Fc fragment of IgA receptor

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)

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Antibodies

Key to terms and symbols

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Antibody											Sp.	Action	Value	Parameter	Reference
BsAb (CD89-CD20)											Hs	Binding	8.5	pK_d	3
⤷	pK_d 8.5 (K_d 3.25x10^-9 M) [3] Description: FACS analysis of antibody binding to CD89-positive PMN cells.

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.

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.

Cell Type Associations

Immuno Cell Type:	Macrophages & monocytes
Cell Ontology Term:	macrophage (CL:0000235) monocyte (CL:0000576)
Comment:	FcαRI (CD89) is constitutively expressed on monocytes/macrophages.
References:	6

Immuno Cell Type:	Granulocytes
Cell Ontology Term:	eosinophil (CL:0000771) neutrophil (CL:0000775)
Comment:	FcαRI (CD89) is constitutively expressed on eosinophils, and neutrophils.
References:	6

References

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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]

How to cite this page

Immunoglobulin like domain containing proteins: Fc fragment of IgA receptor. Last modified on 29/08/2018. Accessed on 03/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2991.

Fc fragment of IgA receptor

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References

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