P08637 (FCG3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Low affinity immunoglobulin gamma Fc region receptor III-A

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

Gene names

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

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	254 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	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.
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.
Sequence caution	The sequence BAD96988.1 differs from that shown. Reason: Erroneous initiation. The sequence BAD97015.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	IgG-binding protein
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	immune response Traceable author statement PubMed 2138330. Source: ProtInc regulation of immune response Traceable author statement. Source: Reactome
Cellular_component	external side of plasma membrane Inferred from direct assay PubMed 10706735. Source: UniProtKB extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane 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

Helical; 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. Ref.9

VAR_008800

Natural variant

66

1

L → R. Ref.9
Corresponds to variant rs10127939 [ dbSNP | Ensembl ].

VAR_008799

Natural variant

147

1

G → D.
Corresponds to variant rs443082 [ dbSNP | Ensembl ].

VAR_058398

Natural variant

158

1

Y → H.
Corresponds to variant rs396716 [ dbSNP | Ensembl ].

VAR_058399

Natural variant

176

1

F → V Shows a higher binding capacity of IgG1, IgG3 and IgG4. Ref.3 Ref.5 Ref.7 Ref.10 Ref.11
Corresponds to variant rs396991 [ dbSNP | Ensembl ].

VAR_003960

Natural variant

203

1

F → S.
Corresponds to variant rs1042206 [ dbSNP | Ensembl ].

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

Secondary structure

1

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254

Helix Strand Turn

Details...

Beta strand

28 – 33

6

Beta strand

35 – 38

4

Beta strand

43 – 47

5

Beta strand

51 – 54

4

Beta strand

60 – 65

6

Beta strand

71 – 78

8

Helix

81 – 83

3

Beta strand

85 – 89

5

Beta strand

100 – 105

6

Beta strand

107 – 112

6

Beta strand

116 – 119

4

Beta strand

124 – 130

7

Helix

131 – 133

3

Beta strand

137 – 143

7

Beta strand

146 – 153

8

Beta strand

157 – 161

5

Helix

164 – 166

3

Beta strand

168 – 176

9

Beta strand

179 – 182

4

Beta strand

186 – 191

6

Sequences

	Sequence		Length	Mass (Da)
	P08637 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: VARIANT VAL-176.
[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] [Europe PMC] [Abstract] Cited for: VARIANT VAL-176.
+	Additional computationally mapped references.

Web resources

FCGR3Abase

FCGR3A mutation db

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_000569.6.
NP_001121064.1. NM_001127592.1.
NP_001121065.1. NM_001127593.1.
NP_001121067.1. NM_001127595.1.
NP_001121068.1. NM_001127596.1.

UniGene

Hs.372679.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3AY4	X-ray	2.20	C	21-193	[»]
3SGJ	X-ray	2.20	C	19-208	[»]
3SGK	X-ray	2.40	C	19-208	[»]

ProteinModelPortal

P08637.

ModBase

Search...

Protein-protein interaction databases

IntAct

P08637. 2 interactions.

STRING

9606.ENSP00000356946.

Protein family/group databases

MEROPS

I43.001.

PTM databases

PhosphoSite

P08637.

Polymorphism databases

DMDM

119876.

Proteomic databases

PaxDb

P08637.

PRIDE

P08637.

Protocols and materials databases

DNASU

2214.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000367967; ENSP00000356944; ENSG00000203747.
ENST00000436743; ENSP00000416607; ENSG00000203747.
ENST00000540048; ENSP00000444971; ENSG00000203747.

GeneID

2214.

KEGG

hsa:2214.

UCSC

uc001gar.3. human.

Organism-specific databases

CTD

2214.

GeneCards

GC01M161511.

HGNC

HGNC:3619. FCGR3A.

HPA

CAB032435.

MIM

146740. gene.

neXtProt

NX_P08637.

PharmGKB

PA28065.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47725.

HOVERGEN

HBG051602.

InParanoid

P08637.

KO

K06463.

OrthoDB

EOG4ZS94D.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P08637.

Bgee

P08637.

CleanEx

HS_FCGR3A.

Genevestigator

P08637.

GermOnline

ENSG00000203747. 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

ChiTaRS

FCGR3A. 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

P08637.

GenomeRNAi

2214.

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:	May 1, 2013
This is version 149 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.