Human Gene PTPN1 (uc002xvl.3) Description and Page Index
Description: Homo sapiens protein tyrosine phosphatase, non-receptor type 1 (PTPN1), mRNA. RefSeq Summary (NM_002827): The protein encoded by this gene is the founding member of the protein tyrosine phosphatase (PTP) family, which was isolated and identified based on its enzymatic activity and amino acid sequence. 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]. Transcript (Including UTRs) Position: hg19 chr20:49,126,891-49,201,086 Size: 74,196 Total Exon Count: 10 Strand: + Coding Region Position: hg19 chr20:49,127,065-49,199,252 Size: 72,188 Coding Exon Count: 10
ID:PTN1_HUMAN DESCRIPTION: RecName: Full=Tyrosine-protein phosphatase non-receptor type 1; EC=126.96.36.199; AltName: Full=Protein-tyrosine phosphatase 1B; Short=PTP-1B; FUNCTION: 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. CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. SUBUNIT: Interacts with EPHA3 (phosphorylated); dephosphorylates EPHA3 and may regulate its trafficking and function. INTERACTION: P15116:Cdh2 (xeno); NbExp=3; IntAct=EBI-968788, EBI-397974; P10912:GHR; NbExp=5; IntAct=EBI-968788, EBI-286316; P63166:Sumo1 (xeno); NbExp=2; IntAct=EBI-968788, EBI-80152; SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Note=Interacts with EPHA3 at the cell membrane. PTM: 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. PTM: Ser-50 is the major site of phosphorylation as compared to Ser-242 and Ser-243. Activated by phosphorylation at Ser-50. PTM: S-nitrosylation of Cys-215 inactivates the enzyme activity. PTM: Sulfhydration at Cys-215 following endoplasmic reticulum stress inactivates the enzyme activity, promoting EIF2AK3/PERK activity. SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily. SIMILARITY: Contains 1 tyrosine-protein phosphatase domain.
Genetic Association Studies of Complex Diseases and Disorders
anthropometric parameters diabetes, type 2 insulin Meshkani, R. et al. 2007, 1484insG Polymorphism of the PTPN1 Gene Is Associated with Insulin Resistance in an Iranian Population, Arch Med Res 2007 38(5) 556-562.
Our results from a sample of Iranian type 2 diabetes cases and controls provide evidence that the 1484insG genotype of the PTPN1 gene may be associated with insulin resistance and other cardiovascular risk factors in non-diabetic male subjects.
atherosclerosis, diabetic Burdon, K. P. et al. 2006, Association of protein tyrosine phosphatase-n1 polymorphisms with coronary calcified plaque in the diabetes heart study, Diabetes 2006 55(3) 651-8.
diabetes or impaired glucose tolerance Mok A et al. 2002, A single nucleotide polymorphism in protein tyrosine phosphatase PTP-1B is associated with protection from diabetes or impaired glucose tolerance in Oji-Cree., The Journal of clinical endocrinology and metabolism. 2002 Feb;87(2):724-7.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P18031
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006470 protein dephosphorylation GO:0006987 activation of signaling protein activity involved in unfolded protein response GO:0007257 activation of JUN kinase activity GO:0008286 insulin receptor signaling pathway GO:0009966 regulation of signal transduction GO:0009968 negative regulation of signal transduction GO:0016311 dephosphorylation GO:0030100 regulation of endocytosis GO:0030948 negative regulation of vascular endothelial growth factor receptor signaling pathway GO:0030968 endoplasmic reticulum unfolded protein response GO:0031532 actin cytoskeleton reorganization GO:0033157 regulation of intracellular protein transport GO:0034976 response to endoplasmic reticulum stress GO:0035335 peptidyl-tyrosine dephosphorylation GO:0035791 platelet-derived growth factor receptor-beta signaling pathway GO:0036498 IRE1-mediated unfolded protein response GO:0043407 negative regulation of MAP kinase activity GO:0046626 regulation of insulin receptor signaling pathway GO:0046627 negative regulation of insulin receptor signaling pathway GO:0060338 regulation of type I interferon-mediated signaling pathway GO:0060397 JAK-STAT cascade involved in growth hormone signaling pathway GO:0061098 positive regulation of protein tyrosine kinase activity GO:0070373 negative regulation of ERK1 and ERK2 cascade GO:1902202 regulation of hepatocyte growth factor receptor signaling pathway GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1903896 positive regulation of IRE1-mediated unfolded protein response GO:1903898 negative regulation of PERK-mediated unfolded protein response GO:1990264 peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity GO:2000646 positive regulation of receptor catabolic process