Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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protein tyrosine phosphatase, non-receptor type 1(PTPN1) protein tyrosine phosphatase, non-receptor type 1(PTPN1) Related Genes Homo sapiens
CHROMOSOME 20,
CYTOBAND 20q13.1-q13.2,
ENSEMBL_GENE_ID ENSG00000196396,
GENERIF_SUMMARY Moderate overabundance of PTP-1B in liver tissue does not alter insulin action on glucose metabolism, and the site of action of PTP-1B is presumably at insulin-responsive target tissue or tissues other than the liver., variation in 3' UTR of hPTP1B increases specific gene expression and associates with insulin resistance, PTP1B reduces the level of gene expression of SOCS3 and other leptin-regulated genes, and conversely, the expression of genes down-regulated by leptin was enhanced by PTP1B over-expression, Data show that an increase in soluble protein-tyrosine phosphatase 1B activity contributes to the anti-migratory, but not anti-mitogenic, actions of human Sprouty 2., PTP1B inhibitory agents can be acquired by targeting the area defined by residues Lys-41, Arg-47, and Asp-48, in addition to the previously identified second aryl phosphate-binding pocket., Data show that Y box-binding protein-1 (YB-1) is a regulator of protein tyrosine phosphatase 1B (PTP1B) expression, and highlight PTP1B as a critical regulator of insulin- and cytokine-mediated signal transduction., PTP1B inhibition by S-nitrosylation is caused by formation of a mixed disulfide, dynamics of the interaction between the insulin receptor and this protein in living cells, PTP1B plays an important role in the integrin-mediated dephosphorylation of LAT in human platelets and is involved in the control of irreversible aggregation upon FcgammaRIIa stimulation, mutation of pro387leu in PTP-1B was not associated with type 2 diabetes in Chinese, PTP-1B appears not only to interact with and dephosphorylate the insulin-stimulated insulin receptor in a perinuclear endosome compartment but is also involved in maintaining the IR in a dephosphorylated state during its biosynthesis, PTP1B has a role as a negative regulator of IR activation in hepatocytes, PTP1B has a role in insulin resistance, analysis the relative abundance of PTP1B in RBCs of different age indicated that the PTP activity undergoes oxidative inactivation that can be further differentiated into reversible and irreversible components, Neither of the HSD3B1 or PTP1B variants were associated with hypertension, PTP1B single nucleotide polymorphisms may interact with environmental factors to induce more severe phenotypes in morbidly obese subjects., protein tyrosine phosphatase 1B can be allosterically inhibited, PTPN1 is a significant contributor to type 2 diabetes susceptibility in the Caucasian population., significant association with metabolic traits consistent with the proposed in vivo role for the PTP-1B protein., Our results provided evidence that upregulation of insulin signaling by reducing PTP1B liver with RNAi can be a potent diabetes treatment method., protein-tyrosine phosphatase 1B has a role in integrin signaling, PTP1B interacts with TRPV6 in vivo and plays a role in TRPV6-mediated calcium influx in HEK293 cells, The association of common single nucleotide polymorphisms (SNPs) and haplotypes in PTPN1 with type 2 diabetes, fasting plasma glucose, and insulin sensitivity in a large collection of subjects is reported., protein tyrosine phosphatase 1B (PTPN1) IVS6+G82G homozygotes showed higher levels of all measures of adiposity and G82 allele heterozygotes are potentially at higher risk for type 2 diabetes, PTP1B was inhibited by cytochrome c and microperoxidase; a variety of redox-active metabolites and hemes can oxidatively inactivate PTPs with potentially profound implications for signal transduction, Data show that protein-tyrosine phosphatase (PTP)-1B is an essential positive regulator of the initiation of outside-in alphaIIbbeta3 integrin signaling in platelets., The association between 6 single nucleotide polymorphisms and their effect on leptin, body fat, insulin sensitivity, and metabolic syndrome in female twins is reported., Catalytic activity of PTP1B is controlled by cell adhesion., PTP-1B/inhibitor complexes show a conformation-assisted inhibition mechanism as the basis for inhibitor selectivity, PTP1B mediates of RhoA-dependent phosphorylation of p130Cas., findings suggest that protein tyrosine phosphatase 1B(PTP1B) plays an important role in neuroendocrine differentiation, and therefore, may possibly be involved in the progression of prostate cancer, PTPN1 variants may modulate the lipid profile, thereby influencing susceptibility to metabolic disease, molecular dynamics study of WPD loop movement in PTP1B, Noonan syndrome affected individuals show heterozygous PTPN11 mutations, PTPase activities of PTP1B or CD45 were abolished by low concentrations of (1)O(2), Direct interaction between ER membrane-bound PTP1B and its plasma membrane-anchored targets was demonstrated., C-terminal domain of protein tyrosine phosphatase-1B shows an improvement in affinity but may also provide for specificity over other phosphatases. [protein tyrosine phosphatase-1B], The significance of exercise-induced alterations in cytosolic SHP2 and insulin-stimulated Akt pSer(473) on the improvement in insulin sensitivity requires further elucidation., Single nucleotide polymorphisms are unlikely to have a major role in the aetiology of type 2 diabetes or obesity in Pima Indians., protein-tyrosine phosphatase 1B governs differential recruitment of signaling pathways involved in EGFR regulation of epithelial ion transport., case-control study in a Polish population did not confirm the reported association between polymorphisms in PTPN1 and Type 2 diabetes, Data suggest that glucose enhances protein tyrosine phosphatase 1B transcription through Sp1 activation by protein kinase C., 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., The PTPN1 promoter variants -1023C>A and -51delA (which appears to be functional) were not associated with T2D or related traits in this study, Data for PTP1B are consistent with a concept that explains the ER membrane anchor of tail-anchored proteins as a physicochemical structure., This study suggests that (a) PTP1B can act as an important activator of Src in colon cancer cells via dephosphorylation at Y530 of Src and (b) elevated levels of PTP1B can increase tumorigenicity of colon cancer cells by activating Src., It may be possible to increase proliferative activity of human corneal endothelial cells, particularly in cells from older donors, by inhibiting the activity of this important protein tyrosine phosphatase., Collectively, our experiments implicate a novel signaling pathway involving calpain 2, PTP1B, and Src in the regulation of invadopodia and breast cancer invasion., PTP1B regulates cortactin tyrosine phosphorylation by targeting Tyr446, PTP1B is a physiological negative regulator of TLR signaling via suppression of both MyD88- and TRIF-dependent production of proinflammatory cytokine and IFN-beta in macrophages., IL-4 induces PTP1B mRNA expression in a phosphatidylinositol 3-kinase-dependent manner and enhances PTP1B protein stability to suppress IL-4-induced STAT6 signaling., PTP1B and TCPTP play distinct and non-redundant roles in the regulation of the Met receptor-tyrosine kinase, Cysteine S-nitrosylation protects protein-tyrosine phosphatase 1B against oxidation-induced permanent inactivation, There were no statistically significant associations of SNPs in the PTPN1 gene with dietary phenotypes or measures of obesity., PTPIP51 and PTP1B, play a role in differentiation and apoptosis of the cytotrophoblast and syncytiotrophoblast, respectively., the PTPase activity in patients with insulin receptor gene mutation and severe insulin resistance may differ from that in ordinary type 2 diabetes, data indicate inactivation of receptor-associated protein tyrosine phosphatase activity by cytokine-generated reactive oxygen species is a physiologic mechanism for amplification of IL-4 receptor activation revealing a role for ROS in cytokine crosstalk, PTP-1B constitutes a key divergent element between leptin/insulin and CNTF signaling pathways at the neuronal level., Data show that phosphorylation of N-ethylmaleimide-sensitive factor on tyrosine residues prevents its SNARE complex dissociation activity and establish a role for PTP1B in the modulation of the membrane fusion machinery., A molecular mechanism by which PTP1B links an important oncogenic receptor tyrosine kinase to signaling pathways that promote aberrant cell division and survival in human breast epithelial cells., the great potential of PTP1B inhibitors in cancer therapy, Studies indicate that PTP1B is currently considered one of the best validated biological targets for non-insulin dependent diabetes, obesity and cancer., Noonan phenotype, a rare PTPN11 mutation was detected, PTP1B and TC-PTP are positively implicated in IGF-2-induced migration of MCF-7 cells, suggesting that they could play a role in metastasis development., PTP-1B polymorphisms contribute to pathogenesis of hypertension in Chinese subjects and PTP-1B SNP may be involved in the development of several features including dyslipidemia and obesity in hypertensive subjects., EGFR-PTP1B interaction occurs by means of direct membrane contacts between the perimeter membrane of multivesicular bodies (MVB) and the endoplasmic reticulum. PTP1B activity promotes the sequestration of EGFR on to MVB internal vesicles., SirT1 is a mediator of human chondrocyte survival via down-regulation of PTP1B, a potent proapoptotic protein that is elevated in osteoarthritis cartilage, Suggest that SNPs in the PTPN1 gene are associated with total plasma and LDL cholesterol levels., Insights into the reaction of protein-tyrosine phosphatase 1B, Results show that PTP1B is overexpressed in gastric cancer cells, and inhibition of PTP1B expression dramatically inhibits gastric cancer cell growth in vitro and in vivo., Germline mutations in PTPN11 cause Noonan and LEOPARD syndromes, which have overlapping clinical features., PTP1B targets the endosomal sorting machinery; dephosphorylation of regulatory sites on the endosomal sorting complex is required for transport component STAM2, Ang II modulates both anti-mitogenic and mitogenic pathways of insulin via the activation of PTP-1B., Cross-talk between serine/threonine protein phosphatase 2A and protein tyrosine phosphatase 1B regulates Src activation and adhesion of integrin alphaIIbbeta3 to fibrinogen., Immunocytochemical results displayed a strict co-localization of PTPIP51 and PTP1B in PVB and UCB. The interaction of both proteins was verified by a proximity ligation assay., Overview of why PTP1B is believed to be an important modulator of RTK activity and discuss how the emerging role of PTP1B in regulating RTK endocytosis helps explain reported effects of PTP1B deficiency, at the cellular and physiological levels.[Review], PTP1B gene Pro303Pro polymorphism might be associated with the pathogenesis of obesity in children and could affect lipid metabolism in obese Chinese children., Epo induced PTP1B cleaveage in TF-1 and differentiated UT-7 cells, PTP1B as an important negative regulator of Stat5 phosphorylation in invasive breast cancer., Identification of new substrates of the protein-tyrosine phosphatase PTP1B by Bayesian integration of proteome evidence., Results reinforce that SNPs in PTPN1 are associated with essential hypertension and obesity., Data demonstrated that the increased expression of DUOX1 in IL-4/IL-13-treated NHEK augments STAT6 phosphorylation via oxidative inactivation of protein tyrosine phosphatase 1B., Overexpression of PTP1B is asscoiated with gastric cancer., PTP1B plays a crucial role in the control of the activity of the IR precursor during its biosynthesis. In addition, this new substrate-trapping mutant may be a valuable tool for the identification of new PTP1B substrates., PTPIP51 is phosphorylated by Lyn and c-Src kinases lacking dephosphorylation by PTP1B in acute myeloid leukemia., Results suggest that a HIF-regulated VHL-PTP1B-Src signaling pathway determines the sensitivity of RCC to Src inhibitors., the PTP-1B 981C>T polymorphism is associated with decreased risk of CAD in Chinese Han population, Studies reveal for the first time that the adaptor protein Dock/Nck attenuates insulin signalling by recruiting PTP61F/PTP1B to its substrate, the IR., inhibition of PTP1B may be a useful strategy to explore in the development of novel therapeutic agents for the treatment of CML, particularly because host drugs currently used in CML such as imatinib focus on inhibiting the kinase activity of Bcr-Abl., Data show that despite the PTP1B contribution to tumor onset, it is not essential for tumor maintenance. This suggests that PTP1B inhibition could be effective in breast tumor prevention., Lack of association of PTPN1 gene polymorphisms with type 2 diabetes in south Indians, The biological buffer bicarbonate/CO(2) potentiates the ability of H(2)O(2) to inactivate PTP1B., Expression of PTP1B is elevated in muscle and adipose tissue in insulin-resistant states and may play a role in the insulin-resistant state associated with diabetes and obesity., In glioblastoma PTPIP51 expression increases with the grade of malignancy and PTPIP51 interacts in situ with 14-3-3ss and PTP1B., VCAM-1 activation of endothelial cell NADPH oxidase/PKCalpha/PTP1B induces transient ERK1/2 activation that is necessary for VCAM-1-dependent leukocyte transendothelial migration., Protein-tyrosine phosphatase 1B modulates early endosome fusion and trafficking of Met and epidermal growth factor receptors., H(2)S in inhibiting PTP1B activity and thereby promoting PERK activity during the response to ER stress, It was found that the protein tyrosine phosphatase PTP1B, a well-established regulator of metabolic signaling, was induced after androgen stimulation of androgen receptor-expressing prostate cancer cells., Studies indicate that PTP1B and TCPTP act together in vitro and in vivo to regulate insulin receptor (IR) signaling and glucose homeostasis., PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in in hepatocellular carcinoma., skeletal muscle PTP1B gene expression is increased in African American subjects with type 2 diabetes mellitus, is negatively associated with whole-body insulin sensitivity, and contributes to modulation of insulin signaling., PTP1B deficiency modulates PERK-eIF2alpha phosphorylation and protein synthesis, This review evaluates the novel data on ER stressors, discusses the mechanisms beyond PTP1B function in the ER stress response, and emphasizes the potential therapeutic exploitation of PTP1B to relieve ER stress.[Review], Studies using PTP1B mutants show that the endoplasmic reticulum anchor plays an important role in restricting its interactions with plasma membrane substrates mainly to regions of cell-cell contact., molecular details associated with loop movement in PTPs from different organisms, ER-bound PTP1B dynamically interacts with the negative regulatory site at the C-terminus of Src at random puncta in the plasma membrane/substrate interface, likely leading to Src activation and recruitment to adhesion complexes., PTP1B is a specific regulator of IFNAR1 endocytosis., Studies show that the crystal structure of PTP1B, the form of the placenta indicated the mechanism of PTP1B-mediated substrate recognition and catalysis., Conformational stability of WPD loop (residues Tyr176-Ser187), and possibly catalytic activity of PTP1B, is significantly affected by the protonation state of Asp181 and position of active site water molecules., Inhibition of PTP1B blocks adiponectin-mediated inhibition of leptin-induced breast cancer growth., Our data indicate that PTPA may activate PP2A through activating PTP1B and thus reducing the level of P-PP2AC, therefore upregulation of PTPA may represent a potential strategy in rescuing PP2A and arresting tau pathology in AD, COP1 physically interacted with PTP1B and suppressed PTP1B phosphatase activity as well as the association of PTP1B with IRbeta., The endoplasmic reticulum associated phosphatase PTP1B is key player in the control of ALK phosphorylation., GPx-1-PTP1B-PP2A axis plays a critical role in countering the inflammatory and proteolytic responses that result in lung-tissue destruction in response to cigarette smoke exposure., PKM2 is a novel substrate of PTP1B tyrosine phosphorylation., PTP1B is a central player of the mechanisms triggered by APAP in hepatotoxicity, suggesting a novel therapeutic target against APAP-induced liver failure., Data suggest growth retardation in idiopathic short stature is related to delayed activation of JAK2 (Janus kinase 2) by PTP1B and SHP1 (protein tyrosine phosphatase, non-receptor type 6) in response to GH/GHR (growth hormone/GH receptor) signaling., multicenter pharmacogenetic study in children (ages 6-11), these results indicate that PRP19beta activates the gp130/Janus kinase (JAK)/STAT signaling pathway during astrocyte differentiation via PTP1B ubiquitination, data indicate a novel signaling pathway connecting calreticulin (CRT), STAT5A, PTP1B and ERK1/2 in the regulation of esophageal squamous cell carcinoma cell migration; findings suggest PTP1B is a downstream effector of CRT signaling and promotes tumor progression, an important role for PTP1B as a negative regulator of BRK and IGF-1Rbeta signaling in ovarian cancer cells., PTP1B expression might play a critical role in the progression of colorectal cancer., Adiponectin restrains leptin-induced signalling and pro-carcinogenic behaviour by inhibiting the early events in leptin-induced signal transduction by activating PTP1B., A conserved rod domain phosphotyrosine that is targeted by the phosphatase PTP1B promotes keratin 8 protein insolubility and filament organization., The endoplasmic reticulum-bound protein tyrosine phosphatase PTP1B has been implicated as a regulator of cell adhesion and migration, Despite the presence of hepatocyte growth factor, LECT2 binding causes an antagonistic effect to MET receptor activation through recruitment of protein tyrosine phosphatase 1B., PTP1B modulation results in (1) alterations in mitochondrial function and (2) changes in apoptosis., the Activin/ALK4 pathway directly recruits PTP1B and stimulates its release from the endoplasmic reticulum through ALK4-mediated cleavage., Nox4-mediated redox regulation of PTP1B serves as a modulator, in part through coronin-1C, of the growth and migration of glioblastoma cells., the activity of SHP-2, PTP-1beta, and PTP-PEST was enhanced by LKB1-expressing cells., M3R preserves the endothelial barrier function through a mechanism potentially maintaining PTP1B activity, keeping the adherens junction proteins (AJPs) dephosphorylation., Data suggest that curcumin is an activator of non-receptor type 1 protein tyrosine phosphatase (PTPN1) and can reduce cell motility in colon cancer via dephosphorylation of pTyr(421)-cortactin (CTTN)., The study demonstrates for the first time that a sustained high PTP1B level or activity in the sperm of obese donors causes a defect of sperm acrosome reaction and that PTP1B is a novel potential therapeutic target for male infertility treatment., PTPN1 mutations lead to reduced phosphatase activity and increased phosphorylation of JAK-STAT pathway members, and are drivers in lymphomagenesis., PTP1B plays an important role in the control of B cell activation and the maintenance of immunological tolerance., Results indicate that, although inhibition of PTP1B has potential benefits for the treatment of diabetes, it accentuates pro-inflammatory responses compromising at least macrophage viability., Findings implicate PTPN1 as a tumor suppressor gene in Primary mediastinal B-cell lymphoma and classical Hodgkin lymphoma and suggest that loss of PTPN1 phosphatase activity may promote the development of these cancers., In vitro studies on epithelial ovarian cancer cells shows that PTPN1 is targeted by miR-210., PTP-1B, SHP-2, and PTEN all play a functional role in Rb/E2F-associated apoptotic signal transduction, protein tyrosine phosphatase 1B is regulated with a conformational rearrangement in helix alpha7, disrupting the triangular interaction among helix alpha7, helix alpha3, and loop11, the hydrogen bond and energy decomposition analyses indicate that apart from residue 181, point mutations have influence on the interactions of substrate with several residues in the active site of PTP1B, TRX1 physically interacts with and reactivates PTP1B and PTEN through a direct thiol disulfide exchange., PTP1b is a key regulator of endothelial VEGFR2 signaling and plays an important role in regulation of the extent of vascular tree formation., PTP1B has a role in the modulation of insulin signaling by acetaminophen in hepatocytes, PTP1B sub-cellular location and tight control of enzymatic activity by diverse post-translational modifications illustrate the dynamic regulation of this enzyme and its ability to modulate numerous signaling pathways, likely in a cell/tissue- and stimulus-dependent manner, with high specificity and precision. [Review], PTP1B is a novel physiological regulator of TrkB and enhanced BDNF/TrkB signaling may contribute to the beneficial metabolic effects of PTP1B deficiency, FGFR3 regulation by PTPN1 and PTPN2 depend on FGFR3 localization and A-loop sequence., Nck1 depletion induces activation of the PI3K/Akt pathway by attenuating PTP1B protein expression, Findings suggest that the second sphere residues of PTP1B active site may play important roles in PTP-mediated function in both normal and diseased states., Data indicate that protein tyrosine phosphatase 1B (PTP1B) association with calnexin is ubiquitin conjugating enzyme 9 (UBC9)-dependent., PTP1B amplification predicts poor survival of gastric cancer patients., PTP1B can promote non-small cell lung cancer proliferation and metastasis by activating src and subsequently ERK1/2., Data shows a relationship between the dephosphorylation rate of different factors in signaling pathways related to cell proliferation and PTP1B activation., Fumosorinone increased glucose uptake and improved insulin resistance by down-regulating the expression of PTP1B and activating the insulin signaling pathway, suggesting that it may possess antidiabetic properties., PTP1B inhibited BRK by dephosphorylating Tyr-342, but activated SRC by antagonizing PAG-dependent inhibition by CSK., our data indicate that by targeting PTP1B, miR-744 plays a feed-forward role in regulating type I IFN signaling pathway., the multiple roles of PTP1B in liver diseases will be presented, with respect to liver regeneration, drug-induced liver disease, non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma--{REVIEW}, On EGF stimulation, complexes containing Mena and PTP1B are recruited to the EGFR, causing receptor dephosphorylation and leading to decreased motility responses., O-GlcNAcylation of PTP1B can influence insulin signal transduction by modulating its own phosphatase activity, which participates in the process of hepatic insulin resistance., Blockade of the interaction between Bcr-Abl and PTB1B by small molecule SBF-1 to overcomes imatinib-resistance of K562 cells., PTP1B dephosphorylates PITX1 to weaken its protein stability and the transcriptional activity for p120RasGAP gene expression, PTP1B directly regulates STAT5 phosphorylation and its activation via the cAMP/PKA pathway downstream of the 5-HT7 receptor is involved in the suppression of beta-casein expression in MCF-12A cells,
OMIM_DISEASE Insulin resistance, susceptibility to,
SP_COMMENT catalytic activity:Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate., function:May play an important role in CKII- and p60c-src-induced signal transduction cascades., 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 4-amino-3-isothiazolidinone serine cross-link, triggering a conformational change that inhibits substrate binding and activity. The active site can be restored by reduction., similarity:Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily., similarity:Contains 1 tyrosine-protein phosphatase domain.,