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Gene Review

Sirpa  -  signal-regulatory protein alpha

Mus musculus

Synonyms: AI835480, 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

  • Mice homozygous for this SHPS-1 mutation have now been shown to manifest thrombocytopenia [1].
  • A soluble SHPS-1 ligand (CD47-Fc) has now been shown to bind to Melan-a non-tumorigenic melanocytes but not to syngeneic B16F10 melanoma cells [2].
  • Resistance of B16 melanoma cells to CD47-induced negative regulation of motility as a result of aberrant N-glycosylation of SHPS-1 [2].
  • As platelets also express CD47, we asked whether inhibitory CD47/SIRPalpha signaling regulates normal platelet turnover and clearance of platelets in immune thrombocytopenic purpura (ITP) [3].
  • It was found that the CNS of SHP-1-deficient mice uniquely displayed demyelination and contained substantially higher levels of virus than did that of normal littermate mice [4].

High impact information on Sirpa


Chemical compound and disease context of Sirpa


Biological context of Sirpa


Anatomical context of Sirpa


Associations of Sirpa with chemical compounds

  • Src homology 2 domain-containing protein tyrosine phosphatase (SHP) substrate-1 (SHPS-1) is a transmembrane protein that is expressed predominantly in macrophages [8].
  • Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1 [1].
  • The adhesion receptor SHPS-1 activates the protein-tyrosine-phosphatase SHP-2 and thereby promotes integrin-mediated reorganization of the cytoskeleton [2].
  • Treatment of mice ears with 2,4-dinitro-1-fluorobenzene significantly reduced the number of epidermal LCs, and that reduction could be reversed by pretreatment with mAb to SHPS-1 or the CD47-Fc fusion protein [10].
  • Treatment of B16F10 cells with 1-deoxymannojirimycin, which prevents N-glycan processing, restored the ability of SHPS-1 derived from these cells to bind CD47-Fc in vitro, indicating that aberrant N-glycosylation of SHPS-1 impairs CD47 binding in B16F10 cells [2].

Physical interactions of Sirpa


Regulatory relationships of Sirpa


Other interactions of Sirpa


Analytical, diagnostic and therapeutic context of Sirpa

  • These results indicate that interspecies incompatibility of CD47 contributes significantly to phagocytosis of xenogeneic cells by macrophages and suggest that genetic manipulation of donor CD47 to improve its interaction with the recipient SIRPalpha may provide a novel approach to prevent phagocyte-mediated xenograft rejection [18].
  • Here we report the cloning of two alternatively spliced forms of P84 and describe its localization within the CNS by in situ hybridization [19].


  1. Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1. Yamao, T., Noguchi, T., Takeuchi, O., Nishiyama, U., Morita, H., Hagiwara, T., Akahori, H., Kato, T., Inagaki, K., Okazawa, H., Hayashi, Y., Matozaki, T., Takeda, K., Akira, S., Kasuga, M. J. Biol. Chem. (2002) [Pubmed]
  2. Resistance of B16 melanoma cells to CD47-induced negative regulation of motility as a result of aberrant N-glycosylation of SHPS-1. Ogura, T., Noguchi, T., Murai-Takebe, R., Hosooka, T., Honma, N., Kasuga, M. J. Biol. Chem. (2004) [Pubmed]
  3. Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia. Olsson, M., Bruhns, P., Frazier, W.A., Ravetch, J.V., Oldenborg, P.A. Blood (2005) [Pubmed]
  4. Critical role for protein tyrosine phosphatase SHP-1 in controlling infection of central nervous system glia and demyelination by Theiler's murine encephalomyelitis virus. Massa, P.T., Ropka, S.L., Saha, S., Fecenko, K.L., Beuler, K.L. J. Virol. (2002) [Pubmed]
  5. CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms. Poe, J.C., Fujimoto, Y., Hasegawa, M., Haas, K.M., Miller, A.S., Sanford, I.G., Bock, C.B., Fujimoto, M., Tedder, T.F. Nat. Immunol. (2004) [Pubmed]
  6. CD47-signal regulatory protein alpha (SIRPalpha) regulates Fcgamma and complement receptor-mediated phagocytosis. Oldenborg, P.A., Gresham, H.D., Lindberg, F.P. J. Exp. Med. (2001) [Pubmed]
  7. SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility. Inagaki, K., Yamao, T., Noguchi, T., Matozaki, T., Fukunaga, K., Takada, T., Hosooka, T., Akira, S., Kasuga, M. EMBO J. (2000) [Pubmed]
  8. Negative regulation of phagocytosis in macrophages by the CD47-SHPS-1 system. Okazawa, H., Motegi, S., Ohyama, N., Ohnishi, H., Tomizawa, T., Kaneko, Y., Oldenborg, P.A., Ishikawa, O., Matozaki, T. J. Immunol. (2005) [Pubmed]
  9. Ectodomain shedding of SHPS-1 and its role in regulation of cell migration. Ohnishi, H., Kobayashi, H., Okazawa, H., Ohe, Y., Tomizawa, K., Sato, R., Matozaki, T. J. Biol. Chem. (2004) [Pubmed]
  10. Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the migration of Langerhans cells from the epidermis to draining lymph nodes. Fukunaga, A., Nagai, H., Noguchi, T., Okazawa, H., Matozaki, T., Yu, X., Lagenaur, C.F., Honma, N., Ichihashi, M., Kasuga, M., Nishigori, C., Horikawa, T. J. Immunol. (2004) [Pubmed]
  11. Expression of a synapse-associated membrane protein, P84/SHPS-1, and its ligand, IAP/CD47, in mouse retina. Mi, Z.P., Jiang, P., Weng, W.L., Lindberg, F.P., Narayanan, V., Lagenaur, C.F. J. Comp. Neurol. (2000) [Pubmed]
  12. SHPS-1 induces aggregation of Ba/F3 pro-B cells via an interaction with CD47. Babic, I., Schallhorn, A., Lindberg, F.P., Jirik, F.R. J. Immunol. (2000) [Pubmed]
  13. SHP-2 complex formation with the SHP-2 substrate-1 during C2C12 myogenesis. Kontaridis, M.I., Liu, X., Zhang, L., Bennett, A.M. J. Cell. Sci. (2001) [Pubmed]
  14. Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD) mice. Oldenborg, P.A., Gresham, H.D., Chen, Y., Izui, S., Lindberg, F.P. Blood (2002) [Pubmed]
  15. A role for SHPS-1/SIRPalpha1 in IL-1beta- and TNFalpha-dependent signaling. Ruhul Amin, A.R., Machida, K., Oshima, K., Oo, M.L., Thant, A.A., Senga, T., Matsuda, S., Akhand, A.A., Maeda, A., Kurosaki, T., Hamaguchi, M. Oncogene (2002) [Pubmed]
  16. The PLC-PKC cascade is required for IL-1beta-dependent Erk and Akt activation: their role in proliferation. Amin, A.R., Ichigotani, Y., Oo, M.L., Biswas, M.H., Yuan, H., Huang, P., Mon, N.N., Hamaguchi, M. Int. J. Oncol. (2003) [Pubmed]
  17. B cell defects in SLP65/BLNK-deficient mice can be partially corrected by the absence of CD22, an inhibitory coreceptor for BCR signaling. Gerlach, J., Ghosh, S., Jumaa, H., Reth, M., Wienands, J., Chan, A.C., Nitschke, L. Eur. J. Immunol. (2003) [Pubmed]
  18. Attenuation of phagocytosis of xenogeneic cells by manipulating CD47. Wang, H., Verhalen, J., Madariaga, M.L., Xiang, S., Wang, S., Lan, P., Oldenborg, P.A., Sykes, M., Yang, Y.G. Blood (2007) [Pubmed]
  19. The murine P84 neural adhesion molecule is SHPS-1, a member of the phosphatase-binding protein family. Comu, S., Weng, W., Olinsky, S., Ishwad, P., Mi, Z., Hempel, J., Watkins, S., Lagenaur, C.F., Narayanan, V. J. Neurosci. (1997) [Pubmed]
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