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FLASH GENE
Symbol TET2 contributors: mct/ - updated : 31-05-2018
HGNC name tet oncogene family member 2
HGNC id 25941
Location 4q24      Physical location : 106.067.942 - 106.200.958
Synonym name
  • KIAA1546 protein
  • ten-eleven translocation 2
  • Synonym symbol(s) MGC125715, KIAA1546, FLJ20032, MDS
    EC.number 1.14.11.n2
    DNA
    TYPE functioning gene
    STRUCTURE 133.02 kb     11 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 9677 - 2002 - 2009 19262601
    3 - 9215 - 1165 - 2009 19262601
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Hearing/Equilibriumear   highly
    Reproductivefemale systembreastmammary gland highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmature hematopoietic Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
  • TET family
  • CATEGORY DNA associated , tumor suppressor
    SUBCELLULAR LOCALIZATION
    basic FUNCTION
  • has an important role in hematopoiesis and in the pathogenesis of myelodysplasia and myeloid malignancies
  • implicated in myeloproliferative neoplasm and myelodysplastic syndromes through the identification of acquired mutations affecting hematopoietic stem cells
  • PARP1 and TET2 contribute to an epigenetic program that directs subsequent transcriptional induction at pluripotency loci during somatic cell reprogramming
  • enzyme that catalyzes the conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5-hmC)
  • has a critical role in survival and hematopoietic stem cell homeostasis
  • implicated in hematopoietic differentiation and the formation of myeloid malignancies when mutated
  • is critical for the full activation of >50 genes that become upregulated during pre-B cell to macrophage transdifferentiation
  • TET2-dependent O-GlcNAcylation of chromatinand the double epigenetic modifications on both DNA and histones by TET2 and OGT coordinate together for the regulation of gene transcription
  • TET2, TET3 are required for 5-hydroxymethylcytosine (5hmC) enrichment at enhancers, a condition necessary for expression of adjacent genes
  • neuronal TET2 is positively involved in the regulation of cell survival
  • in the absence of TET2, mast cell differentiation is under the control of compensatory mechanisms mediated by other TET family members, while proliferation is strictly dependent on TET2 expression
  • molecular circuitry in which opposing functions of TET1 and TET2 control acquisition of alternative pluripotent states
  • TET2 plays a role in the iron and heme metabolism in erythroblasts
  • TET2-mediated DNA demethylation promotes the expression of ferroportin and erythroferrone against oxidative stress
  • protective role of TET2 in erythroid iron homeostasis against oxidative stress and erythropoiesis
  • TET2 catalyzes the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, leading to DNA demethylation, and also affects transcription by recruiting histone modifiers
  • TET2 is an important regulator of CD8+ T cell fate decisions
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • TET2–OGT complex might be involved in transcriptional activation in embryonic stem cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TET2 helps CEBPA rapidly derepress myeloid genes during the conversion of pre-B cells into macrophages
  • TET2 directly binds to the methylated promoters of its target genes, resulting in hydroxylation and correlating with the genes strong activation
  • TET2 and TET3 associate with OGT, an enzyme that by itself catalyses the addition of O-GlcNAc onto serine and threonine residues (O-GlcNAcylation)
  • OGT associates with TET2 at transcription start sites
  • PRDM14 maintains pluripotency of embryonic stem cells through TET1, TET2-mediated active DNA demethylation
  • ZNF281 interacts with TET1, but not TET2
  • dual role for TET2 in promoting and inhibiting HSC differentiation, the loss of which, along with DNMT3A, obstructs differentiation, leading to transformation
  • histone H3K4 methyltransferase SETD1A is differentially recruited between macrophages (MACs) and osteoclasts (OCs) in a TET2-dependent manner
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23)
    tumoral     --low  
    lower in myelodysplasia cells regardless of mutational status, raising the possibility of nonmutational TET2 dysregulation in cases lacking mutations
    tumoral somatic mutation      
    is associated with poor prognosis in AML patients with intermediate-risk cytogenetics, especially when it is combined with other adverse molecular markers
    tumoral somatic mutation      
    affect global methylation in chronic myelomonocytic leukemia but most of the changes are likely to be outside gene promoters
    constitutional somatic mutation      
    present in normal elderly individuals with myeloid skewing and are associated with epigenetic alterations
    tumoral germinal mutation      
    in B cells of patients affected by angioimmunoblastic T-cell lymphoma (AITL)
    constitutional     --low  
    results in hypermethylation of promoter CpG islands (CGIs) and enhancers in loci largely overlapping with those induced by oxidative stress (OS)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • Tet2(+/-) mice also displayed increased stem cell self-renewal and extramedullary hematopoiesis, suggesting that Tet2 haploinsufficiency contributes to hematopoietic transformation
  • ANIMAL & CELL MODELS