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Fc fragment of IgG receptor IIIa

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 3017

Nomenclature: Fc fragment of IgG receptor IIIa

Systematic Nomenclature: CD16A

Family: CD molecules, Immunoglobulin like domain containing proteins

Gene and Protein Information Click here for help
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 Click here for help
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 Click here for help
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file go icon to follow link

Antibodies
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Antibody Sp. Action Value Parameter Reference
AFM13 Peptide Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Binding 9.1 – 9.4 pKd 2
pKd 9.1 – 9.4 (Kd 8.4x10-10 – 3.9x10-10 M) [2]
Description: Binding to CD16a 158V and 158F proteins by SPR.
bemarituzumab Peptide Click here for species-specific activity table Hs Binding 8.0 pKd 3
pKd 8.0 (Kd 9.2x10-9 M) [3]
Description: Binding affinity of FcγRIIIa (V158) for immobilised antibody by SPR.
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
Immuno Process:  Inflammation
GO Annotations:  Associated to 4 GO processes
GO:0001788 antibody-dependent cellular cytotoxicity IDA
GO:0042116 macrophage activation IDA
GO:0042267 natural killer cell mediated cytotoxicity IDA
GO:0043320 natural killer cell degranulation IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 4 GO processes
GO:0019772 low-affinity IgG receptor activity IDA
GO:0032819 positive regulation of natural killer cell proliferation IDA
GO:0038094 Fc-gamma receptor signaling pathway IDA
GO:0050776 regulation of immune response IBA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 6 GO processes
GO:0019772 low-affinity IgG receptor activity IDA
GO:0030101 natural killer cell activation IDA
GO:0032819 positive regulation of natural killer cell proliferation IDA
GO:0038094 Fc-gamma receptor signaling pathway IDA
GO:0042116 macrophage activation IDA
GO:0043320 natural killer cell degranulation IDA
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].

References

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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]

How to cite this page

Immunoglobulin like domain containing proteins: Fc fragment of IgG receptor IIIa. Last modified on 06/04/2022. Accessed on 05/02/2023. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3017.