P12314 (FCGR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
High affinity immunoglobulin gamma Fc receptor I
Short name=IgG Fc receptor I

Alternative name(s):
Fc-gamma RI
Short name=FcRI
Fc-gamma RIA
Short name=FcgammaRIa
CD_antigen=CD64

Gene names

Name:	FCGR1A
Synonyms:	FCG1, FCGR1, IGFR1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	374 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses. Ref.9 Ref.10 Ref.11 Ref.12
Subunit structure	Interacts with FCERG1; forms a functional signaling complex. Interacts with FLNA; prevents FCGR1A degradation. Interacts with EPB41L2, LAT and PPL. Interacts with HCK and LYN. Ref.8 Ref.9 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17
Subcellular location	Cell membrane; Single-pass type I membrane protein. Note: Stabilized at the cell membrane through interaction with FCER1G. Ref.9 Ref.14
Tissue specificity	Monocyte/macrophage specific.
Post-translational modification	Phosphorylated on serine residues By similarity.
Sequence similarities	Belongs to the immunoglobulin superfamily. FCGR1 family. Contains 3 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Immunity Innate immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	IgG-binding protein
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	antibody-dependent cellular cytotoxicity Inferred from electronic annotation. Source: Compara antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Traceable author statement. Source: Reactome defense response to bacterium Inferred from electronic annotation. Source: Compara interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome phagocytosis, engulfment Traceable author statement PubMed 10879688. Source: ProtInc phagocytosis, recognition Inferred from electronic annotation. Source: Compara positive regulation of phagocytosis Inferred from electronic annotation. Source: Compara positive regulation of type III hypersensitivity Inferred from electronic annotation. Source: Compara positive regulation of type IIa hypersensitivity Inferred from electronic annotation. Source: Compara receptor-mediated endocytosis Inferred from electronic annotation. Source: Compara
Cellular_component	clathrin-coated endocytic vesicle membrane Traceable author statement. Source: Reactome early endosome membrane Traceable author statement. Source: Reactome external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay Ref.16. Source: BHF-UCL
Molecular_function	IgG receptor activity Inferred from electronic annotation. Source: Compara receptor signaling protein activity Traceable author statement PubMed 10879688. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P12314-1)

Also known as: A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P12314-2)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     333-374: HEKKVISSLQEDRHLEEELKCQEQKEEQLQEGVHRKEPQGAT → GQALEAPTQGCA

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 15	15	Ref.6
	Chain	16 – 374	359	High affinity immunoglobulin gamma Fc receptor I		PRO_0000015139
Regions
	Topological domain	16 – 292	277	Extracellular Potential
	Transmembrane	293 – 313	21	Helical; Potential
	Topological domain	314 – 374	61	Cytoplasmic Potential
	Domain	22 – 101	80	Ig-like C2-type 1
	Domain	95 – 184	90	Ig-like C2-type 2
	Domain	190 – 277	88	Ig-like C2-type 3
	Region	312 – 332	21	Interaction with EPB41L2
Amino acid modifications
	Glycosylation	59	1	N-linked (GlcNAc...) Potential
	Glycosylation	78	1	N-linked (GlcNAc...) Ref.18
	Glycosylation	152	1	N-linked (GlcNAc...) Potential
	Glycosylation	159	1	N-linked (GlcNAc...) Potential
	Glycosylation	163	1	N-linked (GlcNAc...) Potential
	Glycosylation	195	1	N-linked (GlcNAc...) Potential
	Glycosylation	240	1	N-linked (GlcNAc...) Potential
	Disulfide bond	43 ↔ 85		By similarity
	Disulfide bond	124 ↔ 168		By similarity
	Disulfide bond	212 ↔ 260		By similarity
Natural variations
	Alternative sequence	333 – 374	42	HEKKV…PQGAT → GQALEAPTQGCA in isoform 2.		VSP_002637
	Natural variant	105	1	L → P. Corresponds to variant rs619322 [ dbSNP | Ensembl ].		VAR_019522
Experimental info
	Mutagenesis	306	1	N → D: Decreases cell membrane expression by 50% in absence of FCER1G. Ref.14
	Mutagenesis	306	1	N → G: Increases cell membrane expression in absence of FCER1G. Ref.14
	Sequence conflict	25	1	T → S in CAA32537. Ref.1
	Sequence conflict	115	1	T → M in AAA58414. Ref.4
	Sequence conflict	183	1	V → QY in AAA58414. Ref.4
	Sequence conflict	284	1	Q → R in AAA58414. Ref.4
	Sequence conflict	324	1	D → N in AAA58414. Ref.4
	Sequence conflict	338	1	I → T Ref.1
	Sequence conflict	338	1	I → T Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A) [UniParc]. Last modified July 19, 2004. Version 2. Checksum: D33D59398CEEA699	FASTA	374	42,632
	10 20 30 40 50 60 MWFLTTLLLW VPVDGQVDTT KAVITLQPPW VSVFQEETVT LHCEVLHLPG SSSTQWFLNG 70 80 90 100 110 120 TATQTSTPSY RITSASVNDS GEYRCQRGLS GRSDPIQLEI HRGWLLLQVS SRVFTEGEPL 130 140 150 160 170 180 ALRCHAWKDK LVYNVLYYRN GKAFKFFHWN SNLTILKTNI SHNGTYHCSG MGKHRYTSAG 190 200 210 220 230 240 ISVTVKELFP APVLNASVTS PLLEGNLVTL SCETKLLLQR PGLQLYFSFY MGSKTLRGRN 250 260 270 280 290 300 TSSEYQILTA RREDSGLYWC EAATEDGNVL KRSPELELQV LGLQLPTPVW FHVLFYLAVG 310 320 330 340 350 360 IMFLVNTVLW VTIRKELKRK KKWDLEISLD SGHEKKVISS LQEDRHLEEE LKCQEQKEEQ 370 LQEGVHRKEP QGAT
	Isoform 2 (B) [UniParc]. Checksum: DDBE5DE64A66F6B8	FASTA	344	38,795
	10 20 30 40 50 60 MWFLTTLLLW VPVDGQVDTT KAVITLQPPW VSVFQEETVT LHCEVLHLPG SSSTQWFLNG 70 80 90 100 110 120 TATQTSTPSY RITSASVNDS GEYRCQRGLS GRSDPIQLEI HRGWLLLQVS SRVFTEGEPL 130 140 150 160 170 180 ALRCHAWKDK LVYNVLYYRN GKAFKFFHWN SNLTILKTNI SHNGTYHCSG MGKHRYTSAG 190 200 210 220 230 240 ISVTVKELFP APVLNASVTS PLLEGNLVTL SCETKLLLQR PGLQLYFSFY MGSKTLRGRN 250 260 270 280 290 300 TSSEYQILTA RREDSGLYWC EAATEDGNVL KRSPELELQV LGLQLPTPVW FHVLFYLAVG 310 320 330 340 IMFLVNTVLW VTIRKELKRK KKWDLEISLD SGGQALEAPT QGCA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of three cDNAs for the human high affinity Fc receptor (FcRI)." Allen J.M., Seed B. Nucleic Acids Res. 16:11824-11824(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[2]	"Isolation and expression of functional high-affinity Fc receptor complementary DNAs." Allen J.M., Seed B. Science 243:378-381(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Novel Fc gamma receptor I family gene products in human mononuclear cells." Porges A.J., Redecha P.B., Doebele R., Pan L.C., Salmon J.E., Kimberly R.P. J. Clin. Invest. 90:2102-2109(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Blood.
[4]	"Definition of interferon gamma-response elements in a novel human Fc gamma receptor gene (Fc gamma RIb) and characterization of the gene structure." Benech P.D., Sastry K.N., Iyer R.R., Eichbaum Q.G., Raveh D.P., Ezekowitz R.A. J. Exp. Med. 176:1115-1123(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Blood.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-30.
[7]	"Three genes for the human high affinity Fc receptor for IgG (Fc gamma RI) encode four distinct transcription products." Ernst L.K., van de Winkel J.G., Chiu I.M., Anderson C.L. J. Biol. Chem. 267:15692-15700(1992) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING.
[8]	"Physical and functional association of the high affinity immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and Lyn." Wang A.V., Scholl P.R., Geha R.S. J. Exp. Med. 180:1165-1170(1994) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCK AND LYN.
[9]	"FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo." van Vugt M.J., Heijnen I.A.F.M., Capel P.J.A., Park S.Y., Ra C., Saito T., Verbeek J.S., van de Winkel J.G.J. Blood 87:3593-3599(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FCER1G, SUBCELLULAR LOCATION.
[10]	"Molecular characterization of six variant Fcgamma receptor class I (CD64) transcripts." Ernst L.K., Duchemin A.-M., Miller K.L., Anderson C.L. Mol. Immunol. 35:943-954(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ALTERNATIVE SPLICING, GLYCOSYLATION.
[11]	"The FcgammaRIa (CD64) ligand binding chain triggers major histocompatibility complex class II antigen presentation independently of its associated FcR gamma-chain." van Vugt M.J., Kleijmeer M.J., Keler T., Zeelenberg I., van Dijk M.A., Leusen J.H.W., Geuze H.J., van de Winkel J.G.J. Blood 94:808-817(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"The cytoplasmic domain of human FcgammaRIa alters the functional properties of the FcgammaRI.gamma-chain receptor complex." Edberg J.C., Yee A.M., Rakshit D.S., Chang D.J., Gokhale J.A., Indik Z.K., Schreiber A.D., Kimberly R.P. J. Biol. Chem. 274:30328-30333(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FCER1G.
[13]	"The adapter protein LAT enhances fcgamma receptor-mediated signal transduction in myeloid cells." Tridandapani S., Lyden T.W., Smith J.L., Carter J.E., Coggeshall K.M., Anderson C.L. J. Biol. Chem. 275:20480-20487(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LAT.
[14]	"Fcgamma receptor transmembrane domains: role in cell surface expression, gamma chain interaction, and phagocytosis." Kim M.-K., Huang Z.-Y., Hwang P.-H., Jones B.A., Sato N., Hunter S., Kim-Han T.-H., Worth R.G., Indik Z.K., Schreiber A.D. Blood 101:4479-4484(2003) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASN-306, SUBCELLULAR LOCATION.
[15]	"Direct interaction between FcgammaRI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity." Beekman J.M., Bakema J.E., van de Winkel J.G.J., Leusen J.H.W. Proc. Natl. Acad. Sci. U.S.A. 101:10392-10397(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PPL.
[16]	"Filamin A stabilizes FcgammaRI surface expression and prevents its lysosomal routing." Beekman J.M., van der Poel C.E., van der Linden J.A., van den Berg D.L.C., van den Berghe P.V.E., van de Winkel J.G.J., Leusen J.H.W. J. Immunol. 180:3938-3945(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FLNA.
[17]	"Protein 4.1G binds to a unique motif within the FcgammaRI cytoplasmic tail." Beekman J.M., Bakema J.E., van der Poel C.E., van der Linden J.A., van de Winkel J.G.J., Leusen J.H.W. Mol. Immunol. 45:2069-2075(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EPB41L2.
[18]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Web resources

FCGR1Abase

FCGR1A mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X14356 mRNA. Translation: CAA32537.1.
X14355 mRNA. Translation: CAA32536.1.
L03418 mRNA. Translation: AAA36049.1.
M91555 , M91550, M91551, M91552, M91553, M91554 Genomic DNA. Translation: AAA58414.1.
AL591493 Genomic DNA. Translation: CAI12557.1.

IPI

IPI00023502.
IPI00375293.

PIR

A39878.
A41357.

RefSeq

NP_000557.1. NM_000566.3.

UniGene

Hs.77424.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3RJD	X-ray	2.65	A	21-282	[»]

ProteinModelPortal

P12314.

ModBase

Search...

Protein-protein interaction databases

IntAct

P12314. 1 interaction.

STRING

9606.ENSP00000358165.

PTM databases

PhosphoSite

P12314.

Polymorphism databases

DMDM

50403717.

Proteomic databases

PaxDb

P12314.

PRIDE

P12314.

Protocols and materials databases

DNASU

2209.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000369168; ENSP00000358165; ENSG00000150337.
ENST00000580698; ENSP00000462402; ENSG00000266332.

GeneID

2209.

KEGG

hsa:2209.

UCSC

uc001esp.4. human.

Organism-specific databases

CTD

2209.

GeneCards

GC01P149754.

H-InvDB

HIX0000999.

HGNC

HGNC:3613. FCGR1A.

MIM

146760. gene.

neXtProt

NX_P12314.

PharmGKB

PA28060.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG277652.

HOGENOM

HOG000251632.

HOVERGEN

HBG051602.

InParanoid

P12314.

KO

K06498.

OMA

FPAPVLN.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P12314.

Bgee

P12314.

CleanEx

HS_FCGR1A.

Genevestigator

P12314.

GermOnline

ENSG00000150337. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 3 hits.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
[Graphical view]

Pfam

PF00047. ig. 1 hit.
[Graphical view]

SMART

SM00409. IG. 2 hits.
SM00408. IGc2. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P12314.

ChEMBL

CHEMBL5349.

DrugBank

DB00054. Abciximab.
DB00051. Adalimumab.
DB00092. Alefacept.
DB00087. Alemtuzumab.
DB00074. Basiliximab.
DB00112. Bevacizumab.
DB00002. Cetuximab.
DB00111. Daclizumab.
DB00095. Efalizumab.
DB00005. Etanercept.
DB00056. Gemtuzumab ozogamicin.
DB00078. Ibritumomab.
DB00028. Immune globulin.
DB00992. Methyl aminolevulinate.
DB00075. Muromonab.
DB00108. Natalizumab.
DB00110. Palivizumab.
DB00707. Porfimer.
DB00073. Rituximab.
DB00081. Tositumomab.
DB00072. Trastuzumab.

GenomeRNAi

2209.

NextBio

8947.

SOURCE

Search...

Entry information

Entry name

FCGR1_HUMAN

Accession

Primary (citable) accession number: P12314
Secondary accession number(s): P12315 , Q5QNW7, Q92495, Q92663

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	July 19, 2004
Last modified:	May 1, 2013
This is version 143 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.