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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
Location 18p11.21      Physical location : 12.785.480 - 12.884.334
Synonym name T-cell protein tyrosine phosphatase
Synonym symbol(s) PTPT, TCPTP, TC-PTP, TCELLPTP
EC.number 3.1.3.48
DNA
TYPE functioning gene
STRUCTURE 98.86 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Physical map
FLJ34907 18p11.21 hypothetical protein FLJ34907 LOC388463 18 similar to acyl-malonyl condensing enzyme LOC388464 18 hypothetical gene supported by D86974 GNAL 18p11.31 guanine nucleotide binding protein (G protein), alpha activating activity polypeptide, olfactory type CHMP1.5 18p11.21 CHMP1.5 protein MPPE1 18p11.21-p11.1 CHMP1.5 protein IMPA2 18p11.22-p11.21 inositol(myo)-1(or 4)-monophosphatase 2 LOC284226 18p11.21 similar to Kinesin-like protein KIF1C LOC284227 18p11.21 similar to single stranded DNA binding protein 4 LOC162835 18p11.21 similar to G protein-coupled receptor 124 LOC342850 18p11.21 similar to KIAA1074 protein LOC390832 18 similar to Phosphomannomutase 2 (PMM 2) CIDEA 18p11.21 cell death-inducing DFFA-like effector a MGC4083 18p11.21 tubulin beta MGC4083 AFG3L2 18p11 AFG3 ATPase family gene 3-like 2 (yeast) HFL-EDDG1 18p11.21 erythroid differentiation and denucleation factor 1 Spir-1 18p11.21 Spir-1 protein C18orf9 18p11.21 chromosome 18 open reading frame 9 HCCA3 18p11.21 hepatocellular carcinoma susceptibility protein PTPN2 18p11.22-p11.21 protein tyrosine phosphatase, non-receptor type 2 SEC13L 18p11.21 sec13-like protein LOC390833 18 similar to ribosomal protein P0-like protein; 60S acidic ribosomal protein PO; ribosomal protein, large, P0-like LOC388465 18 LOC388465 FLJ31338 18p11.21 hypothetical protein FLJ31338 C18orf1 18p11.2 chromosome 18 open reading frame 1 MGC24180 18p11.21 hypothetical protein MGC24180 RNMT 18p11.22 RNA (guanine-7-) methyltransferase MC5R 18p11.2 melanocortin 5 receptor MC2R 18p11.21 melanocortin 2 receptor (adrenocorticotropic hormone) LOC284230 18p11.21 similar to large subunit ribosomal protein L36a LOC162655 LOC342853 18p11.21 similar to KIAA0685 protein LOC388466 18 hypothetical gene supported by NM_032250 LOC284232 18p11.21 similar to Ankyrin repeat domain protein 18A LOC284235 18p11.21 similar to telomeric repeat binding factor 1 isoform 2; Telomeric repeat binding factor 1; telomeric repeat binding protein 1 LOC390834 18 similar to fem-1 homolog a (C.elegans) LOC388467 18 LOC388467 LOC390835 18 hypothetical gene supported by AF124598; NM_001338 LOC388468 18 hypothetical gene supported by BX649118; NM_174981 OR4K7P 18q21.32 olfactory receptor, family 4, subfamily K, member 7 pseudogene LOC390836 18 similar to Olfactory receptor 4K15 LOC341753 18p11.21 similar to Sorting nexin 19
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