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Gene Review

SIRPA  -  signal-regulatory protein alpha

Homo sapiens

Synonyms: BIT, Bit, Brain Ig-like molecule with tyrosine-based activation motifs, CD172 antigen-like family member A, CD172A, ...
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Disease relevance of SIRPA


Psychiatry related information on SIRPA

  • Rats subjected to eight cycles of food deprivation and refeeding (MFR group) showed significantly decreased circulating leptin levels when compared with control rats (nearly 50% decrease in leptin levels, P < 0.01) [6].

High impact information on SIRPA


Biological context of SIRPA


Anatomical context of SIRPA


Associations of SIRPA with chemical compounds


Physical interactions of SIRPA

  • Here we report the crystal structures of the catalytic domain of SHP-1 complexed with two peptide substrates derived from SIRPalpha, a member of the signal-regulatory proteins [19].

Regulatory relationships of SIRPA


Other interactions of SIRPA

  • We also identified CD44 as a plasma membrane protein which, like MFR, is highly expressed at the onset of fusion [24].
  • Two ligands for CD47, thrombospondin and SIRPalpha, have been described [13].
  • In fact, whereas SIRPalpha mRNA and CD47 mRNA were detected in all samples, the levels of SHP-1 mRNA varied among donors [25].
  • Furthermore, for Shc to be phosphorylated in response to IGF-I requires that Shc must associate with SHPS-1 and this association is mediated in part by SHP-2 [14].
  • Consistent with the idea that increased phosphorylation activates SIRP function, we overexpressed human SIRPalpha1 in U87MG glioblastoma cells in order to examine how SIRPalpha1 modulates EGFR signaling pathways [26].

Analytical, diagnostic and therapeutic context of SIRPA


  1. 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]
  2. A family of proteins that inhibit signalling through tyrosine kinase receptors. Kharitonenkov, A., Chen, Z., Sures, I., Wang, H., Schilling, J., Ullrich, A. Nature (1997) [Pubmed]
  3. 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]
  4. Human signal-regulatory protein is expressed on normal, but not on subsets of leukemic myeloid cells and mediates cellular adhesion involving its counterreceptor CD47. Seiffert, M., Cant, C., Chen, Z., Rappold, I., Brugger, W., Kanz, L., Brown, E.J., Ullrich, A., Bühring, H.J. Blood (1999) [Pubmed]
  5. Transcriptional regulation of signal regulatory protein alpha1 inhibitory receptors by epidermal growth factor receptor signaling. Kapoor, G.S., Kapitonov, D., O'Rourke, D.M. Cancer Res. (2004) [Pubmed]
  6. The effects of weight cycling on serum leptin levels and lipogenic enzyme activities in adipose tissue. Kochan, Z., Karbowska, J., Swierczynski, J. J. Physiol. Pharmacol. (2006) [Pubmed]
  7. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Gardai, S.J., Xiao, Y.Q., Dickinson, M., Nick, J.A., Voelker, D.R., Greene, K.E., Henson, P.M. Cell (2003) [Pubmed]
  8. A Bit-role for integrins in apoptosis. Stupack, D.G., Cheresh, D.A. Nat. Cell Biol. (2004) [Pubmed]
  9. Endocytosis of GPI-linked membrane folate receptor-alpha. Rijnboutt, S., Jansen, G., Posthuma, G., Hynes, J.B., Schornagel, J.H., Strous, G.J. J. Cell Biol. (1996) [Pubmed]
  10. 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]
  11. Differential galactosylation of neuronal and haematopoietic signal regulatory protein-alpha determines its cellular binding-specificity. van den Nieuwenhof, I.M., Renardel de Lavalette, C., Diaz, N., van Die, I., van den Berg, T.K. J. Cell. Sci. (2001) [Pubmed]
  12. 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]
  13. Signal regulatory protein (SIRPalpha), a cellular ligand for CD47, regulates neutrophil transmigration. Liu, Y., Bühring, H.J., Zen, K., Burst, S.L., Schnell, F.J., Williams, I.R., Parkos, C.A. J. Biol. Chem. (2002) [Pubmed]
  14. Role of SHPS-1 in the regulation of insulin-like growth factor I-stimulated Shc and mitogen-activated protein kinase activation in vascular smooth muscle cells. Ling, Y., Maile, L.A., Lieskovska, J., Badley-Clarke, J., Clemmons, D.R. Mol. Biol. Cell (2005) [Pubmed]
  15. Functional analysis of SIRPalpha in the growth cone. Wang, X.X., Pfenninger, K.H. J. Cell. Sci. (2006) [Pubmed]
  16. Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation. Fukunaga, A., Nagai, H., Yu, X., Oniki, S., Okazawa, H., Motegi, S., Suzuki, R., Honma, N., Matozaki, T., Nishigori, C., Horikawa, T. Eur. J. Immunol. (2006) [Pubmed]
  17. Semimature stage: a checkpoint in a dendritic cell maturation program that allows for functional reversion after signal-regulatory protein-alpha ligation and maturation signals. Braun, D., Galibert, L., Nakajima, T., Saito, H., Quang, V.V., Rubio, M., Sarfati, M. J. Immunol. (2006) [Pubmed]
  18. Dual regulation of SIRPalpha phosphorylation by integrins and CD47. Johansen, M.L., Brown, E.J. J. Biol. Chem. (2007) [Pubmed]
  19. Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1. Yang, J., Cheng, Z., Niu, T., Liang, X., Zhao, Z.J., Zhou, G.W. J. Biol. Chem. (2000) [Pubmed]
  20. The ability of protein tyrosine phosphatase SHP-1 to suppress NFkappaB can be inhibited by dominant negative mutant of SIRPalpha. Neznanov, N., Neznanova, L., Kondratov, R.V., O'Rourke, D.M., Ullrich, A., Gudkov, A.V. DNA Cell Biol. (2004) [Pubmed]
  21. Interaction between Src homology 2 domain bearing protein tyrosine phosphatase substrate-1 and CD47 mediates the adhesion of human B lymphocytes to nonactivated endothelial cells. Yoshida, H., Tomiyama, Y., Oritani, K., Murayama, Y., Ishikawa, J., Kato, H., Miyagawa Ji, J., Honma, N., Nishiura, T., Matsuzawa, Y. J. Immunol. (2002) [Pubmed]
  22. Signal regulatory proteins negatively regulate immunoreceptor-dependent cell activation. Liénard, H., Bruhns, P., Malbec, O., Fridman, W.H., Daëron, M. J. Biol. Chem. (1999) [Pubmed]
  23. Ubiquitination-mediated regulation of biosynthesis of the adhesion receptor SHPS-1 in response to endoplasmic reticulum stress. Murai-Takebe, R., Noguchi, T., Ogura, T., Mikami, T., Yanagi, K., Inagaki, K., Ohnishi, H., Matozaki, T., Kasuga, M. J. Biol. Chem. (2004) [Pubmed]
  24. Osteoclasts and giant cells: macrophage-macrophage fusion mechanism. Vignery, A. International journal of experimental pathology. (2000) [Pubmed]
  25. Evaluation of normal and neoplastic human mast cells for expression of CD172a (SIRPalpha), CD47, and SHP-1. Florian, S., Ghannadan, M., Mayerhofer, M., Aichberger, K.J., Hauswirth, A.W., Schernthaner, G.H., Printz, D., Fritsch, G., Böhm, A., Sonneck, K., Krauth, M.T., Müller, M.R., Sillaber, C., Sperr, W.R., Bühring, H.J., Valent, P. J. Leukoc. Biol. (2005) [Pubmed]
  26. Inhibition of EGFR-mediated phosphoinositide-3-OH kinase (PI3-K) signaling and glioblastoma phenotype by signal-regulatory proteins (SIRPs). Wu, C.J., Chen, Z., Ullrich, A., Greene, M.I., O'Rourke, D.M. Oncogene (2000) [Pubmed]
  27. 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]
  28. 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]
  29. Membrane mobility and clustering of Integrin Associated Protein (IAP, CD47)--major differences between mouse and man and implications for signaling. Subramanian, S., Tsai, R., Sen, S., Dahl, K.N., Discher, D.E. Blood Cells Mol. Dis. (2006) [Pubmed]
  30. Role for CD47-SIRP{alpha} signaling in xenograft rejection by macrophages. Ide, K., Wang, H., Tahara, H., Liu, J., Wang, X., Asahara, T., Sykes, M., Yang, Y.G., Ohdan, H. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
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