ID CFAI_MOUSE Reviewed; 603 AA.
AC Q61129; B2RWX8; Q9WU07;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 27-MAR-2024, entry version 197.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=8604219; DOI=10.1016/0161-5890(95)00116-6;
RA Minta J.O., Wong M.J., Kozak C.A., Kunnath-Muglia L.M., Goldberger G.;
RT "cDNA cloning, sequencing and chromosomal assignment of the gene for mouse
RT complement factor I (C3b/C4b inactivator): identification of a species
RT specific divergent segment in factor I.";
RL Mol. Immunol. 33:101-112(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 114-334.
RC STRAIN=129/Sv; TISSUE=Kidney;
RX PubMed=10204086; DOI=10.1080/15216549900201523;
RA Yun Y.-S., Goldberger G., Minta J.O.;
RT "Cloning and characterization of the non-catalytic heavy chain of mouse
RT complement factor I gene: structure comparison with the human homologue.";
RL Biochem. Mol. Biol. Int. 47:493-500(1999).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-116.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=16944957; DOI=10.1021/pr060186m;
RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT "Proteome-wide characterization of N-glycosylation events by diagonal
RT chromatography.";
RL J. Proteome Res. 5:2438-2447(2006).
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-514.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=17330941; DOI=10.1021/pr0604559;
RA Bernhard O.K., Kapp E.A., Simpson R.J.;
RT "Enhanced analysis of the mouse plasma proteome using cysteine-containing
RT tryptic glycopeptides.";
RL J. Proteome Res. 6:987-995(2007).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=18202746; DOI=10.1172/jci32525;
RA Rose K.L., Paixao-Cavalcante D., Fish J., Manderson A.P., Malik T.H.,
RA Bygrave A.E., Lin T., Sacks S.H., Walport M.J., Cook H.T., Botto M.,
RA Pickering M.C.;
RT "Factor I is required for the development of membranoproliferative
RT glomerulonephritis in factor H-deficient mice.";
RL J. Clin. Invest. 118:608-618(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Liver, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. Essential cofactors for these reactions
CC include factor H and C4BP in the fluid phase and membrane cofactor
CC protein/CD46 and CR1 on cell surfaces. The presence of these cofactors
CC on healthy cells allows degradation of deposited C3b by CFI in order to
CC prevent undesired complement activation, while in apoptotic cells or
CC microbes, the absence of such cofactors leads to C3b-mediated
CC complement activation and subsequent opsonization.
CC {ECO:0000250|UniProtKB:P05156}.
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. Interacts with C3b. Interacts with complement factor H.
CC {ECO:0000250|UniProtKB:P05156}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space
CC {ECO:0000250|UniProtKB:P05156}.
CC -!- TISSUE SPECIFICITY: Expressed in the liver by hepatocytes. Also present
CC in other cells such as monocytes, fibroblasts or keratinocytes.
CC {ECO:0000250|UniProtKB:P05156}.
CC -!- DISRUPTION PHENOTYPE: CFI-deficient mice are viable and fertile under
CC specific pathogen-free conditions. In the absence of factor I/CFI,
CC physiological cleavage of the alpha-chain of C3b is prevented, and
CC reduced plasma C3, factor B, and factor H levels are observed.
CC {ECO:0000269|PubMed:18202746}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; U47810; AAB00438.1; -; mRNA.
DR EMBL; BC150751; AAI50752.1; -; mRNA.
DR EMBL; AH007741; AAD32965.1; -; Genomic_DNA.
DR CCDS; CCDS17835.1; -.
DR RefSeq; NP_031712.2; NM_007686.3.
DR AlphaFoldDB; Q61129; -.
DR SMR; Q61129; -.
DR BioGRID; 198683; 2.
DR STRING; 10090.ENSMUSP00000077074; -.
DR MEROPS; S01.199; -.
DR GlyCosmos; Q61129; 7 sites, No reported glycans.
DR GlyGen; Q61129; 7 sites.
DR iPTMnet; Q61129; -.
DR PhosphoSitePlus; Q61129; -.
DR SwissPalm; Q61129; -.
DR CPTAC; non-CPTAC-3319; -.
DR MaxQB; Q61129; -.
DR PaxDb; 10090-ENSMUSP00000077074; -.
DR PeptideAtlas; Q61129; -.
DR ProteomicsDB; 281113; -.
DR DNASU; 12630; -.
DR Ensembl; ENSMUST00000077918.7; ENSMUSP00000077074.6; ENSMUSG00000058952.13.
DR GeneID; 12630; -.
DR KEGG; mmu:12630; -.
DR UCSC; uc008rin.1; mouse.
DR AGR; MGI:105937; -.
DR CTD; 3426; -.
DR MGI; MGI:105937; Cfi.
DR VEuPathDB; HostDB:ENSMUSG00000058952; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00930000151042; -.
DR HOGENOM; CLU_006842_19_6_1; -.
DR InParanoid; Q61129; -.
DR OMA; YECQQPK; -.
DR OrthoDB; 4629979at2759; -.
DR PhylomeDB; Q61129; -.
DR TreeFam; TF330647; -.
DR BRENDA; 3.4.21.45; 3474.
DR Reactome; R-MMU-977606; Regulation of Complement cascade.
DR BioGRID-ORCS; 12630; 1 hit in 78 CRISPR screens.
DR ChiTaRS; Cfi; mouse.
DR PRO; PR:Q61129; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q61129; Protein.
DR Bgee; ENSMUSG00000058952; Expressed in left lobe of liver and 116 other cell types or tissues.
DR ExpressionAtlas; Q61129; baseline and differential.
DR Genevisible; Q61129; MM.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
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; IEA:UniProtKB-EC.
DR GO; GO:0006956; P:complement activation; IMP:MGI.
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; cd00104; KAZAL_FS; 1.
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; PTHR24252; ACROSIN-RELATED; 1.
DR PANTHER; PTHR24252:SF7; HYALIN; 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.
PE 1: Evidence at protein level;
KW Calcium; Cleavage on pair of basic residues; Complement pathway;
KW Disulfide bond; Glycoprotein; Hydrolase; Immunity; Innate immunity;
KW Metal-binding; Protease; Reference proteome; Repeat; Secreted;
KW Serine protease; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..603
FT /note="Complement factor I"
FT /id="PRO_0000027571"
FT CHAIN 19..356
FT /note="Complement factor I heavy chain"
FT /id="PRO_0000027572"
FT CHAIN 361..603
FT /note="Complement factor I light chain"
FT /id="PRO_0000027573"
FT DOMAIN 58..111
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 117..217
FT /note="SRCR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 218..262
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 263..299
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 361..594
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 401
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P00750"
FT ACT_SITE 449
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P00750"
FT ACT_SITE 545
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P00750"
FT BINDING 244
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 247
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 249
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 251
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 257
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 258
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 281
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 284
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 286
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 288
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 294
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT BINDING 295
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 514
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17330941"
FT CARBOHYD 556
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 36..260
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 46..57
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 51..62
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 64..96
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 70..89
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 78..109
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 144..186
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 157..219
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 191..201
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 234..252
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 246..261
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 264..276
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 271..289
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 283..298
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 348..473
FT /note="Interchain (between heavy and light chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000255|PROSITE-ProRule:PRU00196, ECO:0000255|PROSITE-
FT ProRule:PRU00274, ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 386..402
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 394..464
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 473
FT /note="Interchain (with C-327)"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 487..551
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 515..530
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 541..570
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT CONFLICT 114
FT /note="K -> N (in Ref. 1; AAB00438)"
FT /evidence="ECO:0000305"
FT CONFLICT 236..252
FT /note="NGKHIPQEKACNGVNDC -> MGSTFLRRKPATVSMTV (in Ref. 1;
FT AAB00438)"
FT /evidence="ECO:0000305"
FT CONFLICT 554
FT /note="I -> T (in Ref. 1; AAB00438)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 603 AA; 67261 MW; A9B90E1EC78AEE37 CRC64;
MKLAHLSLFL LALHLSSSRS PSASDLPQEE LVDQKCLLQK YTHRSCNKVF CQPWQRCIEG
TCICKLPYQC PRAGTPVCAM NGRSYPTYCH QKSFECLHPE IKFSHNGTCA AEGKFNVSLI
YGRTKTEGLV QVKLVDQDER MFICKNSWSM AEANVACVDL GFPLGVRDIQ GSFNISGNLH
INDTECLHVH CRGVETSLAE CAFTKRRTEL SNGLAGVVCY KQDADFPTSL SFQCVNGKHI
PQEKACNGVN DCGDQSDELC CKGCRGNASL CKSGVCIPDQ YKCNGEVDCI TGEDESRCEE
DRQQNIPKGL ARSAQGEAEI ETEETEMLTP GMDNERKRIK SLLPKLSCGV KRNTHTRRKR
VIGGKPANVG DYPWQVAIKD GQRITCGGIY IGGCWILTAA HCVRPSRAHS YQVWTALLDW
LKPNSQLGIQ TVKRVIVHEK YNGATFQNDI ALIEMKMHTG KKECELPNSV PACVPWSPYL
FQPNDRCIIS GWGRGKDNQK VYSLRWGEVD LIGNCSQFYP DRYYEKEMQC AGTRDGSIDA
CKGDSGGPLV CEDINNVTYV WGIVSWGENC GKPEFPGVYT RVANYFDWIS YHVGRSLVSQ
HNV
//
