FCG3A_MACMU
ID FCG3A_MACMU Reviewed; 254 AA.
AC A3RFZ7; A3RFZ3; A3RFZ4; A3RFZ5; A3RFZ6; A3RFZ8; A3RFZ9; Q09TM0; Q09TM1;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 1.
DT 03-AUG-2022, entry version 74.
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:0000303|Ref.2};
DE AltName: CD_antigen=CD16a {ECO:0000303|Ref.2};
DE Flags: Precursor;
GN Name=FCGR3A {ECO:0000303|PubMed:33208458, ECO:0000303|Ref.2};
GN Synonyms=FCGR3;
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP VARIANTS MET-229 AND ILE-233.
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] (ISOFORMS 1 AND 3), AND VARIANTS MET-229 AND
RP ILE-233.
RA Miller C.J., Dutra J.C.;
RT "Macaca mulatta FcgammaRIIIa (CD16a)(FCGR3A) mRNA in rituxan-treated
RT animals.";
RL Submitted (JAN-2007) 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).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND POLYMORPHISM.
RX PubMed=33208458; DOI=10.4049/jimmunol.2000501;
RA Grunst M.W., Grandea A.G. III, Janaka S.K., Hammad I., Grimes P.,
RA Karl J.A., Wiseman R., O'Connor D.H., Evans D.T.;
RT "Functional Interactions of Common Allotypes of Rhesus Macaque FcgammaR2A
RT and FcgammaR3A with Human and Macaque IgG Subclasses.";
RL J. Immunol. 205:3319-3332(2020).
RN [5]
RP FUNCTION.
RX PubMed=34485821; DOI=10.1093/abt/tbab016;
RA Mao C., Near R., Zhong X., Gao W.;
RT "Cross-species higher sensitivities of FcgammaRIIIA/FcgammaRIV to
RT afucosylated IgG for enhanced ADCC.";
RL Antib Ther 4:159-170(2021).
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
CC (PubMed:33208458). Mediates IgG effector functions on natural killer
CC (NK) 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 (PubMed:34485821).
CC {ECO:0000250|UniProtKB:P08637, ECO:0000269|PubMed:33208458,
CC ECO:0000269|PubMed:34485821}.
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:0000269|PubMed:33208458};
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A3RFZ7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A3RFZ7-2; Sequence=VSP_037763;
CC Name=3;
CC IsoId=A3RFZ7-3; Sequence=VSP_037764;
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}.
CC -!- POLYMORPHISM: Three common alleles are identified in Indian-origin
CC rhesus macaques: 3A:01, 3A:02 and 3A:03. These alleles display similar
CC IgG responses. {ECO:0000269|PubMed:33208458}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABN69099.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=ABN69100.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=ABN69101.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=ABN69103.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=ABN69104.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; DQ423379; ABD83659.1; -; mRNA.
DR EMBL; DQ423380; ABD83660.1; -; mRNA.
DR EMBL; EF396932; ABN69096.1; -; mRNA.
DR EMBL; EF396933; ABN69097.1; -; mRNA.
DR EMBL; EF396934; ABN69098.1; -; mRNA.
DR EMBL; EF396935; ABN69099.1; ALT_INIT; mRNA.
DR EMBL; EF396936; ABN69100.1; ALT_INIT; mRNA.
DR EMBL; EF396937; ABN69101.1; ALT_INIT; mRNA.
DR EMBL; EF396938; ABN69102.1; -; mRNA.
DR EMBL; EF396939; ABN69103.1; ALT_INIT; mRNA.
DR EMBL; EF396940; ABN69104.1; ALT_INIT; mRNA.
DR RefSeq; NP_001041713.1; NM_001048248.1.
DR RefSeq; NP_001258582.1; NM_001271653.1.
DR RefSeq; NP_001258583.1; NM_001271654.1.
DR RefSeq; NP_001258584.1; NM_001271655.1.
DR RefSeq; NP_001258585.1; NM_001271656.1.
DR RefSeq; NP_001258586.1; NM_001271657.1.
DR RefSeq; XP_014968657.1; XM_015113171.1. [A3RFZ7-3]
DR RefSeq; XP_014968661.1; XM_015113175.1. [A3RFZ7-1]
DR PDB; 6MJ3; X-ray; 3.80 A; C/F=18-209.
DR PDB; 6MJO; X-ray; 1.90 A; C=18-209.
DR PDB; 7KCZ; X-ray; 3.15 A; C/F=18-209.
DR PDBsum; 6MJ3; -.
DR PDBsum; 6MJO; -.
DR PDBsum; 7KCZ; -.
DR AlphaFoldDB; A3RFZ7; -.
DR SMR; A3RFZ7; -.
DR STRING; 9544.ENSMMUP00000021295; -.
DR PRIDE; A3RFZ7; -.
DR Ensembl; ENSMMUT00000022769; ENSMMUP00000021295; ENSMMUG00000016206. [A3RFZ7-2]
DR GeneID; 720006; -.
DR KEGG; mcc:720006; -.
DR CTD; 14131; -.
DR VEuPathDB; HostDB:ENSMMUG00000016206; -.
DR eggNOG; ENOG502RU1M; Eukaryota.
DR GeneTree; ENSGT01050000244808; -.
DR InParanoid; A3RFZ7; -.
DR OrthoDB; 866496at2759; -.
DR Proteomes; UP000006718; Chromosome 1.
DR Bgee; ENSMMUG00000016206; Expressed in spleen and 20 other tissues.
DR ExpressionAtlas; A3RFZ7; baseline.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0019864; F:IgG binding; IEA:UniProtKB-KW.
DR GO; GO:0019770; F:IgG receptor activity; IDA:UniProtKB.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
DR GO; GO:0001788; P:antibody-dependent cellular cytotoxicity; IDA:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; ISS:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central.
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 GO; GO:0050776; P:regulation of immune response; IBA:GO_Central.
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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; IgG-binding protein; Immunity; Immunoglobulin domain;
KW Membrane; Receptor; Reference proteome; Repeat; Secreted; Signal;
KW 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_0000379977"
FT TOPO_DOM 21..206
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..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 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 VAR_SEQ 14..20
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16951347"
FT /id="VSP_037763"
FT VAR_SEQ 21
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_037764"
FT VARIANT 26
FT /note="A -> S"
FT VARIANT 229
FT /note="V -> M"
FT /evidence="ECO:0000269|PubMed:16951347, ECO:0000269|Ref.2"
FT VARIANT 233
FT /note="V -> I"
FT /evidence="ECO:0000269|PubMed:16951347, ECO:0000269|Ref.2"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:7KCZ"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 71..78
FT /evidence="ECO:0007829|PDB:6MJO"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 85..91
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:7KCZ"
FT STRAND 100..105
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:6MJO"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 136..143
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 146..153
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:6MJO"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 168..176
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 179..182
FT /evidence="ECO:0007829|PDB:6MJO"
FT STRAND 186..191
FT /evidence="ECO:0007829|PDB:6MJO"
SQ SEQUENCE 254 AA; 29005 MW; 51AE94602AF97911 CRC64;
MWQLLLPTAL LLLVSAGMRA EDLPKAVVFL EPQWYRVLEK DSVTLKCQGA YSPEDNSTRW
FHNESLISSQ TSSYFIAAAR VNNSGEYRCQ TSLSTLSDPV QLEVHIGWLL LQAPRWVFKE
EESIHLRCHS WKNTLLHKVT YLQNGKGRKY FHQNSDFYIP KATLKDSGSY FCRGLIGSKN
VSSETVNITI TQDLAVSSIS SFFPPGYQVS FCLVMVLLFA VDTGLYFSVK KSVPSSTRDW
EDHKFKWSKD PQDK
