PTPN2

Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling.

PTPN2

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. Also plays 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.

B cell differentiationISS:UniProtKB
Erythrocyte differentiationISS:UniProtKB
Glucose homeostasisISS:UniProtKB
Insulin receptor signaling pathwayISS:UniProtKB
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of chemotaxisISS:UniProtKB
Negative regulation of epidermal growth factor receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of ERK1 and ERK2 cascadeISS:UniProtKB
Negative regulation of inflammatory responseISS:UniProtKB
Negative regulation of insulin receptor signaling pathwayISS:UniProtKB
Negative regulation of interferon-gamma-mediated signaling pathwayISS:UniProtKB
Negative regulation of interleukin-2-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of interleukin-4-mediated signaling pathwayIMP:UniProtKB
Negative regulation of interleukin-6-mediated signaling pathwayIMP:UniProtKB
Negative regulation of lipid storageISS:UniProtKB
Negative regulation of macrophage colony-stimulating factor signaling pathwayISS:UniProtKB
Negative regulation of macrophage differentiationISS:UniProtKB
Negative regulation of platelet-derived growth factor receptor-beta signaling pathwayISS:UniProtKB
Negative regulation of positive thymic T cell selectionISS:UniProtKB
Negative regulation of protein tyrosine kinase activityIEA:Ensembl
Negative regulation of receptor signaling pathway via JAK-STATManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of T cell receptor signaling pathwayISS:UniProtKB
Negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Negative regulation of tumor necrosis factor-mediated signaling pathwayISS:UniProtKB
Negative regulation of type I interferon-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of tyrosine phosphorylation of STAT proteinManual Assertion Based On ExperimentIDA:UniProtKB
Peptidyl-tyrosine dephosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathwayIEA:Ensembl
Positive regulation of gluconeogenesisISS:UniProtKB
Positive regulation of PERK-mediated unfolded protein responseIEA:Ensembl
Regulation of hepatocyte growth factor receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of interferon-gamma-mediated signaling pathwayTAS:Reactome
T cell differentiationISS:UniProtKB

Isoform 1
Endoplasmic reticulum
Endoplasmic reticulum-Golgi intermediate compartment
Targeted to the endoplasmic reticulum by its C-terminal hydrophobic region.
Isoform 2
Nucleus
Cytoplasm
Cell membrane
Predominantly localizes to chromatin (By similarity).
Able to shuttle between the nucleus and the cytoplasm and to dephosphorylate plasma membrane receptors (PubMed:9488479).
Recruited by activated ITGA1 at the plasma membrane

Isoform 2
Specifically phosphorylated in a cell cycle-dependent manner by cyclin-dependent kinases CDK1 and CDK2. Probably activated through phosphorylation by PKR.