TET1_MOUSE
ID TET1_MOUSE Reviewed; 2007 AA.
AC Q3URK3; Q6ZPK2; Q9CY36;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Methylcytosine dioxygenase TET1;
DE EC=1.14.11.n2 {ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:21778364};
DE AltName: Full=CXXC-type zinc finger protein 6;
DE AltName: Full=Ten-eleven translocation 1 gene protein homolog;
GN Name=Tet1; Synonyms=Cxxc6, Kiaa1676;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 655-1066 AND 1773-2007.
RC STRAIN=C57BL/6J; TISSUE=Liver, and Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1351-1946.
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF HIS-1620 AND ASP-1622.
RX PubMed=20639862; DOI=10.1038/nature09303;
RA Ito S., D'Alessio A.C., Taranova O.V., Hong K., Sowers L.C., Zhang Y.;
RT "Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and
RT inner cell mass specification.";
RL Nature 466:1129-1133(2010).
RN [5]
RP FUNCTION IN DNA DEMETHYLATION.
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 [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=21816367; DOI=10.1016/j.stem.2011.07.010;
RA Dawlaty M.M., Ganz K., Powell B.E., Hu Y.C., Markoulaki S., Cheng A.W.,
RA Gao Q., Kim J., Choi S.W., Page D.C., Jaenisch R.;
RT "Tet1 is dispensable for maintaining pluripotency and its loss is
RT compatible with embryonic and postnatal development.";
RL Cell Stem Cell 9:166-175(2011).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=23352810; DOI=10.1016/j.devcel.2012.12.015;
RA Dawlaty M.M., Breiling A., Le T., Raddatz G., Barrasa M.I., Cheng A.W.,
RA Gao Q., Powell B.E., Li Z., Xu M., Faull K.F., Lyko F., Jaenisch R.;
RT "Combined deficiency of tet1 and tet2 causes epigenetic abnormalities but
RT is compatible with postnatal development.";
RL Dev. Cell 24:310-323(2013).
RN [8]
RP FUNCTION.
RX PubMed=21514197; DOI=10.1016/j.molcel.2011.04.005;
RA Xu Y., Wu F., Tan L., Kong L., Xiong L., Deng J., Barbera A.J., Zheng L.,
RA Zhang H., Huang S., Min J., Nicholson T., Chen T., Xu G., Shi Y., Zhang K.,
RA Shi Y.G.;
RT "Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1
RT hydroxylase in mouse embryonic stem cells.";
RL Mol. Cell 42:451-464(2011).
RN [9]
RP FUNCTION IN TRANSCRIPTIONAL REPRESSION, AND 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 [10]
RP FUNCTION IN TRANSCRIPTIONAL REPRESSION.
RX PubMed=21451524; DOI=10.1038/nature09934;
RA Wu H., D'Alessio A.C., Ito S., Xia K., Wang Z., Cui K., Zhao K.,
RA Eve Sun Y., Zhang Y.;
RT "Dual functions of Tet1 in transcriptional regulation in mouse embryonic
RT stem cells.";
RL Nature 473:389-393(2011).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-1620 AND ASP-1622.
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 FUNCTION, INTERACTION WITH OGT AND HCFC1, AND GLYCOSYLATION.
RX PubMed=23352454; DOI=10.1016/j.molcel.2012.12.019;
RA Vella P., Scelfo A., Jammula S., Chiacchiera F., Williams K., Cuomo A.,
RA Roberto A., Christensen J., Bonaldi T., Helin K., Pasini D.;
RT "Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to
RT chromatin in embryonic stem cells.";
RL Mol. Cell 49:645-656(2013).
RN [13]
RP FUNCTION.
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 IDENTIFICATION IN A COMPLEX WITH SIN3A; SINHCAF; HDAC1; RBBP4; SAP30 AND
RP OGT.
RX PubMed=28554894; DOI=10.15252/embj.201696307;
RA Streubel G., Fitzpatrick D.J., Oliviero G., Scelfo A., Moran B., Das S.,
RA Munawar N., Watson A., Wynne K., Negri G.L., Dillon E.T., Jammula S.,
RA Hokamp K., O'Connor D.P., Pasini D., Cagney G., Bracken A.P.;
RT "Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells
RT required for self-renewal.";
RL EMBO J. 36:2216-2232(2017).
RN [15]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28504700; DOI=10.1038/ng.3868;
RA Khoueiry R., Sohni A., Thienpont B., Luo X., Velde J.V., Bartoccetti M.,
RA Boeckx B., Zwijsen A., Rao A., Lambrechts D., Koh K.P.;
RT "Lineage-specific functions of TET1 in the postimplantation mouse embryo.";
RL Nat. Genet. 49:1061-1072(2017).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31089182; DOI=10.1038/s41598-019-43767-6;
RA Burleson J.D., Siniard D., Yadagiri V.K., Chen X., Weirauch M.T.,
RA Ruff B.P., Brandt E.B., Hershey G.K.K., Ji H.;
RT "TET1 contributes to allergic airway inflammation and regulates interferon
RT and aryl hydrocarbon receptor signaling pathways in bronchial epithelial
RT cells.";
RL Sci. Rep. 9:7361-7361(2019).
RN [17]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32855402; DOI=10.1038/s41467-020-18054-y;
RA Damal Villivalam S., You D., Kim J., Lim H.W., Xiao H., Zushin P.H.,
RA Oguri Y., Amin P., Kang S.;
RT "TET1 is a beige adipocyte-selective epigenetic suppressor of
RT thermogenesis.";
RL Nat. Commun. 11:4313-4313(2020).
RN [18]
RP FUNCTION, INTERACTION WITH NONO, AND SUBCELLULAR LOCATION.
RX PubMed=32286661; DOI=10.1093/nar/gkaa213;
RA Li W., Karwacki-Neisius V., Ma C., Tan L., Shi Y., Wu F., Shi Y.G.;
RT "Nono deficiency compromises TET1 chromatin association and impedes
RT neuronal differentiation of mouse embryonic stem cells.";
RL Nucleic Acids Res. 48:4827-4838(2020).
RN [19]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=33895792; DOI=10.1182/blood.2020008986;
RA Jiang L., Wang J., Wang K., Wang H., Wu Q., Yang C., Yu Y., Ni P.,
RA Zhong Y., Song Z., Xie E., Hu R., Min J., Wang F.;
RT "RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity
RT by modulating ferroportin degradation.";
RL Blood 138:689-705(2021).
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:21496894).
CC Also mediates subsequent conversion of 5hmC into 5-formylcytosine
CC (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC)
CC (PubMed:21778364). In addition to its role in DNA demethylation, plays
CC 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:28504700, PubMed:32286661). Plays therefore a role
CC in many biological processes and diseases, including stem cell
CC maintenance, T and B-cell development, inflammation regulation, iron
CC homeostasis, neural activity or DNA repair (PubMed:31089182,
CC PubMed:32855402, PubMed:33895792). Involved in the balance between
CC pluripotency and lineage commitment of cells it plays a role in
CC embryonic stem cells maintenance and inner cell mass cell specification
CC (PubMed:28504700). 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 (By
CC similarity). Plays an essential role in the protection and maintenance
CC of transcriptional and developmental programs together with QSER1 to
CC inhibit the binding of DNMT3A/3B and therefore de novo methylation (By
CC similarity). {ECO:0000250|UniProtKB:Q8NFU7,
CC ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:21451524,
CC ECO:0000269|PubMed:21490601, ECO:0000269|PubMed:21496894,
CC ECO:0000269|PubMed:21514197, ECO:0000269|PubMed:21778364,
CC ECO:0000269|PubMed:23352454, ECO:0000269|PubMed:25284789,
CC ECO:0000269|PubMed:28504700, ECO:0000269|PubMed:31089182,
CC ECO:0000269|PubMed:32286661, ECO:0000269|PubMed:32855402,
CC ECO:0000269|PubMed:33895792}.
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:20639862,
CC ECO:0000269|PubMed:21778364};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q6N021};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q6N021};
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 SIN3A; recruits the transcriptional co-
CC repressor SIN3A to gene promoters (PubMed:21490601). Interacts with
CC HCFC1 and OGT (PubMed:23352454). Found in a complex composed of at
CC least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1
CC (PubMed:28554894). Interacts with QSER1 (By similarity). Interacts with
CC NONO (via DNA-binding domain); this interaction recruits TET1 to
CC genomic loci (PubMed:32286661). {ECO:0000250|UniProtKB:Q8NFU7,
CC ECO:0000269|PubMed:21490601, ECO:0000269|PubMed:23352454,
CC ECO:0000269|PubMed:28554894, ECO:0000269|PubMed:32286661}.
CC -!- INTERACTION:
CC Q3URK3; Q60520: Sin3a; NbExp=2; IntAct=EBI-4291699, EBI-349034;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20639862}. Chromosome
CC {ECO:0000269|PubMed:32286661}.
CC -!- TISSUE SPECIFICITY: Present in embryonic stem cells (ES cells) when its
CC paralogs TET2 and TET3 are not detectably expressed.
CC {ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:28504700}.
CC -!- DOMAIN: The CXXC zinc finger mediates binding to CpG-DNA.
CC {ECO:0000250|UniProtKB:Q8NFU7}.
CC -!- PTM: Glycosylated. Interaction with OGT leads to GlcNAcylation.
CC {ECO:0000269|PubMed:23352454}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype; mice are viable, fertile
CC and grossly normal, although some mice have a slightly smaller body
CC size at birth. Embryonic stem cells (ESCs) have reduced levels of 5-
CC hydroxymethylcytosine (5hmC) and slight changes in global gene
CC expression, but are pluripotent and support development. However,
CC deletion mice have an altered response to iron overload
CC (PubMed:33895792). Mice lacking both Tet1 and Tet2 are fertile, with
CC females having smaller ovaries and reduced fertility. They display
CC decreased 5hmC and abnormal methylation at various imprinted loci. ESCs
CC lacking both Tet1 and Tet2 remain pluripotent but lack 5hmC, leading to
CC developmental defects in chimeric embryos.
CC {ECO:0000269|PubMed:21816367, ECO:0000269|PubMed:23352810}.
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. {ECO:0000305|PubMed:21496894}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB27288.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC98231.1; Type=Miscellaneous discrepancy; Note=Partially unspliced pre-RNA.; Evidence={ECO:0000305};
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DR EMBL; AC166359; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK010953; BAB27288.1; ALT_INIT; mRNA.
DR EMBL; AK141438; BAE24685.1; -; mRNA.
DR EMBL; AK129421; BAC98231.1; ALT_SEQ; Transcribed_RNA.
DR RefSeq; NP_081660.1; NM_027384.1.
DR AlphaFoldDB; Q3URK3; -.
DR SMR; Q3URK3; -.
DR BioGRID; 206599; 12.
DR ComplexPortal; CPX-3441; SIN3A histone deacetylase complex, ES cell-specific variant.
DR IntAct; Q3URK3; 9.
DR STRING; 10090.ENSMUSP00000133279; -.
DR iPTMnet; Q3URK3; -.
DR PhosphoSitePlus; Q3URK3; -.
DR PaxDb; Q3URK3; -.
DR PeptideAtlas; Q3URK3; -.
DR PRIDE; Q3URK3; -.
DR ProteomicsDB; 262871; -.
DR Antibodypedia; 14634; 361 antibodies from 30 providers.
DR Ensembl; ENSMUST00000050826; ENSMUSP00000059527; ENSMUSG00000047146.
DR UCSC; uc007fje.2; mouse.
DR MGI; MGI:1098693; Tet1.
DR VEuPathDB; HostDB:ENSMUSG00000047146; -.
DR eggNOG; ENOG502QURD; Eukaryota.
DR GeneTree; ENSGT00940000158935; -.
DR InParanoid; Q3URK3; -.
DR OMA; VKEQLMH; -.
DR OrthoDB; 29059at2759; -.
DR PhylomeDB; Q3URK3; -.
DR BioGRID-ORCS; 52463; 0 hits in 77 CRISPR screens.
DR ChiTaRS; Tet1; mouse.
DR PRO; PR:Q3URK3; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q3URK3; protein.
DR Bgee; ENSMUSG00000047146; Expressed in trophoblast giant cell and 221 other tissues.
DR ExpressionAtlas; Q3URK3; baseline and differential.
DR Genevisible; Q3URK3; MM.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016580; C:Sin3 complex; IC:ComplexPortal.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0008327; F:methyl-CpG binding; ISS:UniProtKB.
DR GO; GO:0070579; F:methylcytosine dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS: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:0048813; P:dendrite morphogenesis; IMP:CACAO.
DR GO; GO:0080111; P:DNA demethylation; IDA:MGI.
DR GO; GO:0001826; P:inner cell mass cell differentiation; IMP: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; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0031062; P:positive regulation of histone methylation; ISS: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; IMP:UniProtKB.
DR GO; GO:0006493; P:protein O-linked glycosylation; IMP:UniProtKB.
DR GO; GO:0044030; P:regulation of DNA methylation; IMP:MGI.
DR GO; GO:2000653; P:regulation of genetic imprinting; IMP:MGI.
DR GO; GO:0019827; P:stem cell population maintenance; IMP: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 Activator; Chromatin regulator; Chromosome; Dioxygenase; DNA-binding;
KW Glycoprotein; Iron; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Zinc; Zinc-finger.
FT CHAIN 1..2007
FT /note="Methylcytosine dioxygenase TET1"
FT /id="PRO_0000377549"
FT ZN_FING 567..608
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 227..286
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 512..657
FT /note="Sufficient for binding to genomic CpG islands"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT REGION 613..670
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 711..735
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 820..859
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 882..906
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 964..993
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1050..1129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1209..1240
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1322..1341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1528..1541
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT REGION 1702..1728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1798..1869
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..65
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 148..168
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..284
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 625..640
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 655..670
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 713..735
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 821..835
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1050..1064
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1077..1092
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1094..1114
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1115..1129
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1215..1240
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1714..1728
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1814..1844
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1845..1867
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 574
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 577
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 580
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 586
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 589
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 592
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 602
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 607
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 1371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1373
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1430
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1456
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1458
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1499
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1509
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1511
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1527
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1536
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1596
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1612
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1618
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1620
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1622
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1625
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1653
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1907
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1922..1924
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1928..1930
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1938
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT MOD_RES 854
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU7"
FT MUTAGEN 1620
FT /note="H->Y: Loss of enzyme activity; when associated with
FT A-1622."
FT /evidence="ECO:0000269|PubMed:20639862,
FT ECO:0000269|PubMed:21778364"
FT MUTAGEN 1622
FT /note="D->A: Loss of enzyme activity; when associated with
FT Y-1620."
FT /evidence="ECO:0000269|PubMed:20639862,
FT ECO:0000269|PubMed:21778364"
SQ SEQUENCE 2007 AA; 219261 MW; C563672511ACFFC6 CRC64;
MSRSRPAKPS KSVKTKLQKK KDIQMKTKTS KQAVRHGASA KAVNPGKPKQ LIKRRDGKKE
TEDKTPTPAP SFLTRAGAAR MNRDRNQVLF QNPDSLTCNG FTMALRRTSL SWRLSQRPVV
TPKPKKVPPS KKQCTHNIQD EPGVKHSEND SVPSQHATVS PGTENGEQNR CLVEGESQEI
TQSCPVFEER IEDTQSCISA SGNLEAEISW PLEGTHCEEL LSHQTSDNEC TSPQECAPLP
QRSTSEVTSQ KNTSNQLADL SSQVESIKLS DPSPNPTGSD HNGFPDSSFR IVPELDLKTC
MPLDESVYPT ALIRFILAGS QPDVFDTKPQ EKTLITTPEQ VGSHPNQVLD ATSVLGQAFS
TLPLQWGFSG ANLVQVEALG KGSDSPEDLG AITMLNQQET VAMDMDRNAT PDLPIFLPKP
PNTVATYSSP LLGPEPHSST SCGLEVQGAT PILTLDSGHT PQLPPNPESS SVPLVIAANG
TRAEKQFGTS LFPAVPQGFT VAAENEVQHA PLDLTQGSQA APSKLEGEIS RVSITGSADV
KATAMSMPVT QASTSSPPCN STPPMVERRK RKACGVCEPC QQKANCGECT YCKNRKNSHQ
ICKKRKCEVL KKKPEATSQA QVTKENKRPQ REKKPKVLKT DFNNKPVNGP KSESMDCSRR
GHGEEEQRLD LITHPLENVR KNAGGMTGIE VEKWAPNKKS HLAEGQVKGS CDANLTGVEN
PQPSEDDKQQ TNPSPTFAQT IRNGMKNVHC LPTDTHLPLN KLNHEEFSKA LGNNSSKLLT
DPSNCKDAMS VTTSGGECDH LKGPRNTLLF QKPGLNCRSG AEPTIFNNHP NTHSAGSRPH
PPEKVPNKEP KDGSPVQPSL LSLMKDRRLT LEQVVAIEAL TQLSEAPSES SSPSKPEKDE
EAHQKTASLL NSCKAILHSV RKDLQDPNVQ GKGLHHDTVV FNGQNRTFKS PDSFATNQAL
IKSQGYPSSP TAEKKGAAGG RAPFDGFENS HPLPIESHNL ENCSQVLSCD QNLSSHDPSC
QDAPYSQIEE DVAAQLTQLA STINHINAEV RNAESTPESL VAKNTKQKHS QEKRMVHQKP
PSSTQTKPSV PSAKPKKAQK KARATPHANK RKKKPPARSS QENDQKKQEQ LAIEYSKMHD
IWMSSKFQRF GQSSPRSFPV LLRNIPVFNQ ILKPVTQSKT PSQHNELFPP INQIKFTRNP
ELAKEKVKVE PSDSLPTCQF KTESGGQTFA EPADNSQGQP MVSVNQEAHP LPQSPPSNQC
ANIMAGAAQT QFHLGAQENL VHQIPPPTLP GTSPDTLLPD PASILRKGKV LHFDGITVVT
EKREAQTSSN GPLGPTTDSA QSEFKESIMD LLSKPAKNLI AGLKEQEAAP CDCDGGTQKE
KGPYYTHLGA GPSVAAVREL METRFGQKGK AIRIEKIVFT GKEGKSSQGC PVAKWVIRRS
GPEEKLICLV RERVDHHCST AVIVVLILLW EGIPRLMADR LYKELTENLR SYSGHPTDRR
CTLNKKRTCT CQGIDPKTCG ASFSFGCSWS MYFNGCKFGR SENPRKFRLA PNYPLHEKQL
EKNLQELATV LAPLYKQMAP VAYQNQVEYE EVAGDCRLGN EEGRPFSGVT CCMDFCAHSH
KDIHNMHNGS TVVCTLIRAD GRDTNCPEDE QLHVLPLYRL ADTDEFGSVE GMKAKIKSGA
IQVNGPTRKR RLRFTEPVPR CGKRAKMKQN HNKSGSHNTK SFSSASSTSH LVKDESTDFC
PLQASSAETS TCTYSKTASG GFAETSSILH CTMPSGAHSG ANAAAGECTG TVQPAEVAAH
PHQSLPTADS PVHAEPLTSP SEQLTSNQSN QQLPLLSNSQ KLASCQVEDE RHPEADEPQH
PEDDNLPQLD EFWSDSEEIY ADPSFGGVAI APIHGSVLIE CARKELHATT SLRSPKRGVP
FRVSLVFYQH KSLNKPNHGF DINKIKCKCK KVTKKKPADR ECPDVSPEAN LSHQIPSRVA
STLTRDNVVT VSPYSLTHVA GPYNRWV
