TET1_HUMAN
ID TET1_HUMAN Reviewed; 2136 AA.
AC Q8NFU7; Q5VUP7; Q7Z6B6; Q8TCR1; Q9C0I7;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Methylcytosine dioxygenase TET1;
DE EC=1.14.11.n2 {ECO:0000269|PubMed:19372391, ECO:0000269|PubMed:21496894};
DE AltName: Full=CXXC-type zinc finger protein 6;
DE AltName: Full=Leukemia-associated protein with a CXXC domain;
DE AltName: Full=Ten-eleven translocation 1 gene protein;
GN Name=TET1 {ECO:0000303|PubMed:28397838, ECO:0000312|HGNC:HGNC:29484};
GN Synonyms=CXXC6, KIAA1676, LCX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-1123, FUNCTION, TISSUE SPECIFICITY,
RP AND CHROMOSOMAL TRANSLOCATION WITH KMT2A/MLL1.
RC TISSUE=Leukemia;
RX PubMed=12124344;
RA Ono R., Taki T., Taketani T., Taniwaki M., Kobayashi H., Hayashi Y.;
RT "LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in
RT acute myeloid leukemia with trilineage dysplasia having
RT t(10;11)(q22;q23).";
RL Cancer Res. 62:4075-4080(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1402-2136.
RC TISSUE=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1665-2074.
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1809-2136.
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP CHROMOSOMAL TRANSLOCATION WITH KMT2A/MLL1, TISSUE SPECIFICITY, AND
RP INVOLVEMENT IN ACUTE LEUKEMIAS.
RX PubMed=12646957; DOI=10.1038/sj.leu.2402834;
RA Lorsbach R.B., Moore J., Mathew S., Raimondi S.C., Mukatira S.T.,
RA Downing J.R.;
RT "TET1, a member of a novel protein family, is fused to MLL in acute myeloid
RT leukemia containing the t(10;11)(q22;q23).";
RL Leukemia 17:637-641(2003).
RN [7]
RP FUNCTION.
RX PubMed=19372393; DOI=10.1126/science.1169786;
RA Kriaucionis S., Heintz N.;
RT "The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje
RT neurons and the brain.";
RL Science 324:929-930(2009).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, DNA-BINDING, COFACTOR, AND MUTAGENESIS OF
RP HIS-1672 AND ASP-1674.
RX PubMed=19372391; DOI=10.1126/science.1170116;
RA Tahiliani M., Koh K.P., Shen Y., Pastor W.A., Bandukwala H., Brudno Y.,
RA Agarwal S., Iyer L.M., Liu D.R., Aravind L., Rao A.;
RT "Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA
RT by the MLL fusion partner TET1.";
RL Science 324:930-935(2009).
RN [9]
RP FUNCTION IN DNA DEMETHYLATION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP HIS-1672 AND ASP-1674.
RX PubMed=21496894; DOI=10.1016/j.cell.2011.03.022;
RA Guo J.U., Su Y., Zhong C., Ming G.L., Song H.;
RT "Hydroxylation of 5-methylcytosine by TET1 promotes active DNA
RT demethylation in the adult brain.";
RL Cell 145:423-434(2011).
RN [10]
RP INTERACTION WITH SIN3A.
RX PubMed=21490601; DOI=10.1038/nature10066;
RA Williams K., Christensen J., Pedersen M.T., Johansen J.V., Cloos P.A.,
RA Rappsilber J., Helin K.;
RT "TET1 and hydroxymethylcytosine in transcription and DNA methylation
RT fidelity.";
RL Nature 473:343-348(2011).
RN [11]
RP FUNCTION.
RX PubMed=21778364; DOI=10.1126/science.1210597;
RA Ito S., Shen L., Dai Q., Wu S.C., Collins L.B., Swenberg J.A., He C.,
RA Zhang Y.;
RT "Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-
RT carboxylcytosine.";
RL Science 333:1300-1303(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-871, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25284789; DOI=10.1016/j.celrep.2014.08.071;
RA Takai H., Masuda K., Sato T., Sakaguchi Y., Suzuki T., Suzuki T.,
RA Koyama-Nasu R., Nasu-Nishimura Y., Katou Y., Ogawa H., Morishita Y.,
RA Kozuka-Hata H., Oyama M., Todo T., Ino Y., Mukasa A., Saito N.,
RA Toyoshima C., Shirahige K., Akiyama T.;
RT "5-Hydroxymethylcytosine plays a critical role in glioblastomagenesis by
RT recruiting the CHTOP-methylosome complex.";
RL Cell Rep. 9:48-60(2014).
RN [14]
RP FUNCTION IN DNA REPAIR.
RX PubMed=31278917; DOI=10.1016/j.taap.2019.114646;
RA Kuhns K.J., Lopez-Bertoni H., Coulter J.B., Bressler J.P.;
RT "TET1 regulates DNA repair in human glial cells.";
RL Toxicol. Appl. Pharmacol. 380:114646-114646(2019).
RN [15]
RP FUNCTION, INTERACTION WITH QSER1, AND SUBCELLULAR LOCATION.
RX PubMed=33833093; DOI=10.1126/science.abd0875;
RA Dixon G., Pan H., Yang D., Rosen B.P., Jashari T., Verma N., Pulecio J.,
RA Caspi I., Lee K., Stransky S., Glezer A., Liu C., Rivas M., Kumar R.,
RA Lan Y., Torregroza I., He C., Sidoli S., Evans T., Elemento O., Huangfu D.;
RT "QSER1 protects DNA methylation valleys from de novo methylation.";
RL Science 372:0-0(2021).
RN [16] {ECO:0007744|PDB:6ASD}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 587-632 IN COMPLEX WITH CPG DNA,
RP FUNCTION, DOMAIN CXXC-TYPE ZINC-FINGER, AND ZINC-BINDING.
RX PubMed=29276034; DOI=10.1016/j.str.2017.11.022;
RA Xu C., Liu K., Lei M., Yang A., Li Y., Hughes T.R., Min J.;
RT "DNA Sequence Recognition of Human CXXC Domains and Their Structural
RT Determinants.";
RL Structure 26:85-95.e3(2018).
RN [17]
RP VARIANT ASN-2056.
RX PubMed=28397838; DOI=10.1038/mp.2017.60;
RA Harripaul R., Vasli N., Mikhailov A., Rafiq M.A., Mittal K.,
RA Windpassinger C., Sheikh T.I., Noor A., Mahmood H., Downey S., Johnson M.,
RA Vleuten K., Bell L., Ilyas M., Khan F.S., Khan V., Moradi M., Ayaz M.,
RA Naeem F., Heidari A., Ahmed I., Ghadami S., Agha Z., Zeinali S., Qamar R.,
RA Mozhdehipanah H., John P., Mir A., Ansar M., French L., Ayub M.,
RA Vincent J.B.;
RT "Mapping autosomal recessive intellectual disability: combined microarray
RT and exome sequencing identifies 26 novel candidate genes in 192
RT consanguineous families.";
RL Mol. Psychiatry 23:973-984(2018).
CC -!- FUNCTION: Dioxygenase that catalyzes the conversion of the modified
CC genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC)
CC and plays a key role in active DNA demethylation (PubMed:19372391,
CC PubMed:21496894). Also mediates subsequent conversion of 5hmC into 5-
CC formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine
CC (5caC) (PubMed:21778364). In addition to its role in DNA demethylation,
CC plays a more general role in chromatin regulation by recruiting histone
CC modifying protein complexes to alter histone marks and chromatin
CC accessibility, leading to both activation and repression of gene
CC expression (PubMed:33833093). Plays therefore a role in many biological
CC processes and diseases, including stem cell maintenance, T and B-cell
CC development, inflammation regulation, genomic imprinting, neural
CC activity or DNA repair (PubMed:31278917). Involved in the balance
CC between pluripotency and lineage commitment of cells it plays a role in
CC embryonic stem cells maintenance and inner cell mass cell
CC specification. Plays an important role in the tumorigenicity of
CC glioblastoma cells. TET1-mediated production of 5hmC acts as a
CC recruitment signal for the CHTOP-methylosome complex to selective sites
CC on the chromosome, where it methylates H4R3 and activates the
CC transcription of genes involved in glioblastomagenesis
CC (PubMed:25284789). Binds preferentially to DNA containing cytidine-
CC phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C),
CC hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG
CC (PubMed:29276034). Plays an essential role in the protection and
CC maintenance of transcriptional and developmental programs together with
CC QSER1 to inhibit the binding of DNMT3A/3B and therefore de novo
CC methylation (PubMed:33833093). {ECO:0000269|PubMed:12124344,
CC ECO:0000269|PubMed:19372391, ECO:0000269|PubMed:19372393,
CC ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21778364,
CC ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:29276034,
CC ECO:0000269|PubMed:31278917, ECO:0000269|PubMed:33833093}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 5-methyl-2'-deoxycytidine in DNA + O2 = a
CC 5-hydroxymethyl-2'-deoxycytidine in DNA + CO2 + succinate;
CC Xref=Rhea:RHEA:52636, Rhea:RHEA-COMP:11370, Rhea:RHEA-COMP:13315,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:85454, ChEBI:CHEBI:136731;
CC EC=1.14.11.n2; Evidence={ECO:0000269|PubMed:19372391,
CC ECO:0000269|PubMed:21496894};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 5-hydroxymethyl-2'-deoxycytidine in DNA +
CC O2 = a 5-formyl-2'-deoxycytidine in DNA + CO2 + H2O + succinate;
CC Xref=Rhea:RHEA:53828, Rhea:RHEA-COMP:13315, Rhea:RHEA-COMP:13656,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:136731,
CC ChEBI:CHEBI:137731; Evidence={ECO:0000305|PubMed:21778364};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 5-formyl-2'-deoxycytidine in DNA + O2 = a
CC 5-carboxyl-2'-deoxycytidine in DNA + CO2 + H(+) + succinate;
CC Xref=Rhea:RHEA:53832, Rhea:RHEA-COMP:13656, Rhea:RHEA-COMP:13657,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:137731,
CC ChEBI:CHEBI:137732; Evidence={ECO:0000305|PubMed:21778364};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:19372391};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:19372391};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q6N021};
CC Note=Binds 3 zinc ions per subunit. The zinc ions have a structural
CC role. {ECO:0000250|UniProtKB:Q6N021};
CC -!- SUBUNIT: Interacts with HCFC1 and OGT (By similarity). Interacts with
CC SIN3A; recruits the transcriptional corepressor SIN3A to gene promoters
CC (PubMed:21490601). Found in a complex composed of at least SINHCAF,
CC SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1 (By similarity). Interacts
CC with QSER1 (PubMed:33833093). Interacts with NONO (via DNA-binding
CC domain); this interaction recruits TET1 to genomic loci (By
CC similarity). {ECO:0000250|UniProtKB:Q3URK3,
CC ECO:0000269|PubMed:21490601, ECO:0000269|PubMed:33833093}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Chromosome
CC {ECO:0000269|PubMed:33833093}.
CC -!- TISSUE SPECIFICITY: Expressed in fetal heart, lung and brain, and in
CC adult skeletal muscle, thymus and ovary. Not detected in adult heart,
CC lung or brain. Up-regulated in glioblastoma cells (at protein level)
CC (PubMed:25284789). {ECO:0000269|PubMed:12124344,
CC ECO:0000269|PubMed:12646957, ECO:0000269|PubMed:25284789}.
CC -!- DOMAIN: The CXXC zinc finger mediates binding to CpG-DNA.
CC {ECO:0000269|PubMed:29276034}.
CC -!- PTM: Glycosylated. Interaction with OGT leads to GlcNAcylation (By
CC similarity). {ECO:0000250|UniProtKB:Q3URK3}.
CC -!- DISEASE: Note=A chromosomal aberration involving TET1 may be a cause of
CC acute leukemias (PubMed:12646957). Translocation t(10;11)(q22;q23) with
CC KMT2A/MLL1. This is a rare chromosomal translocation 5' KMT2A/MLL1-TET1
CC 3' (PubMed:12124344, PubMed:12646957). {ECO:0000269|PubMed:12124344,
CC ECO:0000269|PubMed:12646957}.
CC -!- SIMILARITY: Belongs to the TET family. {ECO:0000305}.
CC -!- CAUTION: Subsequent steps in cytosine demethylation are subject to
CC discussion. According to a first model cytosine demethylation occurs
CC through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and
CC subsequent replacement by unmethylated cytosine by the base excision
CC repair system (PubMed:21496894). According to another model, cytosine
CC demethylation is rather mediated via conversion of 5hmC into 5fC and
CC 5caC, followed by excision by TDG and replacement by unmethylated
CC cytosine. {ECO:0000305|PubMed:21496894}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD28467.3; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; AF430147; AAM88301.1; -; mRNA.
DR EMBL; AL513534; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL713888; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB051463; BAB21767.1; -; mRNA.
DR EMBL; AL713658; CAD28467.3; ALT_SEQ; mRNA.
DR EMBL; BC053905; AAH53905.1; -; mRNA.
DR CCDS; CCDS7281.1; -.
DR RefSeq; NP_085128.2; NM_030625.2.
DR PDB; 6ASD; X-ray; 1.85 A; C=587-632.
DR PDBsum; 6ASD; -.
DR AlphaFoldDB; Q8NFU7; -.
DR SMR; Q8NFU7; -.
DR BioGRID; 123225; 15.
DR ComplexPortal; CPX-3323; SIN3A histone deacetylase complex, ES cell-specific variant.
DR IntAct; Q8NFU7; 4.
DR MINT; Q8NFU7; -.
DR STRING; 9606.ENSP00000362748; -.
DR BindingDB; Q8NFU7; -.
DR ChEMBL; CHEMBL4523402; -.
DR GlyGen; Q8NFU7; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q8NFU7; -.
DR PhosphoSitePlus; Q8NFU7; -.
DR BioMuta; TET1; -.
DR DMDM; 115502139; -.
DR EPD; Q8NFU7; -.
DR jPOST; Q8NFU7; -.
DR MassIVE; Q8NFU7; -.
DR PaxDb; Q8NFU7; -.
DR PeptideAtlas; Q8NFU7; -.
DR PRIDE; Q8NFU7; -.
DR ProteomicsDB; 73363; -.
DR Antibodypedia; 14634; 361 antibodies from 30 providers.
DR DNASU; 80312; -.
DR Ensembl; ENST00000373644.5; ENSP00000362748.4; ENSG00000138336.9.
DR GeneID; 80312; -.
DR KEGG; hsa:80312; -.
DR MANE-Select; ENST00000373644.5; ENSP00000362748.4; NM_030625.3; NP_085128.2.
DR UCSC; uc001jok.5; human.
DR CTD; 80312; -.
DR DisGeNET; 80312; -.
DR GeneCards; TET1; -.
DR HGNC; HGNC:29484; TET1.
DR HPA; ENSG00000138336; Tissue enhanced (brain).
DR MIM; 607790; gene.
DR neXtProt; NX_Q8NFU7; -.
DR OpenTargets; ENSG00000138336; -.
DR PharmGKB; PA162405605; -.
DR VEuPathDB; HostDB:ENSG00000138336; -.
DR eggNOG; ENOG502QURD; Eukaryota.
DR GeneTree; ENSGT00940000158935; -.
DR HOGENOM; CLU_001618_2_0_1; -.
DR InParanoid; Q8NFU7; -.
DR OMA; VKEQLMH; -.
DR OrthoDB; 29059at2759; -.
DR PhylomeDB; Q8NFU7; -.
DR TreeFam; TF324004; -.
DR PathwayCommons; Q8NFU7; -.
DR Reactome; R-HSA-5221030; TET1,2,3 and TDG demethylate DNA.
DR SignaLink; Q8NFU7; -.
DR SIGNOR; Q8NFU7; -.
DR BioGRID-ORCS; 80312; 11 hits in 1096 CRISPR screens.
DR ChiTaRS; TET1; human.
DR GeneWiki; Tet_methylcytosine_dioxygenase_1; -.
DR GenomeRNAi; 80312; -.
DR Pharos; Q8NFU7; Tbio.
DR PRO; PR:Q8NFU7; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q8NFU7; protein.
DR Bgee; ENSG00000138336; Expressed in ventricular zone and 118 other tissues.
DR Genevisible; Q8NFU7; HS.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016580; C:Sin3 complex; IC:ComplexPortal.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0008327; F:methyl-CpG binding; IDA:UniProtKB.
DR GO; GO:0070579; F:methylcytosine dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006211; P:5-methylcytosine catabolic process; IEA:InterPro.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0080111; P:DNA demethylation; IMP:UniProtKB.
DR GO; GO:0001826; P:inner cell mass cell differentiation; ISS:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IC:ComplexPortal.
DR GO; GO:0090310; P:negative regulation of DNA methylation-dependent heterochromatin assembly; IMP:UniProtKB.
DR GO; GO:1902455; P:negative regulation of stem cell population maintenance; IC:ComplexPortal.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IC:ComplexPortal.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0070989; P:oxidative demethylation; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0031062; P:positive regulation of histone methylation; IMP:UniProtKB.
DR GO; GO:1902459; P:positive regulation of stem cell population maintenance; IC:ComplexPortal.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006493; P:protein O-linked glycosylation; ISS:UniProtKB.
DR GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB.
DR InterPro; IPR024779; 2OGFeDO_noxygenase_dom.
DR InterPro; IPR040175; TET1/2/3.
DR InterPro; IPR002857; Znf_CXXC.
DR PANTHER; PTHR23358; PTHR23358; 1.
DR Pfam; PF12851; Tet_JBP; 1.
DR Pfam; PF02008; zf-CXXC; 1.
DR SMART; SM01333; Tet_JBP; 1.
DR PROSITE; PS51058; ZF_CXXC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Chromatin regulator; Chromosomal rearrangement;
KW Chromosome; Dioxygenase; DNA-binding; Glycoprotein; Iron; Metal-binding;
KW Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..2136
FT /note="Methylcytosine dioxygenase TET1"
FT /id="PRO_0000251949"
FT ZN_FING 584..625
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 528..674
FT /note="Sufficient for binding to genomic CpG islands"
FT REGION 712..746
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 849..876
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 899..923
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1119..1169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1580..1593
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT REGION 1774..1897
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1919..1984
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2074..2100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..24
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..44
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 713..746
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1119..1149
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1783..1811
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1849..1885
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1924..1955
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 591
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:6ASD"
FT BINDING 594
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:6ASD"
FT BINDING 597
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:6ASD"
FT BINDING 603
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:6ASD"
FT BINDING 606
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:6ASD"
FT BINDING 609
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:6ASD"
FT BINDING 619
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:6ASD"
FT BINDING 624
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:6ASD"
FT BINDING 1422
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1424
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1482
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1508
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1510
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1551
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1561
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1563
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1579
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1588
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1648
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1664
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1670
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1672
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21496894"
FT BINDING 1674
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21496894"
FT BINDING 1677
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1706
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 2028
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 2043..2045
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 2049..2051
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 2059
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT SITE 1608..1609
FT /note="Breakpoint for translocation to form KMT2A/MLL1-TET1
FT oncogene"
FT /evidence="ECO:0000269|PubMed:12124344"
FT MOD_RES 871
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 162
FT /note="D -> G (in dbSNP:rs10823229)"
FT /id="VAR_027734"
FT VARIANT 193
FT /note="S -> T (in dbSNP:rs12773594)"
FT /id="VAR_027735"
FT VARIANT 256
FT /note="A -> V (in dbSNP:rs12221107)"
FT /id="VAR_027736"
FT VARIANT 1018
FT /note="N -> S (in dbSNP:rs16925541)"
FT /id="VAR_027737"
FT VARIANT 1123
FT /note="I -> M (in dbSNP:rs3998860)"
FT /evidence="ECO:0000269|PubMed:12124344"
FT /id="VAR_027738"
FT VARIANT 2056
FT /note="K -> N (found in a consanguineous family with
FT intellectual disability; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28397838"
FT /id="VAR_080763"
FT MUTAGEN 1672
FT /note="H->Y: Loss of catalytic activity and loss of the
FT ability to induce DNA demethylation."
FT /evidence="ECO:0000269|PubMed:19372391,
FT ECO:0000269|PubMed:21496894"
FT MUTAGEN 1674
FT /note="D->A: Loss of catalytic activity and loss of the
FT ability to induce DNA demethylation."
FT /evidence="ECO:0000269|PubMed:19372391,
FT ECO:0000269|PubMed:21496894"
FT CONFLICT 2001
FT /note="F -> L (in Ref. 4; CAD28467)"
FT /evidence="ECO:0000305"
FT HELIX 595..598
FT /evidence="ECO:0007829|PDB:6ASD"
FT STRAND 604..606
FT /evidence="ECO:0007829|PDB:6ASD"
FT HELIX 607..610
FT /evidence="ECO:0007829|PDB:6ASD"
FT TURN 611..614
FT /evidence="ECO:0007829|PDB:6ASD"
FT TURN 620..622
FT /evidence="ECO:0007829|PDB:6ASD"
FT HELIX 625..628
FT /evidence="ECO:0007829|PDB:6ASD"
SQ SEQUENCE 2136 AA; 235309 MW; 66E24EF0594A964C CRC64;
MSRSRHARPS RLVRKEDVNK KKKNSQLRKT TKGANKNVAS VKTLSPGKLK QLIQERDVKK
KTEPKPPVPV RSLLTRAGAA RMNLDRTEVL FQNPESLTCN GFTMALRSTS LSRRLSQPPL
VVAKSKKVPL SKGLEKQHDC DYKILPALGV KHSENDSVPM QDTQVLPDIE TLIGVQNPSL
LKGKSQETTQ FWSQRVEDSK INIPTHSGPA AEILPGPLEG TRCGEGLFSE ETLNDTSGSP
KMFAQDTVCA PFPQRATPKV TSQGNPSIQL EELGSRVESL KLSDSYLDPI KSEHDCYPTS
SLNKVIPDLN LRNCLALGGS TSPTSVIKFL LAGSKQATLG AKPDHQEAFE ATANQQEVSD
TTSFLGQAFG AIPHQWELPG ADPVHGEALG ETPDLPEIPG AIPVQGEVFG TILDQQETLG
MSGSVVPDLP VFLPVPPNPI ATFNAPSKWP EPQSTVSYGL AVQGAIQILP LGSGHTPQSS
SNSEKNSLPP VMAISNVENE KQVHISFLPA NTQGFPLAPE RGLFHASLGI AQLSQAGPSK
SDRGSSQVSV TSTVHVVNTT VVTMPVPMVS TSSSSYTTLL PTLEKKKRKR CGVCEPCQQK
TNCGECTYCK NRKNSHQICK KRKCEELKKK PSVVVPLEVI KENKRPQREK KPKVLKADFD
NKPVNGPKSE SMDYSRCGHG EEQKLELNPH TVENVTKNED SMTGIEVEKW TQNKKSQLTD
HVKGDFSANV PEAEKSKNSE VDKKRTKSPK LFVQTVRNGI KHVHCLPAET NVSFKKFNIE
EFGKTLENNS YKFLKDTANH KNAMSSVATD MSCDHLKGRS NVLVFQQPGF NCSSIPHSSH
SIINHHASIH NEGDQPKTPE NIPSKEPKDG SPVQPSLLSL MKDRRLTLEQ VVAIEALTQL
SEAPSENSSP SKSEKDEESE QRTASLLNSC KAILYTVRKD LQDPNLQGEP PKLNHCPSLE
KQSSCNTVVF NGQTTTLSNS HINSATNQAS TKSHEYSKVT NSLSLFIPKS NSSKIDTNKS
IAQGIITLDN CSNDLHQLPP RNNEVEYCNQ LLDSSKKLDS DDLSCQDATH TQIEEDVATQ
LTQLASIIKI NYIKPEDKKV ESTPTSLVTC NVQQKYNQEK GTIQQKPPSS VHNNHGSSLT
KQKNPTQKKT KSTPSRDRRK KKPTVVSYQE NDRQKWEKLS YMYGTICDIW IASKFQNFGQ
FCPHDFPTVF GKISSSTKIW KPLAQTRSIM QPKTVFPPLT QIKLQRYPES AEEKVKVEPL
DSLSLFHLKT ESNGKAFTDK AYNSQVQLTV NANQKAHPLT QPSSPPNQCA NVMAGDDQIR
FQQVVKEQLM HQRLPTLPGI SHETPLPESA LTLRNVNVVC SGGITVVSTK SEEEVCSSSF
GTSEFSTVDS AQKNFNDYAM NFFTNPTKNL VSITKDSELP TCSCLDRVIQ KDKGPYYTHL
GAGPSVAAVR EIMENRYGQK GNAIRIEIVV YTGKEGKSSH GCPIAKWVLR RSSDEEKVLC
LVRQRTGHHC PTAVMVVLIM VWDGIPLPMA DRLYTELTEN LKSYNGHPTD RRCTLNENRT
CTCQGIDPET CGASFSFGCS WSMYFNGCKF GRSPSPRRFR IDPSSPLHEK NLEDNLQSLA
TRLAPIYKQY APVAYQNQVE YENVARECRL GSKEGRPFSG VTACLDFCAH PHRDIHNMNN
GSTVVCTLTR EDNRSLGVIP QDEQLHVLPL YKLSDTDEFG SKEGMEAKIK SGAIEVLAPR
RKKRTCFTQP VPRSGKKRAA MMTEVLAHKI RAVEKKPIPR IKRKNNSTTT NNSKPSSLPT
LGSNTETVQP EVKSETEPHF ILKSSDNTKT YSLMPSAPHP VKEASPGFSW SPKTASATPA
PLKNDATASC GFSERSSTPH CTMPSGRLSG ANAAAADGPG ISQLGEVAPL PTLSAPVMEP
LINSEPSTGV TEPLTPHQPN HQPSFLTSPQ DLASSPMEED EQHSEADEPP SDEPLSDDPL
SPAEEKLPHI DEYWSDSEHI FLDANIGGVA IAPAHGSVLI ECARRELHAT TPVEHPNRNH
PTRLSLVFYQ HKNLNKPQHG FELNKIKFEA KEAKNKKMKA SEQKDQAANE GPEQSSEVNE
LNQIPSHKAL TLTHDNVVTV SPYALTHVAG PYNHWV
