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FLASH GENE
Symbol PTPN2 contributors: mct/npt/pgu - updated : 07-12-2015
HGNC name protein tyrosine phosphatase, non-receptor type 2
HGNC id 9650
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 2477 48 415 - 2013 23328081
  • also called variant 1, isoform 1 or TC48
  • translocates to the Golgi complex along the secretory pathway, whereas its ER localization is maintained by selective retrieval enabled by interactions with p25 and p23
  • predominantly endoplasmic reticulum (ER)-localizing protein, which dephosphorylates some of the substrates of TC45 at the ER
  • interacts with and dephosphorylates syntaxin 17, which is an ER and ERGIC-localizing protein involved in vesicle transport
  • 10 - 1714 - 387 in T-cells and in placenta 2006 16595549
  • also called variant 2, isoform 2
  • lacks the C-terminal 34 aa, and contains a unique 6 aa C-terminus
  • 9 - 1623 - 353 - 2006 16595549
  • also called variant 3, isoform 3
  • lacks the C-terminal 67 aa, and contains an unique 6 aa C-terminus
  • 11 - 1790 - 410 nuclear isoform 2013 23328081
  • also called TC45
  • can dephosphorylate STAT1
  • is a nuclear protein, which has both nuclear and cytoplasmic substrates, and is involved in many signaling events including endocytic recycling of platelet-derived growth factor beta-receptor
  • - - 3313 - 386 - 2006 16595549
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine     Homo sapiens
    Endocrinepancreas    
    Lymphoid/Immunethymus   highly
    Reproductivefemale systembreastmammary gland  
     male systemtestis   
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Homo sapiens
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
  • protein tyrosine phosphatase (PTP) family
  • non-receptor class 1 subfamily
  • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • tyrosine phosphatase, non receptor, that may be involved in protein amino acid dephosphorylation
  • play key roles in switching off tyrosine phosphorylation cascades, such as initiated by cytokine receptors
  • matrix-controlled PTPN2 phosphatase activity can inhibit VEGFR2 signalling, and the growth, migration and differentiation of human endothelial cells
  • playing a functional role in maintaining the intestinal epithelial barrier and in the pathophysiology of Crohn disease
  • regulates cytokine-induced apoptosis and may thereby contribute to the pathogenesis of type 1 diabetes
  • might protect beta-cells from virus-induced apoptosis
  • may contribute to the pathogenesis of diabetes by modifying the beta-cell responses to a viral infection
  • may thus modulate beta-cell apoptosis and/or local release of inflammatory mediators in the course of a viral infection by acting, at least in part, at the pancreatic beta-cell level
  • tyrosine phosphatase that functions as a negative regulator of a variety of tyrosine kinases and other signaling proteins
  • important functional role for PTPN2 as a protector of the intestinal epithelial barrier
  • play an important role in the protection of epithelial barrier function during periods of inflammation by acting as a negative regulator of the proinflammatory cytokine IFNG1
  • attenuates T-cell lymphopenia-induced proliferation
  • in addition to modulating FGFR3 phosphorylation, PTPN1 and PTPN2 constrain the kinase domain by fostering an inactive-state
  • crucial role for PTPN2 in chronic intestinal inflammation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • negative regulator of NUP214-ABL1 kinase activity
  • cooperation between PTPN2 deletion and activating JAK1 gene mutations in T-cell acute lymphoblastic leukemia
  • EGFR, SFKs, and STAT3 can serve as substrates for the protein tyrosine phosphatase TCPTP (PTPN2)
  • interaction between the T-cell protein tyrosine phosphatase (PTPN2) and the C-terminus of connexin43 (GJA1)
  • UBL4A promotes STAT3 dephosphorylation via mediating the interaction between TC45 (the nuclear isoform of PTPN2) and STAT3 specifically
  • in addition to modulating FGFR3 phosphorylation, PTPN1 and PTPN2 constrain the kinase domain by fostering an inactive-state
  • cell & other
    REGULATION
    Other phosphorylation regulated by STAT1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    specifically found in T-ALLs with aberrant expression of the TLX1 transcription factor oncogene
    tumoral     --low  
    sensitizes lymphoid cells to JAK1-mediated transformation and reduces their sensitivity to JAK inhibition
    tumoral     --low  
    in triple-negative breast cancers
    constitutional       loss of function
    results in aberrant T-cell differentiation and intestinal dysbiosis similar to those observed in Crohn disease (CD)
    Susceptibility
  • to type 1 diabetes
  • to Crohn disease
  • Variant & Polymorphism SNP single-nucleotide polymorphisms (SNPs) rs2542151 (PTPN2) associated with Crohn disease
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS