CFAI_RAT
ID CFAI_RAT Reviewed; 604 AA.
AC Q9WUW3; Q5EBC4;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 141.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=10583609; DOI=10.1046/j.1365-2567.1999.00886.x;
RA Schlaf G., Rothermel E., Oppermann M., Schieferdecker H.L., Jungermann K.,
RA Gotze O.;
RT "Rat complement factor I: molecular cloning, sequencing and expression in
RT tissues and isolated cells.";
RL Immunology 98:464-474(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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).
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 -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; Y18965; CAB41688.1; -; mRNA.
DR EMBL; BC089798; AAH89798.1; -; mRNA.
DR RefSeq; NP_077071.1; NM_024157.1.
DR AlphaFoldDB; Q9WUW3; -.
DR SMR; Q9WUW3; -.
DR STRING; 10116.ENSRNOP00000032881; -.
DR MEROPS; S01.199; -.
DR GlyGen; Q9WUW3; 6 sites.
DR iPTMnet; Q9WUW3; -.
DR PhosphoSitePlus; Q9WUW3; -.
DR PaxDb; Q9WUW3; -.
DR PRIDE; Q9WUW3; -.
DR GeneID; 79126; -.
DR KEGG; rno:79126; -.
DR UCSC; RGD:620429; rat.
DR CTD; 3426; -.
DR RGD; 620429; Cfi.
DR eggNOG; KOG3627; Eukaryota.
DR InParanoid; Q9WUW3; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q9WUW3; -.
DR Reactome; R-RNO-977606; Regulation of Complement cascade.
DR PRO; PR:Q9WUW3; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:1905370; C:serine-type endopeptidase complex; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0071354; P:cellular response to interleukin-6; IEP:RGD.
DR GO; GO:0006956; P:complement activation; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0030451; P:regulation of complement activation, alternative pathway; ISO:RGD.
DR CDD; cd00112; LDLa; 2.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 1.
DR Gene3D; 3.10.250.10; -; 1.
DR Gene3D; 4.10.400.10; -; 2.
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 Pfam; PF07648; Kazal_2; 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; SM00280; KAZAL; 1.
DR SMART; SM00192; LDLa; 2.
DR SMART; SM00202; SR; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF100895; SSF100895; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF56487; SSF56487; 1.
DR SUPFAM; SSF57424; SSF57424; 2.
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 2: Evidence at transcript 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..604
FT /note="Complement factor I"
FT /id="PRO_0000027574"
FT CHAIN 19..357
FT /note="Complement factor I heavy chain"
FT /id="PRO_0000027575"
FT CHAIN 362..604
FT /note="Complement factor I light chain"
FT /id="PRO_0000027576"
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 362..595
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 402
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P00750"
FT ACT_SITE 450
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P00750"
FT ACT_SITE 546
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 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 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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:0000255"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 515
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 557
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 349..474
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 387..403
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 395..465
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 474
FT /note="Interchain (with C-327)"
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 488..552
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 516..531
FT /evidence="ECO:0000250|UniProtKB:P05156"
FT DISULFID 542..571
FT /evidence="ECO:0000250|UniProtKB:P05156"
SQ SEQUENCE 604 AA; 67298 MW; C775AE68D2D52D51 CRC64;
MKLALLILLL LNPHLSSSKN TPASGQPQED LVEQKCLLKN YTHHSCDKVF CQPWQKCIEG
TCACKLPYQC PKAGTPVCAT NGRGYPTYCH LKSFECLHPE IKFSNNGTCT AEEKFNVSLI
YGSTDTEGIV QVKLVDQDEK MFICKNSWST VEANVACFDL GFPLGVRDIQ GRFNIPVNHK
INSTECLHVR CQGVETSLAE CTFTKKSSKA PHGLAGVVCY TQDADFPTSQ SFQCVNGKRI
PQEKACDGVN DCGDQSDELC CKGCRGQAFL CKSGVCIPNQ RKCNGEVDCI TGEDESGCEE
DKKNKIHKGL ARSDQGGETE IETEETEMLT PDMDTERKRI KSLLPKLSCG VKRNTHIRRK
RVVGGKPAEM GDYPWQVAIK DGDRITCGGI YIGGCWILTA AHCVRPSRYR NYQVWTSLLD
WLKPNSQLAV QGVSRVVVHE KYNGATYQND IALVEMKKHP GKKECELINS VPACVPWSPY
LFQPNDRCII SGWGREKDNQ KVYSLRWGEV DLIGNCSRFY PGRYYEKEMQ CAGTSDGSID
ACKGDSGGPL VCKDVNNVTY VWGIVSWGEN CGKPEFPGVY TRVASYFDWI SYYVGRPLVS
QYNV
