CD47

Target id: 2943

Nomenclature: CD47

Family: CD molecules

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 :     CD47 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 5 305 3q13.12 CD47 CD47 molecule
Mouse 5 324 16 B5 Cd47 CD47 antigen (Rh-related antigen
Rat 5 303 2308 Cd47 Cd47 molecule
Gene and Protein Information Comments
There are four alternatively spliced isoforms of human CD47 that differ only in the length of their cytoplasmic tail [6]. Although the functional significance of the alternate splice variants is poorly understood., evidence of the highly conserved nature of the isoforms between mouse and man, suggests an important role for the cytoplasmic domains in CD47 function. Isoform 2 is the most widely expressed form that is found in all circulating and immune cells.
Previous and Unofficial Names
CD47 antigen | CD47 antigen (Rh-related antigen, integrin-associated signal transducer) | integrin associated protein IAP | integrin-associated signal transducer | MER6
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Immunopharmacology Comments
CD47 belongs to the immunoglobulin superfamily and is reported to bind membrane integrins and the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). It is a ubiquitously expressed membrane protein that is a 'marker of self', and which is involved in self tolerance. Binding to SIRPα produces an anti-phagocytic signal. CD47 expression is hijacked by cancer cells to evade immune surveillance and macrophage-mediated removal. Anti-CD47 monoclonal antibodies are being investigated as novel immuno-oncology agents [5]. Efficacy of this strategy has been demonstrated in malignant pediatric brain tumours, in vitro and in vivo in patient-derived orthotopic xenograft models [4]. A novel engineered dual-targeting bispecific antibody format, called κλ bodies [3] that selectively block the CD47-SIRPα interaction and simultaneously bind a tumour specific antigen (e.g. CD19 or mesothelin) and mediate immune activation via the Fc portion of the antibody have been shown to effectively kill cancer cells in vitro and in vivo, whilst sparing normal cells [2]. This approach is postulated to be applicable to targeting of other ubiquitously expressed therapeutic proteins.
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  opsonization (GO:0008228) IEA
neutrophil degranulation (GO:0043312) TAS
positive regulation of inflammatory response (GO:0050729) IEA
positive regulation of phagocytosis (GO:0050766) IEA
leukocyte migration (GO:0050900) TAS
References: 
Immuno Process:  T cell (activation)
Immuno Process ID:  4
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  positive regulation of T cell activation (GO:0050870) IDA
References: 
Immuno Process:  Immune regulation
Immuno Process ID:  6
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  positive regulation of inflammatory response (GO:0050729) IEA
positive regulation of T cell activation (GO:0050870) IDA
References: 
Immuno Process:  Chemotaxis & migration
Immuno Process ID:  10
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  positive regulation of T cell activation (GO:0050870) IDA
leukocyte migration (GO:0050900) TAS
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  neutrophil degranulation (GO:0043312) TAS
positive regulation of T cell activation (GO:0050870) IDA
References: 
Immuno Process:  Antigen presentation
Immuno Process ID:  3
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  opsonization (GO:0008228) IEA
positive regulation of phagocytosis (GO:0050766) IEA
References: 
General Comments
CD47 is a ubiquitously expressed membrane protein that is a 'marker of self'. The CD47/SIRPα anti-phagocytic axis is important for self-tolerance. CD47 binds thrombospondin-1 (TSP-1), an interaction with a role in the regulation of angiogenesis and inflammation, and in cellular function including cell migration, adhesion, proliferation and apoptosis. CD47 also binds several membrane integrins [1] (e.g. αvβ3) which is likely involved in modulation of cellular adhesion, spreading and migration. CD47 is an immuno-oncology drug target [7].

References

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1. Brown EJ, Frazier WA. (2001) Integrin-associated protein (CD47) and its ligands. Trends Cell Biol.11 (3): 130-5. [PMID:11306274]

2. Dheilly E, Moine V, Broyer L, Salgado-Pires S, Johnson Z, Papaioannou A, Cons L, Calloud S, Majocchi S, Nelson R et al.. (2017) Selective Blockade of the Ubiquitous Checkpoint Receptor CD47 Is Enabled by Dual-Targeting Bispecific Antibodies. Mol. Ther.25 (2): 523-533. [PMID:28153099]

3. Fischer N, Elson G, Magistrelli G, Dheilly E, Fouque N, Laurendon A, Gueneau F, Ravn U, Depoisier JF, Moine V et al.. (2015) Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG. Nat Commun6: 6113. [PMID:25672245]

4. 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-SIRPĪ± anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. Sci Transl Med9 (381). [PMID:28298418]

5. Liu J, Wang L, Zhao F, Tseng S, Narayanan C, Shura L, Willingham S, Howard M, Prohaska S, Volkmer J et al.. (2015) Pre-Clinical Development of a Humanized Anti-CD47 Antibody with Anti-Cancer Therapeutic Potential. PLoS ONE10 (9): e0137345. [PMID:26390038]

6. Reinhold MI, Lindberg FP, Plas D, Reynolds S, Peters MG, Brown EJ. (1995) In vivo expression of alternatively spliced forms of integrin-associated protein (CD47). J. Cell. Sci.108 ( Pt 11): 3419-25. [PMID:8586654]

7. Sick E, Jeanne A, Schneider C, Dedieu S, Takeda K, Martiny L. (2012) CD47 update: a multifaceted actor in the tumour microenvironment of potential therapeutic interest. Br. J. Pharmacol.167 (7): 1415-30. [PMID:22774848]

How to cite this page

CD molecules: CD47. Last modified on 20/09/2017. Accessed on 16/01/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2943.