FCG3A_CERAT
ID FCG3A_CERAT Reviewed; 254 AA.
AC Q09TM4;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 25-MAY-2022, entry version 43.
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 Cercocebus atys (Sooty mangabey) (Cercocebus torquatus atys).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Cercocebus.
OX NCBI_TaxID=9531;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PTM, 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 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
CC binding. Mediates the antitumor activities of therapeutic antibodies.
CC Upon ligation on monocytes triggers TNFA-dependent ADCC of IgG-coated
CC tumor cells (By similarity). Mediates enhanced ADCC in response to
CC afucosylated IgGs (By similarity). {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, to form a functional receptor
CC complex. Interacts (via transmembrane domain) with signaling subunits;
CC this interaction is a prerequisite for receptor complex expression on
CC the cell surface and intracellular signal transduction. Binds the Fc
CC region of antigen-complexed IgG with a preference for IgG1 and IgG3
CC isotypes (By similarity). Interacts with CD2; this interaction is
CC involved in NK cell activation and cytotoxicity (By similarity).
CC Interacts with S100A4; this interaction inhibits PKC-dependent
CC 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, monocytes and neutrophils.
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; DQ423376; ABD83656.1; -; mRNA.
DR RefSeq; XP_011922883.1; XM_012067493.1.
DR AlphaFoldDB; Q09TM4; -.
DR SMR; Q09TM4; -.
DR STRING; 9531.ENSCATP00000019810; -.
DR GeneID; 105589237; -.
DR KEGG; caty:105589237; -.
DR OrthoDB; 866496at2759; -.
DR Proteomes; UP000233060; Whole Genome Shotgun Assembly.
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; 1.
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..20
FT /evidence="ECO:0000255"
FT CHAIN 21..254
FT /note="Low affinity immunoglobulin gamma Fc region receptor
FT III-A"
FT /id="PRO_0000379976"
FT TRANSMEM 207..229
FT /note="Helical"
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 REGION 234..254
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..254
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 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"
SQ SEQUENCE 254 AA; 28935 MW; 5075E5252A17A271 CRC64;
MWQLLLPTAL LLLVSAGMRA EDLPKAVVFL EPQWYRVLEK DSVTLKCQGA YSPEDNSTRW
FHNESLISSQ TSSYFIAAAR VNNSGEYRCQ TSLSTLSDPV QLEVHIGWLL LQAPRWVFKE
EDSIHLRCHS WKNTLLHKVT YLQNGKGRKY FHQNSDFYIP KATLKDSGSY FCRGLIGSKN
VSSETVNITI TQDLAVSSIS SFFPPGYQVS FCLVMVLLFA VDTGLYFSVK KSIPSSTSDW
KDHKFKWSKD PQDK
