TET3_MOUSE
ID TET3_MOUSE Reviewed; 1803 AA.
AC Q8BG87; K9JH93; L0HN04; Q4VAD3; Q8C8N8; Q8CI60;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2019, sequence version 4.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Methylcytosine dioxygenase TET3;
DE EC=1.14.11.n2 {ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:23690950, ECO:0000269|PubMed:26774490};
GN Name=Tet3;
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] {ECO:0000312|EMBL:ADR57137.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=129/Ola {ECO:0000312|EMBL:ADR57137.1};
RX PubMed=23217707; DOI=10.1016/j.cell.2012.11.014;
RA Xu Y., Xu C., Kato A., Tempel W., Abreu J.G., Bian C., Hu Y., Hu D.,
RA Zhao B., Cerovina T., Diao J., Wu F., He H.H., Cui Q., Clark E., Ma C.,
RA Barbara A., Veenstra G.J.C., Xu G., Kaiser U.B., Liu X.S., Sugrue S.P.,
RA He X., Min J., Kato Y., Shi Y.G.;
RT "Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes
RT for Xenopus eye and neural development.";
RL Cell 151:1200-1213(2012).
RN [2] {ECO:0000312|EMBL:AGB05430.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, CATALYTIC ACTIVITY, AND
RP DNA-BINDING.
RC STRAIN=129/Ola {ECO:0000312|EMBL:AGB05430.1};
RX PubMed=23690950; DOI=10.1371/journal.pone.0062755;
RA Liu N., Wang M., Deng W., Schmidt C.S., Qin W., Leonhardt H., Spada F.;
RT "Intrinsic and extrinsic connections of Tet3 dioxygenase with CXXC zinc
RT finger modules.";
RL PLoS ONE 8:E62755-E62755(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, and Retina;
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 892-1688 (ISOFORMS 1/3).
RC STRAIN=C57BL/6J; TISSUE=Egg;
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 FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP HIS-1085 AND ASP-1087.
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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=21892189; DOI=10.1038/nature10443;
RA Gu T.P., Guo F., Yang H., Wu H.P., Xu G.F., Liu W., Xie Z.G., Shi L.,
RA He X., Jin S.G., Iqbal K., Shi Y.G., Deng Z., Szabo P.E., Pfeifer G.P.,
RA Li J., Xu G.L.;
RT "The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.";
RL Nature 477:606-610(2011).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=21407207; DOI=10.1038/ncomms1240;
RA Wossidlo M., Nakamura T., Lepikhov K., Marques C.J., Zakhartchenko V.,
RA Boiani M., Arand J., Nakano T., Reik W., Walter J.;
RT "5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic
RT reprogramming.";
RL Nat. Commun. 2:241-241(2011).
RN [9]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=21321204; DOI=10.1073/pnas.1014033108;
RA Iqbal K., Jin S.G., Pfeifer G.P., Szabo P.E.;
RT "Reprogramming of the paternal genome upon fertilization involves genome-
RT wide oxidation of 5-methylcytosine.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:3642-3647(2011).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-1085 AND ASP-1087.
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 [11]
RP FUNCTION.
RX PubMed=22722204; DOI=10.1038/nature11093;
RA Nakamura T., Liu Y.J., Nakashima H., Umehara H., Inoue K., Matoba S.,
RA Tachibana M., Ogura A., Shinkai Y., Nakano T.;
RT "PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in
RT early embryos.";
RL Nature 486:415-419(2012).
RN [12]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1271, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=28930672; DOI=10.1016/j.celrep.2017.08.088;
RA Hatanaka Y., Tsusaka T., Shimizu N., Morita K., Suzuki T., Machida S.,
RA Satoh M., Honda A., Hirose M., Kamimura S., Ogonuki N., Nakamura T.,
RA Inoue K., Hosoi Y., Dohmae N., Nakano T., Kurumizaka H., Matsumoto K.,
RA Shinkai Y., Ogura A.;
RT "Histone H3 methylated at arginine 17 is essential for reprogramming the
RT paternal genome in zygotes.";
RL Cell Rep. 20:2756-2765(2017).
RN [14] {ECO:0007744|PDB:5EXH}
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 51-96 IN COMPLEX WITH ZINC AND
RP DNA, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ALTERNATIVE
RP SPLICING, DOMAIN, AND TISSUE SPECIFICITY.
RX PubMed=26774490; DOI=10.1016/j.celrep.2015.12.044;
RA Jin S.G., Zhang Z.M., Dunwell T.L., Harter M.R., Wu X., Johnson J., Li Z.,
RA Liu J., Szabo P.E., Lu Q., Xu G.L., Song J., Pfeifer G.P.;
RT "Tet3 reads 5-carboxylcytosine through its CXXC domain and is a potential
RT guardian against neurodegeneration.";
RL Cell Rep. 14:493-505(2016).
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 epigenetic chromatin reprogramming in the
CC zygote following fertilization. Also mediates subsequent conversion of
CC 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-
CC carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC
CC probably constitutes the first step in cytosine demethylation.
CC Selectively binds to the promoter region of target genes and
CC contributes to regulate the expression of numerous developmental genes.
CC In zygotes, DNA demethylation occurs selectively in the paternal
CC pronucleus before the first cell division, while the adjacent maternal
CC pronucleus and certain paternally-imprinted loci are protected from
CC this process. Participates in DNA demethylation in the paternal
CC pronucleus by mediating conversion of 5mC into 5hmC, 5fC and 5caC. Does
CC not mediate DNA demethylation of maternal pronucleus because of the
CC presence of DPPA3/PGC7 on maternal chromatin that prevents TET3-binding
CC to chromatin. In addition to its role in DNA demethylation, also
CC involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich
CC transcription start sites of active genes, thereby promoting histone
CC H2B GlcNAcylation by OGT. Binds preferentially to DNA containing
CC cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and
CC C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (By
CC similarity). {ECO:0000250|UniProtKB:O43151,
CC ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:21407207,
CC ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:21892189,
CC ECO:0000269|PubMed:22722204, ECO:0000269|PubMed:23690950,
CC ECO:0000269|PubMed:26774490}.
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, ECO:0000269|PubMed:23690950,
CC ECO:0000269|PubMed:26774490};
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=The zinc ions have a structural role.
CC {ECO:0000250|UniProtKB:Q6N021};
CC -!- SUBUNIT: Interacts with HCFC1 and OGT. {ECO:0000250|UniProtKB:O43151}.
CC -!- INTERACTION:
CC Q8BG87; O15294: OGT; Xeno; NbExp=2; IntAct=EBI-9031997, EBI-539828;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21892189,
CC ECO:0000269|PubMed:26774490, ECO:0000269|PubMed:28930672}. Chromosome
CC {ECO:0000269|PubMed:26774490}. Cytoplasm {ECO:0000269|PubMed:21892189}.
CC Note=At the zygotic stage, localizes in the male and female pronucleus,
CC while it localizes to the cytoplasm at other preimplantation stages
CC (PubMed:21892189, PubMed:28930672). Binds to the promoter of target
CC genes, close to the transcription start site (PubMed:26774490).
CC {ECO:0000269|PubMed:21892189, ECO:0000269|PubMed:26774490,
CC ECO:0000269|PubMed:28930672}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=Q8BG87-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BG87-2; Sequence=VSP_060404, VSP_060406, VSP_060407;
CC Name=1;
CC IsoId=Q8BG87-4; Sequence=VSP_060405;
CC -!- TISSUE SPECIFICITY: Highly expressed in oocytes and zygotes. Not
CC expressed in embryonic stem cells (ES cells).
CC {ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:21321204,
CC ECO:0000269|PubMed:21407207, ECO:0000269|PubMed:21892189,
CC ECO:0000269|PubMed:26774490}.
CC -!- DEVELOPMENTAL STAGE: Expressed maternally. Expressed at high levels in
CC oocytes and zygotes, with rapidly declining levels at the two-cell
CC stage. {ECO:0000269|PubMed:21321204, ECO:0000269|PubMed:21407207}.
CC -!- DOMAIN: The CXXC-type zinc-finger domain mediates binding to DNA
CC sequences containing unmethylated cytosine or 5-carboxylcytosine in 5'-
CC CCG-3' DNA sequence motifs (PubMed:26774490). It mediates binding to
CC CpG-DNA (By similarity). {ECO:0000250|UniProtKB:O43151,
CC ECO:0000269|PubMed:26774490}.
CC -!- DISRUPTION PHENOTYPE: Neonatal lethality. A germline-specific
CC conditional knockout produces females that are normal in growth and
CC morphology but display much reduced fecundity in terms of the frequency
CC of successful pregnancy per mating and the litter size. No 5hmC signal
CC is detected in the late male pronuclei of zygotes collected from the
CC conditional knockout females mated with wild-type males. In contrast,
CC deletion of Tet3 from the male germ cells does not seem to affect the
CC change in 5hmC and 5mC. {ECO:0000269|PubMed:21892189}.
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. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH96437.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH96437.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; HQ423151; ADR57137.1; -; mRNA.
DR EMBL; HQ423152; ADR57138.1; -; mRNA.
DR EMBL; JX946278; AGB05430.1; -; mRNA.
DR EMBL; AK044758; BAC32068.1; -; mRNA.
DR EMBL; AK046543; BAC32779.1; -; mRNA.
DR EMBL; AK046552; BAC32784.1; -; mRNA.
DR EMBL; AK046553; BAC32785.1; -; mRNA.
DR EMBL; GL456132; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096437; AAH96437.1; ALT_SEQ; mRNA.
DR CCDS; CCDS85071.1; -. [Q8BG87-1]
DR RefSeq; NP_001334242.1; NM_001347313.1. [Q8BG87-1]
DR RefSeq; XP_006505838.1; XM_006505775.3. [Q8BG87-1]
DR RefSeq; XP_006505839.1; XM_006505776.3. [Q8BG87-1]
DR RefSeq; XP_006505840.1; XM_006505777.3. [Q8BG87-4]
DR RefSeq; XP_017176954.1; XM_017321465.1. [Q8BG87-1]
DR PDB; 5EXH; X-ray; 1.30 A; C=51-96.
DR PDBsum; 5EXH; -.
DR AlphaFoldDB; Q8BG87; -.
DR SMR; Q8BG87; -.
DR BioGRID; 228786; 3.
DR IntAct; Q8BG87; 1.
DR MINT; Q8BG87; -.
DR STRING; 10090.ENSMUSP00000087049; -.
DR iPTMnet; Q8BG87; -.
DR PhosphoSitePlus; Q8BG87; -.
DR jPOST; Q8BG87; -.
DR MaxQB; Q8BG87; -.
DR PaxDb; Q8BG87; -.
DR PeptideAtlas; Q8BG87; -.
DR PRIDE; Q8BG87; -.
DR ProteomicsDB; 262872; -. [Q8BG87-1]
DR ProteomicsDB; 262873; -. [Q8BG87-2]
DR ProteomicsDB; 262874; -. [Q8BG87-4]
DR Antibodypedia; 31410; 380 antibodies from 30 providers.
DR Ensembl; ENSMUST00000186548; ENSMUSP00000139630; ENSMUSG00000034832. [Q8BG87-1]
DR GeneID; 194388; -.
DR KEGG; mmu:194388; -.
DR UCSC; uc009cni.2; mouse. [Q8BG87-1]
DR UCSC; uc009cnl.1; mouse. [Q8BG87-2]
DR UCSC; uc033isr.1; mouse.
DR CTD; 200424; -.
DR MGI; MGI:2446229; Tet3.
DR VEuPathDB; HostDB:ENSMUSG00000034832; -.
DR eggNOG; ENOG502QURD; Eukaryota.
DR GeneTree; ENSGT00940000157631; -.
DR InParanoid; Q8BG87; -.
DR OMA; PDSQWGL; -.
DR OrthoDB; 29059at2759; -.
DR PhylomeDB; Q8BG87; -.
DR TreeFam; TF342373; -.
DR BioGRID-ORCS; 194388; 1 hit in 59 CRISPR screens.
DR ChiTaRS; Tet3; mouse.
DR PRO; PR:Q8BG87; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8BG87; protein.
DR Bgee; ENSMUSG00000034832; Expressed in animal zygote and 121 other tissues.
DR ExpressionAtlas; Q8BG87; baseline and differential.
DR Genevisible; Q8BG87; MM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0001939; C:female pronucleus; IDA:MGI.
DR GO; GO:0001940; C:male pronucleus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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:0080111; P:DNA demethylation; IDA:MGI.
DR GO; GO:0044727; P:DNA demethylation of male pronucleus; IMP:UniProtKB.
DR GO; GO:0080182; P:histone H3-K4 trimethylation; ISS:UniProtKB.
DR GO; GO:0070989; P:oxidative demethylation; IBA:GO_Central.
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 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 SMART; SM01333; Tet_JBP; 1.
DR PROSITE; PS51058; ZF_CXXC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator; Chromosome;
KW Cytoplasm; Developmental protein; Dioxygenase; DNA-binding; Iron;
KW Isopeptide bond; Metal-binding; Methylation; Nucleus; Oxidoreductase;
KW Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1803
FT /note="Methylcytosine dioxygenase TET3"
FT /id="PRO_0000340228"
FT ZN_FING 50..90
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:26774490"
FT REGION 137..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 229..251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 294..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 478..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 632..712
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 993..1006
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT REGION 1354..1456
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1617..1639
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..384
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 407..428
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..526
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 651..666
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 681..701
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1389..1410
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1428..1456
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 57
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 63
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 69
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 72
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 75
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 84
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 89
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 836
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 838
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 896
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 922
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 924
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 964
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 974
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 976
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 992
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1001
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1061
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1077
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1083
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1085
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1087
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1090
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1119
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1681
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1696..1698
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1702..1704
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1712
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT MOD_RES 1271
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CROSSLNK 490
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O43151"
FT CROSSLNK 1196
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O43151"
FT CROSSLNK 1227
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O43151"
FT CROSSLNK 1405
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O43151"
FT CROSSLNK 1569
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O43151"
FT VAR_SEQ 1..135
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_060404"
FT VAR_SEQ 102..120
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:23217707"
FT /id="VSP_060405"
FT VAR_SEQ 840..854
FT /note="EQIVEKDEGPYYTHL -> GRWEWSRAFFLSVEH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_060406"
FT VAR_SEQ 855..1803
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_060407"
FT MUTAGEN 1085
FT /note="H->Y: Loss of enzyme activity; when associated with
FT A-1087."
FT /evidence="ECO:0000269|PubMed:20639862,
FT ECO:0000269|PubMed:21778364"
FT MUTAGEN 1087
FT /note="D->A: Loss of enzyme activity; when associated with
FT Y-1085."
FT /evidence="ECO:0000269|PubMed:20639862,
FT ECO:0000269|PubMed:21778364"
FT CONFLICT 1097
FT /note="V -> A (in Ref. 5; AAH96437)"
FT /evidence="ECO:0000305"
FT HELIX 61..64
FT /evidence="ECO:0007829|PDB:5EXH"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:5EXH"
FT HELIX 73..76
FT /evidence="ECO:0007829|PDB:5EXH"
FT TURN 85..87
FT /evidence="ECO:0007829|PDB:5EXH"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:5EXH"
SQ SEQUENCE 1803 AA; 194792 MW; FE0492ADBC4EBFD5 CRC64;
MSQFQVPLAV QPDLSGLYDF PQGQVMVGGF QGPGLPMAGS ETQLRGGGDG RKKRKRCGTC
DPCRRLENCG SCTSCTNRRT HQICKLRKCE VLKKKAGLLK EVEINAREGT GPWAQGATVK
TGSELSPVDG PVPGQMDSGP VYHGDSRQLS TSGAPVNGAR EPAGPGLLGA AGPWRVDQKP
DWEAASGPTH AARLEDAHDL VAFSAVAEAV SSYGALSTRL YETFNREMSR EAGSNGRGPR
PESCSEGSED LDTLQTALAL ARHGMKPPNC TCDGPECPDF LEWLEGKIKS MAMEGGQGRP
RLPGALPPSE AGLPAPSTRP PLLSSEVPQV PPLEGLPLSQ SALSIAKEKN ISLQTAIAIE
ALTQLSSALP QPSHSTSQAS CPLPEALSPS APFRSPQSYL RAPSWPVVPP EEHPSFAPDS
PAFPPATPRP EFSEAWGTDT PPATPRNSWP VPRPSPDPMA ELEQLLGSAS DYIQSVFKRP
EALPTKPKVK VEAPSSSPAP VPSPISQREA PLLSSEPDTH QKAQTALQQH LHHKRNLFLE
QAQDASFPTS TEPQAPGWWA PPGSPAPRPP DKPPKEKKKK PPTPAGGPVG AEKTTPGIKT
SVRKPIQIKK SRSRDMQPLF LPVRQIVLEG LKPQASEGQA PLPAQLSVPP PASQGAASQS
CATPLTPEPS LALFAPSPSG DSLLPPTQEM RSPSPMVALQ SGSTGGPLPP ADDKLEELIR
QFEAEFGDSF GLPGPPSVPI QEPENQSTCL PAPESPFATR SPKKIKIESS GAVTVLSTTC
FHSEEGGQEA TPTKAENPLT PTLSGFLESP LKYLDTPTKS LLDTPAKKAQ SEFPTCDCVE
QIVEKDEGPY YTHLGSGPTV ASIRELMEDR YGEKGKAIRI EKVIYTGKEG KSSRGCPIAK
WVIRRHTLEE KLLCLVRHRA GHHCQNAVIV ILILAWEGIP RSLGDTLYQE LTDTLRKYGN
PTSRRCGLND DRTCACQGKD PNTCGASFSF GCSWSMYFNG CKYARSKTPR KFRLTGDNPK
EEEVLRNSFQ DLATEVAPLY KRLAPQAYQN QVTNEDVAID CRLGLKEGRP FSGVTACMDF
CAHAHKDQHN LYNGCTVVCT LTKEDNRCVG QIPEDEQLHV LPLYKMASTD EFGSEENQNA
KVSSGAIQVL TAFPREVRRL PEPAKSCRQR QLEARKAAAE KKKLQKEKLS TPEKIKQEAL
ELAGVTTDPG LSLKGGLSQQ SLKPSLKVEP QNHFSSFKYS GNAVVESYSV LGSCRPSDPY
SMSSVYSYHS RYAQPGLASV NGFHSKYTLP SFGYYGFPSS NPVFPSQFLG PSAWGHGGSG
GSFEKKPDLH ALHNSLNPAY GGAEFAELPG QAVATDNHHP IPHHQQPAYP GPKEYLLPKV
PQLHPASRDP SPFAQSSSCY NRSIKQEPID PLTQAESIPR DSAKMSRTPL PEASQNGGPS
HLWGQYSGGP SMSPKRTNSV GGNWGVFPPG ESPTIVPDKL NSFGASCLTP SHFPESQWGL
FTGEGQQSAP HAGARLRGKP WSPCKFGNGT SALTGPSLTE KPWGMGTGDF NPALKGGPGF
QDKLWNPVKV EEGRIPTPGA NPLDKAWQAF GMPLSSNEKL FGALKSEEKL WDPFSLEEGT
AEEPPSKGVV KEEKSGPTVE EDEEELWSDS EHNFLDENIG GVAVAPAHCS ILIECARREL
HATTPLKKPN RCHPTRISLV FYQHKNLNQP NHGLALWEAK MKQLAERARQ RQEEAARLGL
GQQEAKLYGK KRKWGGAMVA EPQHKEKKGA IPTRQALAMP TDSAVTVSSY AYTKVTGPYS
RWI
