Top ▲
Target has curated data in GtoImmuPdb
Target id: 3017
Nomenclature: Fc fragment of IgG receptor IIIa
Systematic Nomenclature: CD16A
Family: Immunoglobulin like domain containing proteins, CD molecules
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 1 | 254 | 1q23.3 | FCGR3A | Fc gamma receptor IIIa | |
Mouse | 1 | 249 | 1 78.53 cM | Fcgr4 | Fc receptor, IgG, low affinity IV | |
Rat | 1 | 249 | 13q24 | Fcgr3a | Fc gamma receptor 3A | |
Gene and Protein Information Comments | ||||||
Alternatively spliced transcript variants encoding different isoforms have been reported for the human gene. |
Previous and Unofficial Names |
Fc receptor, IgG, low affinity IV | Fc receptor | Fc gamma receptor IIIa | FCγRIIIa | FcRIIIA | low affinity immunoglobulin gamma Fc region receptor III-A |
Database Links | |
Alphafold | P08637 (Hs), A0A0B4J1G0 (Mm) |
ChEMBL Target | CHEMBL3856162 (Hs) |
Ensembl Gene | ENSG00000203747 (Hs), ENSMUSG00000059089 (Mm), ENSRNOG00000024382 (Rn) |
Entrez Gene | 2214 (Hs), 246256 (Mm), 304966 (Rn) |
Human Protein Atlas | ENSG00000203747 (Hs) |
KEGG Gene | hsa:2214 (Hs), mmu:246256 (Mm), rno:304966 (Rn) |
OMIM | 146740 (Hs) |
Pharos | P08637 (Hs) |
RefSeq Nucleotide | NM_000569 (Hs), NM_144559 (Mm), NM_207603 (Rn) |
RefSeq Protein | NP_000560 (Hs), NP_653142 (Mm), NP_997486 (Rn) |
UniProtKB | P08637 (Hs), A0A0B4J1G0 (Mm) |
Wikipedia | FCGR3A (Hs) |
Download all structure-activity data for this target as a CSV file
Antibodies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Immunopharmacology Comments |
The FCGR3A gene is expressed by natural killer (NK) cells. The protein product (CD16A or FcγRIIIa) is an integral peptide-tethered membrane glycoprotein. FcγRIIIa is a low-affinity receptor for IgG Fc and is involved in removing antigen-antibody complexes from the circulation and antibody-dependent responses. FcγRIIIa is being exploited for drug development, specifically as a NK cell-engager to mediate NK effector cell killing of cancer cells. For example, Affimed have developed AFM13, a tetravalent bispecific Fv peptide construct that simultaneously engages FcγRIIIa and CD30 on CD30-expressing malignant cells such as Hodgkin lymphoma cells, and AFM24 another tetravalent bispecific construct that targets epidermal growth factor receptor (EGFR) and FcγRIIIa to engage NK cells to destroy otherwise hard to treat EGFR-driven cancers. COVID-19: Analysis of blood from controls and COVID-19 patients was used to show that FcγRIIIa mediates phagocytosis of antibody-opsonised SARS-CoV-2 particles by human monocytes (and macrophages) [1]. Infection of monocytes via this receptor is inhibited by anti-FcγRIIIa antibodies in vitro. The infected monocytes proceed to undergo inflammasome-mediated pyroptosis. Although this cell death halts production of viable virus, it is proposed to contribute to the systemic inflammation that drives much of the pathology (e.g. acute lung injury and ARDS, vascular leak and multi-organ damage) that is observed in patients with severe COVID-19. |
Immuno Process Associations | ||
|
||
|
||
|
General Comments |
FcγRIIIa is an integral membrane glycoprotein anchored through a transmembrane peptide to the surface of natural killer (NK) cells. It is an important mediator of antibody-dependent phagocytosis, and appears to play a role in SARS-CoV-2 internalisation by monocytes in COVID-19 patients [1]. |
1. Junqueira C, Crespo A, Ranjbar S, de Lacerda LB, Lewandrowski M, Ingber J, Parry B, Ravid S, Clark S, Schrimpf MR et al.. (2022) FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation. Nature,. DOI: 10.1038/s41586-022-04702-4
2. Reusch U, Burkhardt C, Fucek I, Le Gall F, Le Gall M, Hoffmann K, Knackmuss SH, Kiprijanov S, Little M, Zhukovsky EA. (2014) A novel tetravalent bispecific TandAb (CD30/CD16A) efficiently recruits NK cells for the lysis of CD30+ tumor cells. MAbs, 6 (3): 728-39. [PMID:24670809]
3. Xiang H, Liu L, Gao Y, Ahene A, Macal M, Hsu AW, Dreiling L, Collins H. (2020) Population pharmacokinetic analysis of phase 1 bemarituzumab data to support phase 2 gastroesophageal adenocarcinoma FIGHT trial. Cancer Chemother Pharmacol, 86 (5): 595-606. [PMID:32965540]
Immunoglobulin like domain containing proteins: Fc fragment of IgG receptor IIIa. Last modified on 06/04/2022. Accessed on 09/11/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=3017.