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FLASH GENE
Symbol TET3 contributors: mct - updated : 25-02-2020
HGNC name tet oncogene family member 3
HGNC id 28313
Location 2p13.1      Physical location : 74.273.449 - 74.335.300
Synonym name probable methylcytosine dioxygenase TET3
Synonym symbol(s) MGC22014, hCG_40738, KIAA0401, KKRk
EC.number 1.14.11.n2
DNA
TYPE functioning gene
STRUCTURE 123.09 kb     9 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 10983 - 1660 - 2019 30836118
11 - 11405 - 1795 - 2019 30836118
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivefemale systemovary  highly Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticerythroid Homo sapiens
Nervousneuron Homo sapiens
Reproductiveoocyte Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • five nuclear localization signals (NLSs, KKRK)
  • several conserved domains, including a CXXC domain, traditionally considered as CpG specific DNA binding domains that are repelled by cytosine modifications, but that does not require the CpG context of cytosine bases
  • and a catalytic domain that is typical of Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenase, that could induce the formation of 5-hydroxymethylcytidine (5-hmrC) in human cells
  • HOMOLOGY
    Homologene
    FAMILY
  • TET family of dioxygenases
  • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • play a role in the DNA methylation
  • acts as a transcription factor located in the nucleus
  • TET3-mediated DNA hydroxylation is potentially involved in epigenetic reprogramming of the zygotic paternal DNA following natural fertilization
  • in the nucleus, TET3 depolymerizes from KPNA2,and KPNB1, and fulfills its function as a transcription factor or dioxygenase
  • novel function of TET3 that likely supports the function of OGT
  • TET2, TET3 are required for 5-hydroxymethylcytosine (5hmC) enrichment at enhancers, a condition necessary for expression of adjacent genes
  • respective functions of TET3 and DNA replication in paternal DNA demethylation and unexpected contribution of TET3 to demethylation of the maternal genome
  • TeT3 serves as a synaptic activity sensor to epigenetically regulate fundamental properties and meta-plasticity of neurons via active DNA demethylation
  • maternal TET3 is dispensable for embryonic development but is required for neonatal growth
  • negatively regulates type I IFN production independent of DNA demethylation
  • TET3, a DNA dioxygenase, can rapidly and efficiently convert fibroblasts directly into functional neurons
  • TET1, TET2, TET3 influence the balance between neuroectodermal and mesodermal fate choice by inhibiting Wnt signaling
  • distinct roles for TET2 and TET3 in human erythropoiesis
  • overexpression of TET3 in donor cells enhances goat somatic cell nuclear transfer efficiency
  • non-catalytic action of TET3 is essentially required for the maintenance of the neural stem cell (NSC) pool in the adult subventricular zone (SVZ) niche by preventing premature differentiation of NSCs into non-neurogenic astrocyte
  • TET2 and TET3 are guardians of Treg cell stability and immune homeostasis
  • CDK5-mediated phosphorylation of TET3 is required for robust activation of neuronal differentiation program
  • is a methylcytosine dioxygenase that initiates DNA demethylation during early zygote formation, embryogenesis, and neuronal differentiation and is intolerant to haploinsufficiency
  • plays an important role in rapidly demethylating the paternal genome after fertilization
  • important role of TET3 in early embryonic development and neuronal function
  • TET3 plays a key role in actively reversing DNA methylation during development
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • tight binding of TET3 to chromatin was inhibited by intranuclear DPPA3 through its binding to H3K9me2-containing chromatin
  • 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 is not only a major TET3-interacting protein but also regulates TET3 subcellular localization and enzymatic activity
  • Vitamin C potentiates TET activity and acts through TET2/TET3 to increase the stability of FOXP3 expression in TGFB1-induced T reg cells
  • catalytic domain of TET3 interacts with HDAC1 and SIN3A, thus enhancing their binding to the IFNB1 promoter
  • TET3 is an ATR kinase target that oxidizes DNA during ATR-dependent DNA damage repair
  • TET3 interacts with different members of the superfamily and also enhances their association to chromatin
  • hepatic TET3 contributes to type-2 diabetes by inducing the HNF4A fetal isoform
  • TET3 binds to target gene promoters, inducing demethylation, which in turn facilitates chromatin remodeling and transcription
  • cell & other
    REGULATION
    Phosphorylated by CDK5 (CDK5 phosphorylates TET3 at the highly conserved serine 1310 and 1379 residues within its catalytic domain, changing its in vitro dioxygenase activity)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    DNA demethylase TET3 is anomalously upregulated in fibrotic livers
    Susceptibility to Systemic lupus erythematosus (SLE)
    Variant & Polymorphism SNP , other multiple independent SNPs increasing the risk of SLE
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    inhibiting TET3 may represent a therapeutic strategy for liver fibrosis and perhaps other fibrotic diseases
    ANIMAL & CELL MODELS
  • female mice depleted of Tet3 in the germ line show severely reduced fecundity and their heterozygous mutant offspring lacking maternal Tet3 suffer an increased incidence of developmental failure