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FLASH GENE
Symbol PTPN1 contributors: mct/ - updated : 28-08-2015
HGNC name protein tyrosine phosphatase, non-receptor type 1
HGNC id 9642
Location 20q13.13      Physical location : 49.126.890 - 49.201.084
Synonym name
  • protein tyrosine phosphatase, placental
  • protein tyrosine phosphatase 1B
  • Synonym symbol(s) PTP1B, PTP-1B
    EC.number 3.1.3.48
    DNA
    TYPE functioning gene
    STRUCTURE 74.20 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3318 - 435 - 2001 11506178
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly Homo sapiens
    Lymphoid/Immunethymus   highly
    Respiratoryrespiratory tracttrachea  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • is attached to the ER via a hydrophobic region made of 35 AAs (AAs 400435) at the C-terminal tail, while the catalytic domain is exposed to the cytosolic side of the ER
  • HOMOLOGY
    Homologene
    FAMILY
  • protein-tyrosine phosphatase family
  • non-receptor class 1 subfamily
  • CATEGORY receptor membrane phosphatase
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    text
  • localized to the cytoplasmic face of the endoplasmic reticulum
  • resident of the ER membrane
  • basic FUNCTION
  • acting as a putative growth suppressor that plays an important role in the regulation of cytokine signaling
  • regulating both insulin, leptin signaling and adipocyte leptin production through its neuronal form and probably is essential for the development of leptin resistance
  • playing a potential role in myeloid development, macrophage activation and a physiological role in immune regulation
  • negatively regulating macrophage development through CSF1 signaling
  • reduces the phosphorylation of PRDX4, and contributes to the redox-controlled processes occurring at the ER
  • role of microtubules and cell contacts in the positioning of ER-bound PTPN1 the peripheral region of growth cones, which may be required for the positive role of PTPN1 in axon elongation, filopodia stabilization, and Src activity
  • implicated in the regulation of the insulin receptor
  • regulates the endosomal sorting machinery
  • can influence RTK signaling in a previously unrecognized manner
  • governs signaling and biological activity of EPHA3
  • modulator of brown fat adipogenesis, suggesting that adipocyte differentiation requires regulated expression of PTPN1
  • in POMC neurons plays a role in short-term cold-induced reduction of spontaneous physical activity and may influence cold-induced thermogenesis via enhanced activation of the thyroid axis
  • major regulator of adiposity and insulin sensitivity
  • negative regulator of IR (insulin receptor) activation and glucose homoeostasis
  • may play a critical role in multiple signaling networks involved in oncogenesis
  • modulates early endosome fusion and trafficking of MET and epidermal growth factor receptors
  • key negative regulator of leptin and insulin signaling, is positively correlated with adiposity and contributes to insulin resistance
  • may play an important role in suppressing hepatocarcinogenesis
  • physiological regulator of glucose homeostasis and body mass, and has been implicated in endoplasmic reticulum (ER) stress
  • negatively regulates ER stress, as well as insulin and leptin resistance
  • PTPN1 and PTPRJ are required for optimal platelet activation and aggregate formation under high arterial shear rates
  • is capable of binding and dephosphorylating IFNAR1
  • in addition to modulating FGFR3 phosphorylation, PTPN1 and PTPN2 constrain the kinase domain by fostering an inactive-state
  • controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with TYK2, JAK2
  • can efficiently catalyze the removal of the phosphoryl group from phosphocaveolin-1 (CAV1)
  • interacting with TRPV6 (with the N-terminal domain of TRPV6 within a region of amino acids 1-191)
  • interacted with STAT6 in an interleukin 4 (IL4)-inducible manner, and negative regulator of interleukin 4-induced STAT6 signaling)
  • interacts with STAM2 at defined phosphotyrosine sites, directly targets STAM2, and tyrosine phosphorylation affects STAM localization and function
  • EPHA3-PTPN1 interaction can occur directly at the plasma membrane
  • important negative regulator of leptin signaling
  • NCK1 interacts with PTPN1 and the NCK1/PTPN1 complex inducibly associates with the IR for the attenuation of IR activation in mammalian cells
  • GRB14 inhibits the activity of PTPN1, the major negative regulator of insulin receptor (INSR) signaling, in a phosphorylation-regulated manner
  • PTPN1 might keep PRDX4 active by reducing its phosphorylation
  • physiologically-relevant modulator of ER stress in brown adipocytes and PTPN1 deficiency modulates EIF2AK3 phosphorylation and protein synthesis
  • SCLY disruption increases the levels of insulin-signaling inhibitor PTPN1
  • PTPN1 is a specific regulator of IFNAR1 endocytosis stimulated by IFN1, but not by ligand-independent inducers of IFNAR1 ubiquitination
  • PTPN1 regulates the phosphorylation state of retinal GAB1
  • CHRM3 preserves the endothelial barrier function through a mechanism potentially maintaining PTPN1 activity, keeping the adherens junction proteins (AJPs) dephosphorylation
  • in addition to modulating FGFR3 phosphorylation, PTPN1 and PTPN2 constrain the kinase domain by fostering an inactive-state
  • NCK1 interacts with PTPN1 and also regulates PTPN1 expression, playing a role in regulating the PI3K/AKT1 pathway
  • cell & other
    REGULATION
    induced by palmitate and inflammatory state, involving these two factors in insulin resistance state
    Other regulated by oxidation, glutathionylation, phosphorylation, and SUMOlyation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in chronic myelogenous leukemia
    tumoral     --over  
    in the mammary gland leads to spontaneous breast cancer development
    constitutional       loss of function
    deficiency enhances insulin signaling, in skeletal muscle and liver, reduces adiposity
    tumoral       loss of function
    when PTPN1 activity is inhibited, BCR-ABL is degraded by the ubiquitin lysosomal pathway
    tumoral     --low  
    significantly associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma (HCC)
    Susceptibility to essential hypertension, hypercholesterolemia and obesity (Japanese people)
    Variant & Polymorphism SNP increasing the risk of essntial hypertension, hypercholesterolemia and obesity
    Candidate gene
    Marker
  • may serve as a valuable prognostic biomarker in hepatocellular carcinoma (HCC)
  • Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    inhibition of PTP1B may be a useful strategy to explore in the development of novel therapeutic agents for the treatment of chronic myelogenous leukemia
    cancerhemopathy 
    potential target for treating myeloid malignancies
    cancerreproductivebreast
    therapeutic target in breast cancer
    neurosensorialear 
    PTPN1 inhibition may be useful for treating deafness associated with hyperglycemia and type 2 diabetes
    cancerdigestiveliver
    potential therapeutic target in hepatocellular carcinoma (HCC)
    neurologyneurodegenerativeParkinson/dementia Parkinsonism
    PTPN1 inhibitor may be used as a potential therapeutic agent against Parkinson's disease
    ANIMAL & CELL MODELS