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FLASH GENE
Symbol TET2 contributors: mct/ - updated : 31-05-2019
HGNC name tet oncogene family member 2
HGNC id 25941
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
Nervousbrain   highly Homo sapiens
Reproductivefemale systembreastmammary gland highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  highly Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticerythroid Homo sapiens
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
  • TET1, TET2, TET3 influence the balance between neuroectodermal and mesodermal fate choice by inhibiting Wnt signaling
  • TET2 plays a role in the iron and heme metabolism in erythroblasts
  • distinct roles for TET2 and TET3 in human erythropoiesis
  • 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
  • TET1 and TET2 play a critical role in maintaining bone marrow MSCs and bone homeostasis through demethylation of P2RX7 to control exosome and miRNA release
  • TET2 was found to be a promoter of both osteogenesis and adipogenesis
  • TET2 and TET3 are guardians of Treg cell stability and immune homeostasis
  • promotes de-methylation of DNA by catalyzing conversion of methylation to 5-hydroxymethylation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • TET2–OGT complex might be involved in transcriptional activation in embryonic stem cells
  • CXXC5 forms a complex with NANOG, POU5F1, TET1, and TET2 and facilitates their proper recruitment to regulatory regions of pluripotency and TET genes in ESCs to positively regulate their transcription
  • 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
  • CXXC4 recruits TET2 to DNA before degradation
  • PRDM14 maintains pluripotency of embryonic stem cells through TET1, TET2-mediated active DNA demethylation
  • Vitamin C potentiates TET activity and acts through TET2/TET3 to increase the stability of FOXP3 expression in TGFB1-induced T reg cells
  • 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
  • CXXC5 binds to the chromatin and is enriched at promoters and enhancers of TET1, TET2, and pluripotency genes
  • STAT3 regulated IFI44L expression and interacted with TET2 which induced DNA demethylation of IFI44L promoter
  • cell & other
    REGULATION
    Other regulated by CXXC4 a reported inhibitor of Wnt signalling that has been implicated in malignant renal cell carcinoma and colonic villous adenoma
    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 to early-onset Alzheimer’s disease (EOAD) and frontotemporal dementia (FTD), late-onset Alzheimer’s disease (LOAD), and ALS (amyotrophic lateral sclerosis)
    Variant & Polymorphism other
  • loss of TET2 function confers risk for EOAD, LOAD, FTD, and ALS, and pecifically, in aggregate, both coding and non-coding qualifying rare variation in TET2 is associated with approximately a 2-fold risk increase across diverse populations of individuals with AD, FTD, and ALS
  • 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
  • reducing Tet2 in mouse hippocampus leads to reduced neurogenesis and impaired memory,58 consistent with its role in promoting adult neurogenesis in mice