A3RFZ7 · FCG3A_MACMU

  • Protein
    Low affinity immunoglobulin gamma Fc region receptor III-A
  • Gene
    FCGR3A
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG). Optimally activated upon binding of clustered antigen-IgG complexes displayed on cell surfaces, triggers lysis of antibody-coated cells, a process known as antibody-dependent cellular cytotoxicity (ADCC). Does not bind free monomeric IgG, thus avoiding inappropriate effector cell activation in the absence of antigenic trigger (PubMed:33208458).
Mediates IgG effector functions on natural killer (NK) cells. Binds antigen-IgG complexes generated upon infection and triggers NK cell-dependent cytokine production and degranulation to limit viral load and propagation. Involved in the generation of memory-like adaptive NK cells capable to produce high amounts of IFNG and to efficiently eliminate virus-infected cells via ADCC. Regulates NK cell survival and proliferation, in particular by preventing NK cell progenitor apoptosis (By similarity).
Fc-binding subunit that associates with CD247 and/or FCER1G adapters to form functional signaling complexes. Following the engagement of antigen-IgG complexes, triggers phosphorylation of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters with subsequent activation of phosphatidylinositol 3-kinase signaling and sustained elevation of intracellular calcium that ultimately drive NK cell activation. The ITAM-dependent signaling coupled to receptor phosphorylation by PKC mediates robust intracellular calcium flux that leads to production of pro-inflammatory cytokines, whereas in the absence of receptor phosphorylation it mainly activates phosphatidylinositol 3-kinase signaling leading to cell degranulation (By similarity).
Costimulates NK cells and trigger lysis of target cells independently of IgG binding (By similarity).
Mediates the antitumor activities of therapeutic antibodies. Upon ligation on monocytes triggers TNFA-dependent ADCC of IgG-coated tumor cells (By similarity).
Mediates enhanced ADCC in response to afucosylated IgGs (PubMed:34485821).

Features

Showing features for site.

TypeIDPosition(s)Description
Site195-196Cleavage; by ADAM17
Site222Important for receptor turnover

GO annotations

AspectTerm
Cellular Componentexternal side of plasma membrane
Cellular Componentextracellular space
Cellular Componentplasma membrane
Molecular FunctionIgG binding
Molecular FunctionIgG receptor activity
Biological Processantibody-dependent cellular cytotoxicity
Biological Processcalcium-mediated signaling
Biological Processcell surface receptor signaling pathway
Biological ProcessFc-gamma receptor signaling pathway
Biological Processnatural killer cell activation
Biological Processnatural killer cell degranulation
Biological Processnatural killer cell mediated cytotoxicity
Biological Processphosphatidylinositol 3-kinase/protein kinase B signal transduction

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Low affinity immunoglobulin gamma Fc region receptor III-A
  • Short names
    IgG Fc receptor III-A
  • Alternative names
    • Fc-gamma RIII-alpha (Fc-gamma RIII; Fc-gamma RIIIa; FcgammaRIIIa
      )
  • CD Antigen Name
    • CD16a

Gene names

    • Name
      FCGR3A
    • Synonyms
      FCGR3

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Macaca

Accessions

  • Primary accession
    A3RFZ7
  • Secondary accessions
    • A3RFZ3
    • A3RFZ4
    • A3RFZ5
    • A3RFZ6
    • A3RFZ8

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Single-pass type I membrane protein
Secreted
Note: Exists also as a soluble receptor.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain21-206Extracellular
Transmembrane207-229Helical
Topological domain230-254Cytoplasmic

Keywords

Phenotypes & Variants

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variant26
Natural variant229
Natural variant233

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 3 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation.

TypeIDPosition(s)Description
Signal1-20
ChainPRO_000037997721-254Low affinity immunoglobulin gamma Fc region receptor III-A
Disulfide bond47↔89
Disulfide bond128↔172
Glycosylation187N-linked (GlcNAc...) asparagine

Post-translational modification

Glycosylated. Glycosylation plays an inhibitory role in the interaction with IgG1 and IgG2.
Undergoes rapid ectodomain shedding upon NK cell stimulation. The soluble form is produced by a proteolytic cleavage mediated by ADAM17. Repeated stimulation causes receptor shedding, a mechanism that allows for increased NK cell motility and detachment from opsonized target cells while avoiding activation-induced NK cell apoptosis.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Lymphocytes and monocytes.

Gene expression databases

Interaction

Subunit

Forms a heterooligomeric complex with ITAM-containing signaling subunits, either a homodimer of CD247, a homodimer of FCER1G or a heterodimer of CD247 and FCER1G, to form a functional receptor complex. Interacts (via transmembrane domain) with signaling subunits; this interaction is a prerequisite for receptor complex expression on the cell surface and intracellular signal transduction. Binds the Fc region of antigen-complexed IgG with a preference for IgG1 and IgG3 isotypes (By similarity).
Interacts with CD2; this interaction is involved in NK cell activation and cytotoxicity (By similarity).
Interacts with S100A4; this interaction inhibits PKC-dependent phosphorylation of FCGR3A (By similarity).

Protein-protein interaction databases

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain24-105Ig-like C2-type 1
Domain107-189Ig-like C2-type 2

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 3 isoforms produced by Alternative splicing.

A3RFZ7-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    254
  • Mass (Da)
    29,005
  • Last updated
    2007-04-03 v1
  • Checksum
    51AE94602AF97911
MWQLLLPTALLLLVSAGMRAEDLPKAVVFLEPQWYRVLEKDSVTLKCQGAYSPEDNSTRWFHNESLISSQTSSYFIAAARVNNSGEYRCQTSLSTLSDPVQLEVHIGWLLLQAPRWVFKEEESIHLRCHSWKNTLLHKVTYLQNGKGRKYFHQNSDFYIPKATLKDSGSYFCRGLIGSKNVSSETVNITITQDLAVSSISSFFPPGYQVSFCLVMVLLFAVDTGLYFSVKKSVPSSTRDWEDHKFKWSKDPQDK

A3RFZ7-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

A3RFZ7-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A1D5QMQ9A0A1D5QMQ9_MACMUFCGR3277

Sequence caution

The sequence ABN69099.1 differs from that shown. Reason: Erroneous initiation
The sequence ABN69100.1 differs from that shown. Reason: Erroneous initiation
The sequence ABN69101.1 differs from that shown. Reason: Erroneous initiation
The sequence ABN69103.1 differs from that shown. Reason: Erroneous initiation
The sequence ABN69104.1 differs from that shown. Reason: Erroneous initiation

Features

Showing features for alternative sequence.

TypeIDPosition(s)Description
Alternative sequenceVSP_03776314-20in isoform 2
Alternative sequenceVSP_03776421in isoform 3

Polymorphism

Three common alleles are identified in Indian-origin rhesus macaques: 3A:01, 3A:02 and 3A:03. These alleles display similar IgG responses.

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DQ423379
EMBL· GenBank· DDBJ
ABD83659.1
EMBL· GenBank· DDBJ
mRNA
DQ423380
EMBL· GenBank· DDBJ
ABD83660.1
EMBL· GenBank· DDBJ
mRNA
EF396932
EMBL· GenBank· DDBJ
ABN69096.1
EMBL· GenBank· DDBJ
mRNA
EF396933
EMBL· GenBank· DDBJ
ABN69097.1
EMBL· GenBank· DDBJ
mRNA
EF396934
EMBL· GenBank· DDBJ
ABN69098.1
EMBL· GenBank· DDBJ
mRNA
EF396935
EMBL· GenBank· DDBJ
ABN69099.1
EMBL· GenBank· DDBJ
mRNA Different initiation
EF396936
EMBL· GenBank· DDBJ
ABN69100.1
EMBL· GenBank· DDBJ
mRNA Different initiation
EF396937
EMBL· GenBank· DDBJ
ABN69101.1
EMBL· GenBank· DDBJ
mRNA Different initiation
EF396938
EMBL· GenBank· DDBJ
ABN69102.1
EMBL· GenBank· DDBJ
mRNA
EF396939
EMBL· GenBank· DDBJ
ABN69103.1
EMBL· GenBank· DDBJ
mRNA Different initiation
EF396940
EMBL· GenBank· DDBJ
ABN69104.1
EMBL· GenBank· DDBJ
mRNA Different initiation

Genome annotation databases

Similar Proteins

Disclaimer

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