FCG3A_CAVPO
ID FCG3A_CAVPO Reviewed; 254 AA.
AC H0VDZ8;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 2.
DT 03-AUG-2022, entry version 47.
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=CD16-2 {ECO:0000250|UniProtKB:A0A0B4J1G0};
DE AltName: Full=FcgammaRIV {ECO:0000250|UniProtKB:A0A0B4J1G0};
DE AltName: CD_antigen=CD16a;
DE Flags: Precursor;
GN Name=Fcgr3a {ECO:0000250|UniProtKB:Q6XPU4};
GN Synonyms=Fcgr4 {ECO:0000250|UniProtKB:Q6XPU4};
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=2N;
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
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).
RN [3] {ECO:0000305}
RP IDENTIFICATION, FUNCTION, AND SUBCELLULAR LOCATION.
RA Mao C., Near R., Gao W.;
RT "Identification of a guinea pig Fcgamma receptor that exhibits enhanced
RT binding to afucosylated human and mouse IgG.";
RL J. Infect. Dis. Med. 1:102-102(2016).
RN [4]
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) (Ref.3). Binds with intermediate affinity to both IgG2a and
CC IgG2b. Can bind to IgG2a and IgG2b monomers. Does not display binding
CC to IgG1 or IgG3 (By similarity). Recognizes neutralizing virus-specific
CC IgGs displayed on the cell surface of infected cells and triggers
CC antibody-dependent cellular cytotoxicity (ADCC). Confers protection to
CC lethal influenza virus infection (By similarity). On splenic dendritic
CC cells, uptakes antigen immune complexes and efficiently divert them
CC into MHC class I and II antigen presentation pathways to provide for
CC superior priming of CD4-positive and CD8-positive T cell immune
CC responses (By similarity). Mediates neutrophil activation by IgG
CC complexes redundantly with FCGR2A (By similarity). Plays a role in
CC promoting bone resorption by enhancing osteoclast differentiation
CC following binding to IgG2a (By similarity). Also acts as a receptor for
CC the Fc region of immunoglobulin epsilon (IgE). Binds with low affinity
CC to both the a and b allotypes of IgE. Has also been shown to bind to
CC IgE allotype a only but not to allotype b. Binds aggregated IgE but not
CC the monomeric form and bound monomeric IgG is readily displaced by IgE
CC complexes. Binding to IgE promotes macrophage-mediated phagocytosis,
CC antigen presentation to T cells, production of pro-inflammatory
CC cytokines and the late phase of cutaneous allergic reactions (By
CC similarity). Mediates enhanced ADCC in response to afucosylated IgGs
CC (PubMed:34485821). {ECO:0000250|UniProtKB:A0A0B4J1G0,
CC ECO:0000269|PubMed:34485821}.
CC -!- SUBUNIT: Forms a heterooligomeric complex with ITAM-containing
CC signaling subunits FCER1G. Interacts (via transmembrane domain) with
CC signaling subunits; this interaction is a prerequisite for receptor
CC complex expression on the cell surface and intracellular signal
CC transduction. Binds the Fc region of antigen-complexed IgG.
CC {ECO:0000250|UniProtKB:A0A0B4J1G0}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:A0A0B4J1G0};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:A0A0B4J1G0}.
CC -!- PTM: Phosphorylated following receptor ligation.
CC {ECO:0000250|UniProtKB:A0A0B4J1G0}.
CC -!- MISCELLANEOUS: Exhibits stronger binding to afucosylated IgG than to
CC the wild-type fucosylated form. {ECO:0000269|Ref.3}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AAKN02043138; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; H0VDZ8; -.
DR SMR; H0VDZ8; -.
DR STRING; 10141.ENSCPOP00000008224; -.
DR eggNOG; ENOG502RU1M; Eukaryota.
DR HOGENOM; CLU_023383_1_0_1; -.
DR InParanoid; H0VDZ8; -.
DR TreeFam; TF335097; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019863; F:IgE binding; IEA:UniProtKB-KW.
DR GO; GO:0019767; F:IgE receptor activity; ISS:UniProtKB.
DR GO; GO:0019864; F:IgG binding; IEA:UniProtKB-KW.
DR GO; GO:0019770; F:IgG receptor activity; ISS:UniProtKB.
DR GO; GO:0042119; P:neutrophil activation; ISS:UniProtKB.
DR GO; GO:0045780; P:positive regulation of bone resorption; 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 InterPro; IPR003598; Ig_sub2.
DR Pfam; PF13895; Ig_2; 2.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 2.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 3: Inferred from homology;
KW Cell membrane; Disulfide bond; Glycoprotein; IgE-binding protein;
KW IgG-binding protein; Immunity; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; 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 /evidence="ECO:0000255"
FT /id="PRO_0000438773"
FT TOPO_DOM 21..209
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 210..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 23..104
FT /note="Ig-like C2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 121..174
FT /note="Ig-like C2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT SITE 223
FT /note="Important for receptor turnover"
FT /evidence="ECO:0000250|UniProtKB:P08637"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 47..90
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 129..173
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 254 AA; 28927 MW; 0F141C89F4DCB442 CRC64;
MWHLLPPSAL LLLISSVTKA ADPSKAVVLL DPPWVRVLTD DNVTLTCQGA YPPENNNTRW
FHNGTHIVGS QAPSYLISGI KVENSGKYQC QTDLSPLSDS VQLQVHADWL VLQTSKWVFQ
KGESIRLRCH SWKNKRLYKV TYLQNGKPKK FFHNNSEFHI PEATVNHTGS YYCRGLIGHN
NKSSGIVAIT FQADFAGPSI APLFPLWQQI AFCLMMGLLF AVDTGLYFFV RRDLRRSMVH
KEEYNFKWSQ AQDK
