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CFI complement factor I [ Homo sapiens (human) ]

Gene ID: 3426, updated on 18-Jun-2019

Summary

Official Symbol
CFIprovided by HGNC
Official Full Name
complement factor Iprovided by HGNC
Primary source
HGNC:HGNC:5394
See related
Ensembl:ENSG00000205403 MIM:217030
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; ARMD13; 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 uremic syndrome, a disease characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Primary glomerulonephritis with immune deposits and age-related macular degeneration are other conditions associated with mutations of this gene. [provided by RefSeq, Dec 2015]
Expression
Biased expression in liver (RPKM 171.8), kidney (RPKM 63.6) and 9 other tissues See more
Orthologs

Genomic context

See CFI in Genome Data Viewer
Location:
4q25
Exon count:
17
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 4 NC_000004.12 (109731221..109802225, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (110661848..110723381, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene mitochondrial calcium uniporter dominant negative beta subunit Neighboring gene caspase 6 Neighboring gene phospholipase A2 group XIIA Neighboring gene GAR1 ribonucleoprotein Neighboring gene retinal pigment epithelium-derived rhodopsin homolog Neighboring gene leucine rich repeat, Ig-like and transmembrane domains 3

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.
NHGRI GWA Catalog
Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.
NHGRI GWA Catalog
Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC).
NHGRI GWA Catalog
Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits.
NHGRI GWA Catalog
Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.
NHGRI GWA Catalog
Seven new loci associated with age-related macular degeneration.
NHGRI GWA Catalog

Pathways from BioSystems

  • Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
    Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
  • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
    Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement and coagulation cascades, conserved biosystem (from KEGG)
    Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement cascade, organism-specific biosystem (from REACTOME)
    Complement cascade, organism-specific biosystemIn the complement cascade, a panel of soluble molecules rapidly and effectively senses a danger or damage and triggers reactions to provide a response that discriminates among foreign intruders, cell...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Regulation of Complement cascade, organism-specific biosystem (from REACTOME)
    Regulation of Complement cascade, organism-specific biosystemTwo inherent features of complement activation make its regulation very important: 1. There is an inherent positive feedback loop because the product of C3 activation forms part of an enzyme that cau...
  • Staphylococcus aureus infection, organism-specific biosystem (from KEGG)
    Staphylococcus aureus infection, organism-specific biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...
  • Staphylococcus aureus infection, conserved biosystem (from KEGG)
    Staphylococcus aureus infection, conserved biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
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
 
endocytosis 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
 
regulation of complement activation TAS
Traceable Author Statement
more info
 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
extracellular exosome HDA PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space HDA PubMed 
membrane IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
complement factor I
Names
C3B/C4B inactivator
C3b-inactivator
Konglutinogen-activating factor
complement component I
complement control protein factor I
complement factor I heavy chain
light chain of factor I
NP_000195.2
NP_001304986.2
NP_001317964.1
XP_006714273.1
XP_011530222.1
XP_016863653.1
XP_016863654.1
XP_016863655.1

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

  1. NG_007569.1 RefSeqGene

    Range
    4807..66294
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_48

mRNA and Protein(s)

  1. NM_000204.4NP_000195.2  complement factor I isoform 2 preproprotein

    See identical proteins and their annotated locations for NP_000195.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) encodes isoform 2.
    Source sequence(s)
    AK290625, BM955734, DC298508, DC392360, J02770, N63668
    Consensus CDS
    CCDS34049.1
    UniProtKB/Swiss-Prot
    P05156
    UniProtKB/TrEMBL
    A8K3L0
    Related
    ENSP00000378130.2, ENST00000394634.6
    Conserved Domains (7) summary
    smart00020
    Location:339569
    Tryp_SPc; Trypsin-like serine protease
    smart00057
    Location:43108
    FIMAC; factor I membrane attack complex
    smart00202
    Location:114215
    SR; Scavenger receptor Cys-rich
    cd00112
    Location:224256
    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:340572
    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 ...
    pfam00057
    Location:257293
    Ldl_recept_a; Low-density lipoprotein receptor domain class A
    pfam00530
    Location:119214
    SRCR; Scavenger receptor cysteine-rich domain
  2. NM_001318057.2NP_001304986.2  complement factor I isoform 1 preproprotein

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) contains an alternate in-frame exon compared to variant 2. The encoded isoform (1) is longer than isoform 2.
    Source sequence(s)
    AC126283
    Consensus CDS
    CCDS82946.1
    Related
    ENSP00000378131.3, ENST00000394635.7
  3. NM_001331035.2NP_001317964.1  complement factor I isoform 3 preproprotein

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon in the central coding region compared to variant 2. The encoded isoform (3) lacks a portion of the heavy chain compared to isoform 2.
    Source sequence(s)
    AK290625, BM955734, BX453590, DC392360, J02770, N63668
    Consensus CDS
    CCDS82945.1
    UniProtKB/Swiss-Prot
    P05156
    UniProtKB/TrEMBL
    A8K3L0, G3XAM2
    Related
    ENSP00000427438.1, ENST00000512148.5
    Conserved Domains (7) summary
    smart00020
    Location:332562
    Tryp_SPc; Trypsin-like serine protease
    smart00057
    Location:43108
    FIMAC; factor I membrane attack complex
    smart00202
    Location:114215
    SR; Scavenger receptor Cys-rich
    cd00112
    Location:224256
    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:333565
    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 ...
    pfam00057
    Location:257293
    Ldl_recept_a; Low-density lipoprotein receptor domain class A
    pfam00530
    Location:119214
    SRCR; Scavenger receptor cysteine-rich domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p13 Primary Assembly

    Range
    109731221..109802225 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017008165.2XP_016863654.1  complement factor I isoform X3

  2. XM_017008164.2XP_016863653.1  complement factor I isoform X2

  3. XM_011531920.2XP_011530222.1  complement factor I isoform X1

    Conserved Domains (8) summary
    smart00020
    Location:347519
    Tryp_SPc; Trypsin-like serine protease
    smart00057
    Location:43108
    FIMAC; factor I membrane attack complex
    smart00202
    Location:114215
    SR; Scavenger receptor Cys-rich
    cd00112
    Location:224256
    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:348519
    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 ...
    pfam00057
    Location:257293
    Ldl_recept_a; Low-density lipoprotein receptor domain class A
    pfam00530
    Location:119214
    SRCR; Scavenger receptor cysteine-rich domain
    pfam13900
    Location:524555
    GVQW; Putative domain of unknown function
  4. XM_017008166.2XP_016863655.1  complement factor I isoform X4

  5. XM_006714210.4XP_006714273.1  complement factor I isoform X5

    Conserved Domains (7) summary
    smart00020
    Location:347520
    Tryp_SPc; Trypsin-like serine protease
    smart00057
    Location:43108
    FIMAC; factor I membrane attack complex
    smart00202
    Location:114215
    SR; Scavenger receptor Cys-rich
    cd00112
    Location:224256
    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:348520
    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 ...
    pfam00057
    Location:257293
    Ldl_recept_a; Low-density lipoprotein receptor domain class A
    pfam00530
    Location:119214
    SRCR; Scavenger receptor cysteine-rich domain
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