SIRPA (CD172a)

Target id: 2942

Nomenclature: SIRPA (CD172a)

Family: CD molecules, Signal regulatory proteins

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

   GtoImmuPdb view: OFF :     SIRPA (CD172a) has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 504 20p13 SIRPA signal regulatory protein alpha
Mouse 1 513 2 F1; 2 63.19 cM Sirpa signal-regulatory protein alpha
Rat 1 509 3q36 Sirpa signal-regulatory protein alpha
Gene and Protein Information Comments
Details are provided for the shorter protein isoform (isoform 1) encoded by the human gene. Isofom 2 is the longer protein at 508 amino acids (see NP_001317657). For the mouse, we show isoform 3 peptide details.
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Immunopharmacology Comments
SIRPα is an important inhibitory immune response regulator. It is expressed by a subset of intestinal dendritic cells (integrin CD103+ DCs) that are critical for maintaining intestinal (mucosal) immune system homeostasis. This subset of CD103+SIRPα+ DCs selectively activates Th17 cells and type 3 innate lymphoid cells (ILC3) [3-4]. 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 [2].

Pharmacological agents which block the SIRPα/CD47 antiphagocytic axis are being investigated as potential immuno-oncology therapeutics which would act to promote immunosurveillance and increase phagocytosis of cancer cells by tumour associated macrophages (TAMs). Specifically, the anti-SIPRα monoclonal antibody OSE-172 (Effi-DEM) is in early stage development (OSE IMMUNOTherapeutics), and proof of concept has been demonstrated in in vivo models. Preclinical testing suggests that the therapeutic effect of OSE-172 is observed in both monotherapy or when combined with other checkpoint inhibitors, or with immune system stimulators. Anti-CD47 antibodies are also in early stage development, as reported by Gholamin et al. (2017) [1].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0043312 neutrophil degranulation TAS
GO:0050900 leukocyte migration TAS
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0050900 leukocyte migration TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
General Comments
The SIPRα protein binding interaction with CD47 produces an antiphagocytic signal, that is often termed a 'don't eat me' signal.

References

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1. Gholamin S, Mitra SS, Feroze AH, Liu J, Kahn SA, Zhang M, Esparza R, Richard C, Ramaswamy V, Remke M et al.. (2017) Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. Sci Transl Med, 9 (381). [PMID:28298418]

2. 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]

3. Joeris T, Müller-Luda K, Agace WW, Mowat AM. (2017) Diversity and functions of intestinal mononuclear phagocytes. Mucosal Immunol, 10 (4): 845-864. [PMID:28378807]

4. Watchmaker PB, Lahl K, Lee M, Baumjohann D, Morton J, Kim SJ, Zeng R, Dent A, Ansel KM, Diamond B et al.. (2014) Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice. Nat. Immunol., 15 (1): 98-108. [PMID:24292363]

How to cite this page

CD molecules: SIRPA (CD172a). Last modified on 06/03/2018. Accessed on 21/07/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2942.