FCGR3A

Protein identityUniProt · HPA

UniProt accession

P08637

Gene

FCGR3A

Ensembl

ENSG00000203747

Chromosome

1

Canonical length

254 aa

Protein class

CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

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 responses, including antibody dependent cellular mediated cytotoxicity and antibody dependent enhancement of virus infections. 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 are associated with immunodeficiency 20, and 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, Aug 2020]

Canonical amino-acid sequenceUniProt

254 residues, UniProt reviewed canonical sequence.

>P08637|FCGR3A
     1  MWQLLLPTAL LLLVSAGMRT EDLPKAVVFL EPQWYRVLEK DSVTLKCQGA YSPEDNSTQW
    61  FHNESLISSQ ASSYFIDAAT VDDSGEYRCQ TNLSTLSDPV QLEVHIGWLL LQAPRWVFKE
   121  EDPIHLRCHS WKNTALHKVT YLQNGKGRKY FHHNSDFYIP KATLKDSGSY FCRGLFGSKN
   181  VSSETVNITI TQGLAVSTIS SFFPPGYQVS FCLVMVLLFA VDTGLYFSVK TNIRSSTRDW
   241  KDHKFKWRKD PQDK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FCGR3A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.39

Highest tissue expression

285 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FCGR3A.

Disease | AllUniProt

Conditions FCGR3A is implicated in, by any mechanism.

• Immunodeficiency 20 (IMD20) MIM:615707

ReferencesPubMed · IEDB

Publications for FCGR3A from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.5

gnomAD pLI

0

gnomAD missense Z

-1.04

DepMap mean gene effect

0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• antibody-dependent cellular cytotoxicity
• calcium-mediated signaling
• cell surface receptor signaling pathway
• Fc-gamma receptor signaling pathway
• immune response
• macrophage activation
• natural killer cell activation
• natural killer cell degranulation
• natural killer cell mediated cytotoxicity
• phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of natural killer cell proliferation
• positive regulation of tumor necrosis factor production

Molecular functions

• IgG binding
• IgG receptor activity
• immune receptor activity
• low-affinity IgG receptor activity

Cellular components

• external side of plasma membrane
• extracellular exosome
• extracellular space
• Fc-gamma receptor III complex
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• Immunoglobulin Fc region receptor
• Immunoglobulin domain

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• IgG-binding protein
• Immunity
• Immunoglobulin domain
• Membrane
• Phosphoprotein
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of FCGR3A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CD2
• S100A4
• IGHG2
• IGHG3
• IGHG1