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Protein

Low affinity immunoglobulin gamma Fc region receptor III-A

Gene

FCGR3A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Ligandi

IgG-binding protein

Enzyme and pathway databases

ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-2029481. FCGR activation.
R-HSA-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-HSA-2029485. Role of phospholipids in phagocytosis.
SIGNORiP08637.

Protein family/group databases

MEROPSiI43.001.

Names & Taxonomyi

Protein namesi
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 namesi
Name:FCGR3A
Synonyms:CD16A, FCG3, FCGR3, IGFR3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:3619. FCGR3A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini17 – 208ExtracellularSequence analysisAdd BLAST192
Transmembranei209 – 229HelicalSequence analysisAdd BLAST21
Topological domaini230 – 254CytoplasmicSequence analysisAdd BLAST25

GO - Cellular componenti

  • external side of plasma membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 20 (IMD20)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare autosomal recessive primary immunodeficiency characterized by functional deficiency of NK cells. Affected individuals typically present with severe herpes viral infections, particularly Epstein Barr virus (EBV), and human papillomavirus (HPV).
See also OMIM:615707
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00880066L → H in IMD20. 4 PublicationsCorresponds to variant rs10127939dbSNPEnsembl.1

Organism-specific databases

DisGeNETi2214.
MalaCardsiFCGR3A.
MIMi615707. phenotype.
OpenTargetsiENSG00000203747.
PharmGKBiPA28065.

Chemistry databases

DrugBankiDB00054. 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. Intravenous Immunoglobulin.
DB00075. Muromonab.
DB00108. Natalizumab.
DB00110. Palivizumab.
DB00073. Rituximab.
DB00081. Tositumomab.
DB00072. Trastuzumab.

Polymorphism and mutation databases

BioMutaiFCGR3A.
DMDMi119876.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
ChainiPRO_000001515017 – 254Low affinity immunoglobulin gamma Fc region receptor III-AAdd BLAST238

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi47 ↔ 89Combined sources2 Publications
Glycosylationi56N-linked (GlcNAc...)Sequence analysis1
Glycosylationi63N-linked (GlcNAc...)2 Publications1
Glycosylationi92N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi128 ↔ 172Combined sources2 Publications
Glycosylationi180N-linked (GlcNAc...)2 Publications1
Glycosylationi187N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

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.2 Publications
The soluble form is produced by a proteolytic cleavage.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP08637.
PeptideAtlasiP08637.
PRIDEiP08637.
TopDownProteomicsiP08637.

PTM databases

iPTMnetiP08637.
PhosphoSitePlusiP08637.

Expressioni

Tissue specificityi

Expressed on natural killer cells, macrophages, subpopulation of T-cells, immature thymocytes and placental trophoblasts.

Gene expression databases

BgeeiENSG00000203747.
CleanExiHS_FCGR3A.
ExpressionAtlasiP08637. baseline and differential.
GenevisibleiP08637. HS.

Organism-specific databases

HPAiCAB032435.
HPA055431.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi108508. 11 interactors.
IntActiP08637. 3 interactors.
STRINGi9606.ENSP00000356946.

Structurei

Secondary structure

1254
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 33Combined sources6
Beta strandi35 – 38Combined sources4
Beta strandi43 – 47Combined sources5
Beta strandi51 – 54Combined sources4
Beta strandi60 – 65Combined sources6
Beta strandi71 – 78Combined sources8
Helixi81 – 83Combined sources3
Beta strandi85 – 89Combined sources5
Beta strandi100 – 105Combined sources6
Beta strandi107 – 112Combined sources6
Beta strandi116 – 119Combined sources4
Beta strandi124 – 130Combined sources7
Helixi131 – 133Combined sources3
Beta strandi137 – 143Combined sources7
Beta strandi146 – 153Combined sources8
Beta strandi157 – 161Combined sources5
Helixi164 – 166Combined sources3
Beta strandi168 – 176Combined sources9
Beta strandi179 – 182Combined sources4
Beta strandi186 – 191Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AY4X-ray2.20C21-193[»]
3SGJX-ray2.20C19-208[»]
3SGKX-ray2.40C19-208[»]
3WN5X-ray2.78C/F18-208[»]
5BW7X-ray3.00C21-193[»]
5D6DX-ray3.13C14-205[»]
ProteinModelPortaliP08637.
SMRiP08637.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08637.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 105Ig-like C2-type 1Add BLAST82
Domaini107 – 189Ig-like C2-type 2Add BLAST83

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IKYD. Eukaryota.
ENOG41114N1. LUCA.
GeneTreeiENSGT00760000119130.
HOVERGENiHBG051602.
InParanoidiP08637.
KOiK06463.
PhylomeDBiP08637.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]
PfamiPF13895. Ig_2. 2 hits.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P08637-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWQLLLPTAL LLLVSAGMRT EDLPKAVVFL EPQWYRVLEK DSVTLKCQGA
60 70 80 90 100
YSPEDNSTQW FHNESLISSQ ASSYFIDAAT VDDSGEYRCQ TNLSTLSDPV
110 120 130 140 150
QLEVHIGWLL LQAPRWVFKE EDPIHLRCHS WKNTALHKVT YLQNGKGRKY
160 170 180 190 200
FHHNSDFYIP KATLKDSGSY FCRGLFGSKN VSSETVNITI TQGLAVSTIS
210 220 230 240 250
SFFPPGYQVS FCLVMVLLFA VDTGLYFSVK TNIRSSTRDW KDHKFKWRKD

PQDK
Length:254
Mass (Da):29,089
Last modified:August 1, 1990 - v2
Checksum:iD38D178D32C67337
GO

Sequence cautioni

The sequence BAD96988 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAD97015 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106I → V in BAD96988 (Ref. 3) Curated1
Sequence conflicti106I → V in BAD97015 (Ref. 3) Curated1
Sequence conflicti195A → S in AAH33678 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00880066L → H in IMD20. 4 PublicationsCorresponds to variant rs10127939dbSNPEnsembl.1
Natural variantiVAR_00879966L → R.1 PublicationCorresponds to variant rs10127939dbSNPEnsembl.1
Natural variantiVAR_058398147G → D.Corresponds to variant rs443082dbSNPEnsembl.1
Natural variantiVAR_058399158Y → H.Corresponds to variant rs396716dbSNPEnsembl.1
Natural variantiVAR_003960176F → V Shows a higher binding capacity of IgG1, IgG3 and IgG4. 5 PublicationsCorresponds to variant rs396991dbSNPEnsembl.1
Natural variantiVAR_058400203F → S.Corresponds to variant rs1042206dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44266.1.
PIRiJL0107.
RefSeqiNP_000560.6. NM_000569.7.
NP_001121064.2. NM_001127592.2.
NP_001121065.1. NM_001127593.1.
NP_001121067.1. NM_001127595.1.
NP_001121068.1. NM_001127596.1.
NP_001316049.1. NM_001329120.1.
UniGeneiHs.372679.

Genome annotation databases

EnsembliENST00000367967; ENSP00000356944; ENSG00000203747.
ENST00000436743; ENSP00000416607; ENSG00000203747.
ENST00000443193; ENSP00000392047; ENSG00000203747.
GeneIDi2214.
KEGGihsa:2214.
UCSCiuc001gat.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

FCGR3Abase

FCGR3A mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44266.1.
PIRiJL0107.
RefSeqiNP_000560.6. NM_000569.7.
NP_001121064.2. NM_001127592.2.
NP_001121065.1. NM_001127593.1.
NP_001121067.1. NM_001127595.1.
NP_001121068.1. NM_001127596.1.
NP_001316049.1. NM_001329120.1.
UniGeneiHs.372679.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AY4X-ray2.20C21-193[»]
3SGJX-ray2.20C19-208[»]
3SGKX-ray2.40C19-208[»]
3WN5X-ray2.78C/F18-208[»]
5BW7X-ray3.00C21-193[»]
5D6DX-ray3.13C14-205[»]
ProteinModelPortaliP08637.
SMRiP08637.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108508. 11 interactors.
IntActiP08637. 3 interactors.
STRINGi9606.ENSP00000356946.

Chemistry databases

DrugBankiDB00054. 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. Intravenous Immunoglobulin.
DB00075. Muromonab.
DB00108. Natalizumab.
DB00110. Palivizumab.
DB00073. Rituximab.
DB00081. Tositumomab.
DB00072. Trastuzumab.

Protein family/group databases

MEROPSiI43.001.

PTM databases

iPTMnetiP08637.
PhosphoSitePlusiP08637.

Polymorphism and mutation databases

BioMutaiFCGR3A.
DMDMi119876.

Proteomic databases

PaxDbiP08637.
PeptideAtlasiP08637.
PRIDEiP08637.
TopDownProteomicsiP08637.

Protocols and materials databases

DNASUi2214.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367967; ENSP00000356944; ENSG00000203747.
ENST00000436743; ENSP00000416607; ENSG00000203747.
ENST00000443193; ENSP00000392047; ENSG00000203747.
GeneIDi2214.
KEGGihsa:2214.
UCSCiuc001gat.5. human.

Organism-specific databases

CTDi2214.
DisGeNETi2214.
GeneCardsiFCGR3A.
HGNCiHGNC:3619. FCGR3A.
HPAiCAB032435.
HPA055431.
MalaCardsiFCGR3A.
MIMi146740. gene.
615707. phenotype.
neXtProtiNX_P08637.
OpenTargetsiENSG00000203747.
PharmGKBiPA28065.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKYD. Eukaryota.
ENOG41114N1. LUCA.
GeneTreeiENSGT00760000119130.
HOVERGENiHBG051602.
InParanoidiP08637.
KOiK06463.
PhylomeDBiP08637.

Enzyme and pathway databases

ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-2029481. FCGR activation.
R-HSA-2029482. Regulation of actin dynamics for phagocytic cup formation.
R-HSA-2029485. Role of phospholipids in phagocytosis.
SIGNORiP08637.

Miscellaneous databases

ChiTaRSiFCGR3A. human.
EvolutionaryTraceiP08637.
GeneWikiiFCGR3A.
GenomeRNAii2214.
PROiP08637.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000203747.
CleanExiHS_FCGR3A.
ExpressionAtlasiP08637. baseline and differential.
GenevisibleiP08637. HS.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]
PfamiPF13895. Ig_2. 2 hits.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFCG3A_HUMAN
AccessioniPrimary (citable) accession number: P08637
Secondary accession number(s): A2N6W9
, Q53FJ0, Q53FL6, Q5EBR4, Q65ZM6, Q6PIJ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1990
Last modified: November 30, 2016
This is version 185 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.