TET3_XENTR
ID TET3_XENTR Reviewed; 1901 AA.
AC A0JP82;
DT 22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Methylcytosine dioxygenase tet3;
DE EC=1.14.11.n2 {ECO:0000269|PubMed:23217707};
GN Name=tet3 {ECO:0000312|Xenbase:XB-GENE-877084};
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364 {ECO:0000312|EMBL:AAI27290.1};
RN [1] {ECO:0000312|EMBL:AAI27290.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis {ECO:0000312|EMBL:AAI27290.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0007744|PDB:4HP1, ECO:0007744|PDB:4HP3}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 58-111 IN COMPLEX WITH ZINC AND
RP TARGET DNA, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DOMAIN,
RP MUTAGENESIS OF HIS-90 AND 1206-HIS--ASP-1208, AND COFACTOR.
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 [3]
RP MUTAGENESIS OF HIS-90.
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).
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 during
CC embryonic development. Conversion of 5mC into 5hmC probably constitutes
CC the first step in cytosine demethylation. Selectively binds to the
CC promoter region of target genes and contributes to regulate the
CC expression of numerous developmental genes, including pax6, rax, sox9
CC and six3. May also contribute to the regulation of target genes in ways
CC that do not require its enzyme activity. {ECO:0000269|PubMed:23217707}.
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:23217707};
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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23217707}. Chromosome
CC {ECO:0000269|PubMed:23217707}. Note=Detected on chromatin, where it
CC binds to target gene promoters. {ECO:0000269|PubMed:23217707}.
CC -!- DOMAIN: Binds target DNA that contains at least one unmethylated
CC cytosine via the CXXC-type zinc-finger domain.
CC {ECO:0000269|PubMed:23217707}.
CC -!- SIMILARITY: Belongs to the TET family. {ECO:0000305}.
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DR EMBL; BC127289; AAI27290.1; -; mRNA.
DR RefSeq; NP_001090656.1; NM_001097187.1.
DR PDB; 4HP1; X-ray; 2.25 A; C=58-111.
DR PDB; 4HP3; X-ray; 2.05 A; C=58-111.
DR PDBsum; 4HP1; -.
DR PDBsum; 4HP3; -.
DR AlphaFoldDB; A0JP82; -.
DR SMR; A0JP82; -.
DR GeneID; 100036628; -.
DR KEGG; xtr:100036628; -.
DR CTD; 200424; -.
DR Xenbase; XB-GENE-877084; tet3.
DR eggNOG; ENOG502QURD; Eukaryota.
DR OrthoDB; 29059at2759; -.
DR Proteomes; UP000008143; Chromosome 3.
DR Proteomes; UP000790000; Unplaced.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0070989; P:oxidative demethylation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; Chromatin regulator; Chromosome; Developmental protein;
KW Dioxygenase; DNA-binding; Iron; Metal-binding; Nucleus; Oxidoreductase;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..1901
FT /note="Methylcytosine dioxygenase tet3"
FT /id="PRO_0000442317"
FT ZN_FING 58..99
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT REGION 434..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 602..658
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 751..787
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 808..867
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1282..1338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1457..1501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1591..1624
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1680..1745
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 616..651
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 751..784
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 813..827
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 843..867
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1282..1322
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1323..1338
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1680..1723
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1724..1742
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 65
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 71
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 77
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 80
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 83
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 957
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 959
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1017
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1043
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1045
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1085
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1095
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1097
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1113
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1198
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1204
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1206
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:23217707"
FT BINDING 1208
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:23217707"
FT BINDING 1240
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1780
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1795..1797
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT MUTAGEN 90
FT /note="H->A: Abolishes binding to target DNA. No effect on
FT nuclear location and on enzyme activity."
FT /evidence="ECO:0000269|PubMed:23217707"
FT MUTAGEN 90
FT /note="H->R: Increased binding affinity for CpT dsDNA."
FT /evidence="ECO:0000269|PubMed:29276034"
FT MUTAGEN 1206..1208
FT /note="Missing: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:23217707"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:4HP3"
FT HELIX 69..72
FT /evidence="ECO:0007829|PDB:4HP3"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:4HP3"
FT HELIX 81..84
FT /evidence="ECO:0007829|PDB:4HP3"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:4HP3"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:4HP3"
FT TURN 99..102
FT /evidence="ECO:0007829|PDB:4HP3"
SQ SEQUENCE 1901 AA; 210426 MW; C74D3B847C920212 CRC64;
MDTQPAPVPH VLPQDVYEFP DDQESLGRLR VSEMPAELNG GGGGGSAAAF AMELPEQSNK
KRKRCGVCVP CLRKEPCGAC YNCVNRSTSH QICKMRKCEQ LKKKRVVPMK GVENCSESIL
VDGPKTDQME AGPVNHVQEG RLKQECDSTL PSKGCEDLAN QLLMEANSWL SNTAAPQDPC
NKLNWDKPTI PNHAANNNSN LEDAKNLVAF SAVAEAMSTY GMPASGTPSS VSLQLYEKFN
YETNRDNSGH LEGNAPSCPE DLNTLKAALA LAKHGVKPPN CNCDGPECPD YLEWLENKIK
STVKGSQESP FPNLGQVSKE LVQKQYPKEQ VLNLENKNST CPSGNLPFSQ NALSLAKEKN
ISLQTAIAIE ALTQLSSALP QTNNECPNAP SQPLINPHDQ LTHFPSAKGN QLPMLPVARN
ELFQNQQSQL YTGKNALPVP QSPRQTSWEQ NKKSSYQEGQ YIPENLSHSS SVLPSDASTP
QKPEFLQQWV QNADLLKSPS DPMTGLKQLL GNTDEYIKSV FKGPEALPNK KNVKPKHTIK
SIKKESTEFL KMSPDQQLSQ LLQTNEFHRN TQAALQQHLH HKRNLFVDPN AMEACTQEQQ
NWWVPSSQQA PVSKTTEKPV KERKKRRQSP SQKQVEPKPK PQRKQVQIKK PKVKEGSAVF
MPVSQISLDT FRRVEKEENQ GKEMDAENSL PNNVQTELLE SQSLQLTGSQ ANPDDRKTVN
TQEMCNENQS NIGKANNFAL CVNRANSFVA KDQCPTPSTH DTSSSSGQGD SANQHTNVSD
VPGQNDLSCL DDKLEDLIRQ FEAEFGEDFS LPGSAVPSQN GEGPPKQTPS GDPQFKLPFP
SQLLPPENST KPATHSNPAL SNNPVSREVS NNLDSLFSSK SPKQIKIESS GAITVVSTTC
FYSEENQHLD GTPTKSDLPF NPTLSGFLDS PLKYLTSPTK SLIDTPAKKA QAEFPTCDCV
EQINEKDEGP YYTHLGSGPT VASIRELMEE RFGQKGDAIR IEKVIYTGKE GKSSRGCPIA
KWVIRRQSED EKLMCLVRQR AGHHCENAVI IILIMAWEGI PRSLGDSLYN DITETITKYG
NPTSRRCGLN DDRTCACQGK DPNTCGASFS FGCSWSMYFN GCKYARSKTP RKFRLIGENP
KEEDGLKDNF QNLATKVAPV YKMLAPQAYQ NQVNNEDIAI DCRLGLKEGR PFSGVTACMD
FCAHAHKDQH NLYNGCTVVC TLTKEDNRMI GRVAEDEQLH VLPLYKVSTT DEFGSEEGQL
EKIKKGGIHV LSSFPREVRK LSEPAKSCRQ RQLEAKKAAA EKKKLQKEKL VSPDKTKQEP
SDKKTCQQNP GVPQQQTKPC IKVEPSNHYN NFKYNGNGVV ESYSVLGSCR PSDPYSMNSV
YSYHSFYAQP NLPSVNGFHS KYALPPFGFY GFPNNPVVPN QFMNYGTSDA RNSGWMNNCF
EKKPELQSLA DGMNQSYGSE LSEQSFRRSS EVPHHYSLQN PSSQKSVNVP HRTTPAPVET
TPYSNLPCYN KVIKKEPGSD PLVDSFQRAN SVHSHSPGVN HSLQASDLPI SYKANGALSS
SGRTNAESPC SMFMPNDKNG LEKKDYFGVH SNAPGLKDKQ WPPYGTDVSV RQHDSLDSQS
PGKVWSSCKL SDSSAALPSS ASTQDKNWNG RQVSLNQGMK ESALFQEKLW NSVAASDRCS
ATPSDRSSIT PCSELQDKNW GSFPNPTVNS LKTDSSQNHW DPYSLDDNMD DGQSKSVKEE
DDEEIWSDSE HNFLDENIGG VAVAPGHGSI LIECARRELH ATTPLKKPNR CHPTRISLVF
YQHKNLNQPN HGLALWEAKM KQLAERARAR EEEAAKLGIK QEVKSLGKKR KWGGAATTET
PPVEKKDYTP TRQAATILTD SATTSFSYAY TKVTGPYSRF I
