ID CFAI_HUMAN Reviewed; 583 AA. AC P05156; O60442; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 2. DT 27-MAR-2024, entry version 229. DE RecName: Full=Complement factor I; DE EC=3.4.21.45; DE AltName: Full=C3B/C4B inactivator; DE Contains: DE RecName: Full=Complement factor I heavy chain; DE Contains: DE RecName: Full=Complement factor I light chain; DE Flags: Precursor; GN Name=CFI; Synonyms=IF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-300. RC TISSUE=Liver; RX PubMed=2954545; DOI=10.1042/bj2420849; RA Catterall C.F., Lyons A., Sim R.M., Day A.J., Harris T.J.R.; RT "Characterization of primary amino acid sequence of human complement RT control protein factor I from an analysis of cDNA clones."; RL Biochem. J. 242:849-856(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-300. RX PubMed=2956252; DOI=10.1016/s0021-9258(18)61076-2; RA Goldberger G., Bruns G.A.P., Rits M., Edge M.D., Kwiatkowski D.J.; RT "Human complement factor I: analysis of cDNA-derived primary structure and RT assignment of its gene to chromosome 4."; RL J. Biol. Chem. 262:10065-10071(1987). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18. RC TISSUE=Liver; RX PubMed=9479036; DOI=10.1016/s0378-1119(97)00632-x; RA Minta J.O., Fung M., Turner S., Eren R., Zemach L., Rits M., Goldberger G.; RT "Cloning and characterization of the promoter for the human complement RT factor I (C3b/C4b inactivator) gene."; RL Gene 208:17-24(1998). RN [5] 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 [6] RP FUNCTION. RX PubMed=7360115; DOI=10.1016/0161-5890(80)90119-4; RA Harrison R.A., Lachmann P.J.; RT "The physiological breakdown of the third component of human complement."; RL Mol. Immunol. 17:9-20(1980). RN [7] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=6327681; DOI=10.1016/s0021-9258(20)82168-1; RA Goldberger G., Arnaout M.A., Aden D., Kay R., Rits M., Colten H.R.; RT "Biosynthesis and postsynthetic processing of human C3b/C4b inactivator RT (factor I) in three hepatoma cell lines."; RL J. Biol. Chem. 259:6492-6497(1984). RN [8] RP FUNCTION. RX PubMed=2141838; DOI=10.1093/oxfordjournals.jbchem.a123044; RA Seya T., Okada M., Nishino H., Atkinson J.P.; RT "Regulation of proteolytic activity of complement factor I by pH: C3b/C4b RT receptor (CR1) and membrane cofactor protein (MCP) have different pH optima RT for factor I-mediated cleavage of C3b."; RL J. Biochem. 107:310-315(1990). RN [9] RP PROTEIN SEQUENCE OF 258-269. RX PubMed=7672128; DOI=10.1016/0014-5793(95)00916-w; RA Ullman C.G., Haris P.I., Smith K.F., Sim R.B., Emery V.C., Perkins S.J.; RT "Beta-sheet secondary structure of an LDL receptor domain from complement RT factor I by consensus structure predictions and spectroscopy."; RL FEBS Lett. 371:199-203(1995). RN [10] RP INTERACTION WITH CFH AND C3B. RX PubMed=9291131; DOI=10.1042/bj3260553; RA Soames C.J., Sim R.B.; RT "Interactions between human complement components factor H, factor I and RT C3b."; RL Biochem. J. 326:553-561(1997). RN [11] RP FUNCTION. RX PubMed=9605165; RA Sahu A., Isaacs S.N., Soulika A.M., Lambris J.D.; RT "Interaction of vaccinia virus complement control protein with human RT complement proteins: factor I-mediated degradation of C3b to iC3b1 RT inactivates the alternative complement pathway."; RL J. Immunol. 160:5596-5604(1998). RN [12] RP FUNCTION. RX PubMed=12055245; DOI=10.4049/jimmunol.168.12.6298; RA Barilla-LaBarca M.L., Liszewski M.K., Lambris J.D., Hourcade D., RA Atkinson J.P.; RT "Role of membrane cofactor protein (CD46) in regulation of C4b and C3b RT deposited on cells."; RL J. Immunol. 168:6298-6304(2002). RN [13] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-464. 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 [14] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70; ASN-103; ASN-177; ASN-464 RP AND ASN-536. 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 [15] RP TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=17320177; DOI=10.1016/j.molimm.2007.01.007; RA Timar K.K., Junnikkala S., Dallos A., Jarva H., Bhuiyan Z.A., Meri S., RA Bos J.D., Asghar S.S.; RT "Human keratinocytes produce the complement inhibitor factor I: Synthesis RT is regulated by interferon-gamma."; RL Mol. Immunol. 44:2943-2949(2007). RN [16] RP INTERACTION WITH STAPHYLOCOCCUS AUREUS CLUMPING FACTOR A/CLFA (MICROBIAL RP INFECTION). RX PubMed=18544012; DOI=10.1086/588825; RA Hair P.S., Ward M.D., Semmes O.J., Foster T.J., Cunnion K.M.; RT "Staphylococcus aureus clumping factor A binds to complement regulator RT factor I and increases factor I cleavage of C3b."; RL J. Infect. Dis. 198:125-133(2008). RN [17] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-103. 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 [18] RP GLYCOSYLATION AT ASN-103. 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 [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-103, 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 [20] {ECO:0007744|PDB:2XRC} RP X-RAY CRYSTALLOGRAPHY (2.69 ANGSTROMS) OF 19-583 IN COMPLEX WITH CALCIUM, RP GLYCOSYLATION AT ASN-70; ASN-103; ASN-177; ASN-464; ASN-494 AND ASN-536, RP AND DISULFIDE BONDS. RX PubMed=21768352; DOI=10.1073/pnas.1102167108; RA Roversi P., Johnson S., Caesar J.J., McLean F., Leath K.J., RA Tsiftsoglou S.A., Morgan B.P., Harris C.L., Sim R.B., Lea S.M.; RT "Structural basis for complement factor I control and its disease- RT associated sequence polymorphisms."; RL Proc. Natl. Acad. Sci. U.S.A. 108:12839-12844(2011). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.69 ANGSTROMS) OF 19-339 AND 340-583, INTERACTION RP WITH C3B AND CFH, DISULFIDE BOND, AND 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 [22] RP VARIANT CFI DEFICIENCY LEU-418. RX PubMed=8613545; DOI=10.1172/jci118515; RA Vyse T.J., Morley B.J., Bartok I., Theodoridis E.L., Davies K.A., RA Webster A.D.B., Walport M.J.; RT "The molecular basis of hereditary complement factor I deficiency."; RL J. Clin. Invest. 97:925-933(1996). RN [23] RP INVOLVEMENT IN CFI DEFICIENCY. RX PubMed=12562389; DOI=10.1046/j.1365-2249.2003.02077.x; RA Baracho G.V., Nudelman V., Isaac L.; RT "Molecular characterization of homozygous hereditary factor I deficiency."; RL Clin. Exp. Immunol. 131:280-286(2003). RN [24] RP VARIANT AHUS3 VAL-524. RX PubMed=15173250; DOI=10.1136/jmg.2004.019083; RA Fremeaux-Bacchi V., Dragon-Durey M.-A., Blouin J., Vigneau C., Kuypers D., RA Boudailliez B., Loirat C., Rondeau E., Fridman W.H.; RT "Complement factor I: a susceptibility gene for atypical haemolytic uraemic RT syndrome."; RL J. Med. Genet. 41:E84-E84(2004). RN [25] RP VARIANTS AHUS3 TRP-317 AND ASN-519. RX PubMed=16621965; DOI=10.1182/blood-2005-10-007252; RG The international registry of recurrent and familial HUS/TTP; RA Caprioli J., Noris M., Brioschi S., Pianetti G., Castelletti F., RA Bettinaglio P., Mele C., Bresin E., Cassis L., Gamba S., Porrati F., RA Bucchioni S., Monteferrante G., Fang C.J., Liszewski M.K., Kavanagh D., RA Atkinson J.P., Remuzzi G.; RT "Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical RT presentation, response to treatment, and outcome."; RL Blood 108:1267-1279(2006). RN [26] RP VARIANT CFI DEFICIENCY ASP-243. RX PubMed=17018561; DOI=10.1136/jmg.2006.045328; RA Servais A., Fremeaux-Bacchi V., Lequintrec M., Salomon R., Blouin J., RA Knebelmann B., Gruenfeld J.-P., Lesavre P., Noeel L.-H., Fakhouri F.; RT "Primary glomerulonephritis with isolated C3 deposits: a new entity which RT shares common genetic risk factors with haemolytic uraemic syndrome."; RL J. Med. Genet. 44:193-199(2007). RN [27] RP VARIANT AHUS3 THR-340. RX PubMed=17106690; DOI=10.1007/s00467-006-0320-2; RA Geelen J., van den Dries K., Roos A., van de Kar N., de Kat Angelino C., RA Klasen I., Monnens L., van den Heuvel L.; RT "A missense mutation in factor I (IF) predisposes to atypical haemolytic RT uraemic syndrome."; RL Pediatr. Nephrol. 22:371-375(2007). RN [28] RP VARIANTS AHUS3 LEU-64; ARG-119; ARG-183; ARG-287; LEU-416 AND THR-522. 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 [29] RP VARIANT ARMD13 ARG-119, VARIANT ALA-188, AND CHARACTERIZATION OF VARIANT RP ARMD13 ARG-119. RX PubMed=23685748; DOI=10.1038/ng.2640; RA van de Ven J.P., Nilsson S.C., Tan P.L., Buitendijk G.H., Ristau T., RA Mohlin F.C., Nabuurs S.B., Schoenmaker-Koller F.E., Smailhodzic D., RA Campochiaro P.A., Zack D.J., Duvvari M.R., Bakker B., Paun C.C., Boon C.J., RA Uitterlinden A.G., Liakopoulos S., Klevering B.J., Fauser S., Daha M.R., RA Katsanis N., Klaver C.C., Blom A.M., Hoyng C.B., den Hollander A.I.; RT "A functional variant in the CFI gene confers a high risk of age-related RT macular degeneration."; RL Nat. Genet. 45:813-817(2013). RN [30] RP VARIANT [LARGE SCALE ANALYSIS] ALA-300, AND IDENTIFICATION BY MASS RP 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). CC -!- FUNCTION: Trypsin-like serine protease that plays an essential role in CC regulating the immune response by controlling all complement pathways. CC Inhibits these pathways by cleaving three peptide bonds in the alpha- CC chain of C3b and two bonds in the alpha-chain of C4b thereby CC inactivating these proteins (PubMed:7360115, PubMed:17320177). CC Essential cofactors for these reactions include factor H and C4BP in CC the fluid phase and membrane cofactor protein/CD46 and CR1 on cell CC surfaces (PubMed:2141838, PubMed:9605165, PubMed:12055245). The CC presence of these cofactors on healthy cells allows degradation of CC deposited C3b by CFI in order to prevent undesired complement CC activation, while in apoptotic cells or microbes, the absence of such CC cofactors leads to C3b-mediated complement activation and subsequent CC opsonization (PubMed:28671664). {ECO:0000269|PubMed:12055245, CC ECO:0000269|PubMed:17320177, ECO:0000269|PubMed:2141838, CC ECO:0000269|PubMed:28671664, ECO:0000269|PubMed:7360115, CC ECO:0000269|PubMed:9605165}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Inactivates complement subcomponents C3b, iC3b and C4b by CC proteolytic cleavage.; EC=3.4.21.45; CC -!- SUBUNIT: Heterodimer of a light and heavy chains; disulfide-linked. The CC fully processed and mature protein circulates as a zymogen, and is CC allosterically activated by substrate-induced remodeling of the active CC site (PubMed:21768352). Interacts with C3b (PubMed:9291131, CC PubMed:28671664). Interacts with complement factor H (PubMed:9291131, CC PubMed:28671664). {ECO:0000269|PubMed:21768352, CC ECO:0000269|PubMed:28671664, ECO:0000269|PubMed:9291131}. CC -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus CC clumping factor A/ClfA; this interaction enhances cleavage of C3b into CC iC3b by CFI. {ECO:0000269|PubMed:18544012}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space. Secreted CC {ECO:0000269|PubMed:6327681}. CC -!- TISSUE SPECIFICITY: Expressed in the liver by hepatocytes CC (PubMed:6327681). Also present in other cells such as monocytes, CC fibroblasts or keratinocytes (PubMed:6444659, PubMed:17320177). CC {ECO:0000269|PubMed:17320177, ECO:0000269|PubMed:6327681, CC ECO:0000269|PubMed:6444659}. CC -!- DISEASE: Hemolytic uremic syndrome, atypical, 3 (AHUS3) [MIM:612923]: 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:15173250, ECO:0000269|PubMed:16621965, CC ECO:0000269|PubMed:17106690, ECO:0000269|PubMed:20513133}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. Other genes may play a role in modifying the CC phenotype. CC -!- DISEASE: Complement factor I deficiency (CFI deficiency) [MIM:610984]: CC Autosomal recessive condition associated with a propensity to pyogenic CC infections. {ECO:0000269|PubMed:12562389, ECO:0000269|PubMed:17018561, CC ECO:0000269|PubMed:8613545}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Macular degeneration, age-related, 13 (ARMD13) [MIM:615439]: 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:23685748}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- CC ProRule:PRU00274}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA68416.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=CFIbase; Note=CFI mutation db; CC URL="http://structure.bmc.lu.se/idbase/CFIbase/"; 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; Y00318; CAA68416.1; ALT_INIT; mRNA. DR EMBL; J02770; AAA52455.1; -; mRNA. DR EMBL; AC126283; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF005095; AAC08733.2; -; Genomic_DNA. DR CCDS; CCDS34049.1; -. DR PIR; A29154; A29154. DR RefSeq; NP_000195.2; NM_000204.4. DR RefSeq; NP_001317964.1; NM_001331035.1. DR PDB; 2XRC; X-ray; 2.69 A; A/B/C/D=19-583. DR PDB; 5O32; X-ray; 2.69 A; D/H=19-339, I/J=340-583. DR PDBsum; 2XRC; -. DR PDBsum; 5O32; -. DR AlphaFoldDB; P05156; -. DR SMR; P05156; -. DR BioGRID; 109652; 14. DR ComplexPortal; CPX-6165; Complement factor I complex. DR IntAct; P05156; 11. DR MINT; P05156; -. DR STRING; 9606.ENSP00000378131; -. DR DrugBank; DB09130; Copper. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR MEROPS; S01.199; -. DR GlyConnect; 742; 21 N-Linked glycans (6 sites). DR GlyCosmos; P05156; 6 sites, 33 glycans. DR GlyGen; P05156; 6 sites, 34 N-linked glycans (6 sites). DR iPTMnet; P05156; -. DR PhosphoSitePlus; P05156; -. DR BioMuta; CFI; -. DR DMDM; 317373341; -. DR CPTAC; non-CPTAC-1113; -. DR CPTAC; non-CPTAC-2659; -. DR CPTAC; non-CPTAC-2660; -. DR EPD; P05156; -. DR jPOST; P05156; -. DR MassIVE; P05156; -. DR MaxQB; P05156; -. DR PaxDb; 9606-ENSP00000378130; -. DR PeptideAtlas; P05156; -. DR ProteomicsDB; 51807; -. DR Antibodypedia; 695; 824 antibodies from 33 providers. DR DNASU; 3426; -. DR Ensembl; ENST00000394634.7; ENSP00000378130.2; ENSG00000205403.15. DR GeneID; 3426; -. DR KEGG; hsa:3426; -. DR MANE-Select; ENST00000394634.7; ENSP00000378130.2; NM_000204.5; NP_000195.3. DR UCSC; uc003hzr.5; human. DR AGR; HGNC:5394; -. DR CTD; 3426; -. DR DisGeNET; 3426; -. DR GeneCards; CFI; -. DR GeneReviews; CFI; -. DR HGNC; HGNC:5394; CFI. DR HPA; ENSG00000205403; Tissue enriched (liver). DR MalaCards; CFI; -. DR MIM; 217030; gene. DR MIM; 610984; phenotype. DR MIM; 612923; phenotype. DR MIM; 615439; phenotype. DR neXtProt; NX_P05156; -. DR OpenTargets; ENSG00000205403; -. DR Orphanet; 544472; Atypical hemolytic uremic syndrome with complement gene abnormality. DR Orphanet; 244275; De novo thrombotic microangiopathy after kidney transplantation. DR Orphanet; 75376; Familial drusen. DR Orphanet; 244242; HELLP syndrome. DR Orphanet; 200418; Immunodeficiency with factor I anomaly. DR Orphanet; 279; NON RARE IN EUROPE: Age-related macular degeneration. DR PharmGKB; PA29641; -. DR VEuPathDB; HostDB:ENSG00000205403; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT00930000151042; -. DR InParanoid; P05156; -. DR OrthoDB; 4629979at2759; -. DR PhylomeDB; P05156; -. DR TreeFam; TF330647; -. DR BRENDA; 3.4.21.45; 2681. DR PathwayCommons; P05156; -. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR SignaLink; P05156; -. DR SIGNOR; P05156; -. DR BioGRID-ORCS; 3426; 8 hits in 1147 CRISPR screens. DR ChiTaRS; CFI; human. DR EvolutionaryTrace; P05156; -. DR GeneWiki; Complement_factor_I; -. DR GenomeRNAi; 3426; -. DR Pharos; P05156; Tbio. DR PRO; PR:P05156; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P05156; Protein. DR Bgee; ENSG00000205403; Expressed in germinal epithelium of ovary and 157 other cell types or tissues. DR ExpressionAtlas; P05156; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:ProtInc. DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd00112; LDLa; 2. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 3.30.60.30; -; 1. DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 2. DR Gene3D; 3.10.250.10; SRCR-like domain; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1. DR InterPro; IPR048722; CFAI_FIMAC_N. DR InterPro; IPR048719; CFAI_KAZAL. DR InterPro; IPR003884; FacI_MAC. DR InterPro; IPR002350; Kazal_dom. DR InterPro; IPR036058; Kazal_dom_sf. DR InterPro; IPR036055; LDL_receptor-like_sf. DR InterPro; IPR023415; LDLR_class-A_CS. DR InterPro; IPR002172; LDrepeatLR_classA_rpt. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001190; SRCR. DR InterPro; IPR017448; SRCR-like_dom. DR InterPro; IPR036772; SRCR-like_dom_sf. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24264:SF40; HYALURONAN-BINDING PROTEIN 2; 1. DR PANTHER; PTHR24264; TRYPSIN-RELATED; 1. DR Pfam; PF21286; CFAI_FIMAC_N; 1. DR Pfam; PF21287; CFAI_KAZAL; 1. DR Pfam; PF00057; Ldl_recept_a; 2. DR Pfam; PF00530; SRCR; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00057; FIMAC; 1. DR SMART; SM00192; LDLa; 2. DR SMART; SM00202; SR; 1. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF100895; Kazal-type serine protease inhibitors; 1. DR SUPFAM; SSF57424; LDL receptor-like module; 2. DR SUPFAM; SSF56487; SRCR-like; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS51465; KAZAL_2; 1. DR PROSITE; PS01209; LDLRA_1; 1. DR PROSITE; PS50068; LDLRA_2; 2. DR PROSITE; PS50287; SRCR_2; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. DR SWISS-2DPAGE; P05156; -. DR Genevisible; P05156; HS. PE 1: Evidence at protein level; KW 3D-structure; Age-related macular degeneration; Calcium; KW Cleavage on pair of basic residues; Complement pathway; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Hemolytic uremic syndrome; Host-virus interaction; Hydrolase; Immunity; KW Innate immunity; Metal-binding; Protease; Reference proteome; Repeat; KW Secreted; Serine protease; Signal. FT SIGNAL 1..18 FT CHAIN 19..583 FT /note="Complement factor I" FT /id="PRO_0000027568" FT CHAIN 19..335 FT /note="Complement factor I heavy chain" FT /id="PRO_0000027569" FT CHAIN 340..583 FT /note="Complement factor I light chain" FT /id="PRO_0000027570" FT DOMAIN 55..108 FT /note="Kazal-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 114..212 FT /note="SRCR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DOMAIN 213..257 FT /note="LDL-receptor class A 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 258..294 FT /note="LDL-receptor class A 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 340..574 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 380 FT /note="Charge relay system" FT /evidence="ECO:0000250|UniProtKB:P00750" FT ACT_SITE 429 FT /note="Charge relay system" FT /evidence="ECO:0000250|UniProtKB:P00750" FT ACT_SITE 525 FT /note="Charge relay system" FT /evidence="ECO:0000250|UniProtKB:P00750" FT BINDING 239 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 242 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 244 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 246 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 252 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 253 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 276 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 279 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 281 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 283 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 289 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT BINDING 290 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT CARBOHYD 70 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:21768352, ECO:0007744|PDB:2XRC" FT CARBOHYD 103 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT CARBOHYD 177 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:21768352, ECO:0007744|PDB:2XRC" FT CARBOHYD 464 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT CARBOHYD 494 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT CARBOHYD 536 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:21768352, ECO:0007744|PDB:2XRC" FT DISULFID 33..255 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 43..54 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 48..59 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 61..93 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 67..86 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 75..106 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 141..181 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 154..214 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 186..196 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 229..247 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 241..256 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 259..271 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 266..284 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 278..293 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 327..453 FT /note="Interchain (between heavy and light chains)" FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0007744|PDB:2XRC" FT DISULFID 365..381 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 373..444 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 453 FT /note="Interchain (with C-327)" FT /evidence="ECO:0000269|PubMed:28671664, FT ECO:0007744|PDB:5O32" FT DISULFID 467..531 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 495..510 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT DISULFID 521..550 FT /evidence="ECO:0000269|PubMed:21768352, FT ECO:0000269|PubMed:28671664, ECO:0007744|PDB:2XRC, FT ECO:0007744|PDB:5O32" FT VARIANT 64 FT /note="P -> L (in AHUS3; dbSNP:rs773187287)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063665" FT VARIANT 119 FT /note="G -> R (in AHUS3 and ARMD13; the mutant is both FT expressed and secreted at lower levels than wild-type FT protein; mediates C3 degradation to a lesser extent than FT that of controls; dbSNP:rs141853578)" FT /evidence="ECO:0000269|PubMed:20513133, FT ECO:0000269|PubMed:23685748" FT /id="VAR_063666" FT VARIANT 183 FT /note="H -> R (in AHUS3; dbSNP:rs75612300)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063667" FT VARIANT 188 FT /note="G -> A" FT /evidence="ECO:0000269|PubMed:23685748" FT /id="VAR_070843" FT VARIANT 243 FT /note="G -> D (in CFI deficiency; dbSNP:rs121964916)" FT /evidence="ECO:0000269|PubMed:17018561" FT /id="VAR_034907" FT VARIANT 287 FT /note="G -> R (in AHUS3; dbSNP:rs182078921)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063668" FT VARIANT 300 FT /note="T -> A (in dbSNP:rs11098044)" FT /evidence="ECO:0000269|PubMed:2954545, FT ECO:0000269|PubMed:2956252, ECO:0007744|PubMed:24275569" FT /id="VAR_034908" FT VARIANT 317 FT /note="R -> W (in AHUS3; dbSNP:rs121964917)" FT /evidence="ECO:0000269|PubMed:16621965" FT /id="VAR_063669" FT VARIANT 340 FT /note="I -> T (in AHUS3; dbSNP:rs769419740)" FT /evidence="ECO:0000269|PubMed:17106690" FT /id="VAR_030343" FT VARIANT 416 FT /note="I -> L (in AHUS3; dbSNP:rs61733901)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063670" FT VARIANT 418 FT /note="H -> L (in CFI deficiency; dbSNP:rs121964912)" FT /evidence="ECO:0000269|PubMed:8613545" FT /id="VAR_026757" FT VARIANT 519 FT /note="D -> N (in AHUS3; dbSNP:rs121964918)" FT /evidence="ECO:0000269|PubMed:16621965" FT /id="VAR_063671" FT VARIANT 522 FT /note="K -> T (in AHUS3)" FT /evidence="ECO:0000269|PubMed:20513133" FT /id="VAR_063672" FT VARIANT 524 FT /note="D -> V (in AHUS3; dbSNP:rs121964914)" FT /evidence="ECO:0000269|PubMed:15173250" FT /id="VAR_030344" FT CONFLICT 558 FT /note="V -> F (in Ref. 2; AAA52455)" FT /evidence="ECO:0000305" FT STRAND 31..33 FT /evidence="ECO:0007829|PDB:2XRC" FT TURN 34..36 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 43..45 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 52..55 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 58..61 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 64..66 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 74..76 FT /evidence="ECO:0007829|PDB:2XRC" FT TURN 77..79 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 80..84 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 85..94 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 100..105 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 113..118 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 124..130 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 138..140 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 147..156 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 173..175 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 182..185 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 196..199 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 211..214 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 242..244 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 247..258 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 264..266 FT /evidence="ECO:0007829|PDB:2XRC" FT TURN 267..269 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 270..272 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 274..276 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 279..281 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 284..286 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 290..292 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 312..319 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 346..348 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 356..362 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 368..371 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 374..377 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 379..382 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 390..393 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 409..417 FT /evidence="ECO:0007829|PDB:2XRC" FT TURN 423..425 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 431..435 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 439..442 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 466..470 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 486..491 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 496..499 FT /evidence="ECO:0007829|PDB:2XRC" FT TURN 505..507 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 508..513 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 528..532 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 538..546 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 549..551 FT /evidence="ECO:0007829|PDB:2XRC" FT STRAND 557..561 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 562..565 FT /evidence="ECO:0007829|PDB:2XRC" FT HELIX 566..572 FT /evidence="ECO:0007829|PDB:2XRC" SQ SEQUENCE 583 AA; 65750 MW; F06070EFE6B572A1 CRC64; MKLLHVFLLF LCFHLRFCKV TYTSQEDLVE KKCLAKKYTH LSCDKVFCQP WQRCIEGTCV CKLPYQCPKN GTAVCATNRR SFPTYCQQKS LECLHPGTKF LNNGTCTAEG KFSVSLKHGN TDSEGIVEVK LVDQDKTMFI CKSSWSMREA NVACLDLGFQ QGADTQRRFK LSDLSINSTE CLHVHCRGLE TSLAECTFTK RRTMGYQDFA DVVCYTQKAD SPMDDFFQCV NGKYISQMKA CDGINDCGDQ SDELCCKACQ GKGFHCKSGV CIPSQYQCNG EVDCITGEDE VGCAGFASVT QEETEILTAD MDAERRRIKS LLPKLSCGVK NRMHIRRKRI VGGKRAQLGD LPWQVAIKDA SGITCGGIYI GGCWILTAAH CLRASKTHRY QIWTTVVDWI HPDLKRIVIE YVDRIIFHEN YNAGTYQNDI ALIEMKKDGN KKDCELPRSI PACVPWSPYL FQPNDTCIVS GWGREKDNER VFSLQWGEVK LISNCSKFYG NRFYEKEMEC AGTYDGSIDA CKGDSGGPLV CMDANNVTYV WGVVSWGENC GKPEFPGVYT KVANYFDWIS YHVGRPFISQ YNV //