ID CFAH_HUMAN Reviewed; 1231 AA. AC P08603; P78435; Q14570; Q38G77; Q5TFM3; Q8N708; Q9NU86; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 10-JAN-2006, sequence version 3. DT 21-AUG-2007, entry version 103. DE Complement factor H precursor (H factor 1). GN Name=CFH; Synonyms=HF, HF1, HF2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), GLYCOSYLATION AT RP ASN-529, AND VARIANT TYR-402. RC TISSUE=Liver; RX MEDLINE=88134059; PubMed=2963625; 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; TYR-402; RP THR-551; ILE-890; ASP-936; ILE-1007; ILE-1017; TYR-1050 AND THR-1059. RA Rieder M.J., Johanson E.J., da Ponte S.H., Hastings N.C., Ahearn M.O., RA Bertucci C.B., Wong M.W., Yi Q., Nickerson D.A.; RT "SeattleSNPs. NHLBI HL66682 program for genomic applications, UW- RT FHCRC, Seattle, WA (URL: http://pga.gs.washington.edu)."; RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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] (ISOFORM 2), AND VARIANT RP TYR-402. RC TISSUE=Testis; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 53-445. RX MEDLINE=87054207; PubMed=2946589; 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 RT for C3b."; RL Eur. J. Immunol. 16:1351-1355(1986). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 226-449, AND PROTEIN SEQUENCE OF RP 205-216; 237-246; 320-331; 425-435; 508-518; 645-662; 667-717; RP 858-885; 907-972; 1163-1182 AND 1193-1203. RX MEDLINE=86169701; PubMed=2937845; 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 MEDLINE=91201892; PubMed=1826708; 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 RT reveals a novel member of the short consensus repeat family related to RT the carboxy terminal of the classical 150-kDa molecule."; RL J. Immunol. 146:3190-3196(1991). RN [8] RP PROTEIN SEQUENCE OF 19-35. RX MEDLINE=83048213; PubMed=6215918; 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 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-882, AND MASS RP SPECTROMETRY. 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 [12] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-529 AND ASN-911, AND MASS RP SPECTROMETRY. 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., RA Moore R.J., 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 [13] RP STRUCTURE BY NMR OF 927-985 (SUSHI 16). RX MEDLINE=91278097; 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 [14] RP STRUCTURE BY NMR OF 264-322 (SUSHI 5). RX MEDLINE=92232649; 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 RT of the complement control protein module."; RL Biochemistry 31:3626-3634(1992). RN [15] RP STRUCTURE BY NMR OF 866-985 (SUSHIS 15 AND 16). RX MEDLINE=93323119; PubMed=8331663; DOI=10.1006/jmbi.1993.1381; RA Barlow P.N., Steinkasserer A., Norman D.G., Kieffer B., Wiles A.P., RA Sim B., Campbell I.D.; RT "Solution structure of a pair of complement modules by nuclear RT magnetic resonance."; RL J. Mol. Biol. 232:268-284(1993). RN [16] RP VARIANTS CFH DEFICIENCY ARG-536 AND TYR-959. RX MEDLINE=97460109; 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., RA Vogt B.A., Colten H.R.; RT "Human factor H deficiency. Mutations in framework cysteine residues RT and block in H protein secretion and intracellular catabolism."; RL J. Biol. Chem. 272:25168-25175(1997). RN [17] RP VARIANT HUS GLY-1215. RX PubMed=9551389; DOI=10.1046/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 RT syndrome."; RL Kidney Int. 53:836-844(1998). RN [18] RP VARIANT HUS LEU-1191. RX MEDLINE=20046888; PubMed=10577907; DOI=10.1086/302673; RA Ying L., Katz Y., Schlesinger M., Carmi R., Shalev H., Haider N., RA Beck G., 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 [19] RP VARIANT HUS 1225-TYR--ARG-1231 DELINS PHE-GLN-SER. RX MEDLINE=20311557; 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 [20] RP INVOLVEMENT IN CFH DEFICIENCY. RX PubMed=10803850; DOI=10.1007/s002510050631; RA Sanchez-Corral P., Bellavia D., Amico L., Brai M., RA Rodriguez de Cordoba S.; RT "Molecular basis for factor H and FHL-1 deficiency in an Italian RT family."; RL Immunogenetics 51:366-369(2000). RN [21] RP VARIANTS CFH DEFICIENCY MET-956; LEU-1183; ARG-1189 AND ALA-1197. RX MEDLINE=21090512; 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 RT in atypical hemolytic uremic syndrome."; RL Am. J. Hum. Genet. 68:478-484(2001). RN [22] RP VARIANTS CFH DEFICIENCY 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., RA Venning M.C., Tielemans C.L., Goodship J.A., Goodship T.H.J.; RT "Factor H mutations in hemolytic uremic syndrome cluster in exons 18- RT 20, a domain important for host cell recognition."; RL Am. J. Hum. Genet. 68:485-490(2001). RN [23] RP VARIANTS CFH DEFICIENCY CYS-1210 AND GLN-1215. RX PubMed=11158219; RG Italian Registry of Familial and Recurrent HUS/TTP; RA Caprioli J., Bettinaglio P., Zipfel P.F., Amadei B., Daina E., RA Gamba S., 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 [24] RP VARIANTS HUS MET-956; GLU-1076; GLY-1119; LEU-1183; ARG-1184; RP ARG-1189; LEU-1191; ASP-1194; ALA-1197; CYS-1210; GLY-1215 AND RP 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 [25] RP VARIANT CFH DEFICIENCY ARG-1183. RX PubMed=12020532; DOI=10.1016/S0140-6736(02)08560-4; RA Remuzzi G., Ruggenenti P., Codazzi D., Noris M., Caprioli J., RA Locatelli G., Gridelli B.; RT "Combined kidney and liver transplantation for familial haemolytic RT uraemic syndrome."; RL Lancet 359:1671-1672(2002). RN [26] RP VARIANTS HUS GLY-78; HIS-950; HIS-951; TRP-1163 AND ALA-1198, AND RP VARIANT 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 RT uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms RT are strongly associated with the disease."; RL Hum. Mol. Genet. 12:3385-3395(2003). RN [27] RP VARIANTS HUS 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., RA Skerka C., Lenk D., Bender B.U., Cybulla M., Riegler P., RA Koenigsrainer A., Neyer U., Bock A., Widmer U., Male D.A., Franke G., RA 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 [28] RP VARIANTS CFH DEFICIENCY LEU-127; SER-431 AND SER-673, AND VARIANTS HUS RP LYS-400; 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., RA Niaudet P., 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 [29] RP VARIANT TYR-402. RX PubMed=15895326; DOI=10.1086/431426; RA Zareparsi S., Branham K.E.H., Li M., Shah S., Klein R.J., Ott J., RA Hoh J., Abecasis G.R., Swaroop A.; RT "Strong association of the Y402H variant in complement factor H at RT 1q32 with susceptibility to age-related macular degeneration."; RL Am. J. Hum. Genet. 77:149-153(2005). RN [30] RP VARIANTS ILE-62 AND TYR-402. 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., RA Gehrs K.M., Smith R.J.H., Silvestri G., Russell S.R., Klaver C.C.W., RA Barbazetto I., Chang S., Yannuzzi L.A., Barile G.R., Merriam J.C., RA Smith R.T., Olsh A.K., Bergeron J., Zernant J., Merriam J.E., Gold B., RA Dean M., Allikmets R.; RT "A common haplotype in the complement regulatory gene factor H RT (HF1/CFH) predisposes individuals to age-related macular RT degeneration."; RL Proc. Natl. Acad. Sci. U.S.A. 102:7227-7232(2005). RN [31] RP VARIANT TYR-402. 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 RT degeneration."; RL Science 308:385-389(2005). RN [32] RP VARIANT TYR-402. RX PubMed=15761120; DOI=10.1126/science.1110359; RA Haines J.L., Hauser M.A., Schmidt S., Scott W.K., Olson L.M., RA Gallins P., Spencer K.L., Kwan S.Y., Noureddine M., Gilbert J.R., RA Schnetz-Boutaud N., 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 [33] RP VARIANTS ILE-62 AND TYR-402. 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 RT degeneration."; RL Science 308:421-424(2005). RN [34] RP VARIANT CFH DEFICIENCY LYS-224 DEL, AND CHARACTERIZATION OF VARIANT RP CFH DEFICIENCY LYS-224 DEL. RX PubMed=16612335; DOI=10.1038/sj.ki.5000269; RA Licht C., Heinen S., Jozsi M., Loeschmann I., Saunders R.E., RA Perkins S.J., Waldherr R., Skerka C., Kirschfink M., Hoppe B., RA 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). CC -!- FUNCTION: Factor H functions as a cofactor in the inactivation of CC C3b by factor I and also increases the rate of dissociation of the CC C3bBb complex (C3 convertase) and the (C3b)NBB complex (C5 CC convertase) in the alternative complement pathway. CC -!- SUBCELLULAR LOCATION: Secreted. 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 by the liver and secreted in plasma. CC -!- DISEASE: Defects in CFH are the cause of complement factor H CC deficiency (CFH deficiency) [MIM:609814]. CFH deficiency CC determines uncontrolled activation of the alternative complement CC pathway with consumption of C3 and often other terminal complement CC components. It is associated with a number of renal diseases with CC variable clinical presentation and progression, including CC membranoproliferative glomerulonephritis and atypical hemolytic CC uremic syndrome. CFH deficiency patients may show increased CC susceptibility to meningococcal infections. CC -!- DISEASE: Defects in CFH are a cause of hemolytic-uremic syndrome CC (HUS) [MIM:235400]. HUS is a microvasculature disorder leading to CC microangiopathic hemolytic anemia associated with distorted CC erythrocytes ('burr cells'), thrombocytopenia, and acute renal CC failure. Both dominant and recessive modes of inheritance have CC been reported. Most cases of HUS are associated with epidemics of CC diarrhea caused by verocytotoxin-producing bacteria, but atypical CC cases of HUS not associated with diarrhea (aHUS) also occur. CC -!- DISEASE: Genetic variation in CFH is associated with age-related CC macular degeneration type 4 (ARMD4) [MIM:610698]. ARMD is a CC multifactorial eye disease and the most common cause of CC irreversible vision loss in the developed world. In most patients, CC the disease is manifest as ophthalmoscopically visible yellowish CC accumulations of protein and lipid (known as drusen) that lie CC beneath the retinal pigment epithelium and within an elastin- CC containing structure known as Bruch membrane. CC -!- SIMILARITY: Contains 20 Sushi (CCP/SCR) domains. CC -!- SEQUENCE CAUTION: CC Sequence=CAB41739.1; Type=Frameshift; Positions=341; CC -!- WEB RESOURCE: NAME=GeneReviews; CC URL="http://www.genetests.org/query?gene=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; CAI19672.1; -; Genomic_DNA. DR EMBL; BC037285; AAH37285.1; -; 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 PIR; S00254; NBHUH. DR PIR; S03013; NBHUHS. DR UniGene; Hs.363396; -. DR PDB; 1FHC; Model; A=1105-1231. DR PDB; 1HAQ; Model; A=19-1231. DR PDB; 1HCC; NMR; @=927-985. DR PDB; 1HFH; NMR; @=866-985. DR PDB; 1HFI; NMR; @=866-927. DR PDB; 1KOV; Model; A=321-443. DR PDB; 2BZM; NMR; A=-. DR PDB; 2G7I; X-ray; A=1107-1231. DR IntAct; P08603; -. DR Ensembl; ENSG00000000971; Homo sapiens. DR KEGG; hsa:3075; -. DR HGNC; HGNC:4883; CFH. DR MIM; 134370; gene. DR MIM; 235400; phenotype. DR MIM; 609814; phenotype. DR MIM; 610698; phenotype. DR Orphanet; 90038; Haemolytic-uremic syndrome. DR Orphanet; 2134; Hemolytic uremic syndrome, atypical form. DR Orphanet; 279; Macular degeneration, age-related. DR PharmGKB; PA29261; -. DR LinkHub; P08603; -. DR ArrayExpress; P08603; -. DR GermOnline; ENSG00000000971; Homo sapiens. DR GO; GO:0005615; C:extracellular space; TAS:ProtInc. DR GO; GO:0006956; P:complement activation; TAS:ProtInc. DR InterPro; IPR000436; Sushi_SCR_CCP. DR Pfam; PF00084; Sushi; 20. DR SMART; SM00032; CCP; 20. 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; KW Disease mutation; Glycoprotein; Immune response; Innate immunity; KW Polymorphism; Repeat; Secreted; Signal; Sushi. FT SIGNAL 1 18 FT CHAIN 19 1231 Complement factor H. FT /FTId=PRO_0000005894. FT DOMAIN 19 82 Sushi 1. FT DOMAIN 83 143 Sushi 2. FT DOMAIN 144 207 Sushi 3. FT DOMAIN 208 264 Sushi 4. FT DOMAIN 265 322 Sushi 5. FT DOMAIN 324 386 Sushi 6. FT DOMAIN 387 444 Sushi 7. FT DOMAIN 446 507 Sushi 8. FT DOMAIN 515 566 Sushi 9. FT DOMAIN 567 625 Sushi 10. FT DOMAIN 628 686 Sushi 11. FT DOMAIN 689 746 Sushi 12. FT DOMAIN 751 805 Sushi 13. FT DOMAIN 809 866 Sushi 14. FT DOMAIN 868 928 Sushi 15. FT DOMAIN 929 986 Sushi 16. FT DOMAIN 987 1045 Sushi 17. FT DOMAIN 1046 1104 Sushi 18. FT DOMAIN 1107 1165 Sushi 19. FT DOMAIN 1170 1230 Sushi 20. FT SITE 217 217 Not glycosylated. FT CARBOHYD 529 529 N-linked (GlcNAc...). FT CARBOHYD 718 718 N-linked (GlcNAc...) (Potential). FT CARBOHYD 802 802 N-linked (GlcNAc...). FT CARBOHYD 822 822 N-linked (GlcNAc...). FT CARBOHYD 882 882 N-linked (GlcNAc...). FT CARBOHYD 911 911 N-linked (GlcNAc...). FT CARBOHYD 1029 1029 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1095 1095 N-linked (GlcNAc...) (Potential). FT DISULFID 21 66 By similarity. FT DISULFID 52 80 By similarity. FT DISULFID 85 129 By similarity. FT DISULFID 114 141 By similarity. FT DISULFID 146 192 By similarity. FT DISULFID 178 205 By similarity. FT DISULFID 210 251 By similarity. FT DISULFID 237 262 By similarity. FT DISULFID 267 309 By similarity. FT DISULFID 294 320 By similarity. FT DISULFID 325 374 By similarity. FT DISULFID 357 385 By similarity. FT DISULFID 389 431 By similarity. FT DISULFID 416 442 By similarity. FT DISULFID 448 494 By similarity. FT DISULFID 477 505 By similarity. FT DISULFID 509 553 By similarity. FT DISULFID 536 564 By similarity. FT DISULFID 569 611 By similarity. FT DISULFID 597 623 By similarity. FT DISULFID 630 673 By similarity. FT DISULFID 659 684 By similarity. FT DISULFID 691 733 By similarity. FT DISULFID 719 744 By similarity. FT DISULFID 753 792 By similarity. FT DISULFID 781 803 By similarity. FT DISULFID 811 853 By similarity. FT DISULFID 839 864 By similarity. FT DISULFID 870 915 By similarity. FT DISULFID 901 926 By similarity. FT DISULFID 931 973 By similarity. FT DISULFID 959 984 By similarity. FT DISULFID 989 1032 By similarity. FT DISULFID 1018 1043 By similarity. FT DISULFID 1048 1091 By similarity. FT DISULFID 1077 1102 By similarity. FT DISULFID 1109 1152 By similarity. FT DISULFID 1138 1163 By similarity. FT DISULFID 1167 1218 By similarity. FT DISULFID 1201 1228 By similarity. FT VAR_SEQ 446 449 KTCS -> SFTL (in isoform 2). FT /FTId=VSP_001190. FT VAR_SEQ 450 1231 Missing (in isoform 2). FT /FTId=VSP_001191. FT VARIANT 62 62 V -> I (polymorphism associated with FT ARMD4; dbSNP:rs800292). FT /FTId=VAR_023836. FT VARIANT 78 78 R -> G (in HUS). FT /FTId=VAR_025864. FT VARIANT 127 127 R -> L (in CFH deficiency; with FT membranoproliferative FT glomerulonephritis). FT /FTId=VAR_031978. FT VARIANT 224 224 Missing (in CFH deficiency; with FT membranoproliferative glomerulonephritis; FT affects binding of factor H to C3b and FT shows defective complement regulation). FT /FTId=VAR_031979. FT VARIANT 400 400 Q -> K (in HUS). FT /FTId=VAR_031980. FT VARIANT 402 402 H -> Y (polymorphism associated with FT ARMD4; dbSNP:rs1061170). FT /FTId=VAR_001979. FT VARIANT 431 431 C -> S (in CFH deficiency; with FT membranoproliferative FT glomerulonephritis). FT /FTId=VAR_031981. FT VARIANT 536 536 C -> R (in CFH deficiency). FT /FTId=VAR_019405. FT VARIANT 551 551 I -> T. FT /FTId=VAR_025092. FT VARIANT 630 630 C -> W (in HUS; atypical). FT /FTId=VAR_025865. FT VARIANT 673 673 C -> S (in CFH deficiency; with FT membranoproliferative FT glomerulonephritis). FT /FTId=VAR_031982. FT VARIANT 673 673 C -> Y (in HUS). FT /FTId=VAR_031983. FT VARIANT 850 850 E -> K (in HUS; atypical). FT /FTId=VAR_025866. FT VARIANT 890 890 S -> I. FT /FTId=VAR_025093. FT VARIANT 893 893 H -> R (in HUS; also in a patient with FT severe renal failure). FT /FTId=VAR_031984. FT VARIANT 915 915 C -> S (in HUS). FT /FTId=VAR_031985. FT VARIANT 936 936 E -> D (polymorphism associated with HUS; FT dbSNP:rs1065489). FT /FTId=VAR_020261. FT VARIANT 950 950 Q -> H (in HUS). FT /FTId=VAR_025867. FT VARIANT 951 951 Y -> H (in HUS). FT /FTId=VAR_025868. FT VARIANT 956 956 T -> M (in HUS; atypical). FT /FTId=VAR_025869. FT VARIANT 959 959 C -> Y (in CFH deficiency). FT /FTId=VAR_019406. FT VARIANT 978 978 W -> C (in HUS; atypical). FT /FTId=VAR_025870. FT VARIANT 1007 1007 V -> I. FT /FTId=VAR_025094. FT VARIANT 1017 1017 T -> I. FT /FTId=VAR_025095. FT VARIANT 1021 1021 Y -> F (in HUS; atypical). FT /FTId=VAR_025871. FT VARIANT 1043 1043 C -> R (in HUS; atypical). FT /FTId=VAR_025872. FT VARIANT 1050 1050 N -> Y. FT /FTId=VAR_025096. FT VARIANT 1059 1059 I -> T. FT /FTId=VAR_025097. FT VARIANT 1076 1076 Q -> E (in CFH deficiency). FT /FTId=VAR_025873. FT VARIANT 1119 1119 D -> G (in CFH deficiency). FT /FTId=VAR_025874. FT VARIANT 1134 1134 V -> G (in HUS; atypical). FT /FTId=VAR_025875. FT VARIANT 1142 1142 Y -> D (in HUS; atypical). FT /FTId=VAR_025876. FT VARIANT 1157 1157 W -> R (in HUS; atypical). FT /FTId=VAR_025877. FT VARIANT 1163 1163 C -> W (in HUS). FT /FTId=VAR_025878. FT VARIANT 1183 1183 W -> L (in HUS). FT /FTId=VAR_025879. FT VARIANT 1183 1183 W -> R (in HUS; atypical). FT /FTId=VAR_025880. FT VARIANT 1184 1184 T -> R (in CFH deficiency). FT /FTId=VAR_025881. FT VARIANT 1189 1189 L -> R (in HUS; atypical; nondiarrhea- FT associated). FT /FTId=VAR_019407. FT VARIANT 1191 1191 S -> L (in HUS; dbSNP:rs460897). FT /FTId=VAR_019408. FT VARIANT 1194 1194 G -> D (in HUS). FT /FTId=VAR_025882. FT VARIANT 1197 1197 V -> A (in HUS; atypical). FT /FTId=VAR_025883. FT VARIANT 1198 1198 E -> A (in HUS). FT /FTId=VAR_025884. FT VARIANT 1199 1199 F -> S (in HUS). FT /FTId=VAR_031986. FT VARIANT 1210 1210 R -> C (in CFH deficiency). FT /FTId=VAR_025885. FT VARIANT 1215 1215 R -> G (in HUS). FT /FTId=VAR_025886. FT VARIANT 1215 1215 R -> Q (in CFH deficiency). FT /FTId=VAR_025887. FT VARIANT 1225 1231 YPTCAKR -> FQS (in HUS). FT /FTId=VAR_019409. FT VARIANT 1226 1226 P -> S (in HUS; atypical). FT /FTId=VAR_025888. FT CONFLICT 21 21 C -> Q (in Ref. 8). FT CONFLICT 30 30 T -> V (in Ref. 8). FT CONFLICT 34 34 T -> Q (in Ref. 8). FT CONFLICT 53 54 RP -> IL (in Ref. 5). FT CONFLICT 493 493 T -> R (in Ref. 1). FT STRAND 1118 1122 FT STRAND 1133 1138 FT STRAND 1143 1146 FT STRAND 1148 1153 FT STRAND 1162 1164 FT HELIX 1171 1177 FT STRAND 1179 1182 FT STRAND 1189 1191 FT STRAND 1196 1201 FT STRAND 1214 1217 SQ SEQUENCE 1231 AA; 139070 MW; 2046A9212747B881 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 NHGRKFVQGK 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 //