FCERG_HUMAN
ID FCERG_HUMAN Reviewed; 86 AA.
AC P30273; Q5VTW4;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=High affinity immunoglobulin epsilon receptor subunit gamma;
DE AltName: Full=Fc receptor gamma-chain;
DE Short=FcRgamma;
DE AltName: Full=Fc-epsilon RI-gamma;
DE AltName: Full=IgE Fc receptor subunit gamma;
DE Short=FceRI gamma;
DE Flags: Precursor;
GN Name=FCER1G;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=2138619; DOI=10.1016/s0021-9258(19)39347-0;
RA Kuester H., Thompson H., Kinet J.-P.;
RT "Characterization and expression of the gene for the human Fc receptor
RT gamma subunit. Definition of a new gene family.";
RL J. Biol. Chem. 265:6448-6452(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP FUNCTION, INTERACTION WITH FCGR1A, AND SUBCELLULAR LOCATION.
RX PubMed=8611682;
RA van Vugt M.J., Heijnen I.A.F.M., Capel P.J.A., Park S.Y., Ra C., Saito T.,
RA Verbeek J.S., van de Winkel J.G.J.;
RT "FcR gamma-chain is essential for both surface expression and function of
RT human Fc gamma RI (CD64) in vivo.";
RL Blood 87:3593-3599(1996).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [5]
RP INTERACTION WITH CLEC4E.
RX PubMed=18776906; DOI=10.1038/ni.1651;
RA Yamasaki S., Ishikawa E., Sakuma M., Hara H., Ogata K., Saito T.;
RT "Mincle is an ITAM-coupled activating receptor that senses damaged cells.";
RL Nat. Immunol. 9:1179-1188(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-69, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP INTERACTION WITH TARM1.
RX PubMed=26311901; DOI=10.4049/jimmunol.1401847;
RA Radjabova V., Mastroeni P., Skjoedt K., Zaccone P., de Bono B.,
RA Goodall J.C., Chilvers E.R., Juss J.K., Jones D.C., Trowsdale J.,
RA Barrow A.D.;
RT "TARM1 is a novel leukocyte receptor complex-encoded ITAM receptor that
RT costimulates proinflammatory cytokine secretion by macrophages and
RT neutrophils.";
RL J. Immunol. 195:3149-3159(2015).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [9]
RP INTERACTION WITH FCGR3A.
RX PubMed=28652325; DOI=10.1073/pnas.1706483114;
RA Blazquez-Moreno A., Park S., Im W., Call M.J., Call M.E., Reyburn H.T.;
RT "Transmembrane features governing Fc receptor CD16A assembly with CD16A
RT signaling adaptor molecules.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E5645-E5654(2017).
CC -!- FUNCTION: Adapter protein containing an immunoreceptor tyrosine-based
CC activation motif (ITAM) that transduces activation signals from various
CC immunoreceptors. As a component of the high-affinity immunoglobulin E
CC (IgE) receptor, mediates allergic inflammatory signaling in mast cells.
CC As a constitutive component of interleukin-3 receptor complex,
CC selectively mediates interleukin 4/IL4 production by basophils, priming
CC T-cells toward effector T-helper 2 subset. Associates with pattern
CC recognition receptors CLEC4D and CLEC4E to form a functional signaling
CC complex in myeloid cells. Binding of mycobacterial trehalose 6,6'-
CC dimycolate (TDM) to this receptor complex leads to phosphorylation of
CC ITAM, triggering activation of SYK, CARD9 and NF-kappa-B, consequently
CC driving maturation of antigen-presenting cells and shaping antigen-
CC specific priming of T-cells toward effector T-helper 1 and T-helper 17
CC cell subtypes. May function cooperatively with other activating
CC receptors. Functionally linked to integrin beta-2/ITGB2-mediated
CC neutrophil activation. Also involved in integrin alpha-2/ITGA2-mediated
CC platelet activation. {ECO:0000250|UniProtKB:P20491}.
CC -!- SUBUNIT: IgE Fc receptor is a tetramer of an alpha chain, a beta chain,
CC and two disulfide-linked gamma chains. Associates with FCGR1A; forms a
CC functional signaling complex (PubMed:8611682). The signaling subunit of
CC immunoglobulin gamma (IgG) Fc receptor complex. As a homodimer or a
CC heterodimer of CD247 and FCER1G, associates with the ligand binding
CC subunit FCGR3A to form a functional receptor complex (PubMed:28652325)
CC (By similarity). Associated with CLEC6A (By similarity). Interacts with
CC CLEC4E (PubMed:18776906). Interacts (via ITAM domain) with SYK (via SH2
CC domains); activates SYK, enabling integrin-mediated activation of
CC neutrophils and macrophages (By similarity). Interacts with CSF2RB and
CC recruits SYK in response to IL3 stimulation; this interaction is direct
CC (By similarity). Interacts with CD300LH; the interaction may be
CC indirect (By similarity). Interacts with CD300LD (By similarity).
CC Interacts with TARM1 (PubMed:26311901). {ECO:0000250|UniProtKB:P20411,
CC ECO:0000250|UniProtKB:P20491, ECO:0000269|PubMed:18776906,
CC ECO:0000269|PubMed:26311901, ECO:0000269|PubMed:28652325,
CC ECO:0000269|PubMed:8611682}.
CC -!- INTERACTION:
CC P30273; Q08708: CD300C; NbExp=2; IntAct=EBI-515289, EBI-3915344;
CC P30273; P12314: FCGR1A; NbExp=2; IntAct=EBI-515289, EBI-2869867;
CC P30273; P43405: SYK; NbExp=2; IntAct=EBI-515289, EBI-78302;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8611682};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:8611682}.
CC -!- SIMILARITY: Belongs to the CD3Z/FCER1G family. {ECO:0000305}.
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DR EMBL; M33195; AAA35828.1; -; mRNA.
DR EMBL; M33196; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590714; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS1225.1; -.
DR PIR; A35241; A35241.
DR RefSeq; NP_004097.1; NM_004106.1.
DR PDB; 7Q5T; X-ray; 2.20 A; GGG/HHH/III/JJJ/KKK/LLL=62-81.
DR PDBsum; 7Q5T; -.
DR AlphaFoldDB; P30273; -.
DR SMR; P30273; -.
DR BioGRID; 108501; 80.
DR CORUM; P30273; -.
DR DIP; DIP-29514N; -.
DR ELM; P30273; -.
DR IntAct; P30273; 12.
DR MINT; P30273; -.
DR STRING; 9606.ENSP00000289902; -.
DR DrugBank; DB00895; Benzylpenicilloyl polylysine.
DR GlyGen; P30273; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P30273; -.
DR PhosphoSitePlus; P30273; -.
DR BioMuta; FCER1G; -.
DR DMDM; 232085; -.
DR CPTAC; CPTAC-1168; -.
DR EPD; P30273; -.
DR jPOST; P30273; -.
DR MassIVE; P30273; -.
DR PaxDb; P30273; -.
DR PeptideAtlas; P30273; -.
DR PRIDE; P30273; -.
DR ProteomicsDB; 54646; -.
DR TopDownProteomics; P30273; -.
DR Antibodypedia; 20505; 168 antibodies from 29 providers.
DR DNASU; 2207; -.
DR Ensembl; ENST00000289902.2; ENSP00000289902.1; ENSG00000158869.11.
DR GeneID; 2207; -.
DR KEGG; hsa:2207; -.
DR MANE-Select; ENST00000289902.2; ENSP00000289902.1; NM_004106.2; NP_004097.1.
DR UCSC; uc001fyz.1; human.
DR CTD; 2207; -.
DR DisGeNET; 2207; -.
DR GeneCards; FCER1G; -.
DR HGNC; HGNC:3611; FCER1G.
DR HPA; ENSG00000158869; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 147139; gene.
DR neXtProt; NX_P30273; -.
DR OpenTargets; ENSG00000158869; -.
DR PharmGKB; PA28057; -.
DR VEuPathDB; HostDB:ENSG00000158869; -.
DR eggNOG; ENOG502S7XC; Eukaryota.
DR GeneTree; ENSGT00390000003894; -.
DR HOGENOM; CLU_192374_0_0_1; -.
DR InParanoid; P30273; -.
DR OMA; CRLKIQM; -.
DR OrthoDB; 1577383at2759; -.
DR PhylomeDB; P30273; -.
DR TreeFam; TF330937; -.
DR PathwayCommons; P30273; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-HSA-2454202; Fc epsilon receptor (FCERI) signaling.
DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation.
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-HSA-5621480; Dectin-2 family.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-75892; Platelet Adhesion to exposed collagen.
DR SignaLink; P30273; -.
DR SIGNOR; P30273; -.
DR BioGRID-ORCS; 2207; 6 hits in 1071 CRISPR screens.
DR ChiTaRS; FCER1G; human.
DR GenomeRNAi; 2207; -.
DR Pharos; P30273; Tbio.
DR PRO; PR:P30273; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P30273; protein.
DR Bgee; ENSG00000158869; Expressed in monocyte and 168 other tissues.
DR ExpressionAtlas; P30273; baseline and differential.
DR Genevisible; P30273; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0032998; C:Fc-epsilon receptor I complex; IBA:GO_Central.
DR GO; GO:0033001; C:Fc-gamma receptor III complex; IDA:UniProtKB.
DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IDA:CAFA.
DR GO; GO:0019863; F:IgE binding; IEA:UniProtKB-KW.
DR GO; GO:0019767; F:IgE receptor activity; IBA:GO_Central.
DR GO; GO:0019864; F:IgG binding; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0042590; P:antigen processing and presentation of exogenous peptide antigen via MHC class I; IBA:GO_Central.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; IBA:GO_Central.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISS:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central.
DR GO; GO:0002431; P:Fc receptor mediated stimulatory signaling pathway; IBA:GO_Central.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0038094; P:Fc-gamma receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0038156; P:interleukin-3-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0002283; P:neutrophil activation involved in immune response; IBA:GO_Central.
DR GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IBA:GO_Central.
DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
DR GO; GO:0010543; P:regulation of platelet activation; IBA:GO_Central.
DR GO; GO:0002292; P:T cell differentiation involved in immune response; IBA:GO_Central.
DR DisProt; DP00509; -.
DR InterPro; IPR021663; CD3_zeta/IgE_Fc_rcpt_gamma.
DR InterPro; IPR042340; FCER1G.
DR InterPro; IPR003110; Phos_immunorcpt_sig_ITAM.
DR PANTHER; PTHR16803; PTHR16803; 1.
DR Pfam; PF02189; ITAM; 1.
DR Pfam; PF11628; TCR_zetazeta; 1.
DR SMART; SM00077; ITAM; 1.
DR PROSITE; PS51055; ITAM_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; IgE-binding protein; Immunity;
KW Innate immunity; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..86
FT /note="High affinity immunoglobulin epsilon receptor
FT subunit gamma"
FT /id="PRO_0000016501"
FT TOPO_DOM 19..23
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 24..44
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 45..86
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 54..82
FT /note="ITAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00379"
FT MOD_RES 65
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P20491,
FT ECO:0000255|PROSITE-ProRule:PRU00379"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 76
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P20491,
FT ECO:0000255|PROSITE-ProRule:PRU00379"
FT MOD_RES 78
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P20491"
FT DISULFID 25
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 86 AA; 9667 MW; 2F2C7536513D6165 CRC64;
MIPAVVLLLL LLVEQAAALG EPQLCYILDA ILFLYGIVLT LLYCRLKIQV RKAAITSYEK
SDGVYTGLST RNQETYETLK HEKPPQ
