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FCGR3A Fc fragment of IgG receptor IIIa [ Homo sapiens (human) ]

Gene ID: 2214, updated on 12-Mar-2019

Summary

Official Symbol
FCGR3Aprovided by HGNC
Official Full Name
Fc fragment of IgG receptor IIIaprovided by HGNC
Primary source
HGNC:HGNC:3619
See related
Ensembl:ENSG00000203747 MIM:146740
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
CD16; FCG3; CD16A; FCGR3; IGFR3; IMD20; FCR-10; FCRIII; FCGRIII; FCRIIIA
Summary
This gene encodes a receptor for the Fc portion of immunoglobulin G, and it is involved in the removal of antigen-antibody complexes from the circulation, as well as other other antibody-dependent responses. This gene (FCGR3A) is highly similar to another nearby gene (FCGR3B) located on chromosome 1. The receptor encoded by this gene is expressed on natural killer (NK) cells as an integral membrane glycoprotein anchored through a transmembrane peptide, whereas FCGR3B is expressed on polymorphonuclear neutrophils (PMN) where the receptor is anchored through a phosphatidylinositol (PI) linkage. Mutations in this gene have been linked to susceptibility to recurrent viral infections, susceptibility to systemic lupus erythematosus, and alloimmune neonatal neutropenia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Biased expression in spleen (RPKM 154.1), lung (RPKM 70.6) and 10 other tissues See more
Orthologs

Genomic context

See FCGR3A in Genome Data Viewer
Location:
1q23.3
Exon count:
7
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 1 NC_000001.11 (161541759..161550737, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (161511549..161520413, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ribosomal protein S23 pseudogene 10 Neighboring gene tRNA-Asn (anticodon GTT) 1-1 Neighboring gene Fc fragment of IgG receptor IIc (gene/pseudogene) Neighboring gene heat shock protein family A (Hsp70) member 7

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

Associated conditions

Description Tests
Immunodeficiency 20
MedGen: C3810342 OMIM: 615707 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Genetic predictors of risk and resilience in psychiatric disorders: a cross-disorder genome-wide association study of functional impairment in major depressive disorder, bipolar disorder, and schizophrenia.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 is vertically transmitted more readily by mothers who are heterozygous for high-affinity and low-affinity FCGR3A PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env NK cells that respond with IFN-gamma and TNF-alpha cytokine production to HIV-1 gp120 peptides have reduced CD16 and NKp46 expression and have increased levels of CD57 PubMed
env IgG2 and IgG4 bind more poorly to enzymatically deglycosylated recombinant gp120 (rgp120) than to unchanged rgp120 PubMed
Nef nef Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Nef may antagonize restriction activity of FCGR3A against production of infectious wild-type HIV-1 PubMed
Tat tat HIV-1 Tat upregulates the expression of CCR2, CD16, and TLR4 in monocyte-derived macrophages PubMed
tat HIV-1 Tat inhibits the rise in intracellular free calcium concentration in Natural Killer (NK) cells upon cross-linking of the adhesion molecule CD11a and the activation molecule CD16, indicating Tat is involved in the impairment of NK cell function PubMed
Vpr vpr Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Vpu may antagonize restriction activity of FCGR3A against production of infectious wild-type HIV-1 PubMed
Vpu vpu The ability of HIV-1 Vpu to antagonize tetherin is important for the antibody opsonization of HIV-infected cells, which in turn increases FCGRIII (CD16) signaling PubMed
vpu Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Vpu may antagonize restriction activity of FCGR3A against production of infectious wild-type HIV-1 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • FCGR activation, organism-specific biosystem (from REACTOME)
    FCGR activation, organism-specific biosystemCross-linking of FCGRs with IgG coated immune complexes results in tyrosine phosphorylation of the immuno tyrosine activation motif (ITAMs) of the rececptor by membrane-bound tyrosine kinases of the ...
  • Fc gamma R-mediated phagocytosis, organism-specific biosystem (from KEGG)
    Fc gamma R-mediated phagocytosis, organism-specific biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
  • Fc gamma R-mediated phagocytosis, conserved biosystem (from KEGG)
    Fc gamma R-mediated phagocytosis, conserved biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
  • Fcgamma receptor (FCGR) dependent phagocytosis, organism-specific biosystem (from REACTOME)
    Fcgamma receptor (FCGR) dependent phagocytosis, organism-specific biosystemPhagocytosis is one of the important innate immune responses that function to eliminate invading infectious agents. Monocytes, macrophages, and neutrophils are the professional phagocytic cells. Phag...
  • 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...
  • Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystem (from REACTOME)
    Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystemA number of receptors and cell adhesion molecules play a key role in modifying the response of cells of lymphoid origin (such as B-, T- and NK cells) to self and tumor antigens, as well as to pathoge...
  • 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
  • Leishmaniasis, organism-specific biosystem (from KEGG)
    Leishmaniasis, organism-specific biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
  • Leishmaniasis, conserved biosystem (from KEGG)
    Leishmaniasis, conserved biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
  • Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
    Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
  • Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
    Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
  • Osteoclast differentiation, organism-specific biosystem (from KEGG)
    Osteoclast differentiation, organism-specific biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
  • Osteoclast differentiation, conserved biosystem (from KEGG)
    Osteoclast differentiation, conserved biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
  • Phagosome, organism-specific biosystem (from KEGG)
    Phagosome, organism-specific biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
  • Phagosome, conserved biosystem (from KEGG)
    Phagosome, conserved biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
  • Regulation of actin dynamics for phagocytic cup formation, organism-specific biosystem (from REACTOME)
    Regulation of actin dynamics for phagocytic cup formation, organism-specific biosystemThe actin cytoskeleton is fundamental for phagocytosis and members of the Rho family GTPases RAC and CDC42 are involved in actin cytoskeletal regulation leading to pseudopod extension. Active RAC and...
  • Role of phospholipids in phagocytosis, organism-specific biosystem (from REACTOME)
    Role of phospholipids in phagocytosis, organism-specific biosystemPhospholipases play an integral role in phagocytosis by generating essential second messengers. An early step in phagocytic signaling is the association of PIP2 and IP3 with the phagocytic cup. These...
  • 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...
  • Systemic lupus erythematosus, organism-specific biosystem (from KEGG)
    Systemic lupus erythematosus, organism-specific biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
  • Systemic lupus erythematosus, conserved biosystem (from KEGG)
    Systemic lupus erythematosus, conserved biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
    Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
IgG binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
Fc-gamma receptor signaling pathway involved in phagocytosis TAS
Traceable Author Statement
more info
 
immune response TAS
Traceable Author Statement
more info
PubMed 
regulation of immune response TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
external side of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome HDA PubMed 
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
low affinity immunoglobulin gamma Fc region receptor III-A
Names
CD16a antigen
Fc fragment of IgG, low affinity III, receptor for (CD16)
Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Fc gamma receptor III-A
Fc-gamma RIII-alpha
Fc-gamma receptor III-2 (CD 16)
Fc-gamma receptor IIIb (CD16)
FcgammaRIIIA
igG Fc receptor III-2
immunoglobulin G Fc receptor III
low affinity immunoglobulin gamma receptor III-a Fc fragment
neutrophil-specific antigen NA

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_009066.1 RefSeqGene

    Range
    5001..13865
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_60

mRNA and Protein(s)

  1. NM_000569.7NP_000560.6  low affinity immunoglobulin gamma Fc region receptor III-A isoform a

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) retains an intron in its 5' UTR and 5' coding region compared to variant 3. The encoded isoform (a) has a longer and distinct N-terminus compared to isoform c. This isoform (a) lacks a predicted signal peptide compared to isoform c.
    Source sequence(s)
    AK302126, BC033678
    Consensus CDS
    CCDS1232.2
    UniProtKB/Swiss-Prot
    P08637
    UniProtKB/TrEMBL
    M9MML0
    Related
    ENSP00000356946.4, ENST00000367969.8
    Conserved Domains (3) summary
    cd05752
    Location:131209
    Ig1_FcgammaR_like; Frst immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
    cd05753
    Location:213295
    Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
    smart00410
    Location:137209
    IG_like; Immunoglobulin like
  2. NM_001127592.2NP_001121064.2  low affinity immunoglobulin gamma Fc region receptor III-A isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) retains an intron in its 5' UTR and 5' coding region, and uses an alternate in-frame splice site in its 5' coding region compared to variant 3. The encoded isoform (2) is longer than isoform c. This isoform (b) lacks a predicted signal peptide compared to isoform c.
    Source sequence(s)
    AK302126, BC036723, DA944383, M24853
    UniProtKB/Swiss-Prot
    P08637
    Related
    ENSP00000410180.2, ENST00000426740.6
  3. NM_001127593.1NP_001121065.1  low affinity immunoglobulin gamma Fc region receptor III-A isoform c precursor

    See identical proteins and their annotated locations for NP_001121065.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) encodes isoform c. Variants 3, 4 and 6 encode the same isoform (c).
    Source sequence(s)
    AL590385, BC036723, DA957430, M24853
    Consensus CDS
    CCDS44266.1
    UniProtKB/Swiss-Prot
    P08637
    Related
    ENSP00000416607.1, ENST00000436743.5
    Conserved Domains (3) summary
    cd05752
    Location:26104
    Ig1_FcgammaR_like; Frst immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
    cd05753
    Location:108190
    Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
    smart00410
    Location:32104
    IG_like; Immunoglobulin like
  4. NM_001127595.1NP_001121067.1  low affinity immunoglobulin gamma Fc region receptor III-A isoform c precursor

    See identical proteins and their annotated locations for NP_001121067.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 3. Variants 3, 4 and 6 encode the same isoform (c).
    Source sequence(s)
    AL590385, BC036723, DA933259, DA957430, M24853
    Consensus CDS
    CCDS44266.1
    UniProtKB/Swiss-Prot
    P08637
    Related
    ENSP00000356944.3, ENST00000367967.7
    Conserved Domains (3) summary
    cd05752
    Location:26104
    Ig1_FcgammaR_like; Frst immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
    cd05753
    Location:108190
    Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
    smart00410
    Location:32104
    IG_like; Immunoglobulin like
  5. NM_001127596.1NP_001121068.1  low affinity immunoglobulin gamma Fc region receptor III-A isoform d precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses an alternate in-frame splice site in the 5' coding region compared to variant 3. The encoded isoform (d) is shorter than isoform c.
    Source sequence(s)
    AL590385, BC036723, DA674960, DA957430, M24853
    UniProtKB/Swiss-Prot
    P08637
    Conserved Domains (2) summary
    cd05752
    Location:25103
    Ig1_FcgammaR_like; Frst immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
    cd05753
    Location:107189
    Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
  6. NM_001329120.1NP_001316049.1  low affinity immunoglobulin gamma Fc region receptor III-A isoform c precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 3. Variants 3, 4 and 6 encode the same isoform (c).
    Source sequence(s)
    AL590385, BC036723
    Consensus CDS
    CCDS44266.1
    UniProtKB/Swiss-Prot
    P08637
    Conserved Domains (3) summary
    cd05752
    Location:26104
    Ig1_FcgammaR_like; Frst immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
    cd05753
    Location:108190
    Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
    smart00410
    Location:32104
    IG_like; Immunoglobulin like
  7. NM_001329122.1NP_001316051.1  low affinity immunoglobulin gamma Fc region receptor III-A isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) retains an intron in its 5' UTR and 5' coding region, and lacks an alternate in-frame exon in its 3' coding region compared to variant 3. The encoded isoform is longer than isoform c. This isoform (e) lacks a predicted signal peptide compared to isoform c.
    Source sequence(s)
    AL590385, BC036723

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p12 Primary Assembly

    Range
    161541759..161550737 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024454064.1XP_024309832.1  low affinity immunoglobulin gamma Fc region receptor III-A isoform X1

    Conserved Domains (2) summary
    cd05752
    Location:25103
    Ig1_FcgammaR_like; Frst immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
    cd05753
    Location:107189
    Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs) and similar proteins
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