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Gene Review

CD47  -  CD47 molecule

Homo sapiens

Synonyms: Antigenic surface determinant protein OA3, IAP, Integrin-associated protein, Leukocyte surface antigen CD47, MER6, ...
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Disease relevance of CD47


Psychiatry related information on CD47

  • Few nucleic acids have been characterized in either scrapie or CJD, but previous cloning experiments delineated relatively short LTR regions of the endogenous IAP retrovirus in 120S CJD preparations [7].
  • IAP-catalyzed [32P]ADP-ribosylation was not significantly different between patients and controls, suggesting that the quantity of IAP-sensitive G proteins is unaltered in affective disorder patients [8].

High impact information on CD47

  • The Rh antigen is a multi-subunit complex composed of Rh polypeptides and associated glycoproteins (Rh50, CD47, LW and glycophorin B); these interact in the red cell membrane and are lacking or severely reduced in Rhnull cells [9].
  • Despite the identification of several new apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not clear whether apoptosis inhibition plays a general role in neoplasia [10].
  • Furthermore, pretreatment of cells with IAP (islet-activating protein from the bacterium Bordetella pertussis) eliminates the ACh-induced inward rectification [11].
  • As IAP specifically ADP-ribosylates two GTP-binding proteins, Ni and No, that can interact with mAChRs, we conclude that a guanyl nucleotide-binding protein couples ACh binding to channel activation [11].
  • Opioid inhibition of adenylyl cyclase has been reconstituted in IAP-treated NG108-15 cell membranes with a Gi preparation from brain [12].

Chemical compound and disease context of CD47


Biological context of CD47


Anatomical context of CD47


Associations of CD47 with chemical compounds

  • CD47-activated SS RBC adhesion absolutely requires the Src family tyrosine kinases and is also enhanced by treatment of SS RBCs with low concentrations of cytochalasin D, which may release alpha4beta1 from cytoskeletal restraints [24].
  • CD47 signaling in SS RBCs appears to be independent of large scale changes in cAMP formation but nonetheless promotes alpha4beta1-mediated adhesion via a protein kinase A-dependent, serine phosphorylation of the alpha4 cytoplasmic domain [24].
  • In addition, several membrane components including the Rh proteins and other glycoproteins recently characterized (Rh50 glycoprotein, CD47, glycophorin B, Duffy, LW) are absent or severely decreased on these cells [25].
  • The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells [26].
  • Cholesterol-independent interactions with CD47 enhance alphavbeta3 avidity [27].

Physical interactions of CD47


Co-localisations of CD47


Regulatory relationships of CD47


Other interactions of CD47


Analytical, diagnostic and therapeutic context of CD47

  • Here we report that CD47, its beta3 integrin partner, and Gi proteins form a stable, detergent-soluble complex that can be recovered by immunoprecipitation and affinity chromatography [38].
  • Immunofluorescence analysis of CD47 and BNIP3 revealed a partial colocalization of both molecules under basal conditions [29].
  • A direct interaction between human SIRP and human CD47 was demonstrated using purified recombinant proteins and surface plasmon resonance ruling out the involvement of other proteins known to be associated with CD47 [39].
  • In contrast to SIRPalpha1 and SIRPalpha2, no adhesion of SIRPbeta1 to CD47 could be detected by cell attachment assays and flow cytometry [40].
  • Flow cytometric and immunoblotting analysis revealed a severe reduction of CD47 (up to 80%) and a slower mobility of RhAG on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, possibly reflecting an overglycosylation state [41].



  1. CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia. Mateo, V., Lagneaux, L., Bron, D., Biron, G., Armant, M., Delespesse, G., Sarfati, M. Nat. Med. (1999) [Pubmed]
  2. Role of CD47 as a marker of self on red blood cells. Oldenborg, P.A., Zheleznyak, A., Fang, Y.F., Lagenaur, C.F., Gresham, H.D., Lindberg, F.P. Science (2000) [Pubmed]
  3. Absence of CD47 in protein 4.2-deficient hereditary spherocytosis in man: an interaction between the Rh complex and the band 3 complex. Bruce, L.J., Ghosh, S., King, M.J., Layton, D.M., Mawby, W.J., Stewart, G.W., Oldenborg, P.A., Delaunay, J., Tanner, M.J. Blood (2002) [Pubmed]
  4. CD47 mediates killing of breast tumor cells via Gi-dependent inhibition of protein kinase A. Manna, P.P., Frazier, W.A. Cancer Res. (2004) [Pubmed]
  5. Differential roles of protein kinase C and pertussis toxin-sensitive G-binding proteins in modulation of melanoma cell proliferation and motility by thrombospondin 1. Guo, N., Zabrenetzky, V.S., Chandrasekaran, L., Sipes, J.M., Lawler, J., Krutzsch, H.C., Roberts, D.D. Cancer Res. (1998) [Pubmed]
  6. Correlated expression of CD47 and SIRPA in bone marrow and in peripheral blood predicts recurrence in breast cancer patients. Nagahara, M., Mimori, K., Kataoka, A., Ishii, H., Tanaka, F., Nakagawa, T., Sato, T., Ono, S., Sugihara, K., Mori, M. Clin. Cancer Res. (2010) [Pubmed]
  7. Endogenous viral complexes with long RNA cosediment with the agent of Creutzfeldt-Jakob disease. Akowitz, A., Sklaviadis, T., Manuelidis, L. Nucleic Acids Res. (1994) [Pubmed]
  8. Platelet pertussis toxin-sensitive G proteins in affective disorders. Odagaki, Y., Koyama, T., Yamashita, I. Journal of affective disorders. (1994) [Pubmed]
  9. Candidate gene acting as a suppressor of the RH locus in most cases of Rh-deficiency. Cherif-Zahar, B., Raynal, V., Gane, P., Mattei, M.G., Bailly, P., Gibbs, B., Colin, Y., Cartron, J.P. Nat. Genet. (1996) [Pubmed]
  10. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Ambrosini, G., Adida, C., Altieri, D.C. Nat. Med. (1997) [Pubmed]
  11. GTP-binding proteins couple cardiac muscarinic receptors to a K channel. Pfaffinger, P.J., Martin, J.M., Hunter, D.D., Nathanson, N.M., Hille, B. Nature (1985) [Pubmed]
  12. The molecular basis of opioid receptor function. Simonds, W.F. Endocr. Rev. (1988) [Pubmed]
  13. Regulation of integrin function by CD47 ligands. Differential effects on alpha vbeta 3 and alpha 4beta1 integrin-mediated adhesion. Barazi, H.O., Li, Z., Cashel, J.A., Krutzsch, H.C., Annis, D.S., Mosher, D.F., Roberts, D.D. J. Biol. Chem. (2002) [Pubmed]
  14. CD47 is expressed at normal levels in patients with autoimmune haemolytic anaemia and/or immune thrombocytopenia. Ahrens, N., Pagenkopf, C., Kiesewetter, H., Salama, A. Transfusion medicine (Oxford, England) (2006) [Pubmed]
  15. An ovarian tumor marker with homology to vaccinia virus contains an IgV-like region and multiple transmembrane domains. Campbell, I.G., Freemont, P.S., Foulkes, W., Trowsdale, J. Cancer Res. (1992) [Pubmed]
  16. Does the guanine nucleotide regulatory protein Ni mediate progesterone inhibition of Xenopus oocyte adenylate cyclase? Goodhardt, M., Ferry, N., Buscaglia, M., Baulieu, E.E., Hanoune, J. EMBO J. (1984) [Pubmed]
  17. Integrin-associated protein stimulates alpha2beta1-dependent chemotaxis via Gi-mediated inhibition of adenylate cyclase and extracellular-regulated kinases. Wang, X.Q., Lindberg, F.P., Frazier, W.A. J. Cell Biol. (1999) [Pubmed]
  18. Protein 4.2 is critical to CD47-membrane skeleton attachment in human red cells. Dahl, K.N., Parthasarathy, R., Westhoff, C.M., Layton, D.M., Discher, D.E. Blood (2004) [Pubmed]
  19. Thrombospondin-1 acts via IAP/CD47 to synergize with collagen in alpha2beta1-mediated platelet activation. Chung, J., Wang, X.Q., Lindberg, F.P., Frazier, W.A. Blood (1999) [Pubmed]
  20. Expression and activation of signal regulatory protein alpha on astrocytomas. Chen, T.T., Brown, E.J., Huang, E.J., Seaman, W.E. Cancer Res. (2004) [Pubmed]
  21. Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior. Li, Z., Calzada, M.J., Sipes, J.M., Cashel, J.A., Krutzsch, H.C., Annis, D.S., Mosher, D.F., Roberts, D.D. J. Cell Biol. (2002) [Pubmed]
  22. Thrombospondin-1 and indoleamine 2,3-dioxygenase are major targets of extracellular ATP in human dendritic cells. Marteau, F., Gonzalez, N.S., Communi, D., Goldman, M., Boeynaems, J.M., Communi, D. Blood (2005) [Pubmed]
  23. Species- and cell type-specific interactions between CD47 and human SIRPalpha. Subramanian, S., Parthasarathy, R., Sen, S., Boder, E.T., Discher, D.E. Blood (2006) [Pubmed]
  24. Mechanism of CD47-induced alpha4beta1 integrin activation and adhesion in sickle reticulocytes. Brittain, J.E., Han, J., Ataga, K.I., Orringer, E.P., Parise, L.V. J. Biol. Chem. (2004) [Pubmed]
  25. Defining the Rh blood group antigens. Biochemistry and molecular genetics. Cartron, J.P. Blood Rev. (1994) [Pubmed]
  26. The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells. Rath, G.M., Schneider, C., Dedieu, S., Rothhut, B., Soula-Rothhut, M., Ghoneim, C., Sid, B., Morjani, H., El Btaouri, H., Martiny, L. Biochim. Biophys. Acta (2006) [Pubmed]
  27. Cholesterol-independent interactions with CD47 enhance alphavbeta3 avidity. McDonald, J.F., Zheleznyak, A., Frazier, W.A. J. Biol. Chem. (2004) [Pubmed]
  28. Thrombospondin-bound integrin-associated protein (CD47) physically and functionally modifies integrin alphaIIbbeta3 by its extracellular domain. Fujimoto, T.T., Katsutani, S., Shimomura, T., Fujimura, K. J. Biol. Chem. (2003) [Pubmed]
  29. CD47 and the 19 kDa interacting protein-3 (BNIP3) in T cell apoptosis. Lamy, L., Ticchioni, M., Rouquette-Jazdanian, A.K., Samson, M., Deckert, M., Greenberg, A.H., Bernard, A. J. Biol. Chem. (2003) [Pubmed]
  30. Thrombspondin acts via integrin-associated protein to activate the platelet integrin alphaIIbbeta3. Chung, J., Gao, A.G., Frazier, W.A. J. Biol. Chem. (1997) [Pubmed]
  31. Alpha-Pal/NRF-1 regulates the promoter of the human integrin-associated protein/CD47 gene. Chang, W.T., Huang, A.M. J. Biol. Chem. (2004) [Pubmed]
  32. CD47 regulation of epithelial cell spreading and migration, and its signal transduction. Shinohara, M., Ohyama, N., Murata, Y., Okazawa, H., Ohnishi, H., Ishikawa, O., Matozaki, T. Cancer Sci. (2006) [Pubmed]
  33. Phylogenetic divergence of CD47 interactions with human signal regulatory protein alpha reveals locus of species specificity. Implications for the binding site. Subramanian, S., Boder, E.T., Discher, D.E. J. Biol. Chem. (2007) [Pubmed]
  34. Role of CD47 in the induction of human naive T cell anergy. Avice, M.N., Rubio, M., Sergerie, M., Delespesse, G., Sarfati, M. J. Immunol. (2001) [Pubmed]
  35. Cell spreading distinguishes the mechanism of augmentation of T cell activation by integrin-associated protein/CD47 and CD28. Reinhold, M.I., Green, J.M., Lindberg, F.P., Ticchioni, M., Brown, E.J. Int. Immunol. (1999) [Pubmed]
  36. Advance in the Rh blood group system. Kajii, E. Nippon Hoigaku Zasshi (1998) [Pubmed]
  37. Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family. Brooke, G., Holbrook, J.D., Brown, M.H., Barclay, A.N. J. Immunol. (2004) [Pubmed]
  38. The thrombospondin receptor integrin-associated protein (CD47) functionally couples to heterotrimeric Gi. Frazier, W.A., Gao, A.G., Dimitry, J., Chung, J., Brown, E.J., Lindberg, F.P., Linder, M.E. J. Biol. Chem. (1999) [Pubmed]
  39. CD47 is a ligand for rat macrophage membrane signal regulatory protein SIRP (OX41) and human SIRPalpha 1. Vernon-Wilson, E.F., Kee, W.J., Willis, A.C., Barclay, A.N., Simmons, D.L., Brown, M.H. Eur. J. Immunol. (2000) [Pubmed]
  40. Signal-regulatory protein alpha (SIRPalpha) but not SIRPbeta is involved in T-cell activation, binds to CD47 with high affinity, and is expressed on immature CD34(+)CD38(-) hematopoietic cells. Seiffert, M., Brossart, P., Cant, C., Cella, M., Colonna, M., Brugger, W., Kanz, L., Ullrich, A., Bühring, H.J. Blood (2001) [Pubmed]
  41. Evidence that the red cell skeleton protein 4.2 interacts with the Rh membrane complex member CD47. Mouro-Chanteloup, I., Delaunay, J., Gane, P., Nicolas, V., Johansen, M., Brown, E.J., Peters, L.L., Van Kim, C.L., Cartron, J.P., Colin, Y. Blood (2003) [Pubmed]
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