Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Plays also an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. May also bind DNA. Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily. Ubiquitously expressed. Isoform 2 is probably the major isoform. Isoform 1 is expressed in T-cells and in placenta. 4 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 184.108.40.206; Motility/polarity/chemotaxis; Protein phosphatase, tyrosine (non-receptor)
Molecular Function: integrin binding; non-membrane spanning protein tyrosine phosphatase activity; protein binding; protein kinase binding; protein tyrosine phosphatase activity; receptor tyrosine kinase binding; STAT family protein binding; syntaxin binding
Biological Process: B cell differentiation; erythrocyte differentiation; glucose homeostasis; insulin receptor recycling; insulin receptor signaling pathway; negative regulation of cell population proliferation; negative regulation of chemotaxis; negative regulation of epidermal growth factor receptor signaling pathway; negative regulation of ERK1 and ERK2 cascade; negative regulation of inflammatory response; negative regulation of insulin receptor signaling pathway; negative regulation of interleukin-2-mediated signaling pathway; negative regulation of interleukin-4-mediated signaling pathway; negative regulation of interleukin-6-mediated signaling pathway; negative regulation of lipid storage; negative regulation of macrophage colony-stimulating factor signaling pathway; negative regulation of macrophage differentiation; negative regulation of platelet-derived growth factor receptor-beta signaling pathway; negative regulation of positive thymic T cell selection; negative regulation of protein tyrosine kinase activity; negative regulation of receptor signaling pathway via JAK-STAT; negative regulation of T cell receptor signaling pathway; negative regulation of transcription by RNA polymerase II; negative regulation of tumor necrosis factor-mediated signaling pathway; negative regulation of type I interferon-mediated signaling pathway; negative regulation of type II interferon-mediated signaling pathway; negative regulation of tyrosine phosphorylation of STAT protein; peptidyl-tyrosine dephosphorylation; positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; positive regulation of gluconeogenesis; positive regulation of PERK-mediated unfolded protein response; regulation of hepatocyte growth factor receptor signaling pathway; regulation of type II interferon-mediated signaling pathway; T cell differentiation