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Details on Person UniProt:Q8BG87 Tet3

Class:IdReferenceGeneProduct:356931
_chainChangeLogchain:1-1668 added on Fri February 6 2015;chain:1-1668 for 356931 removed on Sun February 16 2020;chain:1-1803 for 356931 added on Sun February 16 2020
_displayNameUniProt:Q8BG87 Tet3
_timestamp2025-05-21 21:33:48
chainchain:1-1803
checksumFE0492ADBC4EBFD5
commentFUNCTION Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes. In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in DNA demethylation in the paternal pronucleus by mediating conversion of 5mC into 5hmC, 5fC and 5caC. Does not mediate DNA demethylation of maternal pronucleus because of the presence of DPPA3/PGC7 on maternal chromatin that prevents TET3-binding to chromatin. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT. Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (By similarity).CATALYTIC ACTIVITY a 5-methyl-2'-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-hydroxymethyl-2'-deoxycytidine in DNA + succinate + CO2CATALYTIC ACTIVITY a 5-hydroxymethyl-2'-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-formyl-2'-deoxycytidine in DNA + succinate + CO2 + H2OCATALYTIC ACTIVITY a 5-formyl-2'-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-carboxyl-2'-deoxycytidine in DNA + succinate + CO2 + H(+)COFACTOR Binds 1 Fe(2+) ion per subunit.COFACTOR The zinc ions have a structural role.SUBUNIT Interacts with HCFC1 (By similarity). Interacts with OGT (By similarity). Directly interacts (via C-terminus) with the DCAF1 component of the CRL4(VprBP) E3 ubiquitin-protein ligase complex (By similarity).INTERACTION At the zygotic stage, localizes in the male and female pronucleus, while it localizes to the cytoplasm at other preimplantation stages (PubMed:21892189, PubMed:28930672). Binds to the promoter of target genes, close to the transcription start site (PubMed:26774490).ALTERNATIVE PRODUCTS Highly expressed in germinal vesicle (GV) stage and MII-stage oocytes and in early embryos.DEVELOPMENTAL STAGE Expressed maternally. Expressed at high levels in germinal vesicle (GV) stage and MII-stage oocytes. Expressed at lower levels in one-cell embryos until 4-cell stage. Hardly detectable in morula. Expressed mainly in somatic cells from 9.5 dpc until at least 16.5 dpc. Expression in primordial germ cells is undetectable until 13.5 dpc and peaks at 16.5 dpc (PubMed:23151479).DOMAIN The CXXC-type zinc-finger domain mediates binding to DNA sequences containing unmethylated cytosine or 5-carboxylcytosine in 5'-CCG-3' DNA sequence motifs (PubMed:26774490). It mediates binding to CpG-DNA (By similarity).PTM Monoubiquitinated at Lys-1002 by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex; this modification promotes binding to DNA.DISRUPTION PHENOTYPE Neonatal lethality. A germline-specific conditional knockout produces females that are normal in growth and morphology but display much reduced fecundity in terms of the frequency of successful pregnancy per mating and the litter size. No 5hmC signal is detected in the late male pronuclei of zygotes collected from the conditional knockout females mated with wild-type males. In contrast, deletion of Tet3 from the male germ cells does not seem to affect the change in 5hmC and 5mC.SIMILARITY Belongs to the TET family.CAUTION Subsequent steps in cytosine demethylation are subject to discussion. According to a first model cytosine demethylation occurs through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system. According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Contaminating sequence. Potential poly-A sequence.
created[InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12
descriptionrecommendedName: Methylcytosine dioxygenase TET3 ecNumber evidence="5 8 12 15"1.14.11.80
geneNameTet3
Cxxc10
identifierQ8BG87
isSequenceChangedFALSE
keyword3D-structure
Alternative splicing
Chromatin regulator
Chromosome
Cytoplasm
Developmental protein
Dioxygenase
DNA-binding
Iron
Isopeptide bond
Metal-binding
Methylation
Nucleus
Oxidoreductase
Reference proteome
Ubl conjugation
Zinc
Zinc-finger
modified[InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39
[InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18
[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
[InstanceEdit:423310] Kanapin, AA
[InstanceEdit:435478] Kanapin, AA
[InstanceEdit:435871] Kanapin, AA
[InstanceEdit:447347] Kanapin, AA
[InstanceEdit:525883] Kanapin, AA
[InstanceEdit:613449] Kanapin, AA
[InstanceEdit:797602] Kanapin, AA
[InstanceEdit:937368] Yung, CK
[InstanceEdit:1042053] Yung, CK
[InstanceEdit:1220657] Yung, CK
[InstanceEdit:1300696] Yung, CK
[InstanceEdit:1301627] Yung, CK
[InstanceEdit:1551960] Weiser, JD
[InstanceEdit:1995863] Weiser, JD
[InstanceEdit:2132304] Weiser, JD
[InstanceEdit:2265580] Weiser, JD
[InstanceEdit:2587579] Weiser, JD
[InstanceEdit:3445779] Weiser, JD
[InstanceEdit:5433710] Weiser, JD
[InstanceEdit:5618415] Weiser, JD
[InstanceEdit:5634237] Weiser, JD
[InstanceEdit:5673015] Weiser, JD
[InstanceEdit:6807888] Weiser, JD
[InstanceEdit:8869714] Weiser, JD
[InstanceEdit:8944791] Weiser, JD
[InstanceEdit:9037114] Weiser, JD
[InstanceEdit:9637257] Weiser, JD
[InstanceEdit:9657908] Weiser, JD
[InstanceEdit:9676415] Weiser, JD
[InstanceEdit:9688885] Weiser, JD
[InstanceEdit:9730071] Weiser, JD
[InstanceEdit:9750299] Weiser, JD
[InstanceEdit:9834092] Weiser, Joel
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
nameTet3
referenceDatabase[ReferenceDatabase:2] UniProt
secondaryIdentifierTET3_MOUSE
K9JH93
L0HN04
Q4VAD3
Q8C8N8
Q8CI60
sequenceLength1803
species[Species:48892] Mus musculus
(isoformParent)[ReferenceIsoform:356932] UniProt:Q8BG87-2 Tet3 [Mus musculus]
[ReferenceIsoform:410031] UniProt:Q8BG87-1 Tet3 [Mus musculus]
[ReferenceIsoform:9037206] UniProt:Q8BG87-4 Tet3 [Mus musculus]
(referenceEntity)[EntityWithAccessionedSequence:5220994] Tet3 [nucleoplasm] [Mus musculus]
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