Recombinant Human Tyrosine-protein phosphatase non-receptor type substrate 1 (SIRPA), partial (Active)

Function

Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Plays a role in antiviral immunity and limits new world arenavirus infection by decreasing virus internalization (By similarity). Receptor for THBS1 (PubMed:24511121). Interaction with THBS1 stimulates phosphorylation of SIRPA (By similarity). In response to THBS1, involved in ROS signaling in non-phagocytic cells, stimulating NADPH oxidase-derived ROS production (PubMed:24511121)

Subcellular Location

Membrane (Single-pass type I membrane protein)

Tissue Specificity

Ubiquitous. Highly expressed in brain. Detected on myeloid cells, but not T-cells. Detected at lower levels in heart, placenta, lung, testis, ovary, colon, liver, small intestine, prostate, spleen, kidney, skeletal muscle and pancreas

Subunit

Binds PTPN11 when tyrosine-phosphorylated, except in macrophages, where it primarily binds PTPN6. Binds GRB2 in vitro. Binds FGR (By similarity). Binds JAK2 irrespective of its phosphorylation status and forms a stable complex. Binds SCAP1 and/or SCAP2. The resulting complex recruits FYB1. Binds PTK2B. Interacts with TRIM2 (By similarity)

• Yamao T. et al. Mouse and human SHPS-1: molecular cloning of cDNAs and chromosomal localization of genes. — Biochem. Biophys. Res. Commun. (1997)
• Kharitonenkov A. et al. A family of proteins that inhibit signalling through tyrosine kinase receptors. — Nature (1997)
• Sano S. et al. Gene structure of mouse BIT/SHPS-1. — Biochem. J. (1999)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Deloukas P. et al. The DNA sequence and comparative analysis of human chromosome 20. — Nature (2001)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Brooke G.P. et al. 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. (1998)
• Timms J.F. et al. SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages. — Curr. Biol. (1999)