Full text data of FCGR1A
FCGR1A
(FCG1, FCGR1, IGFR1)
[Confidence: low (only semi-automatic identification from reviews)]
High affinity immunoglobulin gamma Fc receptor I; IgG Fc receptor I (Fc-gamma RI; FcRI; Fc-gamma RIA; FcgammaRIa; CD64; Flags: Precursor)
High affinity immunoglobulin gamma Fc receptor I; IgG Fc receptor I (Fc-gamma RI; FcRI; Fc-gamma RIA; FcgammaRIa; CD64; Flags: Precursor)
UniProt
P12314
ID FCGR1_HUMAN Reviewed; 374 AA.
AC P12314; P12315; Q5QNW7; Q92495; Q92663;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 19-JUL-2004, sequence version 2.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=High affinity immunoglobulin gamma Fc receptor I;
DE Short=IgG Fc receptor I;
DE AltName: Full=Fc-gamma RI;
DE Short=FcRI;
DE AltName: Full=Fc-gamma RIA;
DE Short=FcgammaRIa;
DE AltName: CD_antigen=CD64;
DE Flags: Precursor;
GN Name=FCGR1A; Synonyms=FCG1, FCGR1, IGFR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=2974947; DOI=10.1093/nar/16.24.11824;
RA Allen J.M., Seed B.;
RT "Nucleotide sequence of three cDNAs for the human high affinity Fc
RT receptor (FcRI).";
RL Nucleic Acids Res. 16:11824-11824(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2911749; DOI=10.1126/science.2911749;
RA Allen J.M., Seed B.;
RT "Isolation and expression of functional high-affinity Fc receptor
RT complementary DNAs.";
RL Science 243:378-381(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Blood;
RX PubMed=1430234; DOI=10.1172/JCI116094;
RA Porges A.J., Redecha P.B., Doebele R., Pan L.C., Salmon J.E.,
RA Kimberly R.P.;
RT "Novel Fc gamma receptor I family gene products in human mononuclear
RT cells.";
RL J. Clin. Invest. 90:2102-2109(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RX PubMed=1402657; DOI=10.1084/jem.176.4.1115;
RA Benech P.D., Sastry K.N., Iyer R.R., Eichbaum Q.G., Raveh D.P.,
RA Ezekowitz R.A.;
RT "Definition of interferon gamma-response elements in a novel human Fc
RT gamma receptor gene (Fc gamma RIb) and characterization of the gene
RT structure.";
RL J. Exp. Med. 176:1115-1123(1992).
RN [5]
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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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 [6]
RP PROTEIN SEQUENCE OF 16-30.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP ALTERNATIVE SPLICING.
RX PubMed=1379234;
RA Ernst L.K., van de Winkel J.G., Chiu I.M., Anderson C.L.;
RT "Three genes for the human high affinity Fc receptor for IgG (Fc gamma
RT RI) encode four distinct transcription products.";
RL J. Biol. Chem. 267:15692-15700(1992).
RN [8]
RP INTERACTION WITH HCK AND LYN.
RX PubMed=8064233; DOI=10.1084/jem.180.3.1165;
RA Wang A.V., Scholl P.R., Geha R.S.;
RT "Physical and functional association of the high affinity
RT immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and
RT Lyn.";
RL J. Exp. Med. 180:1165-1170(1994).
RN [9]
RP FUNCTION, INTERACTION WITH FCER1G, 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.,
RA Saito T., Verbeek J.S., van de Winkel J.G.J.;
RT "FcR gamma-chain is essential for both surface expression and function
RT of human Fc gamma RI (CD64) in vivo.";
RL Blood 87:3593-3599(1996).
RN [10]
RP FUNCTION, ALTERNATIVE SPLICING, AND GLYCOSYLATION.
RX PubMed=9881690; DOI=10.1016/S0161-5890(98)00079-0;
RA Ernst L.K., Duchemin A.-M., Miller K.L., Anderson C.L.;
RT "Molecular characterization of six variant Fcgamma receptor class I
RT (CD64) transcripts.";
RL Mol. Immunol. 35:943-954(1998).
RN [11]
RP FUNCTION.
RX PubMed=10397749;
RA van Vugt M.J., Kleijmeer M.J., Keler T., Zeelenberg I., van Dijk M.A.,
RA Leusen J.H.W., Geuze H.J., van de Winkel J.G.J.;
RT "The FcgammaRIa (CD64) ligand binding chain triggers major
RT histocompatibility complex class II antigen presentation independently
RT of its associated FcR gamma-chain.";
RL Blood 94:808-817(1999).
RN [12]
RP FUNCTION, AND INTERACTION WITH FCER1G.
RX PubMed=10514529; DOI=10.1074/jbc.274.42.30328;
RA Edberg J.C., Yee A.M., Rakshit D.S., Chang D.J., Gokhale J.A.,
RA Indik Z.K., Schreiber A.D., Kimberly R.P.;
RT "The cytoplasmic domain of human FcgammaRIa alters the functional
RT properties of the FcgammaRI.gamma-chain receptor complex.";
RL J. Biol. Chem. 274:30328-30333(1999).
RN [13]
RP INTERACTION WITH LAT.
RX PubMed=10781611; DOI=10.1074/jbc.M909462199;
RA Tridandapani S., Lyden T.W., Smith J.L., Carter J.E., Coggeshall K.M.,
RA Anderson C.L.;
RT "The adapter protein LAT enhances fcgamma receptor-mediated signal
RT transduction in myeloid cells.";
RL J. Biol. Chem. 275:20480-20487(2000).
RN [14]
RP MUTAGENESIS OF ASN-306, AND SUBCELLULAR LOCATION.
RX PubMed=12756162; DOI=10.1182/blood.V101.11.4479;
RA Kim M.-K., Huang Z.-Y., Hwang P.-H., Jones B.A., Sato N., Hunter S.,
RA Kim-Han T.-H., Worth R.G., Indik Z.K., Schreiber A.D.;
RT "Fcgamma receptor transmembrane domains: role in cell surface
RT expression, gamma chain interaction, and phagocytosis.";
RL Blood 101:4479-4484(2003).
RN [15]
RP INTERACTION WITH PPL.
RX PubMed=15229321; DOI=10.1073/pnas.0401217101;
RA Beekman J.M., Bakema J.E., van de Winkel J.G.J., Leusen J.H.W.;
RT "Direct interaction between FcgammaRI (CD64) and periplakin controls
RT receptor endocytosis and ligand binding capacity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10392-10397(2004).
RN [16]
RP INTERACTION WITH FLNA.
RX PubMed=18322202;
RA Beekman J.M., van der Poel C.E., van der Linden J.A.,
RA van den Berg D.L.C., van den Berghe P.V.E., van de Winkel J.G.J.,
RA Leusen J.H.W.;
RT "Filamin A stabilizes FcgammaRI surface expression and prevents its
RT lysosomal routing.";
RL J. Immunol. 180:3938-3945(2008).
RN [17]
RP INTERACTION WITH EPB41L2.
RX PubMed=18023480; DOI=10.1016/j.molimm.2007.10.024;
RA Beekman J.M., Bakema J.E., van der Poel C.E., van der Linden J.A.,
RA van de Winkel J.G.J., Leusen J.H.W.;
RT "Protein 4.1G binds to a unique motif within the FcgammaRI cytoplasmic
RT tail.";
RL Mol. Immunol. 45:2069-2075(2008).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 21-282, FUNCTION, DISULFIDE
RP BONDS, AND GLYCOSYLATION AT ASN-59; ASN-78; ASN-152; ASN-159; ASN-163
RP AND ASN-195.
RX PubMed=21965667; DOI=10.1074/jbc.M111.257550;
RA Lu J., Ellsworth J.L., Hamacher N., Oak S.W., Sun P.D.;
RT "Crystal structure of Fcgamma receptor I and its implication in high
RT affinity gamma-immunoglobulin binding.";
RL J. Biol. Chem. 286:40608-40613(2011).
CC -!- FUNCTION: High affinity receptor for the Fc region of
CC immunoglobulins gamma. Functions in both innate and adaptive
CC immune responses.
CC -!- SUBUNIT: Interacts with FCERG1; forms a functional signaling
CC complex. Interacts with FLNA; prevents FCGR1A degradation.
CC Interacts with EPB41L2, LAT and PPL. Interacts with HCK and LYN.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Note=Stabilized at the cell membrane through interaction
CC with FCER1G.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=A;
CC IsoId=P12314-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=P12314-2; Sequence=VSP_002637;
CC -!- TISSUE SPECIFICITY: Monocyte/macrophage specific.
CC -!- PTM: Phosphorylated on serine residues (By similarity).
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. FCGR1
CC family.
CC -!- SIMILARITY: Contains 3 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- WEB RESOURCE: Name=FCGR1Abase; Note=FCGR1A mutation db;
CC URL="http://bioinf.uta.fi/FCGR1Abase/";
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DR EMBL; X14356; CAA32537.1; -; mRNA.
DR EMBL; X14355; CAA32536.1; -; mRNA.
DR EMBL; L03418; AAA36049.1; -; mRNA.
DR EMBL; M91555; AAA58414.1; -; Genomic_DNA.
DR EMBL; M91550; AAA58414.1; JOINED; Genomic_DNA.
DR EMBL; M91551; AAA58414.1; JOINED; Genomic_DNA.
DR EMBL; M91552; AAA58414.1; JOINED; Genomic_DNA.
DR EMBL; M91553; AAA58414.1; JOINED; Genomic_DNA.
DR EMBL; M91554; AAA58414.1; JOINED; Genomic_DNA.
DR EMBL; AL591493; CAI12557.1; -; Genomic_DNA.
DR PIR; A39878; A39878.
DR PIR; A41357; A41357.
DR RefSeq; NP_000557.1; NM_000566.3.
DR UniGene; Hs.77424; -.
DR PDB; 3RJD; X-ray; 2.65 A; A=21-282.
DR PDBsum; 3RJD; -.
DR ProteinModelPortal; P12314; -.
DR SMR; P12314; 21-282.
DR IntAct; P12314; 1.
DR MINT; MINT-1538623; -.
DR STRING; 9606.ENSP00000358165; -.
DR BindingDB; P12314; -.
DR ChEMBL; CHEMBL5349; -.
DR DrugBank; DB00054; Abciximab.
DR DrugBank; DB00051; Adalimumab.
DR DrugBank; DB00092; Alefacept.
DR DrugBank; DB00087; Alemtuzumab.
DR DrugBank; DB00074; Basiliximab.
DR DrugBank; DB00112; Bevacizumab.
DR DrugBank; DB00002; Cetuximab.
DR DrugBank; DB00111; Daclizumab.
DR DrugBank; DB00095; Efalizumab.
DR DrugBank; DB00005; Etanercept.
DR DrugBank; DB00056; Gemtuzumab ozogamicin.
DR DrugBank; DB00078; Ibritumomab.
DR DrugBank; DB00028; Immune globulin.
DR DrugBank; DB00992; Methyl aminolevulinate.
DR DrugBank; DB00075; Muromonab.
DR DrugBank; DB00108; Natalizumab.
DR DrugBank; DB00110; Palivizumab.
DR DrugBank; DB00707; Porfimer.
DR DrugBank; DB00073; Rituximab.
DR DrugBank; DB00081; Tositumomab.
DR DrugBank; DB00072; Trastuzumab.
DR PhosphoSite; P12314; -.
DR DMDM; 50403717; -.
DR PaxDb; P12314; -.
DR PRIDE; P12314; -.
DR DNASU; 2209; -.
DR Ensembl; ENST00000369168; ENSP00000358165; ENSG00000150337.
DR Ensembl; ENST00000580698; ENSP00000462402; ENSG00000266332.
DR GeneID; 2209; -.
DR KEGG; hsa:2209; -.
DR UCSC; uc001esp.4; human.
DR CTD; 2209; -.
DR GeneCards; GC01P149754; -.
DR H-InvDB; HIX0000999; -.
DR HGNC; HGNC:3613; FCGR1A.
DR MIM; 146760; gene.
DR neXtProt; NX_P12314; -.
DR PharmGKB; PA28060; -.
DR eggNOG; NOG277652; -.
DR HOGENOM; HOG000251632; -.
DR HOVERGEN; HBG051602; -.
DR InParanoid; P12314; -.
DR KO; K06498; -.
DR OMA; RNSEFTI; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P12314; -.
DR GeneWiki; FCGR1A; -.
DR GenomeRNAi; 2209; -.
DR NextBio; 8947; -.
DR PRO; PR:P12314; -.
DR ArrayExpress; P12314; -.
DR Bgee; P12314; -.
DR CleanEx; HS_FCGR1A; -.
DR Genevestigator; P12314; -.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005057; F:receptor signaling protein activity; TAS:ProtInc.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0006911; P:phagocytosis, engulfment; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR Pfam; PF00047; ig; 1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW IgG-binding protein; Immunity; Immunoglobulin domain; Innate immunity;
KW Membrane; Phosphoprotein; Polymorphism; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1 15
FT CHAIN 16 374 High affinity immunoglobulin gamma Fc
FT receptor I.
FT /FTId=PRO_0000015139.
FT TOPO_DOM 16 292 Extracellular (Potential).
FT TRANSMEM 293 313 Helical; (Potential).
FT TOPO_DOM 314 374 Cytoplasmic (Potential).
FT DOMAIN 22 101 Ig-like C2-type 1.
FT DOMAIN 95 184 Ig-like C2-type 2.
FT DOMAIN 190 277 Ig-like C2-type 3.
FT REGION 312 332 Interaction with EPB41L2.
FT CARBOHYD 59 59 N-linked (GlcNAc...).
FT CARBOHYD 78 78 N-linked (GlcNAc...).
FT CARBOHYD 152 152 N-linked (GlcNAc...).
FT CARBOHYD 159 159 N-linked (GlcNAc...).
FT CARBOHYD 163 163 N-linked (GlcNAc...).
FT CARBOHYD 195 195 N-linked (GlcNAc...).
FT CARBOHYD 240 240 N-linked (GlcNAc...) (Potential).
FT DISULFID 43 85
FT DISULFID 124 168
FT DISULFID 212 260
FT VAR_SEQ 333 374 HEKKVISSLQEDRHLEEELKCQEQKEEQLQEGVHRKEPQGA
FT T -> GQALEAPTQGCA (in isoform 2).
FT /FTId=VSP_002637.
FT VARIANT 105 105 L -> P (in dbSNP:rs619322).
FT /FTId=VAR_019522.
FT MUTAGEN 306 306 N->D: Decreases cell membrane expression
FT by 50% in absence of FCER1G.
FT MUTAGEN 306 306 N->G: Increases cell membrane expression
FT in absence of FCER1G.
FT CONFLICT 25 25 T -> S (in Ref. 1; CAA32537).
FT CONFLICT 115 115 T -> M (in Ref. 4; AAA58414).
FT CONFLICT 183 183 V -> QY (in Ref. 4; AAA58414).
FT CONFLICT 284 284 Q -> R (in Ref. 4; AAA58414).
FT CONFLICT 324 324 D -> N (in Ref. 4; AAA58414).
FT CONFLICT 338 338 I -> T (in Ref. 1 and 2).
FT STRAND 23 28
FT STRAND 31 34
FT STRAND 39 44
FT STRAND 54 58
FT STRAND 67 74
FT HELIX 77 79
FT STRAND 81 90
FT STRAND 96 101
FT STRAND 103 110
FT STRAND 112 115
FT STRAND 120 126
FT HELIX 127 129
FT STRAND 133 139
FT STRAND 142 149
FT STRAND 153 157
FT HELIX 160 162
FT STRAND 164 179
FT STRAND 181 186
FT STRAND 193 198
FT STRAND 200 203
FT STRAND 208 213
FT STRAND 225 231
FT STRAND 234 241
FT STRAND 244 249
FT HELIX 252 254
FT STRAND 256 264
FT STRAND 270 272
FT STRAND 276 278
SQ SEQUENCE 374 AA; 42632 MW; D33D59398CEEA699 CRC64;
MWFLTTLLLW VPVDGQVDTT KAVITLQPPW VSVFQEETVT LHCEVLHLPG SSSTQWFLNG
TATQTSTPSY RITSASVNDS GEYRCQRGLS GRSDPIQLEI HRGWLLLQVS SRVFTEGEPL
ALRCHAWKDK LVYNVLYYRN GKAFKFFHWN SNLTILKTNI SHNGTYHCSG MGKHRYTSAG
ISVTVKELFP APVLNASVTS PLLEGNLVTL SCETKLLLQR PGLQLYFSFY MGSKTLRGRN
TSSEYQILTA RREDSGLYWC EAATEDGNVL KRSPELELQV LGLQLPTPVW FHVLFYLAVG
IMFLVNTVLW VTIRKELKRK KKWDLEISLD SGHEKKVISS LQEDRHLEEE LKCQEQKEEQ
LQEGVHRKEP QGAT
//
ID FCGR1_HUMAN Reviewed; 374 AA.
AC P12314; P12315; Q5QNW7; Q92495; Q92663;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 19-JUL-2004, sequence version 2.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=High affinity immunoglobulin gamma Fc receptor I;
DE Short=IgG Fc receptor I;
DE AltName: Full=Fc-gamma RI;
DE Short=FcRI;
DE AltName: Full=Fc-gamma RIA;
DE Short=FcgammaRIa;
DE AltName: CD_antigen=CD64;
DE Flags: Precursor;
GN Name=FCGR1A; Synonyms=FCG1, FCGR1, IGFR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=2974947; DOI=10.1093/nar/16.24.11824;
RA Allen J.M., Seed B.;
RT "Nucleotide sequence of three cDNAs for the human high affinity Fc
RT receptor (FcRI).";
RL Nucleic Acids Res. 16:11824-11824(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2911749; DOI=10.1126/science.2911749;
RA Allen J.M., Seed B.;
RT "Isolation and expression of functional high-affinity Fc receptor
RT complementary DNAs.";
RL Science 243:378-381(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Blood;
RX PubMed=1430234; DOI=10.1172/JCI116094;
RA Porges A.J., Redecha P.B., Doebele R., Pan L.C., Salmon J.E.,
RA Kimberly R.P.;
RT "Novel Fc gamma receptor I family gene products in human mononuclear
RT cells.";
RL J. Clin. Invest. 90:2102-2109(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RX PubMed=1402657; DOI=10.1084/jem.176.4.1115;
RA Benech P.D., Sastry K.N., Iyer R.R., Eichbaum Q.G., Raveh D.P.,
RA Ezekowitz R.A.;
RT "Definition of interferon gamma-response elements in a novel human Fc
RT gamma receptor gene (Fc gamma RIb) and characterization of the gene
RT structure.";
RL J. Exp. Med. 176:1115-1123(1992).
RN [5]
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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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 [6]
RP PROTEIN SEQUENCE OF 16-30.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP ALTERNATIVE SPLICING.
RX PubMed=1379234;
RA Ernst L.K., van de Winkel J.G., Chiu I.M., Anderson C.L.;
RT "Three genes for the human high affinity Fc receptor for IgG (Fc gamma
RT RI) encode four distinct transcription products.";
RL J. Biol. Chem. 267:15692-15700(1992).
RN [8]
RP INTERACTION WITH HCK AND LYN.
RX PubMed=8064233; DOI=10.1084/jem.180.3.1165;
RA Wang A.V., Scholl P.R., Geha R.S.;
RT "Physical and functional association of the high affinity
RT immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and
RT Lyn.";
RL J. Exp. Med. 180:1165-1170(1994).
RN [9]
RP FUNCTION, INTERACTION WITH FCER1G, 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.,
RA Saito T., Verbeek J.S., van de Winkel J.G.J.;
RT "FcR gamma-chain is essential for both surface expression and function
RT of human Fc gamma RI (CD64) in vivo.";
RL Blood 87:3593-3599(1996).
RN [10]
RP FUNCTION, ALTERNATIVE SPLICING, AND GLYCOSYLATION.
RX PubMed=9881690; DOI=10.1016/S0161-5890(98)00079-0;
RA Ernst L.K., Duchemin A.-M., Miller K.L., Anderson C.L.;
RT "Molecular characterization of six variant Fcgamma receptor class I
RT (CD64) transcripts.";
RL Mol. Immunol. 35:943-954(1998).
RN [11]
RP FUNCTION.
RX PubMed=10397749;
RA van Vugt M.J., Kleijmeer M.J., Keler T., Zeelenberg I., van Dijk M.A.,
RA Leusen J.H.W., Geuze H.J., van de Winkel J.G.J.;
RT "The FcgammaRIa (CD64) ligand binding chain triggers major
RT histocompatibility complex class II antigen presentation independently
RT of its associated FcR gamma-chain.";
RL Blood 94:808-817(1999).
RN [12]
RP FUNCTION, AND INTERACTION WITH FCER1G.
RX PubMed=10514529; DOI=10.1074/jbc.274.42.30328;
RA Edberg J.C., Yee A.M., Rakshit D.S., Chang D.J., Gokhale J.A.,
RA Indik Z.K., Schreiber A.D., Kimberly R.P.;
RT "The cytoplasmic domain of human FcgammaRIa alters the functional
RT properties of the FcgammaRI.gamma-chain receptor complex.";
RL J. Biol. Chem. 274:30328-30333(1999).
RN [13]
RP INTERACTION WITH LAT.
RX PubMed=10781611; DOI=10.1074/jbc.M909462199;
RA Tridandapani S., Lyden T.W., Smith J.L., Carter J.E., Coggeshall K.M.,
RA Anderson C.L.;
RT "The adapter protein LAT enhances fcgamma receptor-mediated signal
RT transduction in myeloid cells.";
RL J. Biol. Chem. 275:20480-20487(2000).
RN [14]
RP MUTAGENESIS OF ASN-306, AND SUBCELLULAR LOCATION.
RX PubMed=12756162; DOI=10.1182/blood.V101.11.4479;
RA Kim M.-K., Huang Z.-Y., Hwang P.-H., Jones B.A., Sato N., Hunter S.,
RA Kim-Han T.-H., Worth R.G., Indik Z.K., Schreiber A.D.;
RT "Fcgamma receptor transmembrane domains: role in cell surface
RT expression, gamma chain interaction, and phagocytosis.";
RL Blood 101:4479-4484(2003).
RN [15]
RP INTERACTION WITH PPL.
RX PubMed=15229321; DOI=10.1073/pnas.0401217101;
RA Beekman J.M., Bakema J.E., van de Winkel J.G.J., Leusen J.H.W.;
RT "Direct interaction between FcgammaRI (CD64) and periplakin controls
RT receptor endocytosis and ligand binding capacity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10392-10397(2004).
RN [16]
RP INTERACTION WITH FLNA.
RX PubMed=18322202;
RA Beekman J.M., van der Poel C.E., van der Linden J.A.,
RA van den Berg D.L.C., van den Berghe P.V.E., van de Winkel J.G.J.,
RA Leusen J.H.W.;
RT "Filamin A stabilizes FcgammaRI surface expression and prevents its
RT lysosomal routing.";
RL J. Immunol. 180:3938-3945(2008).
RN [17]
RP INTERACTION WITH EPB41L2.
RX PubMed=18023480; DOI=10.1016/j.molimm.2007.10.024;
RA Beekman J.M., Bakema J.E., van der Poel C.E., van der Linden J.A.,
RA van de Winkel J.G.J., Leusen J.H.W.;
RT "Protein 4.1G binds to a unique motif within the FcgammaRI cytoplasmic
RT tail.";
RL Mol. Immunol. 45:2069-2075(2008).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 21-282, FUNCTION, DISULFIDE
RP BONDS, AND GLYCOSYLATION AT ASN-59; ASN-78; ASN-152; ASN-159; ASN-163
RP AND ASN-195.
RX PubMed=21965667; DOI=10.1074/jbc.M111.257550;
RA Lu J., Ellsworth J.L., Hamacher N., Oak S.W., Sun P.D.;
RT "Crystal structure of Fcgamma receptor I and its implication in high
RT affinity gamma-immunoglobulin binding.";
RL J. Biol. Chem. 286:40608-40613(2011).
CC -!- FUNCTION: High affinity receptor for the Fc region of
CC immunoglobulins gamma. Functions in both innate and adaptive
CC immune responses.
CC -!- SUBUNIT: Interacts with FCERG1; forms a functional signaling
CC complex. Interacts with FLNA; prevents FCGR1A degradation.
CC Interacts with EPB41L2, LAT and PPL. Interacts with HCK and LYN.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Note=Stabilized at the cell membrane through interaction
CC with FCER1G.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=A;
CC IsoId=P12314-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=P12314-2; Sequence=VSP_002637;
CC -!- TISSUE SPECIFICITY: Monocyte/macrophage specific.
CC -!- PTM: Phosphorylated on serine residues (By similarity).
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. FCGR1
CC family.
CC -!- SIMILARITY: Contains 3 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- WEB RESOURCE: Name=FCGR1Abase; Note=FCGR1A mutation db;
CC URL="http://bioinf.uta.fi/FCGR1Abase/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X14356; CAA32537.1; -; mRNA.
DR EMBL; X14355; CAA32536.1; -; mRNA.
DR EMBL; L03418; AAA36049.1; -; mRNA.
DR EMBL; M91555; AAA58414.1; -; Genomic_DNA.
DR EMBL; M91550; AAA58414.1; JOINED; Genomic_DNA.
DR EMBL; M91551; AAA58414.1; JOINED; Genomic_DNA.
DR EMBL; M91552; AAA58414.1; JOINED; Genomic_DNA.
DR EMBL; M91553; AAA58414.1; JOINED; Genomic_DNA.
DR EMBL; M91554; AAA58414.1; JOINED; Genomic_DNA.
DR EMBL; AL591493; CAI12557.1; -; Genomic_DNA.
DR PIR; A39878; A39878.
DR PIR; A41357; A41357.
DR RefSeq; NP_000557.1; NM_000566.3.
DR UniGene; Hs.77424; -.
DR PDB; 3RJD; X-ray; 2.65 A; A=21-282.
DR PDBsum; 3RJD; -.
DR ProteinModelPortal; P12314; -.
DR SMR; P12314; 21-282.
DR IntAct; P12314; 1.
DR MINT; MINT-1538623; -.
DR STRING; 9606.ENSP00000358165; -.
DR BindingDB; P12314; -.
DR ChEMBL; CHEMBL5349; -.
DR DrugBank; DB00054; Abciximab.
DR DrugBank; DB00051; Adalimumab.
DR DrugBank; DB00092; Alefacept.
DR DrugBank; DB00087; Alemtuzumab.
DR DrugBank; DB00074; Basiliximab.
DR DrugBank; DB00112; Bevacizumab.
DR DrugBank; DB00002; Cetuximab.
DR DrugBank; DB00111; Daclizumab.
DR DrugBank; DB00095; Efalizumab.
DR DrugBank; DB00005; Etanercept.
DR DrugBank; DB00056; Gemtuzumab ozogamicin.
DR DrugBank; DB00078; Ibritumomab.
DR DrugBank; DB00028; Immune globulin.
DR DrugBank; DB00992; Methyl aminolevulinate.
DR DrugBank; DB00075; Muromonab.
DR DrugBank; DB00108; Natalizumab.
DR DrugBank; DB00110; Palivizumab.
DR DrugBank; DB00707; Porfimer.
DR DrugBank; DB00073; Rituximab.
DR DrugBank; DB00081; Tositumomab.
DR DrugBank; DB00072; Trastuzumab.
DR PhosphoSite; P12314; -.
DR DMDM; 50403717; -.
DR PaxDb; P12314; -.
DR PRIDE; P12314; -.
DR DNASU; 2209; -.
DR Ensembl; ENST00000369168; ENSP00000358165; ENSG00000150337.
DR Ensembl; ENST00000580698; ENSP00000462402; ENSG00000266332.
DR GeneID; 2209; -.
DR KEGG; hsa:2209; -.
DR UCSC; uc001esp.4; human.
DR CTD; 2209; -.
DR GeneCards; GC01P149754; -.
DR H-InvDB; HIX0000999; -.
DR HGNC; HGNC:3613; FCGR1A.
DR MIM; 146760; gene.
DR neXtProt; NX_P12314; -.
DR PharmGKB; PA28060; -.
DR eggNOG; NOG277652; -.
DR HOGENOM; HOG000251632; -.
DR HOVERGEN; HBG051602; -.
DR InParanoid; P12314; -.
DR KO; K06498; -.
DR OMA; RNSEFTI; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P12314; -.
DR GeneWiki; FCGR1A; -.
DR GenomeRNAi; 2209; -.
DR NextBio; 8947; -.
DR PRO; PR:P12314; -.
DR ArrayExpress; P12314; -.
DR Bgee; P12314; -.
DR CleanEx; HS_FCGR1A; -.
DR Genevestigator; P12314; -.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005057; F:receptor signaling protein activity; TAS:ProtInc.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0006911; P:phagocytosis, engulfment; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR Pfam; PF00047; ig; 1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW IgG-binding protein; Immunity; Immunoglobulin domain; Innate immunity;
KW Membrane; Phosphoprotein; Polymorphism; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1 15
FT CHAIN 16 374 High affinity immunoglobulin gamma Fc
FT receptor I.
FT /FTId=PRO_0000015139.
FT TOPO_DOM 16 292 Extracellular (Potential).
FT TRANSMEM 293 313 Helical; (Potential).
FT TOPO_DOM 314 374 Cytoplasmic (Potential).
FT DOMAIN 22 101 Ig-like C2-type 1.
FT DOMAIN 95 184 Ig-like C2-type 2.
FT DOMAIN 190 277 Ig-like C2-type 3.
FT REGION 312 332 Interaction with EPB41L2.
FT CARBOHYD 59 59 N-linked (GlcNAc...).
FT CARBOHYD 78 78 N-linked (GlcNAc...).
FT CARBOHYD 152 152 N-linked (GlcNAc...).
FT CARBOHYD 159 159 N-linked (GlcNAc...).
FT CARBOHYD 163 163 N-linked (GlcNAc...).
FT CARBOHYD 195 195 N-linked (GlcNAc...).
FT CARBOHYD 240 240 N-linked (GlcNAc...) (Potential).
FT DISULFID 43 85
FT DISULFID 124 168
FT DISULFID 212 260
FT VAR_SEQ 333 374 HEKKVISSLQEDRHLEEELKCQEQKEEQLQEGVHRKEPQGA
FT T -> GQALEAPTQGCA (in isoform 2).
FT /FTId=VSP_002637.
FT VARIANT 105 105 L -> P (in dbSNP:rs619322).
FT /FTId=VAR_019522.
FT MUTAGEN 306 306 N->D: Decreases cell membrane expression
FT by 50% in absence of FCER1G.
FT MUTAGEN 306 306 N->G: Increases cell membrane expression
FT in absence of FCER1G.
FT CONFLICT 25 25 T -> S (in Ref. 1; CAA32537).
FT CONFLICT 115 115 T -> M (in Ref. 4; AAA58414).
FT CONFLICT 183 183 V -> QY (in Ref. 4; AAA58414).
FT CONFLICT 284 284 Q -> R (in Ref. 4; AAA58414).
FT CONFLICT 324 324 D -> N (in Ref. 4; AAA58414).
FT CONFLICT 338 338 I -> T (in Ref. 1 and 2).
FT STRAND 23 28
FT STRAND 31 34
FT STRAND 39 44
FT STRAND 54 58
FT STRAND 67 74
FT HELIX 77 79
FT STRAND 81 90
FT STRAND 96 101
FT STRAND 103 110
FT STRAND 112 115
FT STRAND 120 126
FT HELIX 127 129
FT STRAND 133 139
FT STRAND 142 149
FT STRAND 153 157
FT HELIX 160 162
FT STRAND 164 179
FT STRAND 181 186
FT STRAND 193 198
FT STRAND 200 203
FT STRAND 208 213
FT STRAND 225 231
FT STRAND 234 241
FT STRAND 244 249
FT HELIX 252 254
FT STRAND 256 264
FT STRAND 270 272
FT STRAND 276 278
SQ SEQUENCE 374 AA; 42632 MW; D33D59398CEEA699 CRC64;
MWFLTTLLLW VPVDGQVDTT KAVITLQPPW VSVFQEETVT LHCEVLHLPG SSSTQWFLNG
TATQTSTPSY RITSASVNDS GEYRCQRGLS GRSDPIQLEI HRGWLLLQVS SRVFTEGEPL
ALRCHAWKDK LVYNVLYYRN GKAFKFFHWN SNLTILKTNI SHNGTYHCSG MGKHRYTSAG
ISVTVKELFP APVLNASVTS PLLEGNLVTL SCETKLLLQR PGLQLYFSFY MGSKTLRGRN
TSSEYQILTA RREDSGLYWC EAATEDGNVL KRSPELELQV LGLQLPTPVW FHVLFYLAVG
IMFLVNTVLW VTIRKELKRK KKWDLEISLD SGHEKKVISS LQEDRHLEEE LKCQEQKEEQ
LQEGVHRKEP QGAT
//
MIM
146760
*RECORD*
*FIELD* NO
146760
*FIELD* TI
*146760 Fc FRAGMENT OF IgG, HIGH AFFINITY Ia, RECEPTOR FOR; FCGR1A
;;IMMUNOGLOBULIN G Fc RECEPTOR I; IGFR1;;
read moreCD64
*FIELD* TX
CLONING
See 146790. By genomic cloning, Pearse et al. (1991) determined the
structure of the gene encoding human Fc-gamma-RI (FCGR1). They focused
on the structure of its promoter and characterized the DNA sequences
responsible for its induction by gamma-interferon (147570). They found a
39-nucleotide sequence, called by them the IFN-gamma response region
(GRR), which was both necessary and sufficient for gamma-interferon
inducibility. The FCGR1 gene encodes a high-affinity Fc-gamma receptor
that plays a pivotal role in the immune response. Also known as CD64, it
is a glycoprotein (MW 72 kD) that is constitutively expressed on human
monocytes and macrophages.
MAPPING
Osman et al. (1992) demonstrated that the Fcg1 locus in the mouse is on
chromosome 3 near the end of the region that shows homology to human
chromosome 1. Analysis of human x rodent somatic cell hybrid cell lines
indicated that the human FCGR1 locus is on human chromosome 1 and
therefore probably linked to the other FCGR genes. Oakey et al. (1992)
also mapped the FCGR1 gene to mouse chromosome 3. It is likely that
FCGR1 is on the short arm of human chromosome 1 close to CD2 (186990),
which is located at 1p13. The related genes FCGR2A (146790) and FCGR3
(146740) are located on human 1q23 and mouse chromosome 1. In fact,
however, Takai et al. (1994) demonstrated by fluorescence in situ
hybridization (FISH) that the FCGR1 gene is located on 1q21.2-q21.3.
By FISH analysis of human cells and Southern analysis of cell lines
containing 1p and 2q, Maresco et al. (1996) demonstrated that the 3
FCGR1 genes, FCGR1A, FCGR1B (601502), and FCGR1C (601503), flank the
centromere of chromosome 1 at bands 1p12 and 1q21. FCGR1B was found at
1p12, whereas both FCGR1A and FCGR1C were localized to 1q21. This placed
the FCGR1 gene family within a large pericentric linkage group that is
conserved between humans and mice. Maresco et al. (1996) hypothesized
that the 3 FCGR1 genes were separated by a pericentric inversion, known
to have occurred on human chromosome 1, which relocated FCGR1A and
FCGR1C to the long arm and left FCGR1B positioned on the short arm.
*FIELD* AV
.0001
IgG RECEPTOR I, PHAGOCYTIC, FAMILIAL DEFICIENCY OF
CD64 DEFICIENCY, FAMILIAL
FCGR1A, ARG92TER
In 4 individuals in the same family, van de Winkel et al. (1995)
demonstrated lack of phagocyte expression of CD64. As a result, their
monocytes were unable to support mouse IgG2a anti-CD3-induced T cell
mitogenesis, i.e., they were nonresponders. Southern blotting showed
that the CD64 gene was present in nonresponders without major structural
changes. Nucleotide sequencing showed identical promoter regions of the
gene in all individuals. At the message level, a distinct difference was
noted between monocytes from control (responder) donors and from
nonresponders. Both a 1.7- and 1.6-kb message was found in responders,
whereas in nonresponders only the 1.6-kb species was detectable. Reverse
transcriptase-PCR analyses showed that the CD64 transcript (encoding a
receptor with 3 extracellular Ig-like domains) was present at a level
approximately 15- to 20-fold lower than in nonresponder monocytes. They
could demonstrate a single nucleotide difference (C-to-T) within the
extracellular domain, exon 1-encoding region of the FCGR1 gene in
nonresponders, resulting in the change of codon 92 from arginine to a
stop. This change probably affected mRNA stability and thereby led to
undetectable expression of CD64 in phagocytes. Despite this defect these
individuals were apparently healthy, suggesting that FCGR1 is
dispensable for phagocyte functioning. The 4 deficient individuals were
sisters. The mother, 2 sisters, and 1 brother of the nonresponder
subjects responded normally and were all healthy. The father had died at
age 45 of cancer.
*FIELD* RF
1. Maresco, D. L.; Chang, E.; Theil, K. S.; Francke, U.; Anderson,
C. L.: The three genes of the human FCGR1 gene family encoding Fc-gamma-RI
flank the centromere of chromosome 1 at 1p12 and 1q21. Cytogenet.
Cell Genet. 73: 157-163, 1996.
2. Oakey, R. J.; Howard, T. A.; Hogarth, P. M.; Tani, K.; Seldin,
M. F.: Chromosomal mapping of the high affinity Fc-gamma receptor
gene. Immunogenetics 35: 279-282, 1992.
3. Osman, N.; Kozak, C. A.; McKenzie, I. F. C.; Hogarth, P. M.: Structure
and mapping of the gene encoding mouse high affinity Fc-gamma-RI and
chromosomal location of the human Fc-gamma-RI gene. J. Immun. 148:
1570-1575, 1992.
4. Pearse, R. N.; Feinman, R.; Ravetch, J. V.: Characterization of
the promoter of the human gene encoding the high-affinity IgG receptor:
transcriptional induction by gamma-interferon is mediated through
common DNA response elements. Proc. Nat. Acad. Sci. 88: 11305-11309,
1991.
5. Takai, S.; Kasama, M.; Yamada, K.; Kai, N.; Hirayama, N.; Namiki,
H.; Taniyama, T.: Human high-affinity Fc-gamma-RI (CD64) gene mapped
to chromosome 1q21.2-q21.3 by fluorescence in situ hybridization. Hum.
Genet. 93: 13-15, 1994.
6. van de Winkel, J. G. J.; de Wit, T. P. M.; Ernst, L. K.; Capel,
P. J. A.; Ceuppens, J. L.: Molecular basis for a familial defect
in phagocyte expression of IgG receptor I (CD64). J. Immun. 154:
2896-2903, 1995.
*FIELD* CD
Victor A. McKusick: 11/9/1988
*FIELD* ED
alopez: 02/27/2013
mark: 11/14/1996
terry: 11/12/1996
mark: 7/9/1995
terry: 5/10/1994
carol: 3/19/1994
carol: 6/16/1992
carol: 5/5/1992
supermim: 3/16/1992
*RECORD*
*FIELD* NO
146760
*FIELD* TI
*146760 Fc FRAGMENT OF IgG, HIGH AFFINITY Ia, RECEPTOR FOR; FCGR1A
;;IMMUNOGLOBULIN G Fc RECEPTOR I; IGFR1;;
read moreCD64
*FIELD* TX
CLONING
See 146790. By genomic cloning, Pearse et al. (1991) determined the
structure of the gene encoding human Fc-gamma-RI (FCGR1). They focused
on the structure of its promoter and characterized the DNA sequences
responsible for its induction by gamma-interferon (147570). They found a
39-nucleotide sequence, called by them the IFN-gamma response region
(GRR), which was both necessary and sufficient for gamma-interferon
inducibility. The FCGR1 gene encodes a high-affinity Fc-gamma receptor
that plays a pivotal role in the immune response. Also known as CD64, it
is a glycoprotein (MW 72 kD) that is constitutively expressed on human
monocytes and macrophages.
MAPPING
Osman et al. (1992) demonstrated that the Fcg1 locus in the mouse is on
chromosome 3 near the end of the region that shows homology to human
chromosome 1. Analysis of human x rodent somatic cell hybrid cell lines
indicated that the human FCGR1 locus is on human chromosome 1 and
therefore probably linked to the other FCGR genes. Oakey et al. (1992)
also mapped the FCGR1 gene to mouse chromosome 3. It is likely that
FCGR1 is on the short arm of human chromosome 1 close to CD2 (186990),
which is located at 1p13. The related genes FCGR2A (146790) and FCGR3
(146740) are located on human 1q23 and mouse chromosome 1. In fact,
however, Takai et al. (1994) demonstrated by fluorescence in situ
hybridization (FISH) that the FCGR1 gene is located on 1q21.2-q21.3.
By FISH analysis of human cells and Southern analysis of cell lines
containing 1p and 2q, Maresco et al. (1996) demonstrated that the 3
FCGR1 genes, FCGR1A, FCGR1B (601502), and FCGR1C (601503), flank the
centromere of chromosome 1 at bands 1p12 and 1q21. FCGR1B was found at
1p12, whereas both FCGR1A and FCGR1C were localized to 1q21. This placed
the FCGR1 gene family within a large pericentric linkage group that is
conserved between humans and mice. Maresco et al. (1996) hypothesized
that the 3 FCGR1 genes were separated by a pericentric inversion, known
to have occurred on human chromosome 1, which relocated FCGR1A and
FCGR1C to the long arm and left FCGR1B positioned on the short arm.
*FIELD* AV
.0001
IgG RECEPTOR I, PHAGOCYTIC, FAMILIAL DEFICIENCY OF
CD64 DEFICIENCY, FAMILIAL
FCGR1A, ARG92TER
In 4 individuals in the same family, van de Winkel et al. (1995)
demonstrated lack of phagocyte expression of CD64. As a result, their
monocytes were unable to support mouse IgG2a anti-CD3-induced T cell
mitogenesis, i.e., they were nonresponders. Southern blotting showed
that the CD64 gene was present in nonresponders without major structural
changes. Nucleotide sequencing showed identical promoter regions of the
gene in all individuals. At the message level, a distinct difference was
noted between monocytes from control (responder) donors and from
nonresponders. Both a 1.7- and 1.6-kb message was found in responders,
whereas in nonresponders only the 1.6-kb species was detectable. Reverse
transcriptase-PCR analyses showed that the CD64 transcript (encoding a
receptor with 3 extracellular Ig-like domains) was present at a level
approximately 15- to 20-fold lower than in nonresponder monocytes. They
could demonstrate a single nucleotide difference (C-to-T) within the
extracellular domain, exon 1-encoding region of the FCGR1 gene in
nonresponders, resulting in the change of codon 92 from arginine to a
stop. This change probably affected mRNA stability and thereby led to
undetectable expression of CD64 in phagocytes. Despite this defect these
individuals were apparently healthy, suggesting that FCGR1 is
dispensable for phagocyte functioning. The 4 deficient individuals were
sisters. The mother, 2 sisters, and 1 brother of the nonresponder
subjects responded normally and were all healthy. The father had died at
age 45 of cancer.
*FIELD* RF
1. Maresco, D. L.; Chang, E.; Theil, K. S.; Francke, U.; Anderson,
C. L.: The three genes of the human FCGR1 gene family encoding Fc-gamma-RI
flank the centromere of chromosome 1 at 1p12 and 1q21. Cytogenet.
Cell Genet. 73: 157-163, 1996.
2. Oakey, R. J.; Howard, T. A.; Hogarth, P. M.; Tani, K.; Seldin,
M. F.: Chromosomal mapping of the high affinity Fc-gamma receptor
gene. Immunogenetics 35: 279-282, 1992.
3. Osman, N.; Kozak, C. A.; McKenzie, I. F. C.; Hogarth, P. M.: Structure
and mapping of the gene encoding mouse high affinity Fc-gamma-RI and
chromosomal location of the human Fc-gamma-RI gene. J. Immun. 148:
1570-1575, 1992.
4. Pearse, R. N.; Feinman, R.; Ravetch, J. V.: Characterization of
the promoter of the human gene encoding the high-affinity IgG receptor:
transcriptional induction by gamma-interferon is mediated through
common DNA response elements. Proc. Nat. Acad. Sci. 88: 11305-11309,
1991.
5. Takai, S.; Kasama, M.; Yamada, K.; Kai, N.; Hirayama, N.; Namiki,
H.; Taniyama, T.: Human high-affinity Fc-gamma-RI (CD64) gene mapped
to chromosome 1q21.2-q21.3 by fluorescence in situ hybridization. Hum.
Genet. 93: 13-15, 1994.
6. van de Winkel, J. G. J.; de Wit, T. P. M.; Ernst, L. K.; Capel,
P. J. A.; Ceuppens, J. L.: Molecular basis for a familial defect
in phagocyte expression of IgG receptor I (CD64). J. Immun. 154:
2896-2903, 1995.
*FIELD* CD
Victor A. McKusick: 11/9/1988
*FIELD* ED
alopez: 02/27/2013
mark: 11/14/1996
terry: 11/12/1996
mark: 7/9/1995
terry: 5/10/1994
carol: 3/19/1994
carol: 6/16/1992
carol: 5/5/1992
supermim: 3/16/1992