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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
Location 12p13.31      Physical location : 7.055.739 - 7.070.479
Synonym name
  • hematopoietic cell phosphatase
  • hematopoietic cell protein-tyrosine phosphatase
  • protein-tyrosine phosphatase SHP-1
  • Synonym symbol(s) HCP, PTP-1C, PTPNG, SHP1, SHP-1L, HCPH, EVI77, HPTP1C, SH-PTP1, SHP-1
    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