem.151.3.501; RA Whaley K.; RT "Biosynthesis of the complement components and the regulatory proteins of RT the alternative complement pathway by human peripheral blood monocytes."; RL J. Exp. Med. 151:501-516(1980). RN [12] RP TISSUE SPECIFICITY. RX PubMed=2968404; DOI=10.4049/jimmunol.141.2.559; RA Katz Y., Strunk R.C.; RT "Synthesis and regulation of complement protein factor H in human skin RT fibroblasts."; RL J. Immunol. 141:559-563(1988). RN [13] RP TISSUE SPECIFICITY. RX PubMed=2139673; DOI=10.4049/jimmunol.144.10.3835; RA Brooimans R.A., van der Ark A.A., Buurman W.A., van Es L.A., Daha M.R.; RT "Differential regulation of complement factor H and C3 production in human RT umbilical vein endothelial cells by IFN-gamma and IL-1."; RL J. Immunol. 144:3835-3840(1990). RN [14] RP FUNCTION, AND INTERACTION WITH ITGAM. RX PubMed=9558116; RA DiScipio R.G., Daffern P.J., Schraufstaetter I.U., Sriramarao P.; RT "Human polymorphonuclear leukocytes adhere to complement factor H through RT an interaction that involves alphaMbeta2 (CD11b/CD18)."; RL J. Immunol. 160:4057-4066(1998). RN [15] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-882. 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 [16] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-529 AND ASN-911. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [17] RP GLYCOSYLATION AT ASN-529; ASN-718; ASN-802; ASN-822; ASN-882; ASN-911; RP ASN-1029 AND ASN-1095. RX PubMed=17591618; DOI=10.1093/glycob/cwm060; RA Fenaille F., Le Mignon M., Groseil C., Ramon C., Riande S., Siret L., RA Bihoreau N.; RT "Site-specific N-glycan characterization of human complement factor H."; RL Glycobiology 17:932-944(2007). RN [18] 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 [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-529; ASN-802; ASN-882; ASN-911 RP AND ASN-1029. 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 [20] RP GLYCOSYLATION AT ASN-217; ASN-882; ASN-911 AND ASN-1029. RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., RA Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core fucosylated RT glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [21] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-882, AND STRUCTURE OF RP CARBOHYDRATES. RC TISSUE=Cerebrospinal fluid; RX PubMed=19838169; DOI=10.1038/nmeth.1392; RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., RA Larson G.; RT "Enrichment of glycopeptides for glycan structure and attachment site RT identification."; RL Nat. Methods 6:809-811(2009). RN [22] RP FUNCTION, AND INTERACTION WITH ITGAM. RX PubMed=20008295; DOI=10.4049/jimmunol.0901702; RA Losse J., Zipfel P.F., Jozsi M.; RT "Factor H and factor H-related protein 1 bind to human neutrophils via RT complement receptor 3, mediate attachment to Candida albicans, and enhance RT neutrophil antimicrobial activity."; RL J. Immunol. 184:912-921(2010). RN [23] RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH P.FALCIPARUM GAP50 RP (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION (MICROBIAL INFECTION). RX PubMed=23332154; DOI=10.1016/j.chom.2012.11.013; RA Simon N., Lasonder E., Scheuermayer M., Kuehn A., Tews S., Fischer R., RA Zipfel P.F., Skerka C., Pradel G.; RT "Malaria parasites co-opt human factor H to prevent complement-mediated RT lysis in the mosquito midgut."; RL Cell Host Microbe 13:29-41(2013). RN [24] 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 [25] RP TISSUE SPECIFICITY, AND SULFATION. RX PubMed=25136834; DOI=10.1371/journal.pone.0105409; RA Kanan Y., Siefert J.C., Kinter M., Al-Ubaidi M.R.; RT "Complement factor H, vitronectin, and opticin are tyrosine-sulfated RT proteins of the retinal pigment epithelium."; RL PLoS ONE 9:E105409-E105409(2014). RN [26] RP FUNCTION, AND INTERACTION WITH P.FALCIPARUM PF92 (MICROBIAL INFECTION). RX PubMed=26700768; DOI=10.4049/jimmunol.1501581; RA Kennedy A.T., Schmidt C.Q., Thompson J.K., Weiss G.E., RA Taechalertpaisarn T., Gilson P.R., Barlow P.N., Crabb B.S., Cowman A.F., RA Tham W.H.; RT "Recruitment of Factor H as a Novel Complement Evasion Strategy for Blood- RT Stage Plasmodium falciparum Infection."; RL J. Immunol. 196:1239-1248(2016). RN [27] RP STRUCTURE BY NMR OF 927-985 (SUSHI 16), AND DISULFIDE BOND. RX PubMed=1829116; DOI=10.1016/0022-2836(91)90666-t; RA Norman D.G., Barlow P.N., Baron M., Day A.J., Sim B., Campbell I.D.; RT "Three-dimensional structure of a complement control protein module in RT solution."; RL J. Mol. Biol. 219:717-725(1991). RN [28] RP STRUCTURE BY NMR OF 264-322 (SUSHI 5). RX PubMed=1533152; DOI=10.1021/bi00129a011; RA Barlow P.N., Norman D.G., Steinkasserer A., Horne T.J., Pearce J., RA Driscoll P.C., Sim B., Campbell I.D.; RT "Solution structure of the fifth repeat of factor H: a second example of RT the complement control protein module."; RL Biochemistry 31:3626-3634(1992). RN [29] RP STRUCTURE BY NMR OF 866-985 (SUSHIS 15 AND 16), AND DISULFIDE BOND. RX PubMed=8331663; DOI=10.1006/jmbi.1993.1381; RA Barlow P.N., Steinkasserer A., Norman D.G., Kieffer B., Wiles A.P., Sim B., RA Campbell I.D.; RT "Solution structure of a pair of complement modules by nuclear magnetic RT resonance."; RL J. Mol. Biol. 232:268-284(1993). RN [30] {ECO:0007744|PDB:3OXU} RP X-RAY CRYSTALLOGRAPHY, AND FUNCTION. 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 [31] RP VARIANTS CFHD ARG-536 AND TYR-959. RX PubMed=9312129; DOI=10.1074/jbc.272.40.25168; RA Ault B.H., Schmidt B.Z., Fowler N.L., Kashtan C.E., Ahmed A.E., Vogt B.A., RA Colten H.R.; RT "Human factor H deficiency. Mutations in framework cysteine residues and RT block in H protein secretion and intracellular catabolism."; RL J. Biol. Chem. 272:25168-25175(1997). RN [32] RP VARIANT AHUS1 GLY-1215. RX PubMed=9551389; DOI=10.1111/j.1523-1755.1998.00824.x; RA Warwicker P., Goodship T.H.J., Donne R.L., Pirson Y., Nicholls A., RA Ward R.M., Turnpenny P., Goodship J.A.; RT "Genetic studies into inherited and sporadic hemolytic uremic syndrome."; RL Kidney Int. 53:836-844(1998). RN [33] RP VARIANT AHUS1 LEU-1191. RX PubMed=10577907; DOI=10.1086/302673; RA Ying L., Katz Y., Schlesinger M., Carmi R., Shalev H., Haider N., Beck G., RA Sheffield V.C., Landau D.; RT "Complement factor H gene mutation associated with autosomal recessive RT atypical hemolytic uremic syndrome."; RL Am. J. Hum. Genet. 65:1538-1546(1999). RN [34] RP VARIANT AHUS1 1225-TYR--ARG-1231 DELINS PHE-GLN-SER. RX PubMed=10762557; DOI=10.1086/302877; RA Buddles M.R.H., Donne R.L., Richards A., Goodship J., Goodship T.H.J.; RT "Complement factor H gene mutation associated with autosomal recessive RT atypical hemolytic uremic syndrome."; RL Am. J. Hum. Genet. 66:1721-1722(2000). RN [35] RP INVOLVEMENT IN CFHD. RX PubMed=10803850; DOI=10.1007/s002510050631; RA Sanchez-Corral P., Bellavia D., Amico L., Brai M., Rodriguez de Cordoba S.; RT "Molecular basis for factor H and FHL-1 deficiency in an Italian family."; RL Immunogenetics 51:366-369(2000). RN [36] RP VARIANTS CFHD MET-956; LEU-1183; ARG-1189 AND ALA-1197. RX PubMed=11170895; DOI=10.1086/318201; RA Perez-Caballero D., Gonzalez-Rubio C., Gallardo M.E., Vera M., RA Lopez-Trascasa M., Rodriguez de Cordoba S., Sanchez-Corral P.; RT "Clustering of missense mutations in the C-terminal region of factor H in RT atypical hemolytic uremic syndrome."; RL Am. J. Hum. Genet. 68:478-484(2001). RN [37] RP VARIANTS CFHD GLU-1076; GLY-1119 AND ARG-1184. RX PubMed=11170896; DOI=10.1086/318203; RA Richards A., Buddles M.R., Donne R.L., Kaplan B.S., Kirk E., Venning M.C., RA Tielemans C.L., Goodship J.A., Goodship T.H.J.; RT "Factor H mutations in hemolytic uremic syndrome cluster in exons 18-20, a RT domain important for host cell recognition."; RL Am. J. Hum. Genet. 68:485-490(2001). RN [38] RP VARIANTS CFHD CYS-1210 AND GLN-1215. RX PubMed=11158219; DOI=10.1681/asn.v122297; RG Italian registry of familial and recurrent HUS/TTP; RA Caprioli J., Bettinaglio P., Zipfel P.F., Amadei B., Daina E., Gamba S., RA Skerka C., Marziliano N., Remuzzi G., Noris M.; RT "The molecular basis of familial hemolytic uremic syndrome: mutation RT analysis of factor H gene reveals a hot spot in short consensus repeat RT 20."; RL J. Am. Soc. Nephrol. 12:297-307(2001). RN [39] RP VARIANTS AHUS1 MET-956; GLU-1076; GLY-1119; LEU-1183; ARG-1184; ARG-1189; RP LEU-1191; ASP-1194; ALA-1197; CYS-1210; GLY-1215 AND GLN-1215. RX PubMed=11851332; DOI=10.1006/jmbi.2001.5337; RA Perkins S.J., Goodship T.H.J.; RT "Molecular modelling of the C-terminal domains of factor H of human RT complement: a correlation between haemolytic uraemic syndrome and a RT predicted heparin binding site."; RL J. Mol. Biol. 316:217-224(2002). RN [40] RP VARIANT CFHD ARG-1183. RX PubMed=12020532; DOI=10.1016/s0140-6736(02)08560-4; RA Remuzzi G., Ruggenenti P., Codazzi D., Noris M., Caprioli J., Locatelli G., RA Gridelli B.; RT "Combined kidney and liver transplantation for familial haemolytic uraemic RT syndrome."; RL Lancet 359:1671-1672(2002). RN [41] RP VARIANTS AHUS1 GLY-78; HIS-950; HIS-951; TRP-1163 AND ALA-1198, AND VARIANT RP ASP-936. RX PubMed=14583443; DOI=10.1093/hmg/ddg363; RG International registry of recurrent and familial HUS/TTP; RA Caprioli J., Castelletti F., Bucchioni S., Bettinaglio P., Bresin E., RA Pianetti G., Gamba S., Brioschi S., Daina E., Remuzzi G., Noris M.; RT "Complement factor H mutations and gene polymorphisms in haemolytic uraemic RT syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly RT associated with the disease."; RL Hum. Mol. Genet. 12:3385-3395(2003). RN [42] RP VARIANTS AHUS1 TRP-630; LYS-850; CYS-978; PHE-1021; ARG-1043; GLY-1134; RP ASP-1142; ARG-1157; ARG-1183 AND SER-1226. RX PubMed=12960213; DOI=10.1136/jmg.40.9.676; RA Neumann H.P.H., Salzmann M., Bohnert-Iwan B., Mannuelian T., Skerka C., RA Lenk D., Bender B.U., Cybulla M., Riegler P., Koenigsrainer A., Neyer U., RA Bock A., Widmer U., Male D.A., Franke G., Zipfel P.F.; RT "Haemolytic uraemic syndrome and mutations of the factor H gene: a RT registry-based study of German speaking countries."; RL J. Med. Genet. 40:676-681(2003). RN [43] RP VARIANTS CFHD LEU-127; SER-431 AND SER-673, AND VARIANTS AHUS1 LYS-400; RP TYR-673; ARG-893; SER-915; LEU-1183 AND SER-1199. RX PubMed=14978182; DOI=10.1097/01.asn.0000115702.28859.a7; RA Dragon-Durey M.-A., Fremeaux-Bacchi V., Loirat C., Blouin J., Niaudet P., RA Deschenes G., Coppo P., Herman Fridman W., Weiss L.; RT "Heterozygous and homozygous factor H deficiencies associated with RT hemolytic uremic syndrome or membranoproliferative glomerulonephritis: RT report and genetic analysis of 16 cases."; RL J. Am. Soc. Nephrol. 15:787-795(2004). RN [44] RP VARIANT HIS-402. RX PubMed=15895326; DOI=10.1086/431426; RA Zareparsi S., Branham K.E.H., Li M., Shah S., Klein R.J., Ott J., Hoh J., RA Abecasis G.R., Swaroop A.; RT "Strong association of the Y402H variant in complement factor H at 1q32 RT with susceptibility to age-related macular degeneration."; RL Am. J. Hum. Genet. 77:149-153(2005). RN [45] RP VARIANTS ILE-62 AND HIS-402, AND ASSOCIATION WITH ARMD. RX PubMed=15870199; DOI=10.1073/pnas.0501536102; RA Hageman G.S., Anderson D.H., Johnson L.V., Hancox L.S., Taiber A.J., RA Hardisty L.I., Hageman J.L., Stockman H.A., Borchardt J.D., Gehrs K.M., RA Smith R.J.H., Silvestri G., Russell S.R., Klaver C.C.W., Barbazetto I., RA Chang S., Yannuzzi L.A., Barile G.R., Merriam J.C., Smith R.T., Olsh A.K., RA Bergeron J., Zernant J., Merriam J.E., Gold B., Dean M., Allikmets R.; RT "A common haplotype in the complement regulatory gene factor H (HF1/CFH) RT predisposes individuals to age-related macular degeneration."; RL Proc. Natl. Acad. Sci. U.S.A. 102:7227-7232(2005). RN [46] RP ASSOCIATION OF VARIANT HIS-402 WITH ARMD. RX PubMed=15761122; DOI=10.1126/science.1109557; RA Klein R.J., Zeiss C., Chew E.Y., Tsai J.-Y., Sackler R.S., Haynes C., RA Henning A.K., SanGiovanni J.P., Mane S.M., Mayne S.T., Bracken M.B., RA Ferris F.L., Ott J., Barnstable C., Hoh J.; RT "Complement factor H polymorphism in age-related macular degeneration."; RL Science 308:385-389(2005). RN [47] RP ASSOCIATION OF VARIANT HIS-402 WITH ARMD. RX PubMed=15761120; DOI=10.1126/science.1110359; RA Haines J.L., Hauser M.A., Schmidt S., Scott W.K., Olson L.M., Gallins P., RA Spencer K.L., Kwan S.Y., Noureddine M., Gilbert J.R., Schnetz-Boutaud N., RA Agarwal A., Postel E.A., Pericak-Vance M.A.; RT "Complement factor H variant increases the risk of age-related macular RT degeneration."; RL Science 308:419-421(2005). RN [48] RP ASSOCIATION OF VARIANT HIS-402 WITH ARMD. RX PubMed=15761121; DOI=10.1126/science.1110189; RA Edwards A.O., Ritter R. III, Abel K.J., Manning A., Panhuysen C., RA Farrer L.A.; RT "Complement factor H polymorphism and age-related macular degeneration."; RL Science 308:421-424(2005). RN [49] RP VARIANT CFHD LYS-224 DEL, AND CHARACTERIZATION OF VARIANT CFHD LYS-224 DEL. RX PubMed=16612335; DOI=10.1038/sj.ki.5000269; RA Licht C., Heinen S., Jozsi M., Loeschmann I., Saunders R.E., Perkins S.J., RA Waldherr R., Skerka C., Kirschfink M., Hoppe B., Zipfel P.F.; RT "Deletion of Lys224 in regulatory domain 4 of factor H reveals a novel RT pathomechanism for dense deposit disease (MPGN II)."; RL Kidney Int. 70:42-50(2006). RN [50] RP INTERACTION WITH WEST NILE VIRUS NON-STRUCTURAL PROTEIN 1. RX PubMed=17132743; DOI=10.1073/pnas.0605668103; RA Chung K.M., Liszewski M.K., Nybakken G., Davis A.E., Townsend R.R., RA Fremont D.H., Atkinson J.P., Diamond M.S.; RT "West Nile virus nonstructural protein NS1 inhibits complement activation RT by binding the regulatory protein factor H."; RL Proc. Natl. Acad. Sci. U.S.A. 103:19111-19116(2006). RN [51] RP INVOLVEMENT IN BASAL LAMINAR DRUSEN, AND VARIANTS HIS-402; GLY-567; RP ASP-936; TYR-1050 AND SER-1078. RX PubMed=18252232; DOI=10.1016/j.ajhg.2007.11.007; RA Boon C.J.F., Klevering B.J., Hoyng C.B., Zonneveld-Vrieling M.N., RA Nabuurs S.B., Blokland E., Cremers F.P.M., den Hollander A.I.; RT "Basal laminar drusen caused by compound heterozygous variants in the CFH RT gene."; RL Am. J. Hum. Genet. 82:516-523(2008). RN [52] RP VARIANTS AHUS1 TYR-325; ILE-609; LEU-1169 AND CYS-1183, AND VARIANT RP ASP-936. 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 [53] RP VARIANTS ILE-62; LYS-850; TYR-959 AND GLU-1143, AND IDENTIFICATION BY MASS RP 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 [54] RP VARIANT ARMD4 CYS-1210. RX PubMed=22019782; DOI=10.1038/ng.976; RA Raychaudhuri S., Iartchouk O., Chin K., Tan P.L., Tai A.K., Ripke S., RA Gowrisankar S., Vemuri S., Montgomery K., Yu Y., Reynolds R., Zack D.J., RA Campochiaro B., Campochiaro P., Katsanis N., Daly M.J., Seddon J.M.; RT "A rare penetrant mutation in CFH confers high risk of age-related macular RT degeneration."; RL Nat. Genet. 43:1232-1236(2011). RN [55] RP X-RAY CRYSTALLOGRAPHY, INTERACTION WITH C3B AND GLYCOSAMINOGLYCANS, RP MUTAGENESIS OF ARG-1182; LYS-1186 AND LYS-1188, DISULFIDE BOND, AND RP CHARACTERIZATION OF VARIANTS AHUS1 LEU-1183 AND ALA-1198. RX PubMed=16601698; DOI=10.1038/sj.emboj.7601052; RA Jokiranta T.S., Jaakola V.P., Lehtinen M.J., Paerepalo M., Meri S., RA Goldman A.; RT "Structure of complement factor H carboxyl-terminus reveals molecular basis RT of atypical haemolytic uremic syndrome."; RL EMBO J. 25:1784-1794(2006). RN [56] RP STRUCTURE BY NMR OF 386-446, AND DISULFIDE BONDS. RX PubMed=17360715; DOI=10.1074/jbc.m609636200; RA Herbert A.P., Deakin J.A., Schmidt C.Q., Blaum B.S., Egan C., RA Ferreira V.P., Pangburn M.K., Lyon M., Uhrin D., Barlow P.N.; RT "Structure shows that a glycosaminoglycan and protein recognition site in RT factor H is perturbed by age-related macular degeneration-linked single RT nucleotide polymorphism."; RL J. Biol. Chem. 282:18960-18968(2007). RN [57] RP X-RAY CRYSTALLOGRAPHY, INTERACTION WITH GLYCOSAMINOGLYCANS, MUTAGENESIS OF RP HIS-337 AND ARG-341, AND DISULFIDE BOND. RX PubMed=17893204; DOI=10.1084/jem.20071069; RA Prosser B.E., Johnson S., Roversi P., Herbert A.P., Blaum B.S., Tyrrell J., RA Jowitt T.A., Clark S.J., Tarelli E., Uhrin D., Barlow P.N., Sim R.B., RA Day A.J., Lea S.M.; RT "Structural basis for complement factor H linked age-related macular RT degeneration."; RL J. Exp. Med. 204:2277-2283(2007). RN [58] RP STRUCTURE BY NMR OF 20-206, FUNCTION, DOMAIN, AND DISULFIDE BOND. RX PubMed=18252712; DOI=10.1074/jbc.m709587200; RA Hocking H.G., Herbert A.P., Kavanagh D., Soares D.C., Ferreira V.P., RA Pangburn M.K., Uhrin D., Barlow P.N.; RT "Structure of the N-terminal region of complement factor H and RT conformational implications of disease-linked sequence variations."; RL J. Biol. Chem. 283:9475-9487(2008). RN [59] RP X-RAY CRYSTALLOGRAPHY, AND SUBUNIT. RX PubMed=18005991; DOI=10.1016/j.jmb.2007.09.026; RA Okemefuna A.I., Gilbert H.E., Griggs K.M., Ormsby R.J., Gordon D.L., RA Perkins S.J.; RT "The regulatory SCR-1/5 and cell surface-binding SCR-16/20 fragments of RT factor H reveal partially folded-back solution structures and different RT self-associative properties."; RL J. Mol. Biol. 375:80-101(2008). RN [60] RP X-RAY CRYSTALLOGRAPHY, AND SUBUNIT. RX PubMed=19505476; DOI=10.1016/j.jmb.2009.06.010; RA Okemefuna A.I., Nan R., Gor J., Perkins S.J.; RT "Electrostatic interactions contribute to the folded-back conformation of RT wild type human factor H."; RL J. Mol. Biol. 391:98-118(2009). RN [61] RP X-RAY CRYSTALLOGRAPHY, INTERACTION WITH PROTEIN C3B, FUNCTION, AND RP DISULFIDE BOND. RX PubMed=19503104; DOI=10.1038/ni.1755; RA Wu J., Wu Y.Q., Ricklin D., Janssen B.J., Lambris J.D., Gros P.; RT "Structure of complement fragment C3b-factor H and implications for host RT protection by complement regulators."; RL Nat. Immunol. 10:728-733(2009). RN [62] RP X-RAY CRYSTALLOGRAPHY, INTERACTION WITH NEISSERIA MENINGITIDIS PROTEIN FHBP RP (MICROBIAL INFECTION), AND DISULFIDE BOND. RX PubMed=19225461; DOI=10.1038/nature07769; RA Schneider M.C., Prosser B.E., Caesar J.J., Kugelberg E., Li S., Zhang Q., RA Quoraishi S., Lovett J.E., Deane J.E., Sim R.B., Roversi P., Johnson S., RA Tang C.M., Lea S.M.; RT "Neisseria meningitidis recruits factor H using protein mimicry of host RT carbohydrates."; RL Nature 458:890-893(2009). RN [63] RP STRUCTURE BY NMR OF 690-804, AND DISULFIDE BONDS. RX PubMed=19835885; DOI=10.1016/j.jmb.2009.10.010; RA Schmidt C.Q., Herbert A.P., Mertens H.D., Guariento M., Soares D.C., RA Uhrin D., Rowe A.J., Svergun D.I., Barlow P.N.; RT "The central portion of factor H (modules 10-15) is compact and contains a RT structurally deviant CCP module."; RL J. Mol. Biol. 395:105-122(2010). RN [64] RP X-RAY CRYSTALLOGRAPHY, INTERACTION WITH C3B AND C3D, AND DISULFIDE BOND. RX PubMed=20378178; DOI=10.1016/j.molimm.2010.03.007; RA Bhattacharjee A., Lehtinen M.J., Kajander T., Goldman A., Jokiranta T.S.; RT "Both domain 19 and domain 20 of factor H are involved in binding to RT complement C3b and C3d."; RL Mol. Immunol. 47:1686-1691(2010). RN [65] RP X-RAY CRYSTALLOGRAPHY, INTERACTION WITH C3B AND C3D, FUNCTION, DOMAIN, AND RP DISULFIDE BOND. 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 [66] RP X-RAY CRYSTALLOGRAPHY, INTERACTION WITH NEISSERIA MENINGITIDIS PROTEIN FHBP RP (MICROBIAL INFECTION), AND DISULFIDE BOND. RX PubMed=23133374; DOI=10.1371/journal.ppat.1002981; RA Johnson S., Tan L., van der Veen S., Caesar J., Goicoechea De Jorge E., RA Harding R.J., Bai X., Exley R.M., Ward P.N., Ruivo N., Trivedi K., RA Cumber E., Jones R., Newham L., Staunton D., Ufret-Vincenty R., Borrow R., RA Pickering M.C., Lea S.M., Tang C.M.; RT "Design and evaluation of meningococcal vaccines through structure-based RT modification of host and pathogen molecules."; RL PLoS Pathog. 8:E1002981-E1002981(2012). RN [67] RP STRUCTURE BY NMR OF 566-687, AND DISULFIDE BONDS. RX PubMed=23017427; DOI=10.1016/j.jmb.2012.09.013; RA Makou E., Mertens H.D., Maciejewski M., Soares D.C., Matis I., RA Schmidt C.Q., Herbert A.P., Svergun D.I., Barlow P.N.; RT "Solution structure of CCP modules 10-12 illuminates functional RT architecture of the complement regulator, factor H."; RL J. Mol. Biol. 424:295-312(2012). RN [68] RP X-RAY CRYSTALLOGRAPHY, AND DISULFIDE BONDS. RX PubMed=22389686; DOI=10.1371/journal.pone.0032187; RA Morgan H.P., Mertens H.D., Guariento M., Schmidt C.Q., Soares D.C., RA Svergun D.I., Herbert A.P., Barlow P.N., Hannan J.P.; RT "Structural analysis of the C-terminal region (modules 18-20) of complement RT regulator factor H (FH)."; RL PLoS ONE 7:e32187-e32187(2012). RN [69] RP X-RAY CRYSTALLOGRAPHY, INTERACTION WITH BORRELIA BURGDORFERI OUTER SURFACE RP PROTEIN E/OSPE (MICROBIAL INFECTION), AND DISULFIDE BOND. RX PubMed=23658013; DOI=10.1074/jbc.m113.459040; RA Bhattacharjee A., Oeemig J.S., Kolodziejczyk R., Meri T., Kajander T., RA Lehtinen M.J., Iwai H., Jokiranta T.S., Goldman A.; RT "Structural basis for complement evasion by Lyme disease pathogen Borrelia RT burgdorferi."; RL J. Biol. Chem. 288:18685-18695(2013). RN [70] RP INTERACTION WITH C.ALBICANS GPD2 (MICROBIAL INFECTION). RX PubMed=23204165; DOI=10.1093/infdis/jis718; RA Luo S., Hoffmann R., Skerka C., Zipfel P.F.; RT "Glycerol-3-phosphate dehydrogenase 2 is a novel factor H-, factor H-like RT protein 1-, and plasminogen-binding surface protein of Candida albicans."; RL J. Infect. Dis. 207:594-603(2013). RN [71] RP X-RAY CRYSTALLOGRAPHY, INTERACTION WITH STREPTOCOCCUS PNEUMONIAE PROTEIN RP VIRULENCE FACTOR CHOLINE-BINDING PROTEIN A/CBPAN (MICROBIAL INFECTION), AND RP DISULFIDE BOND. RX PubMed=25330773; DOI=10.1042/bj20141069; RA Achila D., Liu A., Banerjee R., Li Y., Martinez-Hackert E., Zhang J.R., RA Yan H.; RT "Structural determinants of host specificity of complement Factor H RT recruitment by Streptococcus pneumoniae."; RL Biochem. J. 465:325-335(2015). RN [72] RP X-RAY CRYSTALLOGRAPHY, FUNCTION, AND DISULFIDE BOND. RX PubMed=25402769; DOI=10.1038/nchembio.1696; RA Blaum B.S., Hannan J.P., Herbert A.P., Kavanagh D., Uhrin D., Stehle T.; RT "Structural basis for sialic acid-mediated self-recognition by complement RT factor H."; RL Nat. Chem. Biol. 11:77-82(2015). RN [73] RP X-RAY CRYSTALLOGRAPHY, AND INTERACTION WITH STAPHYLOCOCCUS AUREUS SURFACE RP PROTEIN SERINE-ASPARTATE REPEAT PROTEIN E/SDRE (MICROBIAL INFECTION). RX PubMed=28258151; DOI=10.1042/bcj20170085; RA Zhang Y., Wu M., Hang T., Wang C., Yang Y., Pan W., Zang J., Zhang M., RA Zhang X.; RT "Staphylococcus aureus SdrE captures complement factor H's C-terminus via a RT novel 'close, dock, lock and latch' mechanism for complement evasion."; RL Biochem. J. 474:1619-1631(2017). RN [74] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH CFH AND C3B, DISULFIDE BONDS, AND RP FUNCTION. RX PubMed=28671664; DOI=10.1038/nsmb.3427; RA Xue X., Wu J., Ricklin D., Forneris F., Di Crescenzio P., Schmidt C.Q., RA Granneman J., Sharp T.H., Lambris J.D., Gros P.; RT "Regulator-dependent mechanisms of C3b processing by factor I allow RT differentiation of immune responses."; RL Nat. Struct. Mol. Biol. 24:643-651(2017). RN [75] RP X-RAY CRYSTALLOGRAPHY, INTERACTION WITH CD3D AND BORRELIA BURGDORFERI OUTER RP SURFACE PROTEIN E/OSPE (MICROBIAL INFECTION), AND DISULFIDE BOND. RX PubMed=29190743; DOI=10.1371/journal.pone.0188127; RA Kolodziejczyk R., Mikula K.M., Kotila T., Postis V.L.G., Jokiranta T.S., RA Goldman A., Meri T.; RT "Crystal structure of a tripartite complex between C3dg, C-terminal domains RT of factor H and OspE of Borrelia burgdorferi."; RL PLoS ONE 12:E0188127-E0188127(2017). RN [76] RP INTERACTION WITH C.ALBICANS GPD2 (MICROBIAL INFECTION). RX PubMed=34986357; DOI=10.1016/j.celrep.2021.110183; RA Kumwenda P., Cottier F., Hendry A.C., Kneafsey D., Keevan B., Gallagher H., RA Tsai H.J., Hall R.A.; RT "Estrogen promotes innate immune evasion of Candida albicans through RT inactivation of the alternative complement system."; RL Cell Rep. 38:110183-110183(2022). CC -!- FUNCTION: Glycoprotein that plays an essential role in maintaining a CC well-balanced immune response by modulating complement activation. Acts CC as a soluble inhibitor of complement, where its binding to self markers CC such as glycan structures prevents complement activation and CC amplification on cell surfaces (PubMed:21285368, PubMed:21317894, CC PubMed:25402769). Accelerates the decay of the complement alternative CC pathway (AP) C3 convertase C3bBb, thus preventing local formation of CC more C3b, the central player of the complement amplification loop CC (PubMed:19503104, PubMed:21317894, PubMed:26700768). As a cofactor of CC the serine protease factor I, CFH also regulates proteolytic CC degradation of already-deposited C3b (PubMed:18252712, PubMed:23332154, CC PubMed:28671664). In addition, mediates several cellular responses CC through interaction with specific receptors. For example, interacts CC with CR3/ITGAM receptor and thereby mediates the adhesion of human CC neutrophils to different pathogens. In turn, these pathogens are CC phagocytosed and destroyed (PubMed:20008295, PubMed:9558116). CC {ECO:0000269|PubMed:18252712, ECO:0000269|PubMed:19503104, CC ECO:0000269|PubMed:20008295, ECO:0000269|PubMed:21285368, CC ECO:0000269|PubMed:21317894, ECO:0000269|PubMed:23332154, CC ECO:0000269|PubMed:25402769, ECO:0000269|PubMed:26700768, CC ECO:0000269|PubMed:28671664, ECO:0000269|PubMed:9558116}. CC -!- FUNCTION: (Microbial infection) In the mosquito midgut, binds to the CC surface of parasite P.falciparum gametocytes and protects the parasite CC from alternative complement pathway-mediated elimination. CC {ECO:0000269|PubMed:23332154}. CC -!- SUBUNIT: Homodimer (PubMed:18005991, PubMed:19505476). Also forms CC homooligomers (PubMed:19505476). Interacts with complement protein C3b; CC this interaction inhibits complement activation (PubMed:16601698, CC PubMed:19503104, PubMed:20378178, PubMed:21285368, PubMed:28671664). CC Interacts with complement protein C3d (PubMed:20378178, CC PubMed:21285368, PubMed:29190743). Interacts with CR3/ITGAM; this CC interaction mediates adhesion of neutrophils to pathogens leading to CC pathogen clearance (PubMed:20008295, PubMed:9558116). Interacts with CC complement factor I (PubMed:28671664). {ECO:0000269|PubMed:16601698, CC ECO:0000269|PubMed:18005991, ECO:0000269|PubMed:19503104, CC ECO:0000269|PubMed:19505476, ECO:0000269|PubMed:20008295, CC ECO:0000269|PubMed:20378178, ECO:0000269|PubMed:21285368, CC ECO:0000269|PubMed:28671664, ECO:0000269|PubMed:29190743, CC ECO:0000269|PubMed:9558116}. CC -!- SUBUNIT: (Microbial infection) Interacts with West nile virus non- CC structural protein 1 (NS1); this interaction leads to the degradation CC of C3. {ECO:0000269|PubMed:17132743}. CC -!- SUBUNIT: (Microbial infection) Interacts with C.albicans GPD2; the CC interaction is direct and leads to the degradation of C3 which enables CC the pathogen to evade the host innate immune system. CC {ECO:0000269|PubMed:23204165, ECO:0000269|PubMed:34986357}. CC -!- SUBUNIT: (Microbial infection) Interacts with Neisseria meningitidis CC protein fHbp. {ECO:0000269|PubMed:19225461, CC ECO:0000269|PubMed:23133374}. CC -!- SUBUNIT: (Microbial infection) Interacts with Borrelia burgdorferi CC outer surface protein E/OspE; this interaction recruits complement CC regulator factor H onto the bacterial surface to evade complement- CC mediated cell lysis. {ECO:0000269|PubMed:23658013, CC ECO:0000269|PubMed:29190743}. CC -!- SUBUNIT: (Microbial infection) Interacts with Streptococcus pneumoniae CC protein virulence factor choline-binding protein A/CbpAN; this CC interaction enables Streptococcus pneumoniae to evade surveillance by CC human complement system. {ECO:0000269|PubMed:25330773}. CC -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus CC surface protein serine-aspartate repeat protein E/SdrE; this CC interaction sequesters CFH on the surface of S.aureus for complement CC evasion. {ECO:0000269|PubMed:28258151}. CC -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus CC protein Sbi; this interaction inhibits the complement activation of the CC alternative pathway. {ECO:0000269|PubMed:19112495}. CC -!- SUBUNIT: [Isoform 1]: (Microbial infection) Interacts (via sushi 4-6 CC domains) with P.falciparum surface protein PF92; the interaction CC recruits CFH onto the merozoite surface preventing complement-mediated CC cell lysis (PubMed:26700768). The interaction does not affect CFH CC activity (PubMed:26700768). Interacts (via sushi 6-7 domains) with CC P.falciparum (strain NF54) GAP50; the interaction occurs in the vector CC mosquito midgut at the surface of the activated parasite gametocytes; CC the interaction protects the parasite from alternative complement CC pathway-mediated elimination (PubMed:23332154). CC {ECO:0000269|PubMed:23332154, ECO:0000269|PubMed:26700768}. CC -!- SUBUNIT: [Isoform 2]: (Microbial infection) Interacts (via sushi 4-6 CC domains) with P.falciparum surface protein PF92; the interaction CC recruits FHL-1 isoform onto the merozoite surface preventing CC complement-mediated cell lysis (PubMed:26700768). The interaction does CC not affect FHL-1 isoform activity (PubMed:26700768). Interacts (via CC sushi 6-7 domains) with P.falciparum (strain NF54) GAP50; the CC interaction occurs in the vector mosquito midgut at the surface of the CC activated parasite gametocytes; the interaction protects the parasite CC from alternative complement pathway-mediated elimination CC (PubMed:23332154). {ECO:0000269|PubMed:23332154, CC ECO:0000269|PubMed:26700768}. CC -!- INTERACTION: CC P08603; P02649: APOE; NbExp=8; IntAct=EBI-1223708, EBI-1222467; CC P08603; P01024: C3; NbExp=6; IntAct=EBI-1223708, EBI-905851; CC P08603; PRO_0000005908 [P01024]: C3; NbExp=4; IntAct=EBI-1223708, EBI-6863145; CC P08603; PRO_0000005915 [P01024]: C3; NbExp=2; IntAct=EBI-1223708, EBI-6863106; CC P08603; P08603: CFH; NbExp=5; IntAct=EBI-1223708, EBI-1223708; CC P08603; P02741: CRP; NbExp=39; IntAct=EBI-1223708, EBI-1395983; CC P08603; PRO_0000023526 [P02741]: CRP; NbExp=3; IntAct=EBI-1223708, EBI-22033103; CC P08603; P26022: PTX3; NbExp=21; IntAct=EBI-1223708, EBI-11574553; CC P08603; PRO_0000023545 [P26022]: PTX3; NbExp=8; IntAct=EBI-1223708, EBI-22114950; CC P08603; P02769: ALB; Xeno; NbExp=10; IntAct=EBI-1223708, EBI-2296927; CC P08603; P16946: ennX; Xeno; NbExp=2; IntAct=EBI-1223708, EBI-6403567; CC P08603; Q9JXV4: fhbP; Xeno; NbExp=6; IntAct=EBI-1223708, EBI-15758684; CC P08603; P13605: FMOD; Xeno; NbExp=4; IntAct=EBI-1223708, EBI-5281124; CC P08603; A0A024A2C9: lph; Xeno; NbExp=6; IntAct=EBI-1223708, EBI-12498321; CC P08603; Q932F7: sdrE; Xeno; NbExp=4; IntAct=EBI-1223708, EBI-26369465; CC P08603-1; P02741: CRP; NbExp=3; IntAct=EBI-22027829, EBI-1395983; CC P08603-2; P02741: CRP; NbExp=8; IntAct=EBI-12684810, EBI-1395983; CC P08603-2; P26022: PTX3; NbExp=2; IntAct=EBI-12684810, EBI-11574553; CC P08603-2; PRO_0000023545 [P26022]: PTX3; NbExp=2; IntAct=EBI-12684810, EBI-22114950; CC PRO_0000005894; P02741: CRP; NbExp=5; IntAct=EBI-22114230, EBI-1395983; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- SUBCELLULAR LOCATION: Note=(Microbial infection) In the mosquito CC midgut, localizes to P.falciparum (NF54 strain) macrogamete and young CC zygote cell membranes. {ECO:0000269|PubMed:23332154}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P08603-1; Sequence=Displayed; CC Name=2; Synonyms=FHL-1; CC IsoId=P08603-2; Sequence=VSP_001190, VSP_001191; CC -!- TISSUE SPECIFICITY: Expressed in the retinal pigment epithelium (at CC protein level) (PubMed:25136834). CFH is one of the most abundant CC complement components in blood where the liver is the major source of CC CFH protein in vivo. in addition, CFH is secreted by additional cell CC types including monocytes, fibroblasts, or endothelial cells CC (PubMed:2139673, PubMed:25136834, PubMed:2968404, PubMed:6444659). CC {ECO:0000269|PubMed:2139673, ECO:0000269|PubMed:25136834, CC ECO:0000269|PubMed:2968404, ECO:0000269|PubMed:6444659}. CC -!- DOMAIN: Sushi 1-3 domain represents the minimal unit capable of CC cofactor activity (PubMed:18252712). The property to discriminate self CC surfaces from non-self surfaces depends on the C-terminal region made CC of Sushis 19-20 (PubMed:21285368). {ECO:0000269|PubMed:18252712, CC ECO:0000269|PubMed:21285368}. CC -!- PTM: Sulfated on tyrosine residues. {ECO:0000269|PubMed:25136834}. CC -!- PTM: According to a report, Asn-217 is not glycosylated CC (PubMed:17591618). Another study observed glycosylation at this CC position (PubMed:19139490). {ECO:0000305|PubMed:17591618, CC ECO:0000305|PubMed:19139490}. CC -!- DISEASE: Basal laminar drusen (BLD) [MIM:126700]: Drusen are CC extracellular deposits that accumulate below the retinal pigment CC epithelium on Bruch membrane. Basal laminar drusen refers to an early CC adult-onset drusen phenotype that shows a pattern of uniform small, CC slightly raised yellow subretinal nodules randomly scattered in the CC macula. In later stages, these drusen often become more numerous, with CC clustered groups of drusen scattered throughout the retina. In time CC these small basal laminar drusen may expand and ultimately lead to a CC serous pigment epithelial detachment of the macula that may result in CC vision loss. {ECO:0000269|PubMed:18252232}. Note=The gene represented CC in this entry is involved in disease pathogenesis. CC -!- DISEASE: Complement factor H deficiency (CFHD) [MIM:609814]: A disorder CC that can manifest as several different phenotypes, including CC asymptomatic, recurrent bacterial infections, and renal failure. CC Laboratory features usually include decreased serum levels of factor H, CC complement component C3, and a decrease in other terminal complement CC components, indicating activation of the alternative complement CC pathway. It is associated with a number of renal diseases with variable CC clinical presentation and progression, including membranoproliferative CC glomerulonephritis and atypical hemolytic uremic syndrome. CC {ECO:0000269|PubMed:10803850, ECO:0000269|PubMed:11158219, CC ECO:0000269|PubMed:11170895, ECO:0000269|PubMed:11170896, CC ECO:0000269|PubMed:12020532, ECO:0000269|PubMed:14978182, CC ECO:0000269|PubMed:16612335, ECO:0000269|PubMed:9312129}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Hemolytic uremic syndrome, atypical, 1 (AHUS1) [MIM:235400]: 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:10577907, ECO:0000269|PubMed:10762557, CC ECO:0000269|PubMed:11851332, ECO:0000269|PubMed:12960213, CC ECO:0000269|PubMed:14583443, ECO:0000269|PubMed:14978182, CC ECO:0000269|PubMed:16601698, ECO:0000269|PubMed:20513133, CC ECO:0000269|PubMed:9551389}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. Other genes CC may play a role in modifying the phenotype. CC -!- DISEASE: Macular degeneration, age-related, 4 (ARMD4) [MIM:610698]: 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:22019782}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=CAB41739.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=CFHbase; Note=CFH mutation db; CC URL="https://databases.lovd.nl/shared/genes/CFH"; 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; Y00716; CAA68704.1; -; mRNA. DR EMBL; DQ233256; ABB02180.1; -; Genomic_DNA. DR EMBL; AL049744; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC037285; AAH37285.1; -; mRNA. DR EMBL; BC110643; AAI10644.1; -; mRNA. DR EMBL; BC142699; AAI42700.1; -; mRNA. DR EMBL; X04697; CAB41739.1; ALT_FRAME; mRNA. DR EMBL; X07523; CAA30403.1; -; mRNA. DR EMBL; M12383; AAA52013.1; -; mRNA. DR EMBL; M65294; AAA35948.1; -; mRNA. DR EMBL; U56979; AAB01987.1; -; Genomic_DNA. DR EMBL; Z29665; CAA82763.1; -; Genomic_DNA. DR CCDS; CCDS1385.1; -. [P08603-1] DR CCDS; CCDS53452.1; -. [P08603-2] DR PIR; S00254; NBHUH. DR PIR; S03013; NBHUHS. DR RefSeq; NP_000177.2; NM_000186.4. DR PDB; 1HAQ; X-ray; -; A=19-1231. DR PDB; 1HCC; NMR; -; A=927-985. DR PDB; 1HFH; NMR; -; A=866-985. DR PDB; 1HFI; NMR; -; A=866-927. DR PDB; 2BZM; NMR; -; A=1107-1231. DR PDB; 2G7I; X-ray; 1.75 A; A=1107-1231. DR PDB; 2IC4; X-ray; -; A=321-506. DR PDB; 2JGW; NMR; -; A=386-446. DR PDB; 2JGX; NMR; -; A=386-446. DR PDB; 2KMS; NMR; -; A=690-804. DR PDB; 2QFG; X-ray; -; A=19-322. DR PDB; 2QFH; X-ray; -; A=928-1231. DR PDB; 2RLP; NMR; -; A=20-142. DR PDB; 2RLQ; NMR; -; A=84-206. DR PDB; 2UWN; X-ray; 2.35 A; A=322-506. DR PDB; 2V8E; X-ray; 2.50 A; A=322-506. DR PDB; 2W80; X-ray; 2.35 A; A/B/E/G=321-443. DR PDB; 2W81; X-ray; 2.35 A; A/B/E=321-443. DR PDB; 2WII; X-ray; 2.70 A; C=18-264. DR PDB; 2XQW; X-ray; 2.31 A; C=1103-1231. DR PDB; 3GAU; X-ray; -; A=19-1231. DR PDB; 3GAV; X-ray; -; A=19-1231. DR PDB; 3GAW; X-ray; -; A=19-1231. DR PDB; 3KXV; X-ray; 2.00 A; A=1103-1231. DR PDB; 3KZJ; X-ray; 1.65 A; A=1103-1231. DR PDB; 3OXU; X-ray; 2.10 A; D/E/F=1107-1231. DR PDB; 3R62; X-ray; 1.52 A; A/B=1107-1231. DR PDB; 3RJ3; X-ray; 2.35 A; D/E/F=1107-1231. DR PDB; 3SW0; X-ray; 1.80 A; X=1046-1231. DR PDB; 4AYD; X-ray; 2.40 A; A/B/E=321-443. DR PDB; 4AYE; X-ray; 2.80 A; A/B/E=321-443. DR PDB; 4AYI; X-ray; 2.31 A; A/E=321-443. DR PDB; 4AYM; X-ray; 3.00 A; A/B/E/F=321-443. DR PDB; 4B2R; NMR; -; A=566-687. DR PDB; 4B2S; NMR; -; A=627-747. DR PDB; 4J38; X-ray; 2.83 A; B=1103-1231. DR PDB; 4K12; X-ray; 1.08 A; A=508-567. DR PDB; 4ONT; X-ray; 2.15 A; D/E/F=1107-1231. DR PDB; 4ZH1; X-ray; 2.24 A; D/E/F=1107-1231. DR PDB; 5NBQ; X-ray; 3.18 A; D/E/F=1104-1230. DR PDB; 5O32; X-ray; 4.21 A; C/G=19-264, C/G=387-1107. DR PDB; 5O35; X-ray; 4.20 A; C=19-264, C=388-1107. DR PDB; 5WTB; X-ray; 3.30 A; E/F/G/H=1206-1226. DR PDB; 6ATG; X-ray; 1.80 A; A/D=388-446. DR PDB; 6ZH1; X-ray; 2.20 A; B=1104-1231. DR PDB; 7WKI; X-ray; 2.60 A; A=1046-1231. DR PDB; 7ZJM; X-ray; 2.59 A; B=321-444. DR PDB; 9F7I; X-ray; 2.85 A; B=321-444. DR PDB; 9MLU; X-ray; 1.82 A; A/B=321-443. DR PDB; 9MMU; X-ray; 2.25 A; C/D/G/H=321-443. DR PDB; 9MMX; X-ray; 1.90 A; A/B=321-443. DR AlphaFoldDB; P08603; -. DR MDposit; P08603; -. DR SASBDB; P08603; -. DR SMR; P08603; -. DR BioGRID; 109324; 144. DR ComplexPortal; CPX-6163; Complement factor H complex. DR ComplexPortal; CPX-6164; Complement factor I-H-C3b complex. DR DIP; DIP-38303N; -. DR FunCoup; P08603; 161. DR IntAct; P08603; 49. DR NDEx; IQUERY-CP-CFH; 5 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000356399; -. DR BindingDB; P08603; -. DR ChEMBL; CHEMBL4629; -. DR DrugBank; DB09130; Copper. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR TCDB; 9.B.278.1.7; the organellar-targeting adaptor protein complex (o-apc) family. DR CarbonylDB; P08603; -. DR GlyConnect; P08603; 49 N-Linked glycans (9 sites). DR GlyCosmos; P08603; 11 sites, 140 glycans. DR GlyGen; P08603; 11 sites, 139 N-linked glycans (9 sites), 1 O-linked glycan (1 site). DR iPTMnet; P08603; -. DR PhosphoSitePlus; P08603; -. DR SwissPalm; P08603; -. DR BioMuta; CFH; -. DR DMDM; 158517847; -. DR CPTAC; non-CPTAC-2658; -. DR jPOST; P08603; -. DR MassIVE; P08603; -. DR PaxDb; 9606-ENSP00000356399; -. DR PeptideAtlas; P08603; -. DR ProteomicsDB; 52135; -. [P08603-1] DR ProteomicsDB; 52136; -. [P08603-2] DR Pumba; P08603; -. DR ABCD; P08603; 12 sequenced antibodies. DR Antibodypedia; 3393; 1035 antibodies from 53 providers. DR DNASU; 3075; -. DR Ensembl; ENST00000367429.9; ENSP00000356399.4; ENSG00000000971.18. DR GeneID; 3075; -. DR KEGG; hsa:3075; -. DR MANE-Select; ENST00000367429.9; ENSP00000356399.4; NM_000186.4; NP_000177.2. DR UCSC; uc001gtj.4; human. [P08603-1] DR AGR; HGNC:4883; -. DR ClinPGx; PA29261; -. DR CTD; 3075; -. DR DisGeNET; 3075; -. DR GeneCards; CFH; -. DR GeneReviews; CFH; -. DR HGNC; HGNC:4883; CFH. DR HPA; ENSG00000000971; Tissue enriched (liver). DR MalaCards; CFH; -. DR MIM; 126700; phenotype. DR MIM; 134370; gene. DR MIM; 235400; phenotype. DR MIM; 609814; phenotype. DR MIM; 610698; phenotype. DR OpenTargets; ENSG00000000971; -. DR Orphanet; 544472; Atypical hemolytic uremic syndrome with complement gene abnormality. DR Orphanet; 75376; Autosomal dominant drusen. DR Orphanet; 329931; C3 glomerulonephritis. DR Orphanet; 244275; De novo thrombotic microangiopathy after kidney transplantation. DR Orphanet; 93571; Dense deposit disease. DR Orphanet; 244242; HELLP syndrome. DR Orphanet; 200421; Immunodeficiency with factor H anomaly. DR VEuPathDB; HostDB:ENSG00000000971; -. DR eggNOG; ENOG502QVSB; Eukaryota. DR GeneTree; ENSGT00940000163274; -. DR HOGENOM; CLU_003511_0_0_1; -. DR InParanoid; P08603; -. DR OMA; AASRKYH; -. DR OrthoDB; 10051774at2759; -. DR PAN-GO; P08603; 3 GO annotations based on evolutionary models. DR PhylomeDB; P08603; -. DR PathwayCommons; P08603; -. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR SignaLink; P08603; -. DR SIGNOR; P08603; -. DR Agora; ENSG00000000971; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 3075; 9 hits in 1153 CRISPR screens. DR ChiTaRS; CFH; human. DR EvolutionaryTrace; P08603; -. DR GeneWiki; Factor_H; -. DR GenomeRNAi; 3075; -. DR Pharos; P08603; Tbio. DR PRO; PR:P08603; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P08603; protein. DR Bgee; ENSG00000000971; Expressed in urethra and 190 other cell types or tissues. DR ExpressionAtlas; P08603; baseline and differential. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IBA:GO_Central. DR GO; GO:1905370; C:serine-type endopeptidase complex; IPI:ComplexPortal. DR GO; GO:0106139; C:symbiont cell surface; IDA:UniProtKB. DR GO; GO:0001851; F:complement component C3b binding; IBA:GO_Central. DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IDA:BHF-UCL. DR GO; GO:0008201; F:heparin binding; IDA:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0022010; P:central nervous system myelination; IDA:MGI. DR GO; GO:0006956; P:complement activation; IDA:AgBase. DR GO; GO:0006957; P:complement activation, alternative pathway; IDA:MGI. DR GO; GO:0006954; P:inflammatory response; IDA:MGI. DR GO; GO:0006508; P:proteolysis; IDA:ComplexPortal. DR GO; GO:0030449; P:regulation of complement activation; IDA:MGI. DR GO; GO:0030451; P:regulation of complement activation, alternative pathway; IDA:ComplexPortal. DR GO; GO:1903659; P:regulation of complement-dependent cytotoxicity; IDA:MGI. DR CDD; cd00033; CCP; 16. DR FunFam; 2.10.70.10:FF:000041; Complement factor H; 5. DR FunFam; 2.10.70.10:FF:000130; Complement factor H; 1. DR FunFam; 2.10.70.10:FF:000026; Complement inhibitory factor H; 7. DR FunFam; 2.10.70.10:FF:000054; Complement inhibitory factor H; 1. DR FunFam; 2.10.70.10:FF:000060; Complement inhibitory factor H; 1. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 20. DR InterPro; IPR051503; ComplSys_Reg/VirEntry_Med. DR InterPro; IPR035976; Sushi/SCR/CCP_sf. DR InterPro; IPR000436; Sushi_SCR_CCP_dom. DR PANTHER; PTHR45785:SF7; COMPLEMENT FACTOR H; 1. DR PANTHER; PTHR45785; COMPLEMENT FACTOR H-RELATED; 1. DR Pfam; PF00084; Sushi; 19. DR SMART; SM00032; CCP; 20. DR SUPFAM; SSF57535; Complement control module/SCR domain; 18. DR PROSITE; PS50923; SUSHI; 19. PE 1: Evidence at protein level; KW 3D-structure; Age-related macular degeneration; Alternative splicing; KW Complement alternate pathway; Direct protein sequencing; Disease variant; KW Disulfide bond; Glycoprotein; Hemolytic uremic syndrome; KW Host-virus interaction; Immunity; Innate immunity; KW Proteomics identification; Reference proteome; Repeat; Secreted; Signal; KW Sulfation; Sushi. FT SIGNAL 1..18 FT /evidence="ECO:0000269|PubMed:6215918" FT CHAIN 19..1231 FT /note="Complement factor H" FT /id="PRO_0000005894" FT DOMAIN 19..82 FT /note="Sushi 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 83..143 FT /note="Sushi 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 144..207 FT /note="Sushi 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 208..264 FT /note="Sushi 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 265..322 FT /note="Sushi 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 324..386 FT /note="Sushi 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 387..444 FT /note="Sushi 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 446..507 FT /note="Sushi 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 515..566 FT /note="Sushi 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 567..625 FT /note="Sushi 10" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 628..686 FT /note="Sushi 11" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 689..746 FT /note="Sushi 12" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 751..805 FT /note="Sushi 13" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 809..866 FT /note="Sushi 14" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 868..928 FT /note="Sushi 15" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 929..986 FT /note="Sushi 16" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 987..1045 FT /note="Sushi 17" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 1046..1104 FT /note="Sushi 18" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 1107..1165 FT /note="Sushi 19" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 1170..1230 FT /note="Sushi 20" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT CARBOHYD 217 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:19139490" FT CARBOHYD 529 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:17591618, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:2963625" FT CARBOHYD 718 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17591618" FT CARBOHYD 802 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17591618, FT ECO:0000269|PubMed:19159218" FT CARBOHYD 822 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17591618" FT CARBOHYD 882 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:17591618, ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169" FT CARBOHYD 911 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:17591618, ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218" FT CARBOHYD 1029 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:17591618, FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218" FT CARBOHYD 1095 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17591618" FT DISULFID 21..66 FT /evidence="ECO:0000269|PubMed:18252712, FT ECO:0000269|PubMed:19503104, ECO:0000269|PubMed:28671664" FT DISULFID 52..80 FT /evidence="ECO:0000269|PubMed:18252712, FT ECO:0000269|PubMed:19503104, ECO:0000269|PubMed:28671664" FT DISULFID 85..129 FT /evidence="ECO:0000269|PubMed:18252712, FT ECO:0000269|PubMed:19503104, ECO:0000269|PubMed:28671664" FT DISULFID 114..141 FT /evidence="ECO:0000269|PubMed:18252712, FT ECO:0000269|PubMed:19503104, ECO:0000269|PubMed:28671664" FT DISULFID 146..192 FT /evidence="ECO:0000269|PubMed:19503104, FT ECO:0000269|PubMed:28671664" FT DISULFID 178..205 FT /evidence="ECO:0000269|PubMed:19503104, FT ECO:0000269|PubMed:28671664" FT DISULFID 210..251 FT /evidence="ECO:0000269|PubMed:19503104, FT ECO:0000269|PubMed:28671664" FT DISULFID 237..262 FT /evidence="ECO:0000269|PubMed:19503104, FT ECO:0000269|PubMed:28671664" FT DISULFID 267..309 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 294..320 FT /evidence="ECO:0000269|PubMed:28671664" FT DISULFID 325..374 FT /evidence="ECO:0000269|PubMed:17893204, FT ECO:0000269|PubMed:19225461, ECO:0000269|PubMed:23133374, FT ECO:0000269|PubMed:28671664" FT DISULFID 357..385 FT /evidence="ECO:0000269|PubMed:17893204, FT ECO:0000269|PubMed:19225461, ECO:0000269|PubMed:23133374, FT ECO:0000269|PubMed:28671664" FT DISULFID 389..431 FT /evidence="ECO:0000269|PubMed:17360715, FT ECO:0000269|PubMed:17893204, ECO:0000269|PubMed:19225461, FT ECO:0000269|PubMed:23133374" FT DISULFID 416..442 FT /evidence="ECO:0000269|PubMed:17360715, FT ECO:0000269|PubMed:17893204, ECO:0000269|PubMed:19225461, FT ECO:0000269|PubMed:23133374" FT DISULFID 448..494 FT /evidence="ECO:0000269|PubMed:17893204" FT DISULFID 477..505 FT /evidence="ECO:0000269|PubMed:17893204" FT DISULFID 509..553 FT /evidence="ECO:0000269|PubMed:25330773" FT DISULFID 536..564 FT /evidence="ECO:0000269|PubMed:25330773" FT DISULFID 569..611 FT /evidence="ECO:0000269|PubMed:23017427" FT DISULFID 597..623 FT /evidence="ECO:0000269|PubMed:23017427" FT DISULFID 630..673 FT /evidence="ECO:0000269|PubMed:23017427" FT DISULFID 659..684 FT /evidence="ECO:0000269|PubMed:23017427" FT DISULFID 691..733 FT /evidence="ECO:0000269|PubMed:19835885, FT ECO:0000269|PubMed:23017427" FT DISULFID 719..744 FT /evidence="ECO:0000269|PubMed:19835885, FT ECO:0000269|PubMed:23017427" FT DISULFID 753..792 FT /evidence="ECO:0000269|PubMed:19835885" FT DISULFID 781..803 FT /evidence="ECO:0000269|PubMed:19835885" FT DISULFID 811..853 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 839..864 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 870..915 FT /evidence="ECO:0000269|PubMed:8331663" FT DISULFID 901..926 FT /evidence="ECO:0000269|PubMed:8331663" FT DISULFID 931..973 FT /evidence="ECO:0000269|PubMed:1829116, FT ECO:0000269|PubMed:8331663" FT DISULFID 959..984 FT /evidence="ECO:0000269|PubMed:1829116, FT ECO:0000269|PubMed:8331663" FT DISULFID 989..1032 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1018..1043 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1048..1091 FT /evidence="ECO:0000269|PubMed:22389686" FT DISULFID 1077..1102 FT /evidence="ECO:0000269|PubMed:22389686" FT DISULFID 1109..1152 FT /evidence="ECO:0000269|PubMed:16601698, FT ECO:0000269|PubMed:20378178, ECO:0000269|PubMed:21285368, FT ECO:0000269|PubMed:22389686, ECO:0000269|PubMed:23658013, FT ECO:0000269|PubMed:25402769, ECO:0000269|PubMed:29190743" FT DISULFID 1138..1163 FT /evidence="ECO:0000269|PubMed:16601698, FT ECO:0000269|PubMed:20378178, ECO:0000269|PubMed:21285368, FT ECO:0000269|PubMed:22389686, ECO:0000269|PubMed:23658013, FT ECO:0000269|PubMed:25402769, ECO:0000269|PubMed:29190743" FT DISULFID 1167..1218 FT /evidence="ECO:0000269|PubMed:16601698, FT ECO:0000269|PubMed:20378178, ECO:0000269|PubMed:21285368, FT ECO:0000269|PubMed:22389686, ECO:0000269|PubMed:23658013, FT ECO:0000269|PubMed:25402769, ECO:0000269|PubMed:29190743" FT DISULFID 1201..1228 FT /evidence="ECO:0000269|PubMed:16601698, FT ECO:0000269|PubMed:20378178, ECO:0000269|PubMed:21285368, FT ECO:0000269|PubMed:22389686, ECO:0000269|PubMed:23658013, FT ECO:0000269|PubMed:25402769, ECO:0000269|PubMed:29190743" FT VAR_SEQ 446..449 FT /note="KTCS -> SFTL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:2963625" FT /id="VSP_001190" FT VAR_SEQ 450..1231 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:2963625" FT /id="VSP_001191" FT VARIANT 62 FT /note="V -> I (confirmed at protein level; dbSNP:rs800292)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15870199, ECO:0000269|PubMed:22028381, FT ECO:0000269|Ref.2" FT /id="VAR_023836" FT VARIANT 78 FT /note="R -> G (in AHUS1)" FT /evidence="ECO:0000269|PubMed:14583443" FT /id="VAR_025864" FT VARIANT 127 FT /note="R -> L (in CFHD; with membranoproliferative FT glomerulonephritis; dbSNP:rs121913058)" FT /evidence="ECO:0000269|PubMed:14978182" FT /id="VAR_031978" FT VARIANT 224 FT /note="Missing (in CFHD; with membranoproliferative FT glomerulonephritis; affects binding of factor H to C3b and FT shows defective complement regulation)" FT /evidence="ECO:0000269|PubMed:16612335" FT /id="VAR_031979" FT VARIANT 325 FT /note="C -> Y (in AHUS1)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063648" FT VARIANT 400 FT /note="Q -> K (in AHUS1; dbSNP:rs201671665)" FT /evidence="ECO:0000269|PubMed:14978182" FT /id="VAR_031980" FT VARIANT 402 FT /note="Y -> H (associated with ARMD4; dbSNP:rs1061170)" FT /evidence="ECO:0000269|PubMed:15870199, FT ECO:0000269|PubMed:15895326, ECO:0000269|PubMed:16710414, FT ECO:0000269|PubMed:18252232, ECO:0000269|PubMed:2963625" FT /id="VAR_001979" FT VARIANT 431 FT /note="C -> S (in CFHD; with membranoproliferative FT glomerulonephritis; dbSNP:rs121913056)" FT /evidence="ECO:0000269|PubMed:14978182" FT /id="VAR_031981" FT VARIANT 493 FT /note="T -> R (in dbSNP:rs1061171)" FT /evidence="ECO:0000269|PubMed:2963625" FT /id="VAR_043892" FT VARIANT 536 FT /note="C -> R (in CFHD; dbSNP:rs121913052)" FT /evidence="ECO:0000269|PubMed:9312129" FT /id="VAR_019405" FT VARIANT 551 FT /note="I -> T (in dbSNP:rs35453854)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025092" FT VARIANT 567 FT /note="R -> G (associated with basal laminar drusen; FT dbSNP:rs757756991)" FT /evidence="ECO:0000269|PubMed:18252232" FT /id="VAR_043893" FT VARIANT 609 FT /note="V -> I (in AHUS1; dbSNP:rs148165372)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063649" FT VARIANT 630 FT /note="C -> W (in AHUS1)" FT /evidence="ECO:0000269|PubMed:12960213" FT /id="VAR_025865" FT VARIANT 673 FT /note="C -> S (in CFHD; with membranoproliferative FT glomerulonephritis)" FT /evidence="ECO:0000269|PubMed:14978182" FT /id="VAR_031982" FT VARIANT 673 FT /note="C -> Y (in AHUS1; dbSNP:rs1391815797)" FT /evidence="ECO:0000269|PubMed:14978182" FT /id="VAR_031983" FT VARIANT 850 FT /note="E -> K (in AHUS1; variant confirmed at protein FT level; dbSNP:rs762443267)" FT /evidence="ECO:0000269|PubMed:12960213, FT ECO:0000269|PubMed:22028381" FT /id="VAR_025866" FT VARIANT 890 FT /note="S -> I (in dbSNP:rs515299)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025093" FT VARIANT 893 FT /note="H -> R (in AHUS1; dbSNP:rs1573076722)" FT /evidence="ECO:0000269|PubMed:14978182" FT /id="VAR_031984" FT VARIANT 915 FT /note="C -> S (in AHUS1)" FT /evidence="ECO:0000269|PubMed:14978182" FT /id="VAR_031985" FT VARIANT 936 FT /note="E -> D (associated with hemolytic uremic syndrome FT and basal laminar drusen; dbSNP:rs1065489)" FT /evidence="ECO:0000269|PubMed:14583443, FT ECO:0000269|PubMed:18252232, ECO:0000269|PubMed:20513133, FT ECO:0000269|Ref.2" FT /id="VAR_020261" FT VARIANT 950 FT /note="Q -> H (in AHUS1; dbSNP:rs149474608)" FT /evidence="ECO:0000269|PubMed:14583443" FT /id="VAR_025867" FT VARIANT 951 FT /note="Y -> H (in AHUS1; dbSNP:rs777049051)" FT /evidence="ECO:0000269|PubMed:14583443" FT /id="VAR_025868" FT VARIANT 956 FT /note="T -> M (in AHUS1; dbSNP:rs145975787)" FT /evidence="ECO:0000269|PubMed:11170895, FT ECO:0000269|PubMed:11851332" FT /id="VAR_025869" FT VARIANT 959 FT /note="C -> Y (in CFHD; variant confirmed at protein level; FT dbSNP:rs121913053)" FT /evidence="ECO:0000269|PubMed:22028381, FT ECO:0000269|PubMed:9312129" FT /id="VAR_019406" FT VARIANT 978 FT /note="W -> C (in AHUS1)" FT /evidence="ECO:0000269|PubMed:12960213" FT /id="VAR_025870" FT VARIANT 997 FT /note="N -> T (in dbSNP:rs17575212)" FT /id="VAR_055683" FT VARIANT 1007 FT /note="V -> I" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025094" FT VARIANT 1007 FT /note="V -> L (in dbSNP:rs534399)" FT /id="VAR_043894" FT VARIANT 1010 FT /note="A -> T (in dbSNP:rs11539862)" FT /id="VAR_055684" FT VARIANT 1017 FT /note="T -> I (in dbSNP:rs34362004)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025095" FT VARIANT 1021 FT /note="Y -> F (in AHUS1)" FT /evidence="ECO:0000269|PubMed:12960213" FT /id="VAR_025871" FT VARIANT 1043 FT /note="C -> R (in AHUS1)" FT /evidence="ECO:0000269|PubMed:12960213" FT /id="VAR_025872" FT VARIANT 1050 FT /note="N -> Y (associated with basal laminar drusen; FT dbSNP:rs35274867)" FT /evidence="ECO:0000269|PubMed:18252232, ECO:0000269|Ref.2" FT /id="VAR_025096" FT VARIANT 1059 FT /note="I -> T (in dbSNP:rs35343172)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025097" FT VARIANT 1076 FT /note="Q -> E (in CFHD; dbSNP:rs62625015)" FT /evidence="ECO:0000269|PubMed:11170896, FT ECO:0000269|PubMed:11851332" FT /id="VAR_025873" FT VARIANT 1078 FT /note="R -> S (associated with basal laminar drusen; FT dbSNP:rs121913062)" FT /evidence="ECO:0000269|PubMed:18252232" FT /id="VAR_043895" FT VARIANT 1119 FT /note="D -> G (in CFHD; dbSNP:rs575109631)" FT /evidence="ECO:0000269|PubMed:11170896, FT ECO:0000269|PubMed:11851332" FT /id="VAR_025874" FT VARIANT 1134 FT /note="V -> G (in AHUS1)" FT /evidence="ECO:0000269|PubMed:12960213" FT /id="VAR_025875" FT VARIANT 1142 FT /note="Y -> D (in AHUS1)" FT /evidence="ECO:0000269|PubMed:12960213" FT /id="VAR_025876" FT VARIANT 1143 FT /note="Q -> E (confirmed at protein level; dbSNP:rs15809)" FT /evidence="ECO:0000269|PubMed:22028381" FT /id="VAR_043896" FT VARIANT 1157 FT /note="W -> R (in AHUS1)" FT /evidence="ECO:0000269|PubMed:12960213" FT /id="VAR_025877" FT VARIANT 1163 FT /note="C -> W (in AHUS1)" FT /evidence="ECO:0000269|PubMed:14583443" FT /id="VAR_025878" FT VARIANT 1169 FT /note="I -> L (in AHUS1)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063650" FT VARIANT 1183 FT /note="W -> C (in AHUS1)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063651" FT VARIANT 1183 FT /note="W -> L (in AHUS1; about 40% loss of C3b binding)" FT /evidence="ECO:0000269|PubMed:11170895, FT ECO:0000269|PubMed:11851332, ECO:0000269|PubMed:14978182, FT ECO:0000269|PubMed:16601698" FT /id="VAR_025879" FT VARIANT 1183 FT /note="W -> R (in AHUS1)" FT /evidence="ECO:0000269|PubMed:12020532, FT ECO:0000269|PubMed:12960213" FT /id="VAR_025880" FT VARIANT 1184 FT /note="T -> R (in CFHD)" FT /evidence="ECO:0000269|PubMed:11170896, FT ECO:0000269|PubMed:11851332" FT /id="VAR_025881" FT VARIANT 1189 FT /note="L -> R (in AHUS1; dbSNP:rs121913055)" FT /evidence="ECO:0000269|PubMed:11170895, FT ECO:0000269|PubMed:11851332" FT /id="VAR_019407" FT VARIANT 1191 FT /note="S -> L (in AHUS1; dbSNP:rs460897)" FT /evidence="ECO:0000269|PubMed:10577907, FT ECO:0000269|PubMed:11851332" FT /id="VAR_019408" FT VARIANT 1194 FT /note="G -> D (in AHUS1; dbSNP:rs761877050)" FT /evidence="ECO:0000269|PubMed:11851332" FT /id="VAR_025882" FT VARIANT 1197 FT /note="V -> A (in AHUS1; dbSNP:rs460184)" FT /evidence="ECO:0000269|PubMed:11170895, FT ECO:0000269|PubMed:11851332" FT /id="VAR_025883" FT VARIANT 1198 FT /note="E -> A (in AHUS1; about 30% loss of C3b binding)" FT /evidence="ECO:0000269|PubMed:14583443, FT ECO:0000269|PubMed:16601698" FT /id="VAR_025884" FT VARIANT 1199 FT /note="F -> S (in AHUS1)" FT /evidence="ECO:0000269|PubMed:14978182" FT /id="VAR_031986" FT VARIANT 1210 FT /note="R -> C (in CFHD and ARMD4; rare penetrant mutation FT that confers high risk of age-related macular degeneration; FT dbSNP:rs121913059)" FT /evidence="ECO:0000269|PubMed:11158219, FT ECO:0000269|PubMed:11851332, ECO:0000269|PubMed:22019782" FT /id="VAR_025885" FT VARIANT 1215 FT /note="R -> G (in AHUS1; dbSNP:rs121913051)" FT /evidence="ECO:0000269|PubMed:11851332, FT ECO:0000269|PubMed:9551389" FT /id="VAR_025886" FT VARIANT 1215 FT /note="R -> Q (in CFHD)" FT /evidence="ECO:0000269|PubMed:11158219, FT ECO:0000269|PubMed:11851332" FT /id="VAR_025887" FT VARIANT 1225..1231 FT /note="YPTCAKR -> FQS (in AHUS1)" FT /evidence="ECO:0000269|PubMed:10762557" FT /id="VAR_019409" FT VARIANT 1226 FT /note="P -> S (in AHUS1; atypical)" FT /evidence="ECO:0000269|PubMed:12960213" FT /id="VAR_025888" FT MUTAGEN 337 FT /note="H->A: About 10% loss of heparin-binding." FT /evidence="ECO:0000269|PubMed:17893204" FT MUTAGEN 341 FT /note="R->A: About 20% loss of heparin-binding." FT /evidence="ECO:0000269|PubMed:17893204" FT MUTAGEN 1182 FT /note="R->A: About 50% loss of C3b binding." FT /evidence="ECO:0000269|PubMed:16601698" FT MUTAGEN 1186 FT /note="K->A: About 20% loss of C3b binding." FT /evidence="ECO:0000269|PubMed:16601698" FT MUTAGEN 1188 FT /note="K->A: About 50% loss of C3b binding." FT /evidence="ECO:0000269|PubMed:16601698" FT CONFLICT 21 FT /note="C -> Q (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 30 FT /note="T -> V (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 34 FT /note="T -> Q (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 53..54 FT /note="RP -> IL (in Ref. 5; CAB41739)" FT /evidence="ECO:0000305" FT STRAND 21..23 FT /evidence="ECO:0007829|PDB:2RLP" FT STRAND 29..33 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 47..52 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 62..66 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 68..74 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 94..105 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 109..114 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 118..123 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 126..129 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 131..134 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 140..143 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 155..158 FT /evidence="ECO:0007829|PDB:2RLQ" FT STRAND 159..162 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 172..175 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 182..186 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 188..192 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 196..200 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 204..207 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 218..222 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 232..237 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 241..245 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 247..252 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 255..258 FT /evidence="ECO:0007829|PDB:2WII" FT STRAND 262..264 FT /evidence="ECO:0007829|PDB:2WII" FT HELIX 326..329 FT /evidence="ECO:0007829|PDB:2W81" FT STRAND 333..337 FT /evidence="ECO:0007829|PDB:9MLU" FT HELIX 338..341 FT /evidence="ECO:0007829|PDB:9MLU" FT HELIX 342..344 FT /evidence="ECO:0007829|PDB:9MLU" FT STRAND 352..357 FT /evidence="ECO:0007829|PDB:9MLU" FT STRAND 366..375 FT /evidence="ECO:0007829|PDB:9MLU" FT STRAND 378..383 FT /evidence="ECO:0007829|PDB:9MLU" FT STRAND 385..390 FT /evidence="ECO:0007829|PDB:9MLU" FT TURN 400..403 FT /evidence="ECO:0007829|PDB:6ATG" FT STRAND 405..407 FT /evidence="ECO:0007829|PDB:9MLU" FT STRAND 411..413 FT /evidence="ECO:0007829|PDB:6ATG" FT STRAND 415..417 FT /evidence="ECO:0007829|PDB:2JGW" FT STRAND 420..422 FT /evidence="ECO:0007829|PDB:2JGW" FT HELIX 423..425 FT /evidence="ECO:0007829|PDB:6ATG" FT STRAND 428..432 FT /evidence="ECO:0007829|PDB:6ATG" FT STRAND 435..438 FT /evidence="ECO:0007829|PDB:6ATG" FT STRAND 447..449 FT /evidence="ECO:0007829|PDB:2UWN" FT HELIX 450..452 FT /evidence="ECO:0007829|PDB:2UWN" FT STRAND 456..459 FT /evidence="ECO:0007829|PDB:2UWN" FT STRAND 465..468 FT /evidence="ECO:0007829|PDB:2UWN" FT STRAND 472..477 FT /evidence="ECO:0007829|PDB:2UWN" FT STRAND 484..486 FT /evidence="ECO:0007829|PDB:2UWN" FT STRAND 488..495 FT /evidence="ECO:0007829|PDB:2UWN" FT STRAND 498..500 FT /evidence="ECO:0007829|PDB:2UWN" FT STRAND 508..510 FT /evidence="ECO:0007829|PDB:4K12" FT HELIX 511..514 FT /evidence="ECO:0007829|PDB:4K12" FT STRAND 515..518 FT /evidence="ECO:0007829|PDB:4K12" FT STRAND 524..527 FT /evidence="ECO:0007829|PDB:4K12" FT STRAND 531..536 FT /evidence="ECO:0007829|PDB:4K12" FT STRAND 547..554 FT /evidence="ECO:0007829|PDB:4K12" FT STRAND 557..560 FT /evidence="ECO:0007829|PDB:4K12" FT STRAND 578..582 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 585..587 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 592..597 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 602..605 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 607..613 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 615..618 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 622..625 FT /evidence="ECO:0007829|PDB:4B2R" FT HELIX 633..636 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 637..641 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 654..659 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 663..665 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 669..674 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 675..678 FT /evidence="ECO:0007829|PDB:4B2S" FT STRAND 684..686 FT /evidence="ECO:0007829|PDB:4B2R" FT STRAND 700..703 FT /evidence="ECO:0007829|PDB:2KMS" FT STRAND 714..718 FT /evidence="ECO:0007829|PDB:2KMS" FT STRAND 723..727 FT /evidence="ECO:0007829|PDB:4B2S" FT STRAND 729..732 FT /evidence="ECO:0007829|PDB:2KMS" FT STRAND 737..739 FT /evidence="ECO:0007829|PDB:4B2S" FT STRAND 743..746 FT /evidence="ECO:0007829|PDB:4B2S" FT STRAND 757..760 FT /evidence="ECO:0007829|PDB:2KMS" FT HELIX 765..767 FT /evidence="ECO:0007829|PDB:2KMS" FT STRAND 769..771 FT /evidence="ECO:0007829|PDB:2KMS" FT STRAND 790..792 FT /evidence="ECO:0007829|PDB:2KMS" FT STRAND 797..799 FT /evidence="ECO:0007829|PDB:2KMS" FT STRAND 870..872 FT /evidence="ECO:0007829|PDB:1HFI" FT STRAND 879..881 FT /evidence="ECO:0007829|PDB:1HFH" FT STRAND 883..887 FT /evidence="ECO:0007829|PDB:1HFH" FT STRAND 889..891 FT /evidence="ECO:0007829|PDB:1HFI" FT STRAND 895..904 FT /evidence="ECO:0007829|PDB:1HFH" FT STRAND 906..909 FT /evidence="ECO:0007829|PDB:1HFH" FT STRAND 911..916 FT /evidence="ECO:0007829|PDB:1HFH" FT STRAND 925..927 FT /evidence="ECO:0007829|PDB:1HFH" FT STRAND 940..943 FT /evidence="ECO:0007829|PDB:1HCC" FT STRAND 950..952 FT /evidence="ECO:0007829|PDB:1HFH" FT STRAND 957..959 FT /evidence="ECO:0007829|PDB:1HCC" FT STRAND 965..967 FT /evidence="ECO:0007829|PDB:1HCC" FT STRAND 971..974 FT /evidence="ECO:0007829|PDB:1HCC" FT STRAND 977..979 FT /evidence="ECO:0007829|PDB:1HCC" FT STRAND 1057..1059 FT /evidence="ECO:0007829|PDB:3SW0" FT STRAND 1065..1067 FT /evidence="ECO:0007829|PDB:3SW0" FT STRAND 1072..1077 FT /evidence="ECO:0007829|PDB:3SW0" FT STRAND 1082..1085 FT /evidence="ECO:0007829|PDB:3SW0" FT STRAND 1087..1092 FT /evidence="ECO:0007829|PDB:3SW0" FT STRAND 1101..1103 FT /evidence="ECO:0007829|PDB:3SW0" FT HELIX 1111..1114 FT /evidence="ECO:0007829|PDB:3OXU" FT STRAND 1118..1122 FT /evidence="ECO:0007829|PDB:3R62" FT STRAND 1126..1128 FT /evidence="ECO:0007829|PDB:3R62" FT STRAND 1133..1138 FT /evidence="ECO:0007829|PDB:3R62" FT STRAND 1143..1146 FT /evidence="ECO:0007829|PDB:3R62" FT STRAND 1148..1153 FT /evidence="ECO:0007829|PDB:3R62" FT STRAND 1154..1157 FT /evidence="ECO:0007829|PDB:4ONT" FT HELIX 1158..1161 FT /evidence="ECO:0007829|PDB:3SW0" FT STRAND 1162..1164 FT /evidence="ECO:0007829|PDB:3R62" FT STRAND 1167..1169 FT /evidence="ECO:0007829|PDB:4ONT" FT HELIX 1171..1177 FT /evidence="ECO:0007829|PDB:3R62" FT STRAND 1179..1181 FT /evidence="ECO:0007829|PDB:3R62" FT TURN 1182..1186 FT /evidence="ECO:0007829|PDB:3R62" FT STRAND 1189..1191 FT /evidence="ECO:0007829|PDB:3R62" FT STRAND 1196..1201 FT /evidence="ECO:0007829|PDB:3R62" FT TURN 1202..1204 FT /evidence="ECO:0007829|PDB:2BZM" FT STRAND 1205..1207 FT /evidence="ECO:0007829|PDB:3R62" FT STRAND 1214..1217 FT /evidence="ECO:0007829|PDB:3R62" FT HELIX 1224..1227 FT /evidence="ECO:0007829|PDB:4ONT" FT STRAND 1228..1230 FT /evidence="ECO:0007829|PDB:3R62" SQ SEQUENCE 1231 AA; 139096 MW; 3C26D62A2BF9BFEE CRC64; MRLLAKIICL MLWAICVAED CNELPPRRNT EILTGSWSDQ TYPEGTQAIY KCRPGYRSLG NVIMVCRKGE WVALNPLRKC QKRPCGHPGD TPFGTFTLTG GNVFEYGVKA VYTCNEGYQL LGEINYRECD TDGWTNDIPI CEVVKCLPVT APENGKIVSS AMEPDREYHF GQAVRFVCNS GYKIEGDEEM HCSDDGFWSK EKPKCVEISC KSPDVINGSP ISQKIIYKEN ERFQYKCNMG YEYSERGDAV CTESGWRPLP SCEEKSCDNP YIPNGDYSPL RIKHRTGDEI TYQCRNGFYP ATRGNTAKCT STGWIPAPRC TLKPCDYPDI KHGGLYHENM RRPYFPVAVG KYYSYYCDEH FETPSGSYWD HIHCTQDGWS PAVPCLRKCY FPYLENGYNQ NYGRKFVQGK SIDVACHPGY ALPKAQTTVT CMENGWSPTP RCIRVKTCSK SSIDIENGFI SESQYTYALK EKAKYQCKLG YVTADGETSG SITCGKDGWS AQPTCIKSCD IPVFMNARTK NDFTWFKLND TLDYECHDGY ESNTGSTTGS IVCGYNGWSD LPICYERECE LPKIDVHLVP DRKKDQYKVG EVLKFSCKPG FTIVGPNSVQ CYHFGLSPDL PICKEQVQSC GPPPELLNGN VKEKTKEEYG HSEVVEYYCN PRFLMKGPNK IQCVDGEWTT LPVCIVEEST CGDIPELEHG WAQLSSPPYY YGDSVEFNCS ESFTMIGHRS ITCIHGVWTQ LPQCVAIDKL KKCKSSNLII LEEHLKNKKE FDHNSNIRYR CRGKEGWIHT VCINGRWDPE VNCSMAQIQL CPPPPQIPNS HNMTTTLNYR DGEKVSVLCQ ENYLIQEGEE ITCKDGRWQS IPLCVEKIPC SQPPQIEHGT INSSRSSQES YAHGTKLSYT CEGGFRISEE NETTCYMGKW SSPPQCEGLP CKSPPEISHG VVAHMSDSYQ YGEEVTYKCF EGFGIDGPAI AKCLGEKWSH PPSCIKTDCL SLPSFENAIP MGEKKDVYKA GEQVTYTCAT YYKMDGASNV TCINSRWTGR PTCRDTSCVN PPTVQNAYIV SRQMSKYPSG ERVRYQCRSP YEMFGDEEVM CLNGNWTEPP QCKDSTGKCG PPPPIDNGDI TSFPLSVYAP ASSVEYQCQN LYQLEGNKRI TCRNGQWSEP PKCLHPCVIS REIMENYNIA LRWTAKQKLY SRTGESVEFV CKRGYRLSSR SHTLRTTCWD GKLEYPTCAK R //