Reviewed, UniProtKB/Swiss-Prot P08637 (FCG3A_HUMAN)

Names and origin

Protein names

Recommended name:
    Low affinity immunoglobulin gamma Fc region receptor III-A
Alternative name(s):
    IgG Fc receptor III-2
    Fc-gamma RIII-alpha
      Short name=Fc-gamma RIIIa
      Short name=FcRIIIa
      Short name=Fc-gamma RIII
      Short name=FcRIII
    FcR-10
    CD16a antigen
    CD_antigen=CD16a

Gene names

Name:	FCGR3A
Synonyms:	CD16A, FCG3, FCGR3, IGFR3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	254 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis.
Subunit structure	Exists as a heterooligomeric receptor complex with Fc epsilon receptor I gamma subunit and / or the CD3 zeta subunit. Interacts with INPP5D/SHIP1 By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein Potential. Secreted. Note: Exists also as a soluble receptor.
Tissue specificity	Expressed on natural killer cells, macrophages, subpopulation of T-cells, immature thymocytes and placental trophoblasts.
Post-translational modification	Glycosylated. Contains high mannose- and complex-type oligosaccharides. The soluble form is produced by a proteolytic cleavage.
Polymorphism	Variant Val-157 shows a higher binding capacity of IgG1, IgG3 and IgG4 compared with variant Phe-157. Alleles Leu-66 and Phe-157, and alleles His-66 / Arg-66 and Val-157 are in linkage desequilibrium.
Miscellaneous	Encoded by one of two nearly indentical genes: FCGR3A (Shown here) and FCGR3B which are expressed in a tissue-specific manner. The Phe-203 in III-A determines the transmembrane domains whereas the 'Ser-203' in III-B determines the GPI-anchoring.
Sequence similarities	Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	IgG-binding protein
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	immune response Traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from Experiment. Source: Reactome
Molecular function	IgG binding Inferred from electronic annotation. Source: UniProtKB-KW receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 16	16	Potential
	Chain	17 – 254	238	Low affinity immunoglobulin gamma Fc region receptor III-A		PRO_0000015150
Regions
	Topological domain	17 – 208	192	Extracellular Potential
	Transmembrane	209 – 229	21	Potential
	Topological domain	230 – 254	25	Cytoplasmic Potential
	Domain	24 – 105	82	Ig-like C2-type 1
	Domain	107 – 189	83	Ig-like C2-type 2
Amino acid modifications
	Glycosylation	56	1	N-linked (GlcNAc...) Potential
	Glycosylation	63	1	N-linked (GlcNAc...) Potential
	Glycosylation	92	1	N-linked (GlcNAc...) Potential
	Glycosylation	180	1	N-linked (GlcNAc...) Potential
	Glycosylation	187	1	N-linked (GlcNAc...) Potential
	Disulfide bond	47 ↔ 89		By similarity
	Disulfide bond	128 ↔ 172		By similarity
Natural variations
	Natural variant	66	1	L → H		VAR_008800
	Natural variant	66	1	L → R: dbSNP rs10127939. Ref.9		VAR_008799
	Natural variant	147	1	G → D: dbSNP rs443082.		VAR_058398
	Natural variant	157	1	F → V		VAR_008801
	Natural variant	158	1	Y → H: dbSNP rs396716.		VAR_058399
	Natural variant	176	1	F → V: dbSNP rs396991. Ref.3 Ref.5 Ref.7 Ref.11		VAR_003960
	Natural variant	203	1	F → S: dbSNP rs1042206.		VAR_058400
Experimental info
	Sequence conflict	106	1	I → V in BAD96988. Ref.3
	Sequence conflict	106	1	I → V in BAD97015. Ref.3
	Sequence conflict	195	1	A → S in AAH33678. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P08637-1 [UniParc]. Last modified August 1, 1990. Version 2. Checksum: D38D178D32C67337	FASTA	254	29,089
	10 20 30 40 50 60 MWQLLLPTAL LLLVSAGMRT EDLPKAVVFL EPQWYRVLEK DSVTLKCQGA YSPEDNSTQW 70 80 90 100 110 120 FHNESLISSQ ASSYFIDAAT VDDSGEYRCQ TNLSTLSDPV QLEVHIGWLL LQAPRWVFKE 130 140 150 160 170 180 EDPIHLRCHS WKNTALHKVT YLQNGKGRKY FHHNSDFYIP KATLKDSGSY FCRGLFGSKN 190 200 210 220 230 240 VSSETVNITI TQGLAVSTIS SFFPPGYQVS FCLVMVLLFA VDTGLYFSVK TNIRSSTRDW 250 KDHKFKWRKD PQDK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions." Ravetch J.V., Perussia B. J. Exp. Med. 170:481-497(1989) [PubMed: 2526846] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"IgG Fc receptor III homologues in nonhuman primate species: genetic characterization and ligand interactions." Rogers K.A., Scinicariello F., Attanasio R. J. Immunol. 177:3848-3856(2006) [PubMed: 16951347] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[3]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-176. Tissue: Synovium.
[4]	"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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-176. Tissue: Lung.
[6]	"The human low affinity immunoglobulin G Fc receptor III-A and III-B genes. Molecular characterization of the promoter regions." Gessner J.E., Grussenmeyer T., Kolanus W., Schmidt R.E. J. Biol. Chem. 270:1350-1361(1995) [PubMed: 7836402] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-39. Tissue: Placenta.
[7]	"Human glomerular mesangial cells express CD16 and may be stimulated via this receptor." Morcos M., Hansch G.M., Schonermark M., Ellwanger S., Harle M., Heckl-Ostreicher B. Kidney Int. 46:1627-1634(1994) [PubMed: 7700021] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-254, VARIANT VAL-176.
[8]	"A human immunoglobulin G receptor exists in both polypeptide-anchored and phosphatidylinositol-glycan-anchored forms." Scallon B.J., Scigliano E., Freedman V.H., Miedel M.C., Pan Y.C., Unkeless J.C., Kochan J.P. Proc. Natl. Acad. Sci. U.S.A. 86:5079-5083(1989) [PubMed: 2525780] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-254. Tissue: Lung.
[9]	"A triallelic Fc gamma receptor type IIIA polymorphism influences the binding of human IgG by NK cell Fc gamma RIIIa." de Haas M., Koene H.R., Kleijer M., de Vries E., Simsek S., van Tol M.J.D., Roos D., von dem Borne A.E.G.K. J. Immunol. 156:2948-2955(1996) [PubMed: 8609432] [Abstract] Cited for: VARIANTS ARG-66 AND HIS-66.
[10]	"Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype." Koene H.R., Kleijer M., Algra J., Roos D., von dem Borne A.E.G.K., de Haas M. Blood 90:1109-1114(1997) [PubMed: 9242542] [Abstract] Cited for: VARIANT VAL-157.
[11]	"A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease." Wu J., Edberg J.C., Redecha P.B., Bansal V., Guyre P.M., Coleman K., Salmon J.E., Kimberly R.P. J. Clin. Invest. 100:1059-1070(1997) [PubMed: 9276722] [Abstract] Cited for: VARIANT VAL-176.
+	Additional computationally mapped references.

Web resources

FCGR3Abase

FCGR3A mutation db

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	X52645 mRNA. Translation: CAA36870.1. AK223268 mRNA. Translation: BAD96988.1. Different initiation. AK223295 mRNA. Translation: BAD97015.1. Different initiation. AL590385 Genomic DNA. No translation available. BC017865 mRNA. Translation: AAH17865.1. BC033678 mRNA. Translation: AAH33678.1. Z46222 Genomic DNA. Translation: CAA86295.1. S76824 mRNA. Translation: AAB33925.2. M24853 mRNA. Translation: AAA53506.1.
IPI	IPI00218834.
PIR	JL0107.
RefSeq	NP_000560.5. NP_001121064.1. NP_001121065.1. NP_001121067.1. NP_001121068.1.
UniGene	Hs.372679
3D structure databases
SMR	P08637. Positions 21-193.
ModBase	Search...
Protein-protein interaction databases
STRING	P08637.
Proteomic databases
PRIDE	P08637.
Genome annotation databases
Ensembl	ENST00000367967; ENSP00000356944; ENSG00000203747; Homo sapiens. [Genome view] ENST00000367969; ENSP00000356946; ENSG00000203747; Homo sapiens. [Genome view] ENST00000436743; ENSP00000416607; ENSG00000203747; Homo sapiens. [Genome view]
GeneID	2214.
KEGG	hsa:2214.
UCSC	uc001gat.2. human.
Organism-specific databases
CTD	2214.
GeneCards	GC01M159778.
H-InvDB	HIX0001248.
HGNC	HGNC:3619. FCGR3A.
MIM	146740. gene.
PharmGKB	PA28065.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P08637.
OrthoDB	EOG9642XB
Enzyme and pathway databases
Reactome	REACT_6900. Signaling in Immune system.
Gene expression databases
Bgee	P08637.
CleanEx	HS_FCGR3A.
Genevestigator	P08637.
GermOnline	ENSG00000203747. Homo sapiens.
Family and domain databases
InterPro	IPR013151. Ig. IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR003599. Ig_sub. [Graphical view]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 2 hits.
Pfam	PF00047. ig. 2 hits. [Graphical view]
SMART	SM00409. IG. 2 hits. [Graphical view]
PROSITE	PS50835. IG_LIKE. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
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.
NextBio	8979.
SOURCE	Search...

Entry information

Entry name

FCG3A_HUMAN

Accession

Primary (citable) accession number: P08637
Secondary accession number(s): A2N6W9 , Q53FJ0, Q53FL6, Q5EBR4, Q65ZM6, Q6PIJ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	August 1, 1990
Last modified:	November 24, 2009
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.