P12318 (FCG2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Low affinity immunoglobulin gamma Fc region receptor II-a
Short name=IgG Fc receptor II-a

Alternative name(s):
CDw32
Fc-gamma RII-a
Short name=Fc-gamma-RIIa
Short name=FcRII-a
CD_antigen=CD32

Gene names

Name:	FCGR2A
Synonyms:	CD32, FCG2, FCGR2A1, IGFR2

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	317 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	Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized antigens. Ref.15
Subunit structure	Interacts with INPP5D/SHIP1 and INPPL1/SHIP2, regulating its function. Interacts with APCS and FGR. Interacts with HCK. Ref.9 Ref.10 Ref.12
Subcellular location	Cell membrane; Single-pass type I membrane protein Ref.15.
Tissue specificity	Found on monocytes, neutrophils and eosinophil platelets.
Post-translational modification	Phosphorylated by SRC-type Tyr-kinases such as LYN, BLK, FYN, HCK and SYK. Ref.10 Ref.11
Sequence similarities	Contains 2 Ig-like C2-type (immunoglobulin-like) domains.
Sequence caution	The sequence AAA35932.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	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)
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Non-traceable author statement PubMed 2139735. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P12318-1)

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: P12318-2)

The sequence of this isoform differs from the canonical sequence as follows:
     35-35: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 33

33

Ref.8

Chain

34 – 317

284

Low affinity immunoglobulin gamma Fc region receptor II-a

PRO_0000015145

Regions

Topological domain

34 – 217

184

Extracellular Potential

Transmembrane

218 – 240

23

Helical; Potential

Topological domain

241 – 317

77

Cytoplasmic Potential

Domain

39 – 118

80

Ig-like C2-type 1

Domain

122 – 204

83

Ig-like C2-type 2

Amino acid modifications

Modified residue

288

1

Phosphotyrosine; by SRC-type Tyr-kinases Ref.11

Modified residue

304

1

Phosphotyrosine; by SRC-type Tyr-kinases Ref.11

Glycosylation

97

1

N-linked (GlcNAc...) Ref.8

Glycosylation

178

1

N-linked (GlcNAc...) Ref.8

Disulfide bond

62 ↔ 104

Ref.14 Ref.15

Disulfide bond

143 ↔ 187

Ref.14 Ref.15

Natural variations

Alternative sequence

35

1

Missing in isoform 2.

VSP_036865

Natural variant

63

1

Q → R.
Corresponds to variant rs9427398 [ dbSNP | Ensembl ].

VAR_054857

Natural variant

140

1

M → V.
Corresponds to variant rs4986941 [ dbSNP | Ensembl ].

VAR_054858

Natural variant

167

1

H → R May be associated with susceptibility to lupus nephritis; does not efficiently recognize IgG2. Ref.1 Ref.2 Ref.4 Ref.5 Ref.6 Ref.16
Corresponds to variant rs1801274 [ dbSNP | Ensembl ].

VAR_003955

Natural variant

218

1

I → V. Ref.4
Corresponds to variant rs17851834 [ dbSNP | Ensembl ].

VAR_054859

Experimental info

Sequence conflict

2

1

T → A in AAA35827. Ref.2

Secondary structure

1

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317

Helix Strand Turn

Details...

Beta strand

42 – 47

6

Beta strand

50 – 53

4

Beta strand

57 – 64

8

Beta strand

68 – 71

4

Beta strand

73 – 77

5

Beta strand

80 – 82

3

Beta strand

87 – 93

7

Helix

96 – 98

3

Beta strand

100 – 106

7

Beta strand

107 – 110

4

Beta strand

115 – 120

6

Beta strand

123 – 127

5

Beta strand

131 – 133

3

Beta strand

139 – 145

7

Helix

146 – 148

3

Beta strand

151 – 158

8

Beta strand

161 – 168

8

Beta strand

171 – 176

6

Helix

179 – 181

3

Beta strand

183 – 191

9

Beta strand

194 – 197

4

Beta strand

201 – 205

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 13, 2007. Version 4. Checksum: 07F73F3BB282DFF6	FASTA	317	35,001
	10 20 30 40 50 60 MTMETQMSQN VCPRNLWLLQ PLTVLLLLAS ADSQAAAPPK AVLKLEPPWI NVLQEDSVTL 70 80 90 100 110 120 TCQGARSPES DSIQWFHNGN LIPTHTQPSY RFKANNNDSG EYTCQTGQTS LSDPVHLTVL 130 140 150 160 170 180 SEWLVLQTPH LEFQEGETIM LRCHSWKDKP LVKVTFFQNG KSQKFSHLDP TFSIPQANHS 190 200 210 220 230 240 HSGDYHCTGN IGYTLFSSKP VTITVQVPSM GSSSPMGIIV AVVIATAVAA IVAAVVALIY 250 260 270 280 290 300 CRKKRISANS TDPVKAAQFE PPGRQMIAIR KRQLEETNND YETADGGYMT LNPRAPTDDD 310 KNIYLTLPPN DHVNSNN
	Isoform 2 [UniParc]. Checksum: 3B4B813ECF6DCFCD	FASTA	316	34,930
	10 20 30 40 50 60 MTMETQMSQN VCPRNLWLLQ PLTVLLLLAS ADSQAAPPKA VLKLEPPWIN VLQEDSVTLT 70 80 90 100 110 120 CQGARSPESD SIQWFHNGNL IPTHTQPSYR FKANNNDSGE YTCQTGQTSL SDPVHLTVLS 130 140 150 160 170 180 EWLVLQTPHL EFQEGETIML RCHSWKDKPL VKVTFFQNGK SQKFSHLDPT FSIPQANHSH 190 200 210 220 230 240 SGDYHCTGNI GYTLFSSKPV TITVQVPSMG SSSPMGIIVA VVIATAVAAI VAAVVALIYC 250 260 270 280 290 300 RKKRISANST DPVKAAQFEP PGRQMIAIRK RQLEETNNDY ETADGGYMTL NPRAPTDDDK 310 NIYLTLPPND HVNSNN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and expression of cDNA clones encoding a human receptor for IgG (Fc gamma RII)." Stuart S.G., Trounstine M.L., Vaux D.J.T., Koch T., Martens C.L., Moore K.W. J. Exp. Med. 166:1668-1684(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-167.
[2]	"Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes." Brooks D.G., Qiu W.Q., Luster A.D., Ravetch J.V. J. Exp. Med. 170:1369-1385(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-167.
[3]	"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].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS ARG-167 AND VAL-218. Tissue: Lung and Testis.
[5]	"Molecular cloning of a human immunoglobulin G Fc receptor." Hibbs M.L., Bonadonna L., Scott B.M., McKenzie I.F.C., Hogarth P.M. Proc. Natl. Acad. Sci. U.S.A. 85:2240-2244(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-317 (ISOFORM 1), VARIANT ARG-167.
[6]	"Isolation of cDNAs for two distinct human Fc receptors by ligand affinity cloning." Stengelin S., Stamenkovic I., Seed B. EMBO J. 7:1053-1059(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-317 (ISOFORM 1), VARIANT ARG-167.
[7]	"Identification of multiple isoforms of the low-affinity human IgG Fc receptor." Seki T. Immunogenetics 30:5-12(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-317 (ISOFORM 1).
[8]	"Biochemical analysis and crystallisation of Fc gamma RIIa, the low affinity receptor for IgG." Powell M.S., Barton P.A., Emmanouilidis D., Wines B.D., Neumann G.M., Peitersz G.A., Maxwell K.F., Garrett T.P., Hogarth P.M. Immunol. Lett. 68:17-23(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, GLYCOSYLATION AT ASN-97 AND ASN-178, CRYSTALLIZATION.
[9]	"Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils." Hamada F., Aoki M., Akiyama T., Toyoshima K. Proc. Natl. Acad. Sci. U.S.A. 90:6305-6309(1993) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FGR.
[10]	"Physical and functional association of Src-related protein tyrosine kinases with Fc gamma RII in monocytic THP-1 cells." Ghazizadeh S., Bolen J.B., Fleit H.B. J. Biol. Chem. 269:8878-8884(1994) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCK, PHOSPHORYLATION.
[11]	"In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcgammaRII) phosphorylation." Bewarder N., Weinrich V., Budde P., Hartmann D., Flaswinkel H., Reth M., Frey J. Mol. Cell. Biol. 16:4735-4743(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-288 AND TYR-304.
[12]	"SHIP-2 inositol phosphatase is inducibly expressed in human monocytes and serves to regulate Fcgamma receptor-mediated signaling." Pengal R.A., Ganesan L.P., Fang H., Marsh C.B., Anderson C.L., Tridandapani S. J. Biol. Chem. 278:22657-22663(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INPPL1.
[13]	"Crystal structure of the human leukocyte Fc receptor, Fc gammaRIIa." Maxwell K.F., Powell M.S., Hulett M.D., Barton P.A., McKenzie I.F., Garrett T.P., Hogarth P.M. Nat. Struct. Biol. 6:437-442(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 37-207.
[14]	"Molecular basis for immune complex recognition: a comparison of Fc-receptor structures." Sondermann P., Kaiser J., Jacob U. J. Mol. Biol. 309:737-749(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 37-208, DISULFIDE BONDS.
[15]	"Structural recognition and functional activation of FcgammaR by innate pentraxins." Lu J., Marnell L.L., Marjon K.D., Mold C., Du Clos T.W., Sun P.D. Nature 456:989-992(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 37-207 IN COMPLEX WITH APCS, SUBCELLULAR LOCATION, FUNCTION, DISULFIDE BONDS.
[16]	"Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans." Salmon J.E., Millard S., Schachter L.A., Arnett F.C., Ginzler E.M., Gourley M.F., Ramsey-Goldman R., Peterson M.G.E., Kimberly R.P. J. Clin. Invest. 97:1348-1354(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-167.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00644 mRNA. Translation: CAA68672.1.
M31932 mRNA. Translation: AAA35827.1.
AL590385 Genomic DNA. No translation available.
BC019931 mRNA. Translation: AAH19931.1.
BC020823 mRNA. Translation: AAH20823.1.
J03619 mRNA. Translation: AAA35932.1. Different initiation.

IPI

IPI00023505.
IPI00646445.

PIR

JL0118.

RefSeq

NP_001129691.1. NM_001136219.1.
NP_067674.2. NM_021642.3.

UniGene

Hs.352642.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FCG	X-ray	2.00	A	34-207	[»]
1H9V	X-ray	3.00	A	37-208	[»]
3D5O	X-ray	2.80	F	37-207	[»]
3RY4	X-ray	1.50	A	37-206	[»]
3RY5	X-ray	2.30	A	37-206	[»]
3RY6	X-ray	3.80	C	40-206	[»]

ProteinModelPortal

P12318.

ModBase

Search...

Protein-protein interaction databases

IntAct

P12318. 1 interaction.

STRING

9606.ENSP00000271450.

PTM databases

PhosphoSite

P12318.

Polymorphism databases

DMDM

160332371.

Proteomic databases

PaxDb

P12318.

PRIDE

P12318.

Protocols and materials databases

DNASU

2212.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000271450; ENSP00000271450; ENSG00000143226.
ENST00000367972; ENSP00000356949; ENSG00000143226.

GeneID

2212.

KEGG

hsa:2212.

UCSC

uc001gam.3. human.
uc001gan.3. human.

Organism-specific databases

CTD

2212.

GeneCards

GC01P161475.

H-InvDB

HIX0018571.

HGNC

HGNC:3616. FCGR2A.

HPA

HPA010718.

MIM

146790. gene.

neXtProt

NX_P12318.

PharmGKB

PA28063.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG25177.

HOGENOM

HOG000251632.

HOVERGEN

HBG051602.

InParanoid

P12318.

KO

K06472.

OMA

YTLFSSK.

OrthoDB

EOG4ZS94D.

Enzyme and pathway databases

Pathway_Interaction_DB

ptp1bpathway. Signaling events mediated by PTP1B.

Gene expression databases

ArrayExpress

P12318.

Bgee

P12318.

CleanEx

HS_FCGR2A.

Genevestigator

P12318.

GermOnline

ENSG00000143226. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 2 hits.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]

SMART

SM00409. IG. 2 hits.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P12318.

ChEMBL

CHEMBL5841.

ChiTaRS

FCGR2A. human.

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.
DB00075. Muromonab.
DB00108. Natalizumab.
DB00110. Palivizumab.
DB00073. Rituximab.
DB00081. Tositumomab.
DB00072. Trastuzumab.

EvolutionaryTrace

P12318.

GenomeRNAi

2212.

NextBio

8961.

SOURCE

Search...

Entry information

Entry name

FCG2A_HUMAN

Accession

Primary (citable) accession number: P12318
Secondary accession number(s): Q8WUN1, Q8WW64

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	November 13, 2007
Last modified:	May 1, 2013
This is version 152 of the entry and version 4 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.