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P08637 (FCG3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length254 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Ref.9 Ref.10

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. Glycosylation at Asn-180 is mandatory for high affinity binding to the Fc and for discrimination between fucosylated and afucosylated IgG glycoforms. Ref.9 Ref.10

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Potential
Chain17 – 254238Low affinity immunoglobulin gamma Fc region receptor III-A
PRO_0000015150

Regions

Topological domain17 – 208192Extracellular Potential
Transmembrane209 – 22921Helical; Potential
Topological domain230 – 25425Cytoplasmic Potential
Domain24 – 10582Ig-like C2-type 1
Domain107 – 18983Ig-like C2-type 2

Amino acid modifications

Glycosylation561N-linked (GlcNAc...) Potential
Glycosylation631N-linked (GlcNAc...) Ref.9 Ref.10
Glycosylation921N-linked (GlcNAc...) Potential
Glycosylation1801N-linked (GlcNAc...) Ref.9 Ref.10
Glycosylation1871N-linked (GlcNAc...) Potential
Disulfide bond47 ↔ 89 Ref.9 Ref.10
Disulfide bond128 ↔ 172 Ref.9 Ref.10

Natural variations

Natural variant661L → H. Ref.11
Corresponds to variant rs10127939 [ dbSNP | Ensembl ].
VAR_008800
Natural variant661L → R. Ref.11
Corresponds to variant rs10127939 [ dbSNP | Ensembl ].
VAR_008799
Natural variant1471G → D.
Corresponds to variant rs443082 [ dbSNP | Ensembl ].
VAR_058398
Natural variant1581Y → H.
Corresponds to variant rs396716 [ dbSNP | Ensembl ].
VAR_058399
Natural variant1761F → V Shows a higher binding capacity of IgG1, IgG3 and IgG4. Ref.3 Ref.5 Ref.7 Ref.12 Ref.13
Corresponds to variant rs396991 [ dbSNP | Ensembl ].
VAR_003960
Natural variant2031F → S.
Corresponds to variant rs1042206 [ dbSNP | Ensembl ].
VAR_058400

Experimental info

Sequence conflict1061I → V in BAD96988. Ref.3
Sequence conflict1061I → V in BAD97015. Ref.3
Sequence conflict1951A → S in AAH33678. Ref.5

Secondary structure

........................................ 254
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08637 [UniParc].

Last modified August 1, 1990. Version 2.
Checksum: D38D178D32C67337

FASTA25429,089
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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]"Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans."
Mizushima T., Yagi H., Takemoto E., Shibata-Koyama M., Isoda Y., Iida S., Masuda K., Satoh M., Kato K.
Genes Cells 16:1071-1080(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-193 IN COMPLEX WITH IGHG1, FUNCTION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-63 AND ASN-180.
[10]"Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcgammaRIII and antibodies lacking core fucose."
Ferrara C., Grau S., Jager C., Sondermann P., Brunker P., Waldhauer I., Hennig M., Ruf A., Rufer A.C., Stihle M., Umana P., Benz J.
Proc. Natl. Acad. Sci. U.S.A. 108:12669-12674(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 19-208 IN COMPLEX WITH IGHG1, FUNCTION, DISULFIDE BONDS, GLYCOSYLATION AT ASN-63 AND ASN-180.
[11]"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.
[12]"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.
[13]"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

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.
CCDSCCDS44266.1.
PIRJL0107.
RefSeqNP_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.
UniGeneHs.372679.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3AY4X-ray2.20C21-193[»]
3SGJX-ray2.20C19-208[»]
3SGKX-ray2.40C19-208[»]
ProteinModelPortalP08637.
SMRP08637. Positions 24-231.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108508. 5 interactions.
IntActP08637. 2 interactions.
STRING9606.ENSP00000356946.

Chemistry

DrugBankDB00054. 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.

Protein family/group databases

MEROPSI43.001.

PTM databases

PhosphoSiteP08637.

Polymorphism databases

DMDM119876.

Proteomic databases

PaxDbP08637.
PRIDEP08637.

Protocols and materials databases

DNASU2214.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367967; ENSP00000356944; ENSG00000203747.
ENST00000436743; ENSP00000416607; ENSG00000203747.
ENST00000540048; ENSP00000444971; ENSG00000203747.
GeneID2214.
KEGGhsa:2214.
UCSCuc001gar.3. human.

Organism-specific databases

CTD2214.
GeneCardsGC01M161511.
HGNCHGNC:3619. FCGR3A.
HPACAB032435.
HPA055431.
MIM146740. gene.
neXtProtNX_P08637.
PharmGKBPA28065.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47725.
HOVERGENHBG051602.
InParanoidP08637.
KOK06463.
PhylomeDBP08637.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP08637.
BgeeP08637.
CleanExHS_FCGR3A.
GenevestigatorP08637.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]
SMARTSM00409. IG. 2 hits.
[Graphical view]
PROSITEPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFCGR3A. human.
EvolutionaryTraceP08637.
GeneWikiFCGR3A.
GenomeRNAi2214.
NextBio8979.
PROP08637.
SOURCESearch...

Entry information

Entry nameFCG3A_HUMAN
AccessionPrimary (citable) accession number: P08637
Secondary accession number(s): A2N6W9 expand/collapse secondary AC list , Q53FJ0, Q53FL6, Q5EBR4, Q65ZM6, Q6PIJ0
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1990
Last modified: July 9, 2014
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries