Protein detail

CD47

Leukocyte surface antigen CD47 (Antigenic surface determinant protein OA3) (Integrin-associated protein) (IAP) (Protein MER6) (CD antigen CD47)

Entry name CD47	UniProt ID Q08722	EVMP confidence score 0.88
Supporting publications (n) 29	Transmembrane count 5	Protein classification CD markersPredicted intracellular proteinsPredicted membrane proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

Protein Names

Leukocyte surface antigen CD47 (Antigenic surface determinant protein OA3) (Integrin-associated protein) (IAP) (Protein MER6) (CD antigen CD47)

Protein Class (4)

CD markersPredicted intracellular proteinsPredicted membrane proteinsTransporters

Protein Function (3)

Transporters:Transporter channels and pores
CD markers
Predicted intracellular proteins

Transmembrane

142..162; Helical; 177..197; Helical; 208..228; Helical; 236..256; Helical; 269..289; Helical

Transmembrane Count

Ensembl

ENSG00000196776

Entrez Gene Symbol

CD47

Gene Synonym (3)

IAPMER6OA3

Gene Description

CD47 molecule

Chromosome

Position

108043091-108091862

Supporting publications (n)

EVMP confidence score

0.88

Fluorescence & Localization6

Tissue Specificadipose tissueCell SpecificMegakaryocytesSingle-Nuclei Brain Specificendothelial cellBlood Cell SpecificbasophilBlood Lineage Specificgranulocytes

Function & Pathway7

Protein Function (3)

Transporters:Transporter channels and pores
CD markers
Predicted intracellular proteins

Cellular Component (5)

Molecular Function (5)

Biological Process (3)

KEGG (2)

Reactome (8)

Mediation Categories (5)

Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation

Relations & Evidence56

Ligand-Receptor Signaling (54)

54 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
transferrin	receptor	HPMR	No	Yes	No	Yes	No
cell_adhesion	receptor	ICELLNET	No	Yes	No	Yes	No
receptor	receptor	OmniPath	No	Yes	No	Yes	No
extracellular	extracellular	HPMR	No	No	No	Yes	No
extracellular	extracellular	DGIdb	No	No	No	Yes	No
extracellular	extracellular	OmniPath	No	No	No	Yes	No
intracellular	intracellular	LOCATE	No	No	No	Yes	No
intracellular	intracellular	ComPPI	No	No	No	Yes	No
intracellular	intracellular	GO_Intercell	No	No	No	Yes	No
intracellular	intracellular	OmniPath	No	No	No	Yes	No

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Regulatory Interaction Network (1)

1 record.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
TSP2	P35442	CD47	Q08722	Yes	Yes	No	CellChatDBFantom5_LRdbCellTalkDBHPMR_LRdbiTALKHPMR_CellinkertalklrRamilowski2015SIGNORconnectomeDB2020UniProt_LRdbCellinkerWangLRdbHPMR_talklr	Cellinker:8550562 LRdb:8550562 connectomeDB2020:8550562 CellTalkDB:8550562 SIGNOR:8550562

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential Ultracentrifugation	Mass spectrometry	1	37438638

Sequence, Structure & Domains10

Sequences

Length

323

Mass

35,214

Sequence

MWPLVAALLLGSACCGSAQLLFNKTKSVEFTFCNDTVVIPCFVTNMEAQNTTEVYVKWKFKGRDIYTFDGALNKSTVPTDFSSAKIEVSQLLKGDASLKMDKSDAVSHTGNYTCEVTELTREGETIIELKYRVVSWFSPNENILIVIFPIFAILLFWGQFGIKTLKYRSGGMDEKTIALLVAGLVITVIVIVGAILFVPGEYSLKNATGLGLIVTSTGILILLHYYVFSTAIGLTSFVIAILVIQVIAYILAVVGLSLCIAACIPMHGPLLISGLSILALAQLLGLVYMKFVASNQKTIQPPRKAVEEPLNAFKESKGMMNDE

Alternative Products

Event=Alternative splicing; Named isoforms=4; Name=OA3-323; IsoId=Q08722-1; Sequence=Displayed; Name=OA3-293; IsoId=Q08722-2; Sequence=VSP_002535; Name=OA3-305; IsoId=Q08722-3; Sequence=VSP_002536, VSP_002537; Name=OA3-312; IsoId=Q08722-4; Sequence=VSP_002538

Alternative Sequence

293..323; Missing (in isoform OA3-293); 304..305; KA -> NN (in isoform OA3-305); 306..323; Missing (in isoform OA3-305); 312..323; Missing (in isoform OA3-312)

3D Structural Models

Turn

139..143; 254..260

Helix

51..53; 70..72; 79..81; 88..93; 102..106; 144..164; 178..196; 204..224; 238..253; 268..292

Beta Strand

26..30; 35..39; 42..45; 54..60; 63..69; 74..76; 98..101; 110..118; 121..131; 197..202; 261..264

3D Structure

X-ray crystallography (15)

Domain & Motif Annotations

Domain (FT)

19..127; Ig-like V-type

Clinical Relevance4

Related Diseases (17)

Acute myeloid leukaemia B-cell lymphoma Colorectal cancer Diffuse large B-cell lymphoma Leukaemia Lymphoma Malignant haematopoietic neoplasm Melanoma Multiple myeloma Mycosis fungoides Myelodysplastic syndrome Neuroendocrine carcinoma Non-small-cell lung cancer Ovarian cancer Solid tumour/cancer Squamous cell carcinoma Stomach cancer

Biomarker

Phase 1; Phase 1/2; Phase 2; Phase 3; Phase 2/3

Drugs (5)

EVORPACEPT ABT-510 ONTORPACEPT MAGROLIMAB ANTI-CD47 MONOCLONAL ANTIBODY CC-90002

Antibody (2)

CAB016055 HPA044659

Supporting Publications29

PMID	Title	Abstract
24887393	CD47-dependent immunomodulatory and angiogenic activities of extracellular vesicles produced by T cells.	CD47 also regulates the mRNA content of extracellular vesicles in a manner consistent with some of the resulting alterations in target endothelial cell gene expression. Extracellular vesicles released from cells expressing or lacking CD47 differentially regulate activation of T cells induced by engaging the T cell receptor. Similarly, T cell-derived extracellular vesicles modulate endothelial cell responses to vascular endothelial growth factor and tube formation in a CD47-dependent manner. Therefore, the thrombospondin-1 receptor CD47 directly or indirectly regulates intercellular communication mediated by the transfer of extracellular vesicles between vascular cells. Thrombospondin-1 and its receptor CD47 are expressed on exosomes/ectosomes derived from T cells, and these extracellular vesicles are internalized and modulate signaling in both T cells and endothelial cells. Uptake of T cell derived extracellular vesicles by recipient endothelial cells globally alters gene expression in a CD47-dependent manner.
27728760	Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function.	Functional bioassays using antibodies to these three molecules demonstrated that CD47, TSP1, and to a lesser extent SIRPα facilitate exosome-mediated MDSC chemotaxis and migration.
27819324	A rapid, automated surface protein profiling of single circulating exosomes in human blood.	Our studies show a differential CD47 expression in blood-derived individual circulating exosomes that is correlated with breast cancer status, demonstrating a great potential of individual exosome profiles in biomarker discovery.
28086180	Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis.	Disruption of CD47-SIRPα interaction by SIRPα-exosomes leads to an increase in cells being engulfed by macrophages and a concomitant inhibition of tumor growth in tumor-bearing mice. Given that clustering of native CD47 provides a high binding avidity to ligate dimerized SIRPα on macrophage, nature-derived exosomes could be appreciable platform to antagonize CD47. In this study, we developed an exosome-based immune checkpoint blockade that antagonizes the interaction between CD47 and SIRPα. Moreover, SIRPα-exosomes therapy promotes an intensive T cell infiltration in syngeneic mouse models of cancer, raising the possibility of CD47-targeted therapies to unleash both an innate and adaptive anti-tumor response. These exosomes harboring SIRPα variants (SIRPα-exosomes) were sufficient to induce remarkably augmented tumor phagocytosis, lead to prime effective anti-tumor T cell response.
28607485	Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer.	Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic Kras Here we show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages.
29143228	Effect of exosome biomarkers for diagnosis and prognosis of breast cancer patients.	Exosome biomarkers (such as HER2, CD47, Del-1, miR-1246 and miR-21) in breast cancer patients are significantly higher than those in healthy controls, exosomal GSTP1 and TRPC5 are related to chemotherapy resistance, exosome-carrying TRPC5, NANOG, NEUROD1, HTR7, KISS1R and HOXC are correlated to PFS, DFS or OS, and some exosomal proteins (HER2, KDR, CD49d, CXCR4 and CD44) as well as miRNAs (miR-340-5p, miR-17-5p, miR-130a-3p, miR-93-5p) are associated with tumor recurrence or distant organ metastasis.
29188480	A function-blocking CD47 antibody modulates extracellular vesicle-mediated intercellular signaling between breast carcinoma cells and endothelial cells.	No abstract available
29416092	CD63, MHC class 1, and CD47 identify subsets of extracellular vesicles containing distinct populations of noncoding RNAs.	No abstract available
29679665	Comparison of exosomes and ferritin protein nanocages for the delivery of membrane protein therapeutics.	These analyses allowed us to comprehensively conclude that the therapeutic index of exosome-mediated CD47 blockade against tumor growth inhibition was higher than that of the same dose of ferritin-SIRPα. We characterized membrane-scaffold-based exosomes and protein-scaffold-based ferritin nanocages, both harboring SIRPα (signal regulatory protein α), an antagonist of CD47 on tumor cells.
31143515	Proteomes of exosomes from HPV(+) or HPV(-) head and neck cancer cells: differential enrichment in immunoregulatory proteins.	Only HPV(+) exosomes were enriched in immune effector cell-related CD47 and CD276 antigens; only HPV(-) exosomes contained tumor-protective/growth-promoting antigens, MUC-1 and HLA-DA.

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