Reviewed, UniProtKB/Swiss-Prot P05156 (CFAI_HUMAN)

Names and origin

Protein names

Recommended name:
    Complement factor I
    EC=3.4.21.45
Alternative name(s):
    C3B/C4B inactivator
Cleaved into the following 2 chains:
    1- Recommended name:
            Complement factor I heavy chain
    2- Recommended name:
            Complement factor I light chain

Gene names

Name:	CFI
Synonyms:	IF

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	583 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Responsible for cleaving the alpha-chains of C4b and C3b in the presence of the cofactors C4-binding protein and factor H respectively.
Catalytic activity	Inactivates complement subcomponents C3b, iC3b and C4b by proteolytic cleavage.
Subunit structure	Heterodimer of a light and heavy chains linked by disulfide bonds.
Subcellular location	Secreted › extracellular space.
Tissue specificity	Plasma.
Involvement in disease	Defects in CFI are the cause of component I deficiency (CFI deficiency) [MIM:217030]. CFI deficiency is an autosomal recessive condition associated with a propensity to pyogenic infections. Defects in CFI may be associated with or predispose to hemolytic uraemic syndrome (HUS) [MIM:235400]. HUS, the most frequent cause of acute renal failure in childhood, is characterized by the association of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. The majority of HUS cases occur after an episode of infectious diarrhea, and are associated with E.coli O157:H7 infection. However, atypical cases of HUS occur in the absence of infectious diarrhea, although less commonly. Some are inherited in either an autosomal dominant or a recessive pattern and these patients often experience relapse and progress to hypertension and chronic renal disease. Sporadic forms can occur with many of the same signs and symptoms. Defects in CFI are the cause of complement factor I deficiency (CFI deficiency) [MIM:610984]. CFI deficiency is an autosomal recessive condition associated with a propensity to pyogenic infections.
Sequence similarities	Belongs to the peptidase S1 family. Contains 2 LDL-receptor class A domains. Contains 1 peptidase S1 domain. Contains 1 SRCR domain.

Ontologies

Keywords
Biological process	Complement pathway Immune response Innate immunity
Cellular component	Secreted
Disease	Disease mutation
Domain	Repeat Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	complement activation, classical pathway Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: HPA extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: InterPro nucleus Inferred from direct assay. Source: HPA
Molecular function	scavenger receptor activity Inferred from electronic annotation. Source: InterPro serine-type endopeptidase activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18
	Chain	19 – 583	565	Complement factor I		PRO_0000027568
	Chain	19 – 335	317	Complement factor I heavy chain		PRO_0000027569
	Chain	340 – 583	244	Complement factor I light chain		PRO_0000027570
Regions
	Domain	114 – 212	99	SRCR
	Domain	213 – 257	45	LDL-receptor class A 1
	Domain	258 – 294	37	LDL-receptor class A 2
	Domain	340 – 574	235	Peptidase S1
Sites
	Active site	380	1	Charge relay system By similarity
	Active site	429	1	Charge relay system By similarity
	Active site	525	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	70	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	103	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	177	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	464	1	N-linked (GlcNAc...) Ref.6 Ref.5
	Glycosylation	494	1	N-linked (GlcNAc...) Potential
	Glycosylation	536	1	N-linked (GlcNAc...) Ref.6
	Disulfide bond	154 ↔ 214		By similarity
	Disulfide bond	186 ↔ 196		By similarity
	Disulfide bond	229 ↔ 247		By similarity
	Disulfide bond	241 ↔ 256		By similarity
	Disulfide bond	259 ↔ 271		By similarity
	Disulfide bond	266 ↔ 284		By similarity
	Disulfide bond	278 ↔ 293		By similarity
	Disulfide bond	365 ↔ 381		By similarity
	Disulfide bond	467 ↔ 531		By similarity
	Disulfide bond	495 ↔ 510		By similarity
	Disulfide bond	521 ↔ 550		By similarity
Natural variations
	Natural variant	243	1	G → D in CFI deficiency.		VAR_034907
	Natural variant	300	1	A → T: dbSNP rs11098044.		VAR_034908
	Natural variant	340	1	I → T Predisposes to atypical HUS. Ref.12		VAR_030343
	Natural variant	418	1	H → L in CFI deficiency.		VAR_026757
	Natural variant	524	1	D → V Associated with atypical HUS. Ref.10		VAR_030344
Experimental info
	Sequence conflict	558	1	V → F in AAA52455. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P05156-1 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: 76BB11EAB7F063A8	FASTA	583	65,720
	10 20 30 40 50 60 MKLLHVFLLF LCFHLRFCKV TYTSQEDLVE KKCLAKKYTH LSCDKVFCQP WQRCIEGTCV 70 80 90 100 110 120 CKLPYQCPKN GTAVCATNRR SFPTYCQQKS LECLHPGTKF LNNGTCTAEG KFSVSLKHGN 130 140 150 160 170 180 TDSEGIVEVK LVDQDKTMFI CKSSWSMREA NVACLDLGFQ QGADTQRRFK LSDLSINSTE 190 200 210 220 230 240 CLHVHCRGLE TSLAECTFTK RRTMGYQDFA DVVCYTQKAD SPMDDFFQCV NGKYISQMKA 250 260 270 280 290 300 CDGINDCGDQ SDELCCKACQ GKGFHCKSGV CIPSQYQCNG EVDCITGEDE VGCAGFASVA 310 320 330 340 350 360 QEETEILTAD MDAERRRIKS LLPKLSCGVK NRMHIRRKRI VGGKRAQLGD LPWQVAIKDA 370 380 390 400 410 420 SGITCGGIYI GGCWILTAAH CLRASKTHRY QIWTTVVDWI HPDLKRIVIE YVDRIIFHEN 430 440 450 460 470 480 YNAGTYQNDI ALIEMKKDGN KKDCELPRSI PACVPWSPYL FQPNDTCIVS GWGREKDNER 490 500 510 520 530 540 VFSLQWGEVK LISNCSKFYG NRFYEKEMEC AGTYDGSIDA CKGDSGGPLV CMDANNVTYV 550 560 570 580 WGVVSWGENC GKPEFPGVYT KVANYFDWIS YHVGRPFISQ YNV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of primary amino acid sequence of human complement control protein factor I from an analysis of cDNA clones." Catterall C.F., Lyons A., Sim R.M., Day A.J., Harris T.J.R. Biochem. J. 242:849-856(1987) [PubMed: 2954545] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Human complement factor I: analysis of cDNA-derived primary structure and assignment of its gene to chromosome 4." Goldberger G., Bruns G.A.P., Rits M., Edge M.D., Kwiatkowski D.J. J. Biol. Chem. 262:10065-10071(1987) [PubMed: 2956252] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning and characterization of the promoter for the human complement factor I (C3b/C4b inactivator) gene." Minta J.O., Fung M., Turner S., Eren R., Zemach L., Rits M., Goldberger G. Gene 208:17-24(1998) [PubMed: 9479036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18. Tissue: Liver.
[4]	"Beta-sheet secondary structure of an LDL receptor domain from complement factor I by consensus structure predictions and spectroscopy." Ullman C.G., Haris P.I., Smith K.F., Sim R.B., Emery V.C., Perkins S.J. FEBS Lett. 371:199-203(1995) [PubMed: 7672128] [Abstract] Cited for: PROTEIN SEQUENCE OF 258-269.
[5]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed: 14760718] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-464, MASS SPECTROMETRY. Tissue: Plasma.
[6]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-70; ASN-103; ASN-177; ASN-464 AND ASN-536, MASS SPECTROMETRY. Tissue: Plasma.
[7]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-103, MASS SPECTROMETRY. Tissue: Liver.
[8]	"The molecular basis of hereditary complement factor I deficiency." Vyse T.J., Morley B.J., Bartok I., Theodoridis E.L., Davies K.A., Webster A.D.B., Walport M.J. J. Clin. Invest. 97:925-933(1996) [PubMed: 8613545] [Abstract] Cited for: VARIANT CFI DEFICIENCY LEU-418.
[9]	"Molecular characterization of homozygous hereditary factor I deficiency." Baracho G.V., Nudelman V., Isaac L. Clin. Exp. Immunol. 131:280-286(2003) [PubMed: 12562389] [Abstract] Cited for: INVOLVEMENT IN CFI DEFICIENCY.
[10]	"Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome." Fremeaux-Bacchi V., Dragon-Durey M.-A., Blouin J., Vigneau C., Kuypers D., Boudailliez B., Loirat C., Rondeau E., Fridman W.H. J. Med. Genet. 41:E84-E84(2004) [PubMed: 15173250] [Abstract] Cited for: VARIANT VAL-524.
[11]	"Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome." Servais A., Fremeaux-Bacchi V., Lequintrec M., Salomon R., Blouin J., Knebelmann B., Gruenfeld J.-P., Lesavre P., Noeel L.-H., Fakhouri F. J. Med. Genet. 44:193-199(2007) [PubMed: 17018561] [Abstract] Cited for: VARIANT CFI DEFICIENCY ASP-243.
[12]	"A missense mutation in factor I (IF) predisposes to atypical haemolytic uraemic syndrome." Geelen J., van den Dries K., Roos A., van de Kar N., de Kat Angelino C., Klasen I., Monnens L., van den Heuvel L. Pediatr. Nephrol. 22:371-375(2007) [PubMed: 17106690] [Abstract] Cited for: VARIANT THR-340.
+	Additional computationally mapped references.

Web resources

CFIbase

CFI mutation db

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	Y00318 mRNA. Translation: CAA68416.1. Different initiation. J02770 mRNA. Translation: AAA52455.1. AF005095 Genomic DNA. Translation: AAC08733.2.
IPI	IPI00291867.
PIR	A29154.
RefSeq	NP_000195.2.
UniGene	Hs.312485
3D structure databases
HSSP	HSSP built from PDB template 1RTF based on UniProtKB P00750.
ModBase	Search...
Protein family/group databases
MEROPS	S01.199.
2-D gel databases
SWISS-2DPAGE	P05156.
Proteomic databases
PeptideAtlas	P05156.
PRIDE	P05156.
Genome annotation databases
Ensembl	ENSG00000205403. Homo sapiens. [Contig view]
GeneID	3426.
KEGG	hsa:3426.
Organism-specific databases
GeneCards	GC04M110881.
H-InvDB	HIX0004438.
HGNC	HGNC:5394. CFI.
HPA	CAB016777. HPA001143.
MIM	217030. gene. 235400. phenotype. 610984. phenotype.
Orphanet	2134. Atypical hemolytic uremic syndrome.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P05156.
HOVERGEN	P05156.
Enzyme and pathway databases
BRENDA	3.4.21.45. 247.
Gene expression databases
ArrayExpress	P05156.
Bgee	P05156.
CleanEx	HS_CFI.
GermOnline	ENSG00000205403. Homo sapiens.
Family and domain databases
InterPro	IPR003884. FacI_MAC. IPR002172. LDL_rcpt_classA_cys-rich. IPR018114. Peptidase_S1/S6_AS. IPR001254. Peptidase_S1_S6. IPR001314. Peptidase_S1A. IPR011497. Prot_Inh_Kazal_2. IPR001190. Srcr_rcpt. IPR017448. Srcr_rcpt-rel. [Graphical view]
Gene3D	G3DSA:4.10.400.10. LDL_rcpt_classA_cys-rich. 1 hit.
Pfam	PF07648. Kazal_2. 1 hit. PF00057. Ldl_recept_a. 2 hits. PF00530. SRCR. 1 hit. PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN. PR00261. LDLRECEPTOR.
SMART	SM00057. FIMAC. 1 hit. SM00192. LDLa. 2 hits. SM00202. SR. 1 hit. SM00020. Tryp_SPc. 1 hit. [Graphical view]
PROSITE	PS01209. LDLRA_1. 1 hit. PS50068. LDLRA_2. 2 hits. PS00420. SRCR_1. False negative. PS50287. SRCR_2. 1 hit. PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	13512.
SOURCE	Search...

Entry information

Entry name

CFAI_HUMAN

Accession

Primary (citable) accession number: P05156
Secondary accession number(s): O60442

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 13, 1987
Last modified:	June 16, 2009
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)