CFI complement factor I [Homo sapiens] - Gene

Help top of page

Summary

Official Symbol: CFIprovided by HGNC
Official Full Name: complement factor Iprovided by HGNC
Primary source: HGNC:5394
See related: Ensembl:ENSG00000205403; HPRD:01955; MIM:217030; Vega:OTTHUMG00000161109
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FI; IF; KAF; AHUS3; C3BINA; C3b-INA
Summary: This gene encodes a serine proteinase that is essential for regulating the complement cascade. The encoded preproprotein is cleaved to produce both heavy and light chains, which are linked by disulfide bonds to form a heterodimeric glycoprotein. This heterodimer can cleave and inactivate the complement components C4b and C3b, and it prevents the assembly of the C3 and C5 convertase enzymes. Defects in this gene cause complement factor I deficiency, an autosomal recessive disease associated with a susceptibility to pyogenic infections. Mutations in this gene have been associated with a predisposition to atypical hemolytic uraemic syndrome, a disease characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Primary glomerulonephritis with immmune deposits is another condition associated with mutation of this gene. [provided by RefSeq, Jul 2008]

Help top of page

Genomic context

Location :: 4q25

Sequence :: Chromosome: 4; NC_000004.11 (110661848..110723335, complement)

See CFI in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

Help top of page

Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Help top of page

Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Forster resonance energy transfer was used to investigate the 10 muM K(D) (210 kD) complex between the N-terminal region of the soluble complement regulator, factor H (FH1-4), and the key activation-specific complement fragment, C3b.
Title: Use of time-resolved FRET to validate crystal structure of complement regulatory complex between C3b and factor H (N terminus).
Data show that FI is in a proteolytically inactive form, demonstrating that it circulates in a zymogen-like state.
Title: Structural basis for complement factor I control and its disease-associated sequence polymorphisms.
Study describes the molecular and functional consequences of two novel mutations of FI.
Title: Molecular characterization of two novel cases of complete complement inhibitor Factor I deficiency.
Study identified novel mutations in CFH, CFHR5, CFI, CFB and C3 in American patients with atypical hemolytic uremic syndrome.
Title: Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome.
Role of a common variant near the complement factor I gene in susceptibility to age-related macular degeneration.
Title: Additional evidence to support the role of a common variant near the complement factor I gene in susceptibility to age-related macular degeneration.
Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
In a large cohort of 202 patients with aHUS, we identified 23 patients carrying exonic mutations in CFI
Title: Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome.
the FIMAC domain appears to harbor the main binding sites important for the ability of FI to degrade C4b and C3b
Title: Analysis of binding sites on complement factor I that are required for its activity.
Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome.
Title: Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome.

Submit: New GeneRIF Correction See all (35)

Help top of page

Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.

Complement factor I deficiency

MIM: 610984

Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.

Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC).

Hemolytic uremic syndrome, atypical, susceptibility to

MIM: 235400

Hemolytic uremic syndrome, atypical, susceptibility to, 3

MIM: 612923

Help top of page

Products	Interactant	Other Gene	Source	Pubs	Description
P05156	P01024	C3	HPRD	PubMed
P05156	P08603	CFH	HPRD	PubMed
BioGRID:109652	BioGRID:107179	C3	BioGRID	PubMed	Biochemical Activity; Reconstituted Complex

Function	Evidence Code	Pubs
peptidase activity	IEA Inferred from Electronic Annotation more info
scavenger receptor activity	IEA Inferred from Electronic Annotation more info
serine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
complement activation, classical pathway	IEA Inferred from Electronic Annotation more info
innate immune response	IEA Inferred from Electronic Annotation more info
proteolysis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
extracellular region	IEA Inferred from Electronic Annotation more info
extracellular space	IEA Inferred from Electronic Annotation more info
membrane	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: complement factor I

Names: complement factor I; C3b-inactivator; C3B/C4B inactivator; complement component I; light chain of factor I; Konglutinogen-activating factor; complement factor I heavy chain; complement control protein factor I

NP_000195.2

EC 3.4.21.45

Help top of page

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007569.1 RefSeqGene

Range

4807..66294

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_48

mRNA and Protein(s)

NM_000204.3 → NP_000195.2 complement factor I preproprotein

Status: REVIEWED

Source sequence(s)

AK290625, BM955734, DC392360, J02770, N63668

Consensus CDS

CCDS34049.1

UniProtKB/TrEMBL

A8K3L0

UniProtKB/Swiss-Prot

P05156

Related

ENSP00000378130, ENST00000394634

Conserved Domains (4) summary

cd00112
Location:259 – 293
Blast Score: 108

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd00190
Location:340 – 572
Blast Score: 526

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

smart00057
Location:43 – 108
Blast Score: 256

FIMAC; factor I membrane attack complex

cl02509
Location:114 – 215
Blast Score: 202

SRCR; Scavenger receptor cysteine-rich domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p5 Primary Assembly

Range

110661848..110723335, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

106394822..106455453, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Help top of page

Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC126283.3 (8892..70181)	None
genomic	AF005095.2	AAC08733.2
genomic	CH471057.1	EAX06250.1
		EAX06251.1
		EAX06252.1
mRNA	AK122686.1	None
mRNA	AK290625.1	BAF83314.1
mRNA	AK299232.1	BAG61264.1
mRNA	BC005275.1	None
mRNA	BC020718.1	AAH20718.1
mRNA	BM955734.1	None
mRNA	BP235907.1	None
mRNA	DC392360.1	None
mRNA	J02770.1	AAA52455.1
mRNA	N63668.1	None
mRNA	Y00318.1	CAA68416.1
		CAA68417.1
		CAA68418.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P05156.2	GenPept	UniProtKB/Swiss-Prot:P05156
Q6LAM0	GenPept	UniProtKB/TrEMBL:Q6LAM0
Q6LAM1	GenPept	UniProtKB/TrEMBL:Q6LAM1
Q8WW88	GenPept	UniProtKB/TrEMBL:Q8WW88

Help top of page

Additional Links

Epigenomics
MIM 217030
CFIbase: Mutation registry for Factor I deficiency (previously known as IFbase) CFIbase/
GeneTests for MIM: 217030
Resource of Asian Primary Immunodeficiency Diseases (RAPID) AGID_44
UCSC UCSC
UniGene Hs.312485