FCG3A_MACFA
ID FCG3A_MACFA Reviewed; 254 AA.
AC Q8SPW2; Q09TM3;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Low affinity immunoglobulin gamma Fc region receptor III-A {ECO:0000250|UniProtKB:P08637};
DE Short=IgG Fc receptor III-A;
DE AltName: Full=Fc-gamma RIII-alpha;
DE Short=Fc-gamma RIII;
DE Short=Fc-gamma RIIIa;
DE Short=FcgammaRIIIa {ECO:0000250|UniProtKB:A3RFZ7};
DE AltName: CD_antigen=CD16a {ECO:0000303|PubMed:16951347};
DE Flags: Precursor;
GN Name=FCGR3A; Synonyms=FCGR3;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Blood;
RX PubMed=16951347; DOI=10.4049/jimmunol.177.6.3848;
RA Rogers K.A., Scinicariello F., Attanasio R.;
RT "IgG Fc receptor III homologues in nonhuman primate species: genetic
RT characterization and ligand interactions.";
RL J. Immunol. 177:3848-3856(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RA Namenuk A.K., Hong K., Meng Y.G., Shields R.L., Cromwell M.E.M.,
RA Presta L.G.;
RT "Binding of human IgG to cynomolgus FcR.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NOMENCLATURE.
RX PubMed=7955033;
RA Conrad D., Cooper M., Fridman W.H., Kinet J.P., Ravetch J.;
RT "Nomenclature of Fc receptors. IUIS/WHO Subcommittee on Nomenclature of Fc
RT receptors.";
RL Bull. World Health Organ. 72:809-810(1994).
CC -!- FUNCTION: Receptor for the invariable Fc fragment of immunoglobulin
CC gamma (IgG). Optimally activated upon binding of clustered antigen-IgG
CC complexes displayed on cell surfaces, triggers lysis of antibody-coated
CC cells, a process known as antibody-dependent cellular cytotoxicity
CC (ADCC). Does not bind free monomeric IgG, thus avoiding inappropriate
CC effector cell activation in the absence of antigenic trigger (By
CC similarity). Mediates IgG effector functions on natural killer (NK)
CC cells. Binds antigen-IgG complexes generated upon infection and
CC triggers NK cell-dependent cytokine production and degranulation to
CC limit viral load and propagation. Involved in the generation of memory-
CC like adaptive NK cells capable to produce high amounts of IFNG and to
CC efficiently eliminate virus-infected cells via ADCC. Regulates NK cell
CC survival and proliferation, in particular by preventing NK cell
CC progenitor apoptosis (By similarity). Fc-binding subunit that
CC associates with CD247 and/or FCER1G adapters to form functional
CC signaling complexes. Following the engagement of antigen-IgG complexes,
CC triggers phosphorylation of immunoreceptor tyrosine-based activation
CC motif (ITAM)-containing adapters with subsequent activation of
CC phosphatidylinositol 3-kinase signaling and sustained elevation of
CC intracellular calcium that ultimately drive NK cell activation. The
CC ITAM-dependent signaling coupled to receptor phosphorylation by PKC
CC mediates robust intracellular calcium flux that leads to production of
CC pro-inflammatory cytokines, whereas in the absence of receptor
CC phosphorylation it mainly activates phosphatidylinositol 3-kinase
CC signaling leading to cell degranulation (By similarity). Costimulates
CC NK cells and trigger lysis of target cells independently of IgG binding
CC (By similarity). Mediates the antitumor activities of therapeutic
CC antibodies. Upon ligation on monocytes triggers TNFA-dependent ADCC of
CC IgG-coated tumor cells (By similarity). Mediates enhanced ADCC in
CC response to afucosylated IgGs (By similarity).
CC {ECO:0000250|UniProtKB:P08637}.
CC -!- SUBUNIT: Forms a heterooligomeric complex with ITAM-containing
CC signaling subunits, either a homodimer of CD247, a homodimer of FCER1G
CC or a heterodimer of CD247 and FCER1G. Interacts (via transmembrane
CC domain) with signaling subunits; this interaction is a prerequisite for
CC receptor complex expression on the cell surface and intracellular
CC signal transduction. Binds the Fc region of antigen-complexed IgG with
CC a preference for IgG1 and IgG3 isotypes (By similarity). Interacts with
CC CD2; this interaction is involved in NK cell activation and
CC cytotoxicity (By similarity). Interacts with S100A4; this interaction
CC inhibits PKC-dependent phosphorylation of FCGR3A (By similarity).
CC {ECO:0000250|UniProtKB:P08637}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P08637};
CC Single-pass type I membrane protein {ECO:0000255}. Secreted
CC {ECO:0000250|UniProtKB:P08637}. Note=Exists also as a soluble receptor.
CC {ECO:0000250|UniProtKB:P08637}.
CC -!- TISSUE SPECIFICITY: Lymphocytes and monocytes.
CC {ECO:0000269|PubMed:16951347}.
CC -!- PTM: Glycosylated. Glycosylation plays an inhibitory role in the
CC interaction with IgG1 and IgG2. {ECO:0000250|UniProtKB:P08637}.
CC -!- PTM: Undergoes rapid ectodomain shedding upon NK cell stimulation. The
CC soluble form is produced by a proteolytic cleavage mediated by ADAM17.
CC Repeated stimulation causes receptor shedding, a mechanism that allows
CC for increased NK cell motility and detachment from opsonized target
CC cells while avoiding activation-induced NK cell apoptosis.
CC {ECO:0000250|UniProtKB:P08637}.
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DR EMBL; DQ423377; ABD83657.1; -; mRNA.
DR EMBL; AF485815; AAL92098.1; -; mRNA.
DR RefSeq; NP_001270121.1; NM_001283192.1.
DR AlphaFoldDB; Q8SPW2; -.
DR SMR; Q8SPW2; -.
DR STRING; 9541.XP_005541219.1; -.
DR GeneID; 102140945; -.
DR CTD; 2214; -.
DR eggNOG; ENOG502RU1M; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0019864; F:IgG binding; IEA:UniProtKB-KW.
DR GO; GO:0001788; P:antibody-dependent cellular cytotoxicity; ISS:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; ISS:UniProtKB.
DR GO; GO:0038094; P:Fc-gamma receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030101; P:natural killer cell activation; ISS:UniProtKB.
DR GO; GO:0043320; P:natural killer cell degranulation; ISS:UniProtKB.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; ISS:UniProtKB.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR Pfam; PF13895; Ig_2; 2.
DR SMART; SM00409; IG; 2.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Glycoprotein; IgG-binding protein; Immunity;
KW Immunoglobulin domain; Membrane; Receptor; Reference proteome; Repeat;
KW Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..254
FT /note="Low affinity immunoglobulin gamma Fc region receptor
FT III-A"
FT /id="PRO_0000015153"
FT TOPO_DOM 17..208
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..105
FT /note="Ig-like C2-type 1"
FT DOMAIN 107..189
FT /note="Ig-like C2-type 2"
FT SITE 195..196
FT /note="Cleavage; by ADAM17"
FT /evidence="ECO:0000250|UniProtKB:P08637"
FT SITE 222
FT /note="Important for receptor turnover"
FT /evidence="ECO:0000250|UniProtKB:P08637"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 47..89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 128..172
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 25
FT /note="K -> R (in Ref. 2; ABD83657)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 254 AA; 29120 MW; 11A48E6B3A34AF7B CRC64;
MWQLLLPTAL LLLVSAGMRA EDLPKAVVFL EPQWYRVLEK DRVTLKCQGA YSPEDNSTRW
FHNESLISSQ TSSYFIAAAR VNNSGEYRCQ TSLSTLSDPV QLEVHIGWLL LQAPRWVFKE
EESIHLRCHS WKNTLLHKVT YLQNGKGRKY FHQNSDFYIP KATLKDSGSY FCRGLIGSKN
VSSETVNITI TQDLAVSSIS SFFPPGYQVS FCLVMVLLFA VDTGLYFSMK KSIPSSTRDW
EDHKFKWSKD PQDK
