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Symbol PTPN6 contributors: mct/npt/pgu - updated : 10-04-2013
HGNC name protein tyrosine phosphatase, non-receptor type 6
HGNC id 9658
TYPE functioning gene
STRUCTURE 14.74 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure two promoters, 15 exons coding
MAPPING cloned Y linked N status confirmed
Map see TPI1
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
16 splicing 2321 67 595 - 1995 7665165
  • isoform 1
  • 16 splicing 2234 67 597 - 1995 7665165
  • using a different segment for its 5' UTR and 5' coding region compared to variant 1
  • isoform 2
  • 16 - 2464 70 624 - 1995 7665165
  • isoform 3
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   moderately
     intestinesmall intestine  moderately
    Endocrinethyroid   moderately
    Lymphoid/Immunespleen   predominantly
     thymus   highly
     tonsils   highly
    Respiratorylung   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly Homo sapiensAdult
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmature hematopoietic Homo sapiensAdult
    Lymphoid/ImmuneT cell
    cell lineage hematopoietic cell lineage
    cell lines
    fluid/secretion blood, lymph
    at STAGE
  • two tandemly repeated SH2 domains at N terminus, that is implicated as providing suppression of hematopoietic malignancies
  • three proline-rich, potential SH3-binding motifs, SH3 domain- containing CRKL adaptor protein associating with PTPN6
  • a tyrosine-phosphatase catalytic domain in C terminal region
  • C terminal nuclear localization signal (short cluster of basic AA : KRK), and six-AAs, lipid raft-targeting motif, necessary and sufficient for lipid raft localization and for the function as a negative regulator of TCR signaling
  • conjugated PhosphoP
    mono polymer monomer
    interspecies homolog to rattus Ptpn6 (94.1pc)
    homolog to murine Ptpn6 (94.5pc)
    intraspecies homolog to PTPN11
  • protein-tyrosine phosphatase family
  • non-receptor class 2 subfamily
  • CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
  • lipid raft localization
  • elevation of NaCl significantly decreases the fraction of PTPN6 that is in the nucleus and lowering NaCl does the opposite
  • basic FUNCTION
  • negative regulator of cell signaling in T cells
  • limiting antiapoptotic signal
  • playing a key role in hematopoiesis
  • may directly link growth factor receptors and other signaling proteins through protein-tyrosine phosphorylation via its PTPase activity
  • downregulating IL-3 inducing tyrosine phosphorylation and mitogenesis
  • involved in the regulation of glucose homeostasis through modulation of insulin signaling in liver and muscle as well as hepatic insulin clearance
  • playing a role with PTPRK in the regulation, maintenance, and restitution of cell adhesions in a complex epithelial organ such as the pancreas
  • key negative regulator of TCR-mediated signaling
  • negatively regulated Toll-like receptor-mediated production of proinflammatory cytokines by inhibiting activation of the transcription factor NF-kappaB and mitogen-activated protein kinase
  • contributes to immune homeostasis by balancing the production of proinflammatory cytokines and type I interferons in the innate immune response
  • involved in the inhibition of CD2 signaling (represents a novel mechanism for direct T cell suppression by IL10)
  • playing an important role in airway mucin production through regulating oxidative stress
  • regulates cell growth, inflammation, and injury largely through negative signaling, as by inhibition of STATs, NF-KB, ERK, and the PI3 kinase-Akt pathway
  • regulates cell proliferation, whether it is by controlling mitogenic pathways activated by receptors with tyrosine kinase activity, or by regulating components of the cell-cycle machinery
  • intrinsic global regulator of dendritic cell function, controlling many facets of T cell-mediated immune responses
  • novel role for PTPN6 in the regulation of AKT1 activity through the modulation of the ghrelin/GHSR1a system signaling
  • regulates muscle insulin action in a cell-autonomous manner, further suggesting that the PTPase negatively modulates insulin action through down-regulation of both insulin signaling to AKT1 and SLC2A4 translocation, as well as SLC2A4 expression
  • negative regulator of proinflammatory signaling and autoimmune disease
  • key regulator of dendritic cell functions that protects against autoimmunity
  • role in the regulation of signaling or membrane fusion events involved in phagolysosome biogenesis
  • possible involvement of the PTPN6 phosphatase in regulating other NK functions in mature NK cells
  • CELLULAR PROCESS cell life, proliferation/growth
    text hematopoietic cell development
    signaling signal transduction
    a component
  • forms a complex with receptor activator of NF-kB (TNFRSF11A), LYN and the adapter protein, Grb2-associated binder 2 (GAB2)
  • PLCB3 form the multimolecular SPS complex together with PTPN6 and STAT5
    small molecule
  • CSF2RB
  • activated KIT
  • LAIR1
  • death receptor of TNF (block antiapoptotic signaling in neutrophils)
  • TFG is a novel protein able to modulate PTPN6 activity
  • directly binding to and inhibiting activation of the kinase IRAK1, increasing the production of type I interferon mediated by Toll-like receptors and the helicase DDX58
  • STAT3
  • DNMT1
  • HDAC1
  • physically interact with PTPN6, and age-specific interactions between SIGLEC9 and PTPN6 may influence the altered inflammatory responsiveness and longevity of neonatal polymorphonuclear neutrophils
  • interacting with NFAT5 (Overexpression of PTPN6 greatly decreases high NaCl-induced nuclear localization of native NFAT5)
  • LYN/PLCB3-mediated regulatory mechanism of PTPN6 and STAT5B activities
  • in liver, transcriptional activation of PTPN6 gene by PKNOX1 attenuates insulin signal transduction and reduces glucose storage
  • negatively regulates the nuclear transcriptional function of CTNNB1
  • SIGLEC12 binds to the tyrosine phosphatases PTPN6 and PTPN11 in a phosphorylation-dependent manner
  • inducibly interacts with the SH2 domain of SH3BP2 after the aggregation of FCER1A
  • CRKL adaptor protein associating with PTPN6
  • is an essential negative regulator of IL4 signaling in T lymphocytes
  • inhibitory action of RAP1B on PI3K signaling may be mediated by activation of phosphatase PTPN6
  • ERK-1/2 inhibition or MAPK14 overexpression inhibited CD40-induced PTPN6 activation
  • cell & other
    Other regulated by USF1 and USF2
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    overexpressed in severe congenital neutropenia
    tumoral     --low  
    by aberrant methylation in leukemias/lymphomas
    constitutional     --low  
    in multiple sclerosis (MS)patients with, heightened STAT6 phosphorylation, and an enhanced state of activation relevant to the mechanisms of inflammatory demyelination , and in over a third of MS subjects, abnormally high promoter methylation
    constitutional       loss of function
    inactivation contributes to high NaCl-induced increase in NFAT5 transactivating activity
    constitutional     --other  
    defect in transcriptional regulation of the hematopoietic PTPN6 appears to be involved in the pathogenesis of certain subsets of the heterogeneous group of neutrophilic dermatoses
    Variant & Polymorphism
    Candidate gene
  • of MS, low expression in serum due, in over a third of MS subjects, to abnormally high promoter methylation
  • Therapy target
    therapeutic target for cancer treatment