Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Methylcytosine dioxygenase TET1

Gene

TET1

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 active DNA demethylation. 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. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, plays a more general role in chromatin regulation. Preferentially binds to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes. 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. Also involved in transcription repression of a subset of genes through recruitment of transcriptional repressors to promoters. Involved in the balance between pluripotency and lineage commitment of cells it plays a role in embryonic stem cells maintenance and inner cell mass cell specification. Plays an important role in the tumorigenicity of glioblastoma cells. TET1-mediated production of 5hmC acts as a recruitment signal for the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of genes involved in glioblastomagenesis (PubMed:25284789).6 Publications

Catalytic activityi

DNA 5-methylcytosine + 2-oxoglutarate + O2 = DNA 5-hydroxymethylcytosine + succinate + CO2.2 Publications
DNA 5-hydroxymethylcytosine + 2-oxoglutarate + O2 = DNA 5-formylcytosine + succinate + CO2.1 Publication
DNA 5-formylcytosine + 2-oxoglutarate + O2 = DNA 5-carboxylcytosine + succinate + CO2.1 Publication

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1422Zinc 1By similarity1
Metal bindingi1424Zinc 1By similarity1
Metal bindingi1482Zinc 2By similarity1
Metal bindingi1508Zinc 1; via pros nitrogenBy similarity1
Metal bindingi1510Zinc 1By similarity1
Binding sitei15512-oxoglutarateBy similarity1
Metal bindingi1561Zinc 2By similarity1
Metal bindingi1563Zinc 2By similarity1
Metal bindingi1579Zinc 3By similarity1
Metal bindingi1588Zinc 3By similarity1
Metal bindingi1648Zinc 3By similarity1
Binding sitei16642-oxoglutarateBy similarity1
Metal bindingi1670Zinc 2; via tele nitrogenBy similarity1
Metal bindingi1672Iron; catalytic1
Metal bindingi1674Iron; catalytic1
Binding sitei1677SubstrateBy similarity1
Binding sitei17062-oxoglutarateBy similarity1
Metal bindingi2028Iron; catalyticBy similarity1
Metal bindingi2059Zinc 3; via pros nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri584 – 625CXXC-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

GO - Biological processi

  • 5-methylcytosine catabolic process Source: GO_Central
  • chromatin modification Source: UniProtKB-KW
  • DNA demethylation Source: UniProtKB
  • inner cell mass cell differentiation Source: UniProtKB
  • negative regulation of methylation-dependent chromatin silencing Source: UniProtKB
  • oxidative demethylation Source: GO_Central
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of histone methylation Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • protein O-linked glycosylation Source: UniProtKB
  • stem cell population maintenance Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Dioxygenase, Oxidoreductase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Iron, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000138336-MONOMER.
ReactomeiR-HSA-5221030. TET1,2,3 and TDG demethylate DNA.

Names & Taxonomyi

Protein namesi
Recommended name:
Methylcytosine dioxygenase TET1 (EC:1.14.11.n22 Publications)
Alternative name(s):
CXXC-type zinc finger protein 6
Leukemia-associated protein with a CXXC domain
Ten-eleven translocation 1 gene protein
Gene namesi
Name:TET1
Synonyms:CXXC6, KIAA1676, LCX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:29484. TET1.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving TET1 may be a cause of acute leukemias (PubMed:12646957). Translocation t(10;11)(q22;q23) with KMT2A/MLL1. This is a rare chromosomal translocation 5' KMT2A/MLL1-TET1 3' (PubMed:12124344, PubMed:12646957).

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1672H → Y: Loss of catalytic activity and loss of the ability to induce DNA demethylation. 2 Publications1
Mutagenesisi1674D → A: Loss of catalytic activity and loss of the ability to induce DNA demethylation. 2 Publications1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1608 – 1609Breakpoint for translocation to form KMT2A/MLL1-TET1 oncogene2

Organism-specific databases

DisGeNETi80312.
OpenTargetsiENSG00000138336.
PharmGKBiPA162405605.

Polymorphism and mutation databases

BioMutaiTET1.
DMDMi115502139.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002519491 – 2136Methylcytosine dioxygenase TET1Add BLAST2136

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei871PhosphoserineCombined sources1

Post-translational modificationi

Glycosylated. Interaction with OGT leads to GlcNAcylation (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ8NFU7.
PaxDbiQ8NFU7.
PeptideAtlasiQ8NFU7.
PRIDEiQ8NFU7.

PTM databases

iPTMnetiQ8NFU7.
PhosphoSitePlusiQ8NFU7.

Expressioni

Tissue specificityi

Expressed in fetal heart, lung and brain, and in adult skeletal muscle, thymus and ovary. Not detected in adult heart, lung or brain. Up-regulated in glioblastoma cells (at protein level) (PubMed:25284789).3 Publications

Gene expression databases

BgeeiENSG00000138336.
CleanExiHS_TET1.
GenevisibleiQ8NFU7. HS.

Organism-specific databases

HPAiCAB014886.
HPA019032.
HPA057273.

Interactioni

Subunit structurei

Interacts with HCFC1 and OGT (By similarity). Interacts with SIN3A; recruits the transcriptional corepressor SIN3A to gene promoters.By similarity1 Publication

Protein-protein interaction databases

BioGridi123225. 3 interactors.
IntActiQ8NFU7. 2 interactors.
STRINGi9606.ENSP00000362748.

Structurei

3D structure databases

ProteinModelPortaliQ8NFU7.
SMRiQ8NFU7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni528 – 674Sufficient for binding to genomic CpG islandsAdd BLAST147
Regioni1580 – 1593Interaction with DNABy similarityAdd BLAST14
Regioni2043 – 20452-oxoglutarate bindingBy similarity3
Regioni2049 – 2051Substrate bindingBy similarity3

Sequence similaritiesi

Belongs to the TET family.Curated
Contains 1 CXXC-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri584 – 625CXXC-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IE22. Eukaryota.
ENOG410XPWW. LUCA.
GeneTreeiENSGT00510000046514.
HOGENOMiHOG000154549.
InParanoidiQ8NFU7.
KOiK13097.
OMAiNQKAHPL.
OrthoDBiEOG091G007O.
PhylomeDBiQ8NFU7.
TreeFamiTF324004.

Family and domain databases

InterProiIPR024779. 2OGFeDO_noxygenase_dom.
IPR002857. Znf_CXXC.
[Graphical view]
PfamiPF12851. Tet_JBP. 1 hit.
PF02008. zf-CXXC. 1 hit.
[Graphical view]
SMARTiSM01333. Tet_JBP. 1 hit.
[Graphical view]
PROSITEiPS51058. ZF_CXXC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8NFU7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRSRHARPS RLVRKEDVNK KKKNSQLRKT TKGANKNVAS VKTLSPGKLK
60 70 80 90 100
QLIQERDVKK KTEPKPPVPV RSLLTRAGAA RMNLDRTEVL FQNPESLTCN
110 120 130 140 150
GFTMALRSTS LSRRLSQPPL VVAKSKKVPL SKGLEKQHDC DYKILPALGV
160 170 180 190 200
KHSENDSVPM QDTQVLPDIE TLIGVQNPSL LKGKSQETTQ FWSQRVEDSK
210 220 230 240 250
INIPTHSGPA AEILPGPLEG TRCGEGLFSE ETLNDTSGSP KMFAQDTVCA
260 270 280 290 300
PFPQRATPKV TSQGNPSIQL EELGSRVESL KLSDSYLDPI KSEHDCYPTS
310 320 330 340 350
SLNKVIPDLN LRNCLALGGS TSPTSVIKFL LAGSKQATLG AKPDHQEAFE
360 370 380 390 400
ATANQQEVSD TTSFLGQAFG AIPHQWELPG ADPVHGEALG ETPDLPEIPG
410 420 430 440 450
AIPVQGEVFG TILDQQETLG MSGSVVPDLP VFLPVPPNPI ATFNAPSKWP
460 470 480 490 500
EPQSTVSYGL AVQGAIQILP LGSGHTPQSS SNSEKNSLPP VMAISNVENE
510 520 530 540 550
KQVHISFLPA NTQGFPLAPE RGLFHASLGI AQLSQAGPSK SDRGSSQVSV
560 570 580 590 600
TSTVHVVNTT VVTMPVPMVS TSSSSYTTLL PTLEKKKRKR CGVCEPCQQK
610 620 630 640 650
TNCGECTYCK NRKNSHQICK KRKCEELKKK PSVVVPLEVI KENKRPQREK
660 670 680 690 700
KPKVLKADFD NKPVNGPKSE SMDYSRCGHG EEQKLELNPH TVENVTKNED
710 720 730 740 750
SMTGIEVEKW TQNKKSQLTD HVKGDFSANV PEAEKSKNSE VDKKRTKSPK
760 770 780 790 800
LFVQTVRNGI KHVHCLPAET NVSFKKFNIE EFGKTLENNS YKFLKDTANH
810 820 830 840 850
KNAMSSVATD MSCDHLKGRS NVLVFQQPGF NCSSIPHSSH SIINHHASIH
860 870 880 890 900
NEGDQPKTPE NIPSKEPKDG SPVQPSLLSL MKDRRLTLEQ VVAIEALTQL
910 920 930 940 950
SEAPSENSSP SKSEKDEESE QRTASLLNSC KAILYTVRKD LQDPNLQGEP
960 970 980 990 1000
PKLNHCPSLE KQSSCNTVVF NGQTTTLSNS HINSATNQAS TKSHEYSKVT
1010 1020 1030 1040 1050
NSLSLFIPKS NSSKIDTNKS IAQGIITLDN CSNDLHQLPP RNNEVEYCNQ
1060 1070 1080 1090 1100
LLDSSKKLDS DDLSCQDATH TQIEEDVATQ LTQLASIIKI NYIKPEDKKV
1110 1120 1130 1140 1150
ESTPTSLVTC NVQQKYNQEK GTIQQKPPSS VHNNHGSSLT KQKNPTQKKT
1160 1170 1180 1190 1200
KSTPSRDRRK KKPTVVSYQE NDRQKWEKLS YMYGTICDIW IASKFQNFGQ
1210 1220 1230 1240 1250
FCPHDFPTVF GKISSSTKIW KPLAQTRSIM QPKTVFPPLT QIKLQRYPES
1260 1270 1280 1290 1300
AEEKVKVEPL DSLSLFHLKT ESNGKAFTDK AYNSQVQLTV NANQKAHPLT
1310 1320 1330 1340 1350
QPSSPPNQCA NVMAGDDQIR FQQVVKEQLM HQRLPTLPGI SHETPLPESA
1360 1370 1380 1390 1400
LTLRNVNVVC SGGITVVSTK SEEEVCSSSF GTSEFSTVDS AQKNFNDYAM
1410 1420 1430 1440 1450
NFFTNPTKNL VSITKDSELP TCSCLDRVIQ KDKGPYYTHL GAGPSVAAVR
1460 1470 1480 1490 1500
EIMENRYGQK GNAIRIEIVV YTGKEGKSSH GCPIAKWVLR RSSDEEKVLC
1510 1520 1530 1540 1550
LVRQRTGHHC PTAVMVVLIM VWDGIPLPMA DRLYTELTEN LKSYNGHPTD
1560 1570 1580 1590 1600
RRCTLNENRT CTCQGIDPET CGASFSFGCS WSMYFNGCKF GRSPSPRRFR
1610 1620 1630 1640 1650
IDPSSPLHEK NLEDNLQSLA TRLAPIYKQY APVAYQNQVE YENVARECRL
1660 1670 1680 1690 1700
GSKEGRPFSG VTACLDFCAH PHRDIHNMNN GSTVVCTLTR EDNRSLGVIP
1710 1720 1730 1740 1750
QDEQLHVLPL YKLSDTDEFG SKEGMEAKIK SGAIEVLAPR RKKRTCFTQP
1760 1770 1780 1790 1800
VPRSGKKRAA MMTEVLAHKI RAVEKKPIPR IKRKNNSTTT NNSKPSSLPT
1810 1820 1830 1840 1850
LGSNTETVQP EVKSETEPHF ILKSSDNTKT YSLMPSAPHP VKEASPGFSW
1860 1870 1880 1890 1900
SPKTASATPA PLKNDATASC GFSERSSTPH CTMPSGRLSG ANAAAADGPG
1910 1920 1930 1940 1950
ISQLGEVAPL PTLSAPVMEP LINSEPSTGV TEPLTPHQPN HQPSFLTSPQ
1960 1970 1980 1990 2000
DLASSPMEED EQHSEADEPP SDEPLSDDPL SPAEEKLPHI DEYWSDSEHI
2010 2020 2030 2040 2050
FLDANIGGVA IAPAHGSVLI ECARRELHAT TPVEHPNRNH PTRLSLVFYQ
2060 2070 2080 2090 2100
HKNLNKPQHG FELNKIKFEA KEAKNKKMKA SEQKDQAANE GPEQSSEVNE
2110 2120 2130
LNQIPSHKAL TLTHDNVVTV SPYALTHVAG PYNHWV
Length:2,136
Mass (Da):235,309
Last modified:October 3, 2006 - v2
Checksum:i66E24EF0594A964C
GO

Sequence cautioni

The sequence CAD28467 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2001F → L in CAD28467 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027734162D → G.Corresponds to variant rs10823229dbSNPEnsembl.1
Natural variantiVAR_027735193S → T.Corresponds to variant rs12773594dbSNPEnsembl.1
Natural variantiVAR_027736256A → V.Corresponds to variant rs12221107dbSNPEnsembl.1
Natural variantiVAR_0277371018N → S.Corresponds to variant rs16925541dbSNPEnsembl.1
Natural variantiVAR_0277381123I → M.1 PublicationCorresponds to variant rs3998860dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF430147 mRNA. Translation: AAM88301.1.
AL513534, AL713888 Genomic DNA. Translation: CAH70220.1.
AL713888, AL513534 Genomic DNA. Translation: CAI15118.1.
AB051463 mRNA. Translation: BAB21767.1.
AL713658 mRNA. Translation: CAD28467.3. Sequence problems.
BC053905 mRNA. Translation: AAH53905.1.
CCDSiCCDS7281.1.
RefSeqiNP_085128.2. NM_030625.2.
UniGeneiHs.258855.
Hs.567594.
Hs.598166.
Hs.708977.

Genome annotation databases

EnsembliENST00000373644; ENSP00000362748; ENSG00000138336.
GeneIDi80312.
KEGGihsa:80312.
UCSCiuc001jok.5. human.

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF430147 mRNA. Translation: AAM88301.1.
AL513534, AL713888 Genomic DNA. Translation: CAH70220.1.
AL713888, AL513534 Genomic DNA. Translation: CAI15118.1.
AB051463 mRNA. Translation: BAB21767.1.
AL713658 mRNA. Translation: CAD28467.3. Sequence problems.
BC053905 mRNA. Translation: AAH53905.1.
CCDSiCCDS7281.1.
RefSeqiNP_085128.2. NM_030625.2.
UniGeneiHs.258855.
Hs.567594.
Hs.598166.
Hs.708977.

3D structure databases

ProteinModelPortaliQ8NFU7.
SMRiQ8NFU7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123225. 3 interactors.
IntActiQ8NFU7. 2 interactors.
STRINGi9606.ENSP00000362748.

PTM databases

iPTMnetiQ8NFU7.
PhosphoSitePlusiQ8NFU7.

Polymorphism and mutation databases

BioMutaiTET1.
DMDMi115502139.

Proteomic databases

EPDiQ8NFU7.
PaxDbiQ8NFU7.
PeptideAtlasiQ8NFU7.
PRIDEiQ8NFU7.

Protocols and materials databases

DNASUi80312.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373644; ENSP00000362748; ENSG00000138336.
GeneIDi80312.
KEGGihsa:80312.
UCSCiuc001jok.5. human.

Organism-specific databases

CTDi80312.
DisGeNETi80312.
GeneCardsiTET1.
HGNCiHGNC:29484. TET1.
HPAiCAB014886.
HPA019032.
HPA057273.
MIMi607790. gene.
neXtProtiNX_Q8NFU7.
OpenTargetsiENSG00000138336.
PharmGKBiPA162405605.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE22. Eukaryota.
ENOG410XPWW. LUCA.
GeneTreeiENSGT00510000046514.
HOGENOMiHOG000154549.
InParanoidiQ8NFU7.
KOiK13097.
OMAiNQKAHPL.
OrthoDBiEOG091G007O.
PhylomeDBiQ8NFU7.
TreeFamiTF324004.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000138336-MONOMER.
ReactomeiR-HSA-5221030. TET1,2,3 and TDG demethylate DNA.

Miscellaneous databases

ChiTaRSiTET1. human.
GeneWikiiTet_methylcytosine_dioxygenase_1.
GenomeRNAii80312.
PROiQ8NFU7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138336.
CleanExiHS_TET1.
GenevisibleiQ8NFU7. HS.

Family and domain databases

InterProiIPR024779. 2OGFeDO_noxygenase_dom.
IPR002857. Znf_CXXC.
[Graphical view]
PfamiPF12851. Tet_JBP. 1 hit.
PF02008. zf-CXXC. 1 hit.
[Graphical view]
SMARTiSM01333. Tet_JBP. 1 hit.
[Graphical view]
PROSITEiPS51058. ZF_CXXC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTET1_HUMAN
AccessioniPrimary (citable) accession number: Q8NFU7
Secondary accession number(s): Q5VUP7
, Q7Z6B6, Q8TCR1, Q9C0I7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: October 3, 2006
Last modified: November 30, 2016
This is version 114 of the entry and version 2 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 (PubMed:21496894). According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG and replacement by unmethylated cytosine.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: 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.