TET3_HUMAN
ID TET3_HUMAN Reviewed; 1795 AA.
AC O43151; A6NEI3; J3KNF3; K9JJH7; Q86Z24; Q8TBM9;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2019, sequence version 4.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Methylcytosine dioxygenase TET3 {ECO:0000305};
DE EC=1.14.11.n2 {ECO:0000269|PubMed:31928709};
GN Name=TET3 {ECO:0000312|HGNC:HGNC:28313}; Synonyms=KIAA0401;
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] {ECO:0000312|EMBL:ADU77107.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND FUNCTION.
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 421-1795 (ISOFORM 3).
RA Kim N.-S., Shon H.-Y., Oh J.-H., Lee J.-Y., Kim J.-M., Hahn Y., Kim Y.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 849-1795 (ISOFORM 4).
RC TISSUE=Duodenum;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1336-1795 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [6]
RP IDENTIFICATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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, AND INTERACTION WITH HCFC1 AND OGT.
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 [8]
RP INTERACTION WITH OGT.
RX PubMed=23222540; DOI=10.1038/nature11742;
RA Chen Q., Chen Y., Bian C., Fujiki R., Yu X.;
RT "TET2 promotes histone O-GlcNAcylation during gene transcription.";
RL Nature 493:561-564(2013).
RN [9]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1397, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [10]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-491; LYS-1188; LYS-1219; LYS-1397
RP AND LYS-1561, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [11] {ECO:0007744|PDB:4Z3C}
RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 49-98 IN COMPLEX WITH 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 [12]
RP INVOLVEMENT IN BEFAHRS, VARIANTS BEFAHRS CYS-752; MET-851; LEU-908;
RP CYS-1072; THR-1076; MET-1089; LEU-1677 AND 1695-GLN--ILE-1795 DEL,
RP CHARACTERIZATION OF VARIANTS BEFAHRS CYS-752; LEU-908; CYS-1072; THR-1076
RP AND MET-1089, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP 1077-HIS--ASP-1079.
RX PubMed=31928709; DOI=10.1016/j.ajhg.2019.12.007;
RA Beck D.B., Petracovici A., He C., Moore H.W., Louie R.J., Ansar M.,
RA Douzgou S., Sithambaram S., Cottrell T., Santos-Cortez R.L.P.,
RA Prijoles E.J., Bend R., Keren B., Mignot C., Nougues M.C., Ounap K.,
RA Reimand T., Pajusalu S., Zahid M., Saqib M.A.N., Buratti J., Seaby E.G.,
RA McWalter K., Telegrafi A., Baldridge D., Shinawi M., Leal S.M.,
RA Schaefer G.B., Stevenson R.E., Banka S., Bonasio R., Fahrner J.A.;
RT "Delineation of a Human Mendelian Disorder of the DNA Demethylation
RT Machinery: TET3 Deficiency.";
RL Am. J. Hum. Genet. 106:234-245(2020).
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 (PubMed:31928709). Also mediates
CC subsequent conversion of 5hmC into 5-formylcytosine (5fC), and
CC conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into
CC 5hmC, 5fC and 5caC probably constitutes the first step in cytosine
CC demethylation (By similarity). Selectively binds to the promoter region
CC of target genes and contributes to regulate the expression of numerous
CC developmental genes (PubMed:23217707). In zygotes, DNA demethylation
CC occurs selectively in the paternal pronucleus before the first cell
CC division, while the adjacent maternal pronucleus and certain
CC paternally-imprinted loci are protected from this process. Participates
CC in DNA demethylation in the paternal pronucleus by mediating conversion
CC of 5mC into 5hmC, 5fC and 5caC. Does not mediate DNA demethylation of
CC maternal pronucleus because of the presence of DPPA3/PGC7 on maternal
CC chromatin that prevents TET3-binding to chromatin (By similarity). In
CC addition to its role in DNA demethylation, also involved in the
CC recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription
CC start sites of active genes, thereby promoting histone H2B
CC GlcNAcylation by OGT (PubMed:23353889). Binds preferentially to DNA
CC containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH
CC (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-
CC CpG (PubMed:29276034). {ECO:0000250|UniProtKB:Q8BG87,
CC ECO:0000269|PubMed:23217707, ECO:0000269|PubMed:23353889,
CC ECO:0000269|PubMed:29276034, ECO:0000269|PubMed:31928709}.
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:31928709};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52637;
CC Evidence={ECO:0000305|PubMed:31928709};
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:0000269|PubMed:23222540,
CC ECO:0000269|PubMed:23353889}.
CC -!- INTERACTION:
CC O43151; O15294: OGT; NbExp=7; IntAct=EBI-2831148, EBI-539828;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8BG87}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8BG87}. Chromosome
CC {ECO:0000250|UniProtKB:Q8BG87}. Note=At the zygotic stage, localizes in
CC the male pronucleus, while it localizes to the cytoplasm at other
CC preimplantation stages. Binds to the promoter of target genes, close to
CC the transcription start site. {ECO:0000250|UniProtKB:Q8BG87}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=4;
CC IsoId=O43151-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43151-2; Sequence=VSP_021628;
CC Name=3;
CC IsoId=O43151-3; Sequence=VSP_034192;
CC -!- TISSUE SPECIFICITY: Expressed in colon, muscle, adrenal gland and
CC peripheral blood lymphocytes. {ECO:0000269|PubMed:12646957}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain but not adult brain.
CC {ECO:0000269|PubMed:12646957}.
CC -!- DOMAIN: The CXXC zinc finger mediates binding to CpG-DNA
CC (PubMed:29276034). It mediates binding to DNA sequences containing
CC unmethylated cytosine or 5-carboxylcytosine in 5'-CCG-3' DNA sequence
CC motifs (By similarity). {ECO:0000250|UniProtKB:Q8BG87,
CC ECO:0000269|PubMed:29276034}.
CC -!- DISEASE: Beck-Fahrner syndrome (BEFAHRS) [MIM:618798]: A developmental
CC disorder characterized by mild to severe intellectual disability,
CC global developmental delay, hypotonia, autistic traits, movement
CC disorders, growth abnormalities including overgrowth or poor growth,
CC and facial dysmorphism. Both autosomal dominant and autosomal recessive
CC inheritance has been reported. {ECO:0000269|PubMed:31928709}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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=AAH22243.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAO33386.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAX93057.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; HQ220209; ADU77107.1; -; mRNA.
DR EMBL; AC110801; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073263; AAX93057.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC073046; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF466365; AAO33386.1; ALT_INIT; mRNA.
DR EMBL; BC022243; AAH22243.1; ALT_INIT; mRNA.
DR EMBL; AB007861; BAA23697.1; -; mRNA.
DR CCDS; CCDS46339.2; -. [O43151-1]
DR RefSeq; NP_001274420.1; NM_001287491.1. [O43151-1]
DR RefSeq; XP_005264244.1; XM_005264187.3.
DR PDB; 4Z3C; X-ray; 1.57 A; C=49-98.
DR PDBsum; 4Z3C; -.
DR AlphaFoldDB; O43151; -.
DR SMR; O43151; -.
DR BioGRID; 128327; 18.
DR IntAct; O43151; 32.
DR MINT; O43151; -.
DR STRING; 9606.ENSP00000386869; -.
DR GlyGen; O43151; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43151; -.
DR PhosphoSitePlus; O43151; -.
DR BioMuta; TET3; -.
DR jPOST; O43151; -.
DR MassIVE; O43151; -.
DR MaxQB; O43151; -.
DR PaxDb; O43151; -.
DR PeptideAtlas; O43151; -.
DR PRIDE; O43151; -.
DR ProteomicsDB; 48772; -. [O43151-1]
DR ProteomicsDB; 48773; -. [O43151-2]
DR ProteomicsDB; 48774; -. [O43151-3]
DR Antibodypedia; 31410; 380 antibodies from 30 providers.
DR DNASU; 200424; -.
DR Ensembl; ENST00000409262.8; ENSP00000386869.3; ENSG00000187605.16. [O43151-1]
DR GeneID; 200424; -.
DR KEGG; hsa:200424; -.
DR MANE-Select; ENST00000409262.8; ENSP00000386869.3; NM_001287491.2; NP_001274420.1.
DR UCSC; uc002skb.6; human. [O43151-1]
DR UCSC; uc061kse.1; human.
DR CTD; 200424; -.
DR DisGeNET; 200424; -.
DR GeneCards; TET3; -.
DR HGNC; HGNC:28313; TET3.
DR HPA; ENSG00000187605; Tissue enhanced (bone).
DR MalaCards; TET3; -.
DR MIM; 613555; gene.
DR MIM; 618798; phenotype.
DR neXtProt; NX_O43151; -.
DR OpenTargets; ENSG00000187605; -.
DR PharmGKB; PA162405645; -.
DR VEuPathDB; HostDB:ENSG00000187605; -.
DR eggNOG; ENOG502QURD; Eukaryota.
DR GeneTree; ENSGT00940000157631; -.
DR HOGENOM; CLU_001618_3_0_1; -.
DR InParanoid; O43151; -.
DR OMA; PDSQWGL; -.
DR PhylomeDB; O43151; -.
DR TreeFam; TF342373; -.
DR PathwayCommons; O43151; -.
DR Reactome; R-HSA-5221030; TET1,2,3 and TDG demethylate DNA.
DR SignaLink; O43151; -.
DR SIGNOR; O43151; -.
DR BioGRID-ORCS; 200424; 16 hits in 1091 CRISPR screens.
DR ChiTaRS; TET3; human.
DR GenomeRNAi; 200424; -.
DR Pharos; O43151; Tbio.
DR PRO; PR:O43151; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O43151; protein.
DR Bgee; ENSG00000187605; Expressed in oocyte and 183 other tissues.
DR ExpressionAtlas; O43151; baseline and differential.
DR Genevisible; O43151; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0001939; C:female pronucleus; IEA:Ensembl.
DR GO; GO:0001940; C:male pronucleus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0008327; F:methyl-CpG binding; IDA:UniProtKB.
DR GO; GO:0070579; F:methylcytosine dioxygenase activity; ISS: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; ISS:UniProtKB.
DR GO; GO:0044727; P:DNA demethylation of male pronucleus; ISS:UniProtKB.
DR GO; GO:0080182; P:histone H3-K4 trimethylation; IMP:UniProtKB.
DR GO; GO:0070989; P:oxidative demethylation; IBA:GO_Central.
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 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; Alternative splicing; Chromatin regulator; Chromosome;
KW Cytoplasm; Developmental protein; Dioxygenase; Disease variant;
KW DNA-binding; Intellectual disability; Iron; Isopeptide bond; Metal-binding;
KW Nucleus; Oxidoreductase; Reference proteome; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..1795
FT /note="Methylcytosine dioxygenase TET3"
FT /id="PRO_0000050750"
FT ZN_FING 50..90
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034"
FT REGION 142..172
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 370..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 408..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 478..704
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 985..998
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT REGION 1345..1366
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1395..1430
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1608..1638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 509..527
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 554..570
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 650..666
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..694
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 ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4Z3C"
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 ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4Z3C"
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 ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4Z3C"
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 ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4Z3C"
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 ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4Z3C"
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 ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4Z3C"
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 ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4Z3C"
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 ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4Z3C"
FT BINDING 828
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 830
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 888
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 914
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 916
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 956
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 966
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 968
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 984
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 993
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1053
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1069
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1075
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1077
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1079
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1082
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1111
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1673
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1688..1690
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1694..1696
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1704
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT CROSSLNK 491
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1188
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1219
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1397
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1561
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 863..1795
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_034192"
FT VAR_SEQ 1575..1690
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9455477"
FT /id="VSP_021628"
FT VARIANT 712
FT /note="R -> Q (in dbSNP:rs57955681)"
FT /id="VAR_062235"
FT VARIANT 752
FT /note="R -> C (in BEFAHRS; unknown pathological
FT significance; no effect on methylcytosine dioxygenase
FT activity; dbSNP:rs534089911)"
FT /evidence="ECO:0000269|PubMed:31928709"
FT /id="VAR_083831"
FT VARIANT 851
FT /note="T -> M (in BEFAHRS; dbSNP:rs1573856970)"
FT /evidence="ECO:0000269|PubMed:31928709"
FT /id="VAR_083832"
FT VARIANT 908
FT /note="V -> L (in BEFAHRS; decreases methylcytosine
FT dioxygenase activity; dbSNP:rs1227643933)"
FT /evidence="ECO:0000269|PubMed:31928709"
FT /id="VAR_083833"
FT VARIANT 1072
FT /note="F -> C (in BEFAHRS; decreases methylcytosine
FT dioxygenase activity; dbSNP:rs1573906351)"
FT /evidence="ECO:0000269|PubMed:31928709"
FT /id="VAR_083834"
FT VARIANT 1076
FT /note="A -> T (in BEFAHRS; decreases methylcytosine
FT dioxygenase activity; dbSNP:rs1573906389)"
FT /evidence="ECO:0000269|PubMed:31928709"
FT /id="VAR_083835"
FT VARIANT 1089
FT /note="V -> M (in BEFAHRS; decreases methylcytosine
FT dioxygenase activity; dbSNP:rs1174857008)"
FT /evidence="ECO:0000269|PubMed:31928709"
FT /id="VAR_083836"
FT VARIANT 1677
FT /note="P -> L (in BEFAHRS)"
FT /evidence="ECO:0000269|PubMed:31928709"
FT /id="VAR_083837"
FT VARIANT 1695..1795
FT /note="Missing (in BEFAHRS)"
FT /evidence="ECO:0000269|PubMed:31928709"
FT /id="VAR_083838"
FT MUTAGEN 1077..1079
FT /note="HKD->YKA: Abolishes methylcytosine dioxygenase
FT activity."
FT /evidence="ECO:0000269|PubMed:31928709"
FT HELIX 61..64
FT /evidence="ECO:0007829|PDB:4Z3C"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:4Z3C"
FT HELIX 73..76
FT /evidence="ECO:0007829|PDB:4Z3C"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:4Z3C"
FT TURN 85..87
FT /evidence="ECO:0007829|PDB:4Z3C"
FT TURN 90..93
FT /evidence="ECO:0007829|PDB:4Z3C"
SQ SEQUENCE 1795 AA; 193705 MW; 7D1041E2C45C4F18 CRC64;
MSQFQVPLAV QPDLPGLYDF PQRQVMVGSF PGSGLSMAGS ESQLRGGGDG RKKRKRCGTC
EPCRRLENCG ACTSCTNRRT HQICKLRKCE VLKKKVGLLK EVEIKAGEGA GPWGQGAAVK
TGSELSPVDG PVPGQMDSGP VYHGDSRQLS ASGVPVNGAR EPAGPSLLGT GGPWRVDQKP
DWEAAPGPAH TARLEDAHDL VAFSAVAEAV SSYGALSTRL YETFNREMSR EAGNNSRGPR
PGPEGCSAGS EDLDTLQTAL ALARHGMKPP NCNCDGPECP DYLEWLEGKI KSVVMEGGEE
RPRLPGPLPP GEAGLPAPST RPLLSSEVPQ ISPQEGLPLS QSALSIAKEK NISLQTAIAI
EALTQLSSAL PQPSHSTPQA SCPLPEALSP PAPFRSPQSY LRAPSWPVVP PEEHSSFAPD
SSAFPPATPR TEFPEAWGTD TPPATPRSSW PMPRPSPDPM AELEQLLGSA SDYIQSVFKR
PEALPTKPKV KVEAPSSSPA PAPSPVLQRE APTPSSEPDT HQKAQTALQQ HLHHKRSLFL
EQVHDTSFPA PSEPSAPGWW PPPSSPVPRL PDRPPKEKKK KLPTPAGGPV GTEKAAPGIK
PSVRKPIQIK KSRPREAQPL FPPVRQIVLE GLRSPASQEV QAHPPAPLPA SQGSAVPLPP
EPSLALFAPS PSRDSLLPPT QEMRSPSPMT ALQPGSTGPL PPADDKLEEL IRQFEAEFGD
SFGLPGPPSV PIQDPENQQT CLPAPESPFA TRSPKQIKIE SSGAVTVLST TCFHSEEGGQ
EATPTKAENP LTPTLSGFLE SPLKYLDTPT KSLLDTPAKR AQAEFPTCDC VEQIVEKDEG
PYYTHLGSGP TVASIRELME ERYGEKGKAI RIEKVIYTGK EGKSSRGCPI AKWVIRRHTL
EEKLLCLVRH RAGHHCQNAV IVILILAWEG IPRSLGDTLY QELTDTLRKY GNPTSRRCGL
NDDRTCACQG KDPNTCGASF SFGCSWSMYF NGCKYARSKT PRKFRLAGDN PKEEEVLRKS
FQDLATEVAP LYKRLAPQAY QNQVTNEEIA IDCRLGLKEG RPFAGVTACM DFCAHAHKDQ
HNLYNGCTVV CTLTKEDNRC VGKIPEDEQL HVLPLYKMAN TDEFGSEENQ NAKVGSGAIQ
VLTAFPREVR RLPEPAKSCR QRQLEARKAA AEKKKIQKEK LSTPEKIKQE ALELAGITSD
PGLSLKGGLS QQGLKPSLKV EPQNHFSSFK YSGNAVVESY SVLGNCRPSD PYSMNSVYSY
HSYYAQPSLT SVNGFHSKYA LPSFSYYGFP SSNPVFPSQF LGPGAWGHSG SSGSFEKKPD
LHALHNSLSP AYGGAEFAEL PSQAVPTDAH HPTPHHQQPA YPGPKEYLLP KAPLLHSVSR
DPSPFAQSSN CYNRSIKQEP VDPLTQAEPV PRDAGKMGKT PLSEVSQNGG PSHLWGQYSG
GPSMSPKRTN GVGGSWGVFS SGESPAIVPD KLSSFGASCL APSHFTDGQW GLFPGEGQQA
ASHSGGRLRG KPWSPCKFGN STSALAGPSL TEKPWALGAG DFNSALKGSP GFQDKLWNPM
KGEEGRIPAA GASQLDRAWQ SFGLPLGSSE KLFGALKSEE KLWDPFSLEE GPAEEPPSKG
AVKEEKGGGG AEEEEEELWS DSEHNFLDEN IGGVAVAPAH GSILIECARR ELHATTPLKK
PNRCHPTRIS LVFYQHKNLN QPNHGLALWE AKMKQLAERA RARQEEAARL GLGQQEAKLY
GKKRKWGGTV VAEPQQKEKK GVVPTRQALA VPTDSAVTVS SYAYTKVTGP YSRWI