PTPN1

PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. 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. This PTP has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase. This PTP was also reported to dephosphorylate epidermal growth factor receptor kinase, as well as JAK2 and TYK2 kinases, which implicated the role of this PTP in cell growth control, and cell response to interferon stimulation.

PTPN1

Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET.

Actin cytoskeleton reorganizationManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to unfolded proteinManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Endoplasmic reticulum unfolded protein responseManual Assertion Based On ExperimentIDA:UniProtKB
Growth hormone receptor signaling pathway via JAK-STATTAS:Reactome
Insulin receptor signaling pathwayIEA:Ensembl
IRE1-mediated unfolded protein responseISS:ARUK-UCL
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathwayISS:ARUK-UCL
Negative regulation of ERK1 and ERK2 cascadeISS:BHF-UCL
Negative regulation of insulin receptor signaling pathway1 PublicationNAS:BHF-UCL
Negative regulation of MAP kinase activityManual Assertion Based On ExperimentIMP:CACAO
Negative regulation of PERK-mediated unfolded protein responseManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of signal transductionTAS:Reactome
Negative regulation of vascular endothelial growth factor receptor signaling pathwayISS:BHF-UCL
Peptidyl-tyrosine dephosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activityISS:BHF-UCL
Platelet-derived growth factor receptor-beta signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of IRE1-mediated unfolded protein responseManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Positive regulation of JUN kinase activityISS:ARUK-UCL
Positive regulation of protein tyrosine kinase activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of receptor catabolic processManual Assertion Based On ExperimentIMP:CACAO
Protein dephosphorylationManual Assertion Based On ExperimentIMP:CACAO
Regulation of endocytosisManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of hepatocyte growth factor receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of intracellular protein transportManual Assertion Based On ExperimentIMP:CACAO
Regulation of signal transductionManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of type I interferon-mediated signaling pathwayTAS:Reactome

Endoplasmic reticulum membrane
Interacts with EPHA3 at the cell membrane.

Oxidized on Cys-215; the Cys-SOH formed in response to redox signaling reacts with the alpha-amido of the following residue to form a sulfenamide cross-link, triggering a conformational change that inhibits substrate binding and activity. The active site can be restored by reduction.
Ser-50 is the major site of phosphorylation as compared to Ser-242 and Ser-243. Activated by phosphorylation at Ser-50.
S-nitrosylation of Cys-215 inactivates the enzyme activity.
Sulfhydration at Cys-215 following endoplasmic reticulum stress inactivates the enzyme activity, promoting EIF2AK3/PERK activity.