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target has curated data in GtoImmuPdb
Target id: 2991
Nomenclature: Fc fragment of IgA receptor
Abbreviated Name: FcαRI
Systematic Nomenclature: CD89
Family: Immunoglobulin like domain containing proteins, CD molecules
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 1 | 287 | 19q13.42 | FCAR | Fc alpha receptor | 2,6 |
Rat | 1 | 280 | 1q12 | Fcar | Fc alpha receptor | |
Gene and Protein Information Comments | ||||||
Alternative transcripts from the human gene produce shorter protein isoforms: isoforms b-h which vary in length from 178-275 aa. There is no mouse FCAR homolog. |
Database Links | |
Alphafold | P24071 (Hs) |
Ensembl Gene | ENSG00000186431 (Hs), ENSRNOG00000027855 (Rn) |
Entrez Gene | 2204 (Hs), 365183 (Rn) |
Human Protein Atlas | ENSG00000186431 (Hs) |
KEGG Gene | hsa:2204 (Hs), rno:365183 (Rn) |
OMIM | 147045 (Hs) |
Pharos | P24071 (Hs) |
RefSeq Nucleotide | NM_002000 (Hs), NM_201992 (Rn) |
RefSeq Protein | NP_001991 (Hs), NP_973721 (Rn) |
UniProtKB | P24071 (Hs) |
Wikipedia | FCAR (Hs) |
Download all structure-activity data for this target as a CSV file
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Immunopharmacology Comments |
FcαRI is the cognate receptor for immunoglobulin A (IgA). In humans, IgA is predominantly expressed in the intestine, where it is important for maintaining mucosal homeostasis. IgA serves as a first-line defence to protect the gut epithelium from pathogens and enteric toxins [4,7], facilitates immune exclusion (clearance of mucous-entrapped antigens and pathogens by peristaltic and mucociliary activities), and is also crucial for sensing commensal bacteria [5]. FcαRI actions include ADCC, phagocytosis, induction of respiratory bursts, and inflammatory mediator/cytokine release [8]. Studies by Hansen et al. (2018) have shown that CD103+SIRPα+ DCs can be transformed in to pro-inflammatory cells via a process involving FcαRI co-stimulation-induced glycolytic reprogramming. This work shows how IgA-immune complexes in the human intestine can convert a tolerogenic milieu to a pro-inflammatory one, following exposure to environmental agents [1]. An anti-FcαRI/anti-CD20 bispecific monoclonal antibody (BsAb (CD89-CD20)) that mediates recruitment of macrophages to tumour cells has been reported to enhance tumour cell killing [3], indicating that exploiting FcαRI-expressing cells as effector cells is a valid immuno-oncology strategy. |
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1. Hansen IS, Krabbendam L, Bernink JH, Loayza-Puch F, Hoepel W, van Burgsteden JA, Kuijper EC, Buskens CJ, Bemelman WA, Zaat SAJ et al.. (2018) FcαRI co-stimulation converts human intestinal CD103+dendritic cells into pro-inflammatory cells through glycolytic reprogramming. Nat Commun, 9 (1): 863. [PMID:29491406]
2. Kremer EJ, Kalatzis V, Baker E, Callen DF, Sutherland GR, Maliszewski CR. (1992) The gene for the human IgA Fc receptor maps to 19q13.4. Hum Genet, 89 (1): 107-8. [PMID:1577457]
3. Li B, Xu L, Pi C, Yin Y, Xie K, Tao F, Li R, Gu H, Fang J. (2017) CD89-mediated recruitment of macrophages via a bispecific antibody enhances anti-tumor efficacy. Oncoimmunology, 7 (1): e1380142. [PMID:29296544]
4. Mantis NJ, Rol N, Corthésy B. (2011) Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol, 4 (6): 603-11. [PMID:21975936]
5. Mathias A, Pais B, Favre L, Benyacoub J, Corthésy B. (2014) Role of secretory IgA in the mucosal sensing of commensal bacteria. Gut Microbes, 5 (6): 688-95. [PMID:25536286]
6. Morton HC, van Egmond M, van de Winkel JG. (1996) Structure and function of human IgA Fc receptors (Fc alpha R). Crit Rev Immunol, 16 (4): 423-40. [PMID:8954257]
7. Pabst O. (2012) New concepts in the generation and functions of IgA. Nat Rev Immunol, 12 (12): 821-32. [PMID:23103985]
8. Stockmeyer B, Dechant M, van Egmond M, Tutt AL, Sundarapandiyan K, Graziano RF, Repp R, Kalden JR, Gramatzki M, Glennie MJ et al.. (2000) Triggering Fc alpha-receptor I (CD89) recruits neutrophils as effector cells for CD20-directed antibody therapy. J Immunol, 165 (10): 5954-61. [PMID:11067958]
Immunoglobulin like domain containing proteins: Fc fragment of IgA receptor. Last modified on 29/08/2018. Accessed on 07/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2991.