A3RFZ7 · FCG3A_MACMU
- ProteinLow affinity immunoglobulin gamma Fc region receptor III-A
- GeneFCGR3A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids254 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 195-196 | Cleavage; by ADAM17 | ||||
Sequence: AV | ||||||
Site | 222 | Important for receptor turnover | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | external side of plasma membrane | |
Cellular Component | extracellular space | |
Cellular Component | plasma membrane | |
Molecular Function | IgG binding | |
Molecular Function | IgG receptor activity | |
Biological Process | antibody-dependent cellular cytotoxicity | |
Biological Process | calcium-mediated signaling | |
Biological Process | cell surface receptor signaling pathway | |
Biological Process | Fc-gamma receptor signaling pathway | |
Biological Process | natural killer cell activation | |
Biological Process | natural killer cell degranulation | |
Biological Process | natural killer cell mediated cytotoxicity | |
Biological Process | phosphatidylinositol 3-kinase/protein kinase B signal transduction |
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameLow affinity immunoglobulin gamma Fc region receptor III-A
- Short namesIgG Fc receptor III-A
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Macaca
Accessions
- Primary accessionA3RFZ7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Note: Exists also as a soluble receptor.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 21-206 | Extracellular | ||||
Sequence: EDLPKAVVFLEPQWYRVLEKDSVTLKCQGAYSPEDNSTRWFHNESLISSQTSSYFIAAARVNNSGEYRCQTSLSTLSDPVQLEVHIGWLLLQAPRWVFKEEESIHLRCHSWKNTLLHKVTYLQNGKGRKYFHQNSDFYIPKATLKDSGSYFCRGLIGSKNVSSETVNITITQDLAVSSISSFFPPG | ||||||
Transmembrane | 207-229 | Helical | ||||
Sequence: YQVSFCLVMVLLFAVDTGLYFSV | ||||||
Topological domain | 230-254 | Cytoplasmic | ||||
Sequence: KKSVPSSTRDWEDHKFKWSKDPQDK |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 26 | |||||
Sequence: A → S | ||||||
Natural variant | 229 | |||||
Sequence: V → M | ||||||
Natural variant | 233 | |||||
Sequence: V → I |
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.
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-20 | |||||
Sequence: MWQLLLPTALLLLVSAGMRA | ||||||
Chain | PRO_0000379977 | 21-254 | Low affinity immunoglobulin gamma Fc region receptor III-A | |||
Sequence: EDLPKAVVFLEPQWYRVLEKDSVTLKCQGAYSPEDNSTRWFHNESLISSQTSSYFIAAARVNNSGEYRCQTSLSTLSDPVQLEVHIGWLLLQAPRWVFKEEESIHLRCHSWKNTLLHKVTYLQNGKGRKYFHQNSDFYIPKATLKDSGSYFCRGLIGSKNVSSETVNITITQDLAVSSISSFFPPGYQVSFCLVMVLLFAVDTGLYFSVKKSVPSSTRDWEDHKFKWSKDPQDK | ||||||
Disulfide bond | 47↔89 | |||||
Sequence: CQGAYSPEDNSTRWFHNESLISSQTSSYFIAAARVNNSGEYRC | ||||||
Disulfide bond | 128↔172 | |||||
Sequence: CHSWKNTLLHKVTYLQNGKGRKYFHQNSDFYIPKATLKDSGSYFC | ||||||
Glycosylation | 187 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
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
- PTM
Proteomic databases
PTM databases
Expression
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).
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
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 24-105 | Ig-like C2-type 1 | ||||
Sequence: PKAVVFLEPQWYRVLEKDSVTLKCQGAYSPEDNSTRWFHNESLISSQTSSYFIAAARVNNSGEYRCQTSLSTLSDPVQLEVH | ||||||
Domain | 107-189 | Ig-like C2-type 2 | ||||
Sequence: GWLLLQAPRWVFKEEESIHLRCHSWKNTLLHKVTYLQNGKGRKYFHQNSDFYIPKATLKDSGSYFCRGLIGSKNVSSETVNIT |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe 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.
- Name1
- Length254
- Mass (Da)29,005
- Last updated2007-04-03 v1
- Checksum51AE94602AF97911
A3RFZ7-2
- Name2
- Differences from canonical
- 14-20: Missing
A3RFZ7-3
- Name3
- Differences from canonical
- 21-21: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1D5QMQ9 | A0A1D5QMQ9_MACMU | FCGR3 | 277 |
Sequence caution
Features
Showing features for alternative sequence.
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
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |