Q8BG87 · TET3_MOUSE
- ProteinMethylcytosine dioxygenase TET3
- GeneTet3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1803 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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
- 2-oxoglutarate + a 5-methyl-2'-deoxycytidine in DNA + O2 = a 5-hydroxymethyl-2'-deoxycytidine in DNA + CO2 + succinate
Cofactor
Protein has several cofactor binding sites:
Note: Binds 1 Fe2+ ion per subunit.
Note: The zinc ions have a structural role.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 57 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 60 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 63 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 69 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 72 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 75 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 84 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 89 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 836 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 838 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 896 | Zn2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 922 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 924 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 964 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 974 | Zn2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 976 | Zn2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 992 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1001 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1061 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1077 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 1083 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 1085 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 1087 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 1090 | substrate | ||||
Sequence: N | ||||||
Binding site | 1119 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 1681 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 1696-1698 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: RIS | ||||||
Binding site | 1702-1704 | substrate | ||||
Sequence: YQH | ||||||
Binding site | 1712 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chromosome | |
Cellular Component | cytoplasm | |
Cellular Component | female pronucleus | |
Cellular Component | male pronucleus | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | 5-methylcytosine dioxygenase activity | |
Molecular Function | methyl-CpG binding | |
Molecular Function | RNA polymerase II cis-regulatory region sequence-specific DNA binding | |
Molecular Function | zinc ion binding | |
Biological Process | 5-methylcytosine catabolic process | |
Biological Process | chromosomal 5-methylcytosine DNA demethylation pathway | |
Biological Process | epigenetic programing of male pronucleus | |
Biological Process | positive regulation of transcription by RNA polymerase II | |
Biological Process | protein O-linked glycosylation |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMethylcytosine dioxygenase TET3
- EC number
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8BG87
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Phenotypes & Variants
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.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 1002 | Strongly decreases ubiquitination, loss of DNA-binding and of 5-methylcytosine demethylase activity in vivo. Loss of nuclear localization, becomes mostly cytoplasmic. | ||||
Sequence: K → E | ||||||
Mutagenesis | 1002 | Strongly decreases ubiquitination, loss of DNA-binding and of 5-methylcytosine demethylase activity in vivo. Loss of nuclear localization, becomes mostly cytoplasmic. | ||||
Sequence: K → N | ||||||
Mutagenesis | 1085 | Loss of enzyme activity; when associated with A-1087. | ||||
Sequence: H → Y | ||||||
Mutagenesis | 1087 | Loss of enzyme activity; when associated with Y-1085. | ||||
Sequence: D → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 78 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, cross-link, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000340228 | 1-1803 | Methylcytosine dioxygenase TET3 | |||
Sequence: MSQFQVPLAVQPDLSGLYDFPQGQVMVGGFQGPGLPMAGSETQLRGGGDGRKKRKRCGTCDPCRRLENCGSCTSCTNRRTHQICKLRKCEVLKKKAGLLKEVEINAREGTGPWAQGATVKTGSELSPVDGPVPGQMDSGPVYHGDSRQLSTSGAPVNGAREPAGPGLLGAAGPWRVDQKPDWEAASGPTHAARLEDAHDLVAFSAVAEAVSSYGALSTRLYETFNREMSREAGSNGRGPRPESCSEGSEDLDTLQTALALARHGMKPPNCTCDGPECPDFLEWLEGKIKSMAMEGGQGRPRLPGALPPSEAGLPAPSTRPPLLSSEVPQVPPLEGLPLSQSALSIAKEKNISLQTAIAIEALTQLSSALPQPSHSTSQASCPLPEALSPSAPFRSPQSYLRAPSWPVVPPEEHPSFAPDSPAFPPATPRPEFSEAWGTDTPPATPRNSWPVPRPSPDPMAELEQLLGSASDYIQSVFKRPEALPTKPKVKVEAPSSSPAPVPSPISQREAPLLSSEPDTHQKAQTALQQHLHHKRNLFLEQAQDASFPTSTEPQAPGWWAPPGSPAPRPPDKPPKEKKKKPPTPAGGPVGAEKTTPGIKTSVRKPIQIKKSRSRDMQPLFLPVRQIVLEGLKPQASEGQAPLPAQLSVPPPASQGAASQSCATPLTPEPSLALFAPSPSGDSLLPPTQEMRSPSPMVALQSGSTGGPLPPADDKLEELIRQFEAEFGDSFGLPGPPSVPIQEPENQSTCLPAPESPFATRSPKKIKIESSGAVTVLSTTCFHSEEGGQEATPTKAENPLTPTLSGFLESPLKYLDTPTKSLLDTPAKKAQSEFPTCDCVEQIVEKDEGPYYTHLGSGPTVASIRELMEDRYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRHTLEEKLLCLVRHRAGHHCQNAVIVILILAWEGIPRSLGDTLYQELTDTLRKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLTGDNPKEEEVLRNSFQDLATEVAPLYKRLAPQAYQNQVTNEDVAIDCRLGLKEGRPFSGVTACMDFCAHAHKDQHNLYNGCTVVCTLTKEDNRCVGQIPEDEQLHVLPLYKMASTDEFGSEENQNAKVSSGAIQVLTAFPREVRRLPEPAKSCRQRQLEARKAAAEKKKLQKEKLSTPEKIKQEALELAGVTTDPGLSLKGGLSQQSLKPSLKVEPQNHFSSFKYSGNAVVESYSVLGSCRPSDPYSMSSVYSYHSRYAQPGLASVNGFHSKYTLPSFGYYGFPSSNPVFPSQFLGPSAWGHGGSGGSFEKKPDLHALHNSLNPAYGGAEFAELPGQAVATDNHHPIPHHQQPAYPGPKEYLLPKVPQLHPASRDPSPFAQSSSCYNRSIKQEPIDPLTQAESIPRDSAKMSRTPLPEASQNGGPSHLWGQYSGGPSMSPKRTNSVGGNWGVFPPGESPTIVPDKLNSFGASCLTPSHFPESQWGLFTGEGQQSAPHAGARLRGKPWSPCKFGNGTSALTGPSLTEKPWGMGTGDFNPALKGGPGFQDKLWNPVKVEEGRIPTPGANPLDKAWQAFGMPLSSNEKLFGALKSEEKLWDPFSLEEGTAEEPPSKGVVKEEKSGPTVEEDEEELWSDSEHNFLDENIGGVAVAPAHCSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKMKQLAERARQRQEEAARLGLGQQEAKLYGKKRKWGGAMVAEPQHKEKKGAIPTRQALAMPTDSAVTVSSYAYTKVTGPYSRWI | ||||||
Cross-link | 490 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 1002 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 1196 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 1227 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 1271 | Asymmetric dimethylarginine | ||||
Sequence: R | ||||||
Cross-link | 1405 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Cross-link | 1569 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K |
Post-translational modification
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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).
Gene expression databases
Interaction
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).
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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | Q8BG87 | OGT O15294 | 2 | EBI-9031997, EBI-539828 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for zinc finger, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 50-90 | CXXC-type | ||||
Sequence: GRKKRKRCGTCDPCRRLENCGSCTSCTNRRTHQICKLRKCE | ||||||
Region | 137-167 | Disordered | ||||
Sequence: DSGPVYHGDSRQLSTSGAPVNGAREPAGPGL | ||||||
Region | 229-251 | Disordered | ||||
Sequence: SREAGSNGRGPRPESCSEGSEDL | ||||||
Region | 294-328 | Disordered | ||||
Sequence: EGGQGRPRLPGALPPSEAGLPAPSTRPPLLSSEVP | ||||||
Compositional bias | 369-384 | Polar residues | ||||
Sequence: LPQPSHSTSQASCPLP | ||||||
Region | 369-460 | Disordered | ||||
Sequence: LPQPSHSTSQASCPLPEALSPSAPFRSPQSYLRAPSWPVVPPEEHPSFAPDSPAFPPATPRPEFSEAWGTDTPPATPRNSWPVPRPSPDPMA | ||||||
Compositional bias | 407-428 | Pro residues | ||||
Sequence: VVPPEEHPSFAPDSPAFPPATP | ||||||
Region | 478-614 | Disordered | ||||
Sequence: KRPEALPTKPKVKVEAPSSSPAPVPSPISQREAPLLSSEPDTHQKAQTALQQHLHHKRNLFLEQAQDASFPTSTEPQAPGWWAPPGSPAPRPPDKPPKEKKKKPPTPAGGPVGAEKTTPGIKTSVRKPIQIKKSRSR | ||||||
Compositional bias | 508-526 | Polar residues | ||||
Sequence: REAPLLSSEPDTHQKAQTA | ||||||
Region | 632-712 | Disordered | ||||
Sequence: KPQASEGQAPLPAQLSVPPPASQGAASQSCATPLTPEPSLALFAPSPSGDSLLPPTQEMRSPSPMVALQSGSTGGPLPPAD | ||||||
Compositional bias | 651-666 | Polar residues | ||||
Sequence: PASQGAASQSCATPLT | ||||||
Compositional bias | 681-701 | Polar residues | ||||
Sequence: DSLLPPTQEMRSPSPMVALQS | ||||||
Region | 993-1006 | Interaction with DNA | ||||
Sequence: SWSMYFNGCKYARS | ||||||
Region | 1354-1456 | Disordered | ||||
Sequence: ATDNHHPIPHHQQPAYPGPKEYLLPKVPQLHPASRDPSPFAQSSSCYNRSIKQEPIDPLTQAESIPRDSAKMSRTPLPEASQNGGPSHLWGQYSGGPSMSPKR | ||||||
Compositional bias | 1389-1410 | Polar residues | ||||
Sequence: DPSPFAQSSSCYNRSIKQEPID | ||||||
Compositional bias | 1428-1456 | Polar residues | ||||
Sequence: TPLPEASQNGGPSHLWGQYSGGPSMSPKR | ||||||
Region | 1617-1639 | Disordered | ||||
Sequence: EEGTAEEPPSKGVVKEEKSGPTV |
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).
It mediates binding to CpG-DNA (By similarity).
Sequence similarities
Belongs to the TET family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q8BG87-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name3
- Length1,803
- Mass (Da)194,792
- Last updated2019-11-13 v4
- ChecksumFE0492ADBC4EBFD5
Q8BG87-2
- Name2
Q8BG87-4
- Name1
- Differences from canonical
- 102-120: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A5K1VVP6 | A0A5K1VVP6_MOUSE | Tet3 | 1668 | ||
A0A087WP90 | A0A087WP90_MOUSE | Tet3 | 141 |
Sequence caution
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_060404 | 1-135 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_060405 | 102-120 | in isoform 1 | |||
Sequence: Missing | ||||||
Compositional bias | 369-384 | Polar residues | ||||
Sequence: LPQPSHSTSQASCPLP | ||||||
Compositional bias | 407-428 | Pro residues | ||||
Sequence: VVPPEEHPSFAPDSPAFPPATP | ||||||
Compositional bias | 508-526 | Polar residues | ||||
Sequence: REAPLLSSEPDTHQKAQTA | ||||||
Compositional bias | 651-666 | Polar residues | ||||
Sequence: PASQGAASQSCATPLT | ||||||
Compositional bias | 681-701 | Polar residues | ||||
Sequence: DSLLPPTQEMRSPSPMVALQS | ||||||
Alternative sequence | VSP_060406 | 840-854 | in isoform 2 | |||
Sequence: EQIVEKDEGPYYTHL → GRWEWSRAFFLSVEH | ||||||
Alternative sequence | VSP_060407 | 855-1803 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 1097 | in Ref. 5; AAH96437 | ||||
Sequence: V → A | ||||||
Compositional bias | 1389-1410 | Polar residues | ||||
Sequence: DPSPFAQSSSCYNRSIKQEPID | ||||||
Compositional bias | 1428-1456 | Polar residues | ||||
Sequence: TPLPEASQNGGPSHLWGQYSGGPSMSPKR |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
HQ423151 EMBL· GenBank· DDBJ | ADR57137.1 EMBL· GenBank· DDBJ | mRNA | ||
HQ423152 EMBL· GenBank· DDBJ | ADR57138.1 EMBL· GenBank· DDBJ | mRNA | ||
JX946278 EMBL· GenBank· DDBJ | AGB05430.1 EMBL· GenBank· DDBJ | mRNA | ||
AK044758 EMBL· GenBank· DDBJ | BAC32068.1 EMBL· GenBank· DDBJ | mRNA | ||
AK046543 EMBL· GenBank· DDBJ | BAC32779.1 EMBL· GenBank· DDBJ | mRNA | ||
AK046552 EMBL· GenBank· DDBJ | BAC32784.1 EMBL· GenBank· DDBJ | mRNA | ||
AK046553 EMBL· GenBank· DDBJ | BAC32785.1 EMBL· GenBank· DDBJ | mRNA | ||
GL456132 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC096437 EMBL· GenBank· DDBJ | AAH96437.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. |