Fc fragment of IgA receptor | Immunoglobulin like domain containing proteins | IUPHAR Guide to IMMUNOPHARMACOLOGY

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Fc fragment of IgA receptor

  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

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 287 19q13.42 FCAR Fc fragment of IgA receptor 2,6
Rat 1 280 1q12 Fcar Fc fragment of IgA 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
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Antibodies
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Antibody Sp. Action Affinity Parameter Reference
BsAb (CD89-CD20) Hs Binding 8.5 pKd 3
pKd 8.5 (Kd 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.
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
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 3 GO processes
GO:0042119 neutrophil activation IDA
GO:0043312 neutrophil degranulation TAS
GO:0071346 cellular response to interferon-gamma IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes
GO:0019766 IgA receptor activity IDA
GO:0033031 positive regulation of neutrophil apoptotic process IDA
GO:0038093 Fc receptor signaling pathway IDA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 5 GO processes
GO:0035457 cellular response to interferon-alpha IDA
GO:0071346 cellular response to interferon-gamma IDA
GO:0071354 cellular response to interleukin-6 IDA
GO:0071356 cellular response to tumor necrosis factor IDA
GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus IDA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 4 GO processes
GO:0019766 IgA receptor activity IDA
GO:0038093 Fc receptor signaling pathway IDA
GO:0042119 neutrophil activation IDA
GO:0043312 neutrophil degranulation TAS

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 21/03/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2991.