TET2_MOUSE
ID TET2_MOUSE Reviewed; 1912 AA.
AC Q4JK59; Q3U5R5; Q3U633; Q3UAI0; Q6ZPN2; Q8K2K3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 3.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Methylcytosine dioxygenase TET2;
DE EC=1.14.11.n2 {ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:21057493, ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:21817016};
DE AltName: Full=Protein Ayu17-449;
GN Name=Tet2; Synonyms=Kiaa1546;
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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=16722336; DOI=10.1016/s0379-4172(06)60068-1;
RA Tang H., Araki K., Yamamura K.;
RT "Cloning and expression analysis of a murine novel gene, Ayu17-449.";
RL Yi Chuan Xue Bao 33:413-419(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 877-1912 (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15 AND SER-23, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP HIS-1295 AND ASP-1297.
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TRP-1204; PRO-1280;
RP HIS-1795; ARG-1810 AND CYS-1827.
RX PubMed=21057493; DOI=10.1038/nature09586;
RA Ko M., Huang Y., Jankowska A.M., Pape U.J., Tahiliani M., Bandukwala H.S.,
RA An J., Lamperti E.D., Koh K.P., Ganetzky R., Liu X.S., Aravind L.,
RA Agarwal S., Maciejewski J.P., Rao A.;
RT "Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant
RT TET2.";
RL Nature 468:839-843(2010).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=21803851; DOI=10.1182/blood-2010-12-325241;
RA Li Z., Cai X., Cai C.L., Wang J., Zhang W., Petersen B.E., Yang F.C.,
RA Xu M.;
RT "Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells
RT and subsequent development of myeloid malignancies.";
RL Blood 118:4509-4518(2011).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=21723200; DOI=10.1016/j.ccr.2011.06.001;
RA Moran-Crusio K., Reavie L., Shih A., Abdel-Wahab O., Ndiaye-Lobry D.,
RA Lobry C., Figueroa M.E., Vasanthakumar A., Patel J., Zhao X., Perna F.,
RA Pandey S., Madzo J., Song C., Dai Q., He C., Ibrahim S., Beran M.,
RA Zavadil J., Nimer S.D., Melnick A., Godley L.A., Aifantis I., Levine R.L.;
RT "Tet2 loss leads to increased hematopoietic stem cell self-renewal and
RT myeloid transformation.";
RL Cancer Cell 20:11-24(2011).
RN [10]
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 [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-1295 AND ASP-1297.
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, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-1295 AND ASP-1297.
RX PubMed=21817016; DOI=10.1126/science.1210944;
RA He Y.F., Li B.Z., Li Z., Liu P., Wang Y., Tang Q., Ding J., Jia Y.,
RA Chen Z., Li L., Sun Y., Li X., Dai Q., Song C.X., Zhang K., He C., Xu G.L.;
RT "Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in
RT mammalian DNA.";
RL Science 333:1303-1307(2011).
RN [13]
RP FUNCTION.
RX PubMed=23353889; DOI=10.1038/emboj.2012.357;
RA Deplus R., Delatte B., Schwinn M.K., Defrance M., Mendez J., Murphy N.,
RA Dawson M.A., Volkmar M., Putmans P., Calonne E., Shih A.H., Levine R.L.,
RA Bernard O., Mercher T., Solary E., Urh M., Daniels D.L., Fuks F.;
RT "TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and
RT SET1/COMPASS.";
RL EMBO J. 32:645-655(2013).
RN [14]
RP FUNCTION, INTERACTION WITH OGT, 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).
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. Has a preference for
CC 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent
CC conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC
CC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC
CC probably constitutes the first step in cytosine demethylation.
CC Methylation at the C5 position of cytosine bases is an epigenetic
CC modification of the mammalian genome which plays an important role in
CC transcriptional regulation. In addition to its role in DNA
CC demethylation, also involved in the recruitment of the O-GlcNAc
CC transferase OGT to CpG-rich transcription start sites of active genes,
CC thereby promoting histone H2B GlcNAcylation by OGT.
CC {ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:21057493,
CC ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:21817016,
CC ECO:0000269|PubMed:23352454, ECO:0000269|PubMed:23353889}.
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:21057493, ECO:0000269|PubMed:21778364,
CC ECO:0000269|PubMed:21817016};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52637;
CC Evidence={ECO:0000250|UniProtKB:Q6N021};
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 HCFC1 (By similarity). Interacts with OGT.
CC {ECO:0000250|UniProtKB:Q6N021, ECO:0000269|PubMed:23352454}.
CC -!- INTERACTION:
CC Q4JK59; Q8CGY8: Ogt; NbExp=2; IntAct=EBI-4291768, EBI-928496;
CC Q4JK59; P22561: Wt1; NbExp=2; IntAct=EBI-4291768, EBI-8327829;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q4JK59-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4JK59-2; Sequence=VSP_032287;
CC Name=3;
CC IsoId=Q4JK59-3; Sequence=VSP_032286;
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, kidney, heart, lung,
CC muscle and stomach. Present in embryonic stem cells (ES cells).
CC {ECO:0000269|PubMed:16722336, ECO:0000269|PubMed:20639862}.
CC -!- PTM: May be glycosylated. It is unclear whether interaction with OGT
CC leads to GlcNAcylation. According to a report, it is GlcNAcylated by
CC OGT (PubMed:23352454). In contrast, another group reports no
CC GlcNAcylation by OGT in human ortholog. {ECO:0000269|PubMed:23352454}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile but develop chronic
CC myelomonocytic leukemia probably caused by dysregulation of
CC hematopoietic stem cells. Mice lacking both Tet1 and Tet2 are fertile,
CC with females having smaller ovaries and reduced fertility. They display
CC decreased 5-hydroxymethylcytosine (5hmC) and abnormal methylation at
CC various imprinted loci. Embryonic stem cells lacking both Tet1 and Tet2
CC remain pluripotent but lack 5hmC, leading to developmental defects in
CC chimeric embryos. {ECO:0000269|PubMed:21723200,
CC ECO:0000269|PubMed:21803851, 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. According to another model, cytosine demethylation is
CC rather mediated via conversion of 5hmC into 5fC and 5caC, followed by
CC excision by TDG (PubMed:21817016). {ECO:0000305|PubMed:21817016}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY90126.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC98199.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE30334.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE30334.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAE31106.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE31842.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE31892.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE32012.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; DQ079067; AAY90126.1; ALT_FRAME; mRNA.
DR EMBL; AK129389; BAC98199.1; ALT_INIT; mRNA.
DR EMBL; BC031159; AAH31159.1; -; mRNA.
DR EMBL; BC040785; AAH40785.1; -; mRNA.
DR EMBL; AK151359; BAE30334.1; ALT_SEQ; mRNA.
DR EMBL; AK152297; BAE31106.1; ALT_INIT; mRNA.
DR EMBL; AK153251; BAE31842.1; ALT_INIT; mRNA.
DR EMBL; AK153311; BAE31892.1; ALT_INIT; mRNA.
DR EMBL; AK153460; BAE32012.1; ALT_INIT; mRNA.
DR CCDS; CCDS51071.1; -. [Q4JK59-1]
DR RefSeq; NP_001035490.2; NM_001040400.2. [Q4JK59-1]
DR RefSeq; NP_001333665.1; NM_001346736.1.
DR AlphaFoldDB; Q4JK59; -.
DR SMR; Q4JK59; -.
DR BioGRID; 229496; 13.
DR IntAct; Q4JK59; 4.
DR MINT; Q4JK59; -.
DR STRING; 10090.ENSMUSP00000096203; -.
DR iPTMnet; Q4JK59; -.
DR PhosphoSitePlus; Q4JK59; -.
DR SwissPalm; Q4JK59; -.
DR EPD; Q4JK59; -.
DR MaxQB; Q4JK59; -.
DR PaxDb; Q4JK59; -.
DR PeptideAtlas; Q4JK59; -.
DR PRIDE; Q4JK59; -.
DR ProteomicsDB; 262757; -. [Q4JK59-1]
DR ProteomicsDB; 262758; -. [Q4JK59-2]
DR ProteomicsDB; 262759; -. [Q4JK59-3]
DR Antibodypedia; 45118; 471 antibodies from 38 providers.
DR Ensembl; ENSMUST00000098603; ENSMUSP00000096203; ENSMUSG00000040943. [Q4JK59-1]
DR GeneID; 214133; -.
DR KEGG; mmu:214133; -.
DR UCSC; uc008rko.2; mouse. [Q4JK59-2]
DR UCSC; uc008rkp.2; mouse. [Q4JK59-3]
DR UCSC; uc008rkq.2; mouse. [Q4JK59-1]
DR CTD; 54790; -.
DR MGI; MGI:2443298; Tet2.
DR VEuPathDB; HostDB:ENSMUSG00000040943; -.
DR eggNOG; ENOG502QURD; Eukaryota.
DR GeneTree; ENSGT00940000160003; -.
DR HOGENOM; CLU_002537_0_0_1; -.
DR InParanoid; Q4JK59; -.
DR PhylomeDB; Q4JK59; -.
DR TreeFam; TF337563; -.
DR BioGRID-ORCS; 214133; 2 hits in 42 CRISPR screens.
DR ChiTaRS; Tet2; mouse.
DR PRO; PR:Q4JK59; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q4JK59; protein.
DR Bgee; ENSMUSG00000040943; Expressed in urethra and 244 other tissues.
DR ExpressionAtlas; Q4JK59; baseline and differential.
DR Genevisible; Q4JK59; MM.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008198; F:ferrous iron 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; ISS:UniProtKB.
DR GO; GO:0019857; P:5-methylcytosine metabolic process; IMP:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0019858; P:cytosine metabolic process; IMP:MGI.
DR GO; GO:0080111; P:DNA demethylation; IDA:MGI.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IMP:MGI.
DR GO; GO:0020027; P:hemoglobin metabolic process; IMP:MGI.
DR GO; GO:0030097; P:hemopoiesis; IMP:MGI.
DR GO; GO:0080182; P:histone H3-K4 trimethylation; IMP:UniProtKB.
DR GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0002521; P:leukocyte differentiation; ISS:UniProtKB.
DR GO; GO:0072576; P:liver morphogenesis; IMP:MGI.
DR GO; GO:0030099; P:myeloid cell differentiation; IMP:UniProtKB.
DR GO; GO:0002318; P:myeloid progenitor cell differentiation; IMP:MGI.
DR GO; GO:0070989; P:oxidative demethylation; IBA:GO_Central.
DR GO; GO:0035511; P:oxidative DNA demethylation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0006493; P:protein O-linked glycosylation; IMP:UniProtKB.
DR GO; GO:0048536; P:spleen development; IMP:MGI.
DR InterPro; IPR024779; 2OGFeDO_noxygenase_dom.
DR InterPro; IPR040175; TET1/2/3.
DR PANTHER; PTHR23358; PTHR23358; 1.
DR Pfam; PF12851; Tet_JBP; 1.
DR SMART; SM01333; Tet_JBP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Chromatin regulator; Dioxygenase;
KW DNA-binding; Glycoprotein; Iron; Metal-binding; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..1912
FT /note="Methylcytosine dioxygenase TET2"
FT /id="PRO_0000324589"
FT REGION 1..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 112..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 367..388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 429..470
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 673..723
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 832..862
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 907..966
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1009..1052
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1203..1216
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT REGION 1379..1414
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1444..1514
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1842..1871
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 51..71
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 112..132
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 133..166
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 433..447
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 832..849
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 907..922
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 938..966
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1017..1049
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1394..1414
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1455..1475
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1476..1514
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1842..1869
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1048
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1106
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1132
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1134
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1174
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1202
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1271
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1287
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1293
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1295
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1297
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1300
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1329
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1795
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1810..1812
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1816..1818
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1826
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT MOD_RES 1036
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT VAR_SEQ 1..1332
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14621295"
FT /id="VSP_032286"
FT VAR_SEQ 1..1300
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_032287"
FT MUTAGEN 1204
FT /note="W->R: Impairs enzyme activity."
FT /evidence="ECO:0000269|PubMed:21057493"
FT MUTAGEN 1280
FT /note="P->S: Impairs enzyme activity."
FT /evidence="ECO:0000269|PubMed:21057493"
FT MUTAGEN 1295
FT /note="H->Y: Loss of enzyme activity; when associated with
FT A-1297."
FT /evidence="ECO:0000269|PubMed:20639862,
FT ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:21817016"
FT MUTAGEN 1297
FT /note="D->A: Loss of enzyme activity; when associated with
FT Y-1295."
FT /evidence="ECO:0000269|PubMed:20639862,
FT ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:21817016"
FT MUTAGEN 1795
FT /note="H->R,Q: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:21057493"
FT MUTAGEN 1810
FT /note="R->S,M: Impairs enzyme activity."
FT /evidence="ECO:0000269|PubMed:21057493"
FT MUTAGEN 1827
FT /note="C->D: Impairs enzyme activity."
FT /evidence="ECO:0000269|PubMed:21057493"
FT CONFLICT 1225
FT /note="H -> R (in Ref. 1; AAY90126)"
FT /evidence="ECO:0000305"
FT CONFLICT 1626
FT /note="Q -> R (in Ref. 4; BAE32012/BAE31842)"
FT /evidence="ECO:0000305"
FT CONFLICT 1736
FT /note="L -> V (in Ref. 4; BAE30334)"
FT /evidence="ECO:0000305"
FT CONFLICT 1737
FT /note="T -> A (in Ref. 4; BAE30334)"
FT /evidence="ECO:0000305"
FT CONFLICT 1743
FT /note="K -> E (in Ref. 4; BAE30334)"
FT /evidence="ECO:0000305"
FT CONFLICT 1767
FT /note="N -> T (in Ref. 4; BAE30334)"
FT /evidence="ECO:0000305"
FT CONFLICT 1772
FT /note="C -> A (in Ref. 4; BAE30334)"
FT /evidence="ECO:0000305"
FT CONFLICT 1773
FT /note="I -> F (in Ref. 4; BAE30334)"
FT /evidence="ECO:0000305"
FT CONFLICT 1795
FT /note="H -> N (in Ref. 4; BAE30334/BAE31106/BAE31892/
FT BAE31842/BAE32012)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1912 AA; 212130 MW; F49DEE206CD05670 CRC64;
MEQDRTTHAE GTRLSPFLIA PPSPISHTEP LAVKLQNGSP LAERPHPEVN GDTKWQSSQS
CYGISHMKGS QSSHESPHED RGYSRCLQNG GIKRTVSEPS LSGLHPNKIL KLDQKAKGES
NIFEESQERN HGKSSRQPNV SGLSDNGEPV TSTTQESSGA DAFPTRNYNG VEIQVLNEQE
GEKGRSVTLL KNKIVLMPNG ATVSAHSEEN TRGELLEKTQ CYPDCVSIAV QSTASHVNTP
SSQAAIELSH EIPQPSLTSA QINFSQTSSL QLPPEPAAMV TKACDADNAS KPAIVPGTCP
FQKAEHQQKS ALDIGPSRAE NKTIQGSMEL FAEEYYPSSD RNLQASHGSS EQYSKQKETN
GAYFRQSSKF PKDSISPTTV TPPSQSLLAP RLVLQPPLEG KGALNDVALE EHHDYPNRSN
RTLLREGKID HQPKTSSSQS LNPSVHTPNP PLMLPEQHQN DCGSPSPEKS RKMSEYLMYY
LPNHGHSGGL QEHSQYLMGH REQEIPKDAN GKQTQGSVQA APGWIELKAP NLHEALHQTK
RKDISLHSVL HSQTGPVNQM SSKQSTGNVN MPGGFQRLPY LQKTAQPEQK AQMYQVQVNQ
GPSPGMGDQH LQFQKALYQE CIPRTDPSSE AHPQAPSVPQ YHFQQRVNPS SDKHLSQQAT
ETQRLSGFLQ HTPQTQASQT PASQNSNFPQ ICQQQQQQQL QRKNKEQMPQ TFSHLQGSND
KQREGSCFGQ IKVEESFCVG NQYSKSSNFQ THNNTQGGLE QVQNINKNFP YSKILTPNSS
NLQILPSNDT HPACEREQAL HPVGSKTSNL QNMQYFPNNV TPNQDVHRCF QEQAQKPQQA
SSLQGLKDRS QGESPAPPAE AAQQRYLVHN EAKALPVPEQ GGSQTQTPPQ KDTQKHAALR
WLLLQKQEQQ QTQQSQPGHN QMLRPIKTEP VSKPSSYRYP LSPPQENMSS RIKQEISSPS
RDNGQPKSII ETMEQHLKQF QLKSLCDYKA LTLKSQKHVK VPTDIQAAES ENHARAAEPQ
ATKSTDCSVL DDVSESDTPG EQSQNGKCEG CNPDKDEAPY YTHLGAGPDV AAIRTLMEER
YGEKGKAIRI EKVIYTGKEG KSSQGCPIAK WVYRRSSEEE KLLCLVRVRP NHTCETAVMV
IAIMLWDGIP KLLASELYSE LTDILGKCGI CTNRRCSQNE TRNCCCQGEN PETCGASFSF
GCSWSMYYNG CKFARSKKPR KFRLHGAEPK EEERLGSHLQ NLATVIAPIY KKLAPDAYNN
QVEFEHQAPD CCLGLKEGRP FSGVTACLDF SAHSHRDQQN MPNGSTVVVT LNREDNREVG
AKPEDEQFHV LPMYIIAPED EFGSTEGQEK KIRMGSIEVL QSFRRRRVIR IGELPKSCKK
KAEPKKAKTK KAARKRSSLE NCSSRTEKGK SSSHTKLMEN ASHMKQMTAQ PQLSGPVIRQ
PPTLQRHLQQ GQRPQQPQPP QPQPQTTPQP QPQPQHIMPG NSQSVGSHCS GSTSVYTRQP
TPHSPYPSSA HTSDIYGDTN HVNFYPTSSH ASGSYLNPSN YMNPYLGLLN QNNQYAPFPY
NGSVPVDNGS PFLGSYSPQA QSRDLHRYPN QDHLTNQNLP PIHTLHQQTF GDSPSKYLSY
GNQNMQRDAF TTNSTLKPNV HHLATFSPYP TPKMDSHFMG AASRSPYSHP HTDYKTSEHH
LPSHTIYSYT AAASGSSSSH AFHNKENDNI ANGLSRVLPG FNHDRTASAQ ELLYSLTGSS
QEKQPEVSGQ DAAAVQEIEY WSDSEHNFQD PCIGGVAIAP THGSILIECA KCEVHATTKV
NDPDRNHPTR ISLVLYRHKN LFLPKHCLAL WEAKMAEKAR KEEECGKNGS DHVSQKNHGK
QEKREPTGPQ EPSYLRFIQS LAENTGSVTT DSTVTTSPYA FTQVTGPYNT FV
