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Signal-regulatory protein alpha: Wikis


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Signal-regulatory protein alpha
Symbols SIRPA; P84; BIT; CD172A; MFR; MYD-1; PTPNS1; SHPS-1; SHPS1; SIRP; SIRP-ALPHA-1; SIRPalpha; SIRPalpha2
External IDs OMIM602461 MGI108563 HomoloGene7246 GeneCards: SIRPA Gene
RNA expression pattern
PBB GE SIRPA 202896 s at tn.png
PBB GE SIRPA 202895 s at tn.png
PBB GE SIRPA 202897 at tn.png
More reference expression data
Species Human Mouse
Entrez 140885 19261
Ensembl ENSG00000198053 ENSMUSG00000037902
UniProt P78324 P97797
RefSeq (mRNA) NM_001040022 NM_007547
RefSeq (protein) NP_001035111 NP_031573
Location (UCSC) Chr 20:
1.82 - 1.87 Mb
Chr 2:
129.28 - 129.32 Mb
PubMed search [1] [2]

Tyrosine-protein phosphatase non-receptor type substrate 1 is an enzyme that in humans is encoded by the SIRPA gene.[1][2][3][4] SIRPA has also recently been designated CD172A (cluster of differentiation 172A).

The protein encoded by this gene is a member of the signal-regulatory-protein (SIRP) family, and also belongs to the immunoglobulin superfamily. SIRP family members are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. This protein can be phosphorylated by tyrosine kinases. The phospho-tyrosine residues of this PTP have been shown to recruit SH2 domain containing tyrosine phosphatases (PTP), and serve as substrates of PTPs. This protein was found to participate in signal transduction mediated by various growth factor receptors. CD47 has been demonstrated to be a ligand for this receptor protein. This gene and its product share very high similarity with several other members of the SIRP family. These related genes are located in close proximity to each other on chromosome 20p13. Multiple alternatively spliced transcript variants have been determined for this gene.[4]

In melanocytic cells SIRPA gene expression may be regulated by MITF[5].


Signal-regulatory protein alpha has been shown to interact with PTPN6.[6][7]


  1. ^ Yamao T, Matozaki T, Amano K, Matsuda Y, Takahashi N, Ochi F, Fujioka Y, Kasuga M (Apr 1997). "Mouse and human SHPS-1: molecular cloning of cDNAs and chromosomal localization of genes". Biochem Biophys Res Commun 231 (1): 61–7. doi:10.1006/bbrc.1996.6047. PMID 9070220.  
  2. ^ Kharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A (Apr 1997). "A family of proteins that inhibit signalling through tyrosine kinase receptors". Nature 386 (6621): 181–6. doi:10.1038/386181a0. PMID 9062191.  
  3. ^ van den Berg TK, van Beek EM, Buhring HJ, Colonna M, Hamaguchi M, Howard CJ, Kasuga M, Liu Y, Matozaki T, Neel BG, Parkos CA, Sano S, Vignery A, Vivier E, Wright M, Zawatzky R, Barclay AN (Dec 2005). "A nomenclature for signal regulatory protein family members". J Immunol 175 (12): 7788–9. PMID 16339511.  
  4. ^ a b "Entrez Gene: SIRPA signal-regulatory protein alpha".  
  5. ^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.  
  6. ^ Mousseau, D D; Banville D, L'Abbé D, Bouchard P, Shen S H (Feb. 2000). "PILRalpha, a novel immunoreceptor tyrosine-based inhibitory motif-bearing protein, recruits SHP-1 upon tyrosine phosphorylation and is paired with the truncated counterpart PILRbeta". J. Biol. Chem. (UNITED STATES) 275 (6): 4467–74. ISSN 0021-9258. PMID 10660620.  
  7. ^ Yang, J; Cheng Z, Niu T, Liang X, Zhao Z J, Zhou G W (Feb. 2000). "Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1". J. Biol. Chem. (UNITED STATES) 275 (6): 4066–71. ISSN 0021-9258. PMID 10660565.  

Further reading

  • Oldenborg PA (2004). "Role of CD47 in erythroid cells and in autoimmunity.". Leuk. Lymphoma 45 (7): 1319–27. doi:10.1080/1042819042000201989. PMID 15359629.  
  • Margolis RL, Breschel TS, Li SH, et al. (1996). "Characterization of cDNA clones containing CCA trinucleotide repeats derived from human brain.". Somat. Cell Mol. Genet. 21 (4): 279–84. doi:10.1007/BF02255782. PMID 8525433.  
  • Ohnishi H, Kubota M, Ohtake A, et al. (1996). "Activation of protein-tyrosine phosphatase SH-PTP2 by a tyrosine-based activation motif of a novel brain molecule.". J. Biol. Chem. 271 (41): 25569–74. doi:10.1074/jbc.271.41.25569. PMID 8810330.  
  • Fujioka Y, Matozaki T, Noguchi T, et al. (1997). "A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion.". Mol. Cell. Biol. 16 (12): 6887–99. PMID 8943344.  
  • Sano S, Ohnishi H, Omori A, et al. (1997). "BIT, an immune antigen receptor-like molecule in the brain.". FEBS Lett. 411 (2-3): 327–34. doi:10.1016/S0014-5793(97)00724-2. PMID 9271230.  
  • Brooke GP, Parsons KR, Howard CJ (1998). "Cloning of two members of the SIRP alpha family of protein tyrosine phosphatase binding proteins in cattle that are expressed on monocytes and a subpopulation of dendritic cells and which mediate binding to CD4 T cells.". Eur. J. Immunol. 28 (1): 1–11. doi:10.1002/(SICI)1521-4141(199801)28:01<1::AID-IMMU1>3.0.CO;2-V. PMID 9485180.  
  • Timms JF, Carlberg K, Gu H, et al. (1998). "Identification of major binding proteins and substrates for the SH2-containing protein tyrosine phosphatase SHP-1 in macrophages.". Mol. Cell. Biol. 18 (7): 3838–50. PMID 9632768.  
  • Veillette A, Thibaudeau E, Latour S (1998). "High expression of inhibitory receptor SHPS-1 and its association with protein-tyrosine phosphatase SHP-1 in macrophages.". J. Biol. Chem. 273 (35): 22719–28. doi:10.1074/jbc.273.35.22719. PMID 9712903.  
  • Jiang P, Lagenaur CF, Narayanan V (1999). "Integrin-associated protein is a ligand for the P84 neural adhesion molecule.". J. Biol. Chem. 274 (2): 559–62. doi:10.1074/jbc.274.2.559. PMID 9872987.  
  • Ohnishi H, Yamada M, Kubota M, et al. (1999). "Tyrosine phosphorylation and association of BIT with SHP-2 induced by neurotrophins.". J. Neurochem. 72 (4): 1402–8. doi:10.1046/j.1471-4159.1999.721402.x. PMID 10098842.  
  • Timms JF, Swanson KD, Marie-Cardine A, et al. (1999). "SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages.". Curr. Biol. 9 (16): 927–30. doi:10.1016/S0960-9822(99)80401-1. PMID 10469599.  
  • Seiffert M, Cant C, Chen Z, et al. (1999). "Human signal-regulatory protein is expressed on normal, but not on subsets of leukemic myeloid cells and mediates cellular adhesion involving its counterreceptor CD47.". Blood 94 (11): 3633–43. PMID 10572074.  
  • Sano S, Ohnishi H, Kubota M (2000). "Gene structure of mouse BIT/SHPS-1.". Biochem. J. 344 Pt 3: 667–75. PMID 10585853.  
  • Yang J, Cheng Z, Niu T, et al. (2000). "Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1.". J. Biol. Chem. 275 (6): 4066–71. doi:10.1074/jbc.275.6.4066. PMID 10660565.  
  • Stofega MR, Argetsinger LS, Wang H, et al. (2000). "Negative regulation of growth hormone receptor/JAK2 signaling by signal regulatory protein alpha.". J. Biol. Chem. 275 (36): 28222–9. doi:10.1074/jbc.M004238200. PMID 10842184.  
  • Wu CJ, Chen Z, Ullrich A, et al. (2000). "Inhibition of EGFR-mediated phosphoinositide-3-OH kinase (PI3-K) signaling and glioblastoma phenotype by signal-regulatory proteins (SIRPs).". Oncogene 19 (35): 3999–4010. doi:10.1038/sj.onc.1203748. PMID 10962556.  
  • Latour S, Tanaka H, Demeure C, et al. (2001). "Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator protein-alpha: down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation.". J. Immunol. 167 (5): 2547–54. PMID 11509594.  
  • Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20.". Nature 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.  

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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