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Protein

Methylcytosine dioxygenase TET3

Gene

TET3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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 (By similarity). 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.By similarity1 Publication

Catalytic activityi

DNA 5-methylcytosine + 2-oxoglutarate + O2 = DNA 5-hydroxymethylcytosine + succinate + CO2.By similarity

Cofactori

Protein has several cofactor binding sites:
  • Fe2+By similarityNote: Binds 1 Fe2+ ion per subunit.By similarity
  • Zn2+By similarityNote: Binds 3 zinc ions per subunit. The zinc ions have a structural role.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi693Zinc 1By similarity1
Metal bindingi695Zinc 1By similarity1
Metal bindingi753Zinc 2By similarity1
Metal bindingi779Zinc 1; via pros nitrogenBy similarity1
Metal bindingi781Zinc 1By similarity1
Binding sitei8212-oxoglutarateBy similarity1
Metal bindingi831Zinc 2By similarity1
Metal bindingi833Zinc 2By similarity1
Metal bindingi849Zinc 3By similarity1
Metal bindingi858Zinc 3By similarity1
Metal bindingi918Zinc 3By similarity1
Binding sitei9342-oxoglutarateBy similarity1
Metal bindingi940Zinc 2; via tele nitrogenBy similarity1
Metal bindingi942Iron; catalyticBy similarity1
Metal bindingi944Iron; catalyticBy similarity1
Binding sitei947SubstrateBy similarity1
Binding sitei9762-oxoglutarateBy similarity1
Metal bindingi1538Iron; catalyticBy similarity1
Metal bindingi1569Zinc 3; via pros nitrogenBy similarity1

GO - Molecular functioni

GO - Biological processi

  • 5-methylcytosine catabolic process Source: GO_Central
  • DNA demethylation Source: UniProtKB
  • DNA demethylation of male pronucleus Source: UniProtKB
  • histone H3-K4 trimethylation Source: UniProtKB
  • oxidative demethylation Source: GO_Central
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • protein O-linked glycosylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Developmental protein, Dioxygenase, Oxidoreductase

Keywords - Ligandi

DNA-binding, Iron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5221030. TET1,2,3 and TDG demethylate DNA.
SIGNORiO43151.

Names & Taxonomyi

Protein namesi
Recommended name:
Methylcytosine dioxygenase TET3 (EC:1.14.11.n2By similarity)
Gene namesi
Name:TET3
Synonyms:KIAA0401
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:28313. TET3.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

  • Note: At the zygotic stage, localizes in the male pronucleus, while it localizes to the cytoplasm at other preimplantation stages.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi200424.
PharmGKBiPA162405645.

Polymorphism and mutation databases

BioMutaiTET3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000507501 – 1660Methylcytosine dioxygenase TET3Add BLAST1660

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki1262Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

MaxQBiO43151.
PaxDbiO43151.
PeptideAtlasiO43151.
PRIDEiO43151.

PTM databases

iPTMnetiO43151.
PhosphoSitePlusiO43151.

Expressioni

Tissue specificityi

Expressed in colon, muscle, adrenal gland and peripheral blood lymphocytes.1 Publication

Developmental stagei

Expressed in fetal brain but not adult brain.1 Publication

Gene expression databases

BgeeiENSG00000187605.
CleanExiHS_TET3.
ExpressionAtlasiO43151. baseline and differential.
GenevisibleiO43151. HS.

Organism-specific databases

HPAiHPA050845.

Interactioni

Subunit structurei

Interacts with HCFC1 and OGT.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
OGTO152944EBI-2831148,EBI-539828

Protein-protein interaction databases

BioGridi128327. 6 interactors.
IntActiO43151. 27 interactors.
STRINGi9606.ENSP00000386869.

Structurei

3D structure databases

ProteinModelPortaliO43151.
SMRiO43151.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni850 – 863Interaction with DNABy similarityAdd BLAST14
Regioni1553 – 15552-oxoglutarate bindingBy similarity3
Regioni1559 – 1561Substrate bindingBy similarity3

Sequence similaritiesi

Belongs to the TET family.Curated

Phylogenomic databases

eggNOGiENOG410IE22. Eukaryota.
ENOG410XPWW. LUCA.
HOGENOMiHOG000154550.
HOVERGENiHBG079550.
InParanoidiO43151.
OrthoDBiEOG091G007O.
PhylomeDBiO43151.
TreeFamiTF342373.

Family and domain databases

InterProiIPR024779. 2OGFeDO_noxygenase_dom.
[Graphical view]
PfamiPF12851. Tet_JBP. 1 hit.
[Graphical view]
SMARTiSM01333. Tet_JBP. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43151-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDSGPVYHGD SRQLSASGVP VNGAREPAGP SLLGTGGPWR VDQKPDWEAA
60 70 80 90 100
PGPAHTARLE DAHDLVAFSA VAEAVSSYGA LSTRLYETFN REMSREAGNN
110 120 130 140 150
SRGPRPGPEG CSAGSEDLDT LQTALALARH GMKPPNCNCD GPECPDYLEW
160 170 180 190 200
LEGKIKSVVM EGGEERPRLP GPLPPGEAGL PAPSTRPLLS SEVPQISPQE
210 220 230 240 250
GLPLSQSALS IAKEKNISLQ TAIAIEALTQ LSSALPQPSH STPQASCPLP
260 270 280 290 300
EALSPPAPFR SPQSYLRAPS WPVVPPEEHS SFAPDSSAFP PATPRTEFPE
310 320 330 340 350
AWGTDTPPAT PRSSWPMPRP SPDPMAELEQ LLGSASDYIQ SVFKRPEALP
360 370 380 390 400
TKPKVKVEAP SSSPAPAPSP VLQREAPTPS SEPDTHQKAQ TALQQHLHHK
410 420 430 440 450
RSLFLEQVHD TSFPAPSEPS APGWWPPPSS PVPRLPDRPP KEKKKKLPTP
460 470 480 490 500
AGGPVGTEKA APGIKPSVRK PIQIKKSRPR EAQPLFPPVR QIVLEGLRSP
510 520 530 540 550
ASQEVQAHPP APLPASQGSA VPLPPEPSLA LFAPSPSRDS LLPPTQEMRS
560 570 580 590 600
PSPMTALQPG STGPLPPADD KLEELIRQFE AEFGDSFGLP GPPSVPIQDP
610 620 630 640 650
ENQQTCLPAP ESPFATRSPK QIKIESSGAV TVLSTTCFHS EEGGQEATPT
660 670 680 690 700
KAENPLTPTL SGFLESPLKY LDTPTKSLLD TPAKRAQAEF PTCDCVEQIV
710 720 730 740 750
EKDEGPYYTH LGSGPTVASI RELMEERYGE KGKAIRIEKV IYTGKEGKSS
760 770 780 790 800
RGCPIAKWVI RRHTLEEKLL CLVRHRAGHH CQNAVIVILI LAWEGIPRSL
810 820 830 840 850
GDTLYQELTD TLRKYGNPTS RRCGLNDDRT CACQGKDPNT CGASFSFGCS
860 870 880 890 900
WSMYFNGCKY ARSKTPRKFR LAGDNPKEEE VLRKSFQDLA TEVAPLYKRL
910 920 930 940 950
APQAYQNQVT NEEIAIDCRL GLKEGRPFAG VTACMDFCAH AHKDQHNLYN
960 970 980 990 1000
GCTVVCTLTK EDNRCVGKIP EDEQLHVLPL YKMANTDEFG SEENQNAKVG
1010 1020 1030 1040 1050
SGAIQVLTAF PREVRRLPEP AKSCRQRQLE ARKAAAEKKK IQKEKLSTPE
1060 1070 1080 1090 1100
KIKQEALELA GITSDPGLSL KGGLSQQGLK PSLKVEPQNH FSSFKYSGNA
1110 1120 1130 1140 1150
VVESYSVLGN CRPSDPYSMN SVYSYHSYYA QPSLTSVNGF HSKYALPSFS
1160 1170 1180 1190 1200
YYGFPSSNPV FPSQFLGPGA WGHSGSSGSF EKKPDLHALH NSLSPAYGGA
1210 1220 1230 1240 1250
EFAELPSQAV PTDAHHPTPH HQQPAYPGPK EYLLPKAPLL HSVSRDPSPF
1260 1270 1280 1290 1300
AQSSNCYNRS IKQEPVDPLT QAEPVPRDAG KMGKTPLSEV SQNGGPSHLW
1310 1320 1330 1340 1350
GQYSGGPSMS PKRTNGVGGS WGVFSSGESP AIVPDKLSSF GASCLAPSHF
1360 1370 1380 1390 1400
TDGQWGLFPG EGQQAASHSG GRLRGKPWSP CKFGNSTSAL AGPSLTEKPW
1410 1420 1430 1440 1450
ALGAGDFNSA LKGSPGFQDK LWNPMKGEEG RIPAAGASQL DRAWQSFGLP
1460 1470 1480 1490 1500
LGSSEKLFGA LKSEEKLWDP FSLEEGPAEE PPSKGAVKEE KGGGGAEEEE
1510 1520 1530 1540 1550
EELWSDSEHN FLDENIGGVA VAPAHGSILI ECARRELHAT TPLKKPNRCH
1560 1570 1580 1590 1600
PTRISLVFYQ HKNLNQPNHG LALWEAKMKQ LAERARARQE EAARLGLGQQ
1610 1620 1630 1640 1650
EAKLYGKKRK WGGTVVAEPQ QKEKKGVVPT RQALAVPTDS AVTVSSYAYT
1660
KVTGPYSRWI
Length:1,660
Mass (Da):179,350
Last modified:June 10, 2008 - v3
Checksum:i181024BFAC9B54D2
GO
Isoform 2 (identifier: O43151-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1440-1555: Missing.

Note: No experimental confirmation available.
Show »
Length:1,544
Mass (Da):166,706
Checksum:iDD049A7E3E8C6941
GO
Isoform 3 (identifier: O43151-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     728-1660: Missing.

Note: No experimental confirmation available.
Show »
Length:727
Mass (Da):77,471
Checksum:i936458DE78E8F254
GO

Sequence cautioni

The sequence AAH22243 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAX93057 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence BAA23697 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_062235577R → Q.Corresponds to variant rs57955681dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_034192728 – 1660Missing in isoform 3. 1 PublicationAdd BLAST933
Alternative sequenceiVSP_0216281440 – 1555Missing in isoform 2. 1 PublicationAdd BLAST116

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC073263 Genomic DNA. Translation: AAX93057.1. Sequence problems.
AC110801 Genomic DNA. No translation available.
AF466365 mRNA. Translation: AAO33386.1.
BC022243 mRNA. Translation: AAH22243.1. Different initiation.
AB007861 mRNA. Translation: BAA23697.1. Different initiation.
UniGeneiHs.516107.

Genome annotation databases

EnsembliENST00000409262; ENSP00000386869; ENSG00000187605.
UCSCiuc002skb.6. human. [O43151-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC073263 Genomic DNA. Translation: AAX93057.1. Sequence problems.
AC110801 Genomic DNA. No translation available.
AF466365 mRNA. Translation: AAO33386.1.
BC022243 mRNA. Translation: AAH22243.1. Different initiation.
AB007861 mRNA. Translation: BAA23697.1. Different initiation.
UniGeneiHs.516107.

3D structure databases

ProteinModelPortaliO43151.
SMRiO43151.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128327. 6 interactors.
IntActiO43151. 27 interactors.
STRINGi9606.ENSP00000386869.

PTM databases

iPTMnetiO43151.
PhosphoSitePlusiO43151.

Polymorphism and mutation databases

BioMutaiTET3.

Proteomic databases

MaxQBiO43151.
PaxDbiO43151.
PeptideAtlasiO43151.
PRIDEiO43151.

Protocols and materials databases

DNASUi200424.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000409262; ENSP00000386869; ENSG00000187605.
UCSCiuc002skb.6. human. [O43151-1]

Organism-specific databases

DisGeNETi200424.
GeneCardsiTET3.
H-InvDBHIX0200247.
HGNCiHGNC:28313. TET3.
HPAiHPA050845.
MIMi613555. gene.
neXtProtiNX_O43151.
PharmGKBiPA162405645.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE22. Eukaryota.
ENOG410XPWW. LUCA.
HOGENOMiHOG000154550.
HOVERGENiHBG079550.
InParanoidiO43151.
OrthoDBiEOG091G007O.
PhylomeDBiO43151.
TreeFamiTF342373.

Enzyme and pathway databases

ReactomeiR-HSA-5221030. TET1,2,3 and TDG demethylate DNA.
SIGNORiO43151.

Miscellaneous databases

ChiTaRSiTET3. human.
PROiO43151.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187605.
CleanExiHS_TET3.
ExpressionAtlasiO43151. baseline and differential.
GenevisibleiO43151. HS.

Family and domain databases

InterProiIPR024779. 2OGFeDO_noxygenase_dom.
[Graphical view]
PfamiPF12851. Tet_JBP. 1 hit.
[Graphical view]
SMARTiSM01333. Tet_JBP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTET3_HUMAN
AccessioniPrimary (citable) accession number: O43151
Secondary accession number(s): A6NEI3, Q86Z24, Q8TBM9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: June 10, 2008
Last modified: November 30, 2016
This is version 112 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

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.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.