TET3B_XENLA
ID TET3B_XENLA Reviewed; 1915 AA.
AC K9JHZ4;
DT 22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=Methylcytosine dioxygenase tet3-B;
DE EC=1.14.11.n2 {ECO:0000269|PubMed:23217707};
GN Name=tet3-b {ECO:0000312|EMBL:ADU77106.1};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355 {ECO:0000312|EMBL:ADU77106.1};
RN [1] {ECO:0000312|EMBL:ADU77106.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, DISRUPTION
RP PHENOTYPE, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
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).
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:0000250|UniProtKB:A0JP82}.
CC Chromosome {ECO:0000250|UniProtKB:A0JP82}. Note=Detected on chromatin,
CC where it binds to target gene promoters.
CC {ECO:0000250|UniProtKB:A0JP82}.
CC -!- TISSUE SPECIFICITY: Detected in embryo (at protein level). Detected in
CC embryonic head, in developing brain and eye.
CC {ECO:0000269|PubMed:23217707}.
CC -!- DEVELOPMENTAL STAGE: Expression in oocytes is very low. Barely
CC detectable from stage 2 (2-cell stage) to stage 9. Increases strongly
CC from stage 9 to 17, and decreases again at stage 25.
CC {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:0000250|UniProtKB:A0JP82}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of both tet3-a and tet3-b
CC causes defects in embryonic development, including malformations of the
CC eye (eyeless), small head, and missing pigmentation along the lateral
CC body, leading to embryonic death between stages 35 and 40.
CC {ECO:0000269|PubMed:23217707}.
CC -!- SIMILARITY: Belongs to the TET family. {ECO:0000305}.
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DR EMBL; HQ220208; ADU77106.1; -; mRNA.
DR AlphaFoldDB; K9JHZ4; -.
DR SMR; K9JHZ4; -.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0070579; F:methylcytosine dioxygenase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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; IEA:InterPro.
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 Chromatin regulator; Chromosome; Coiled coil; Developmental protein;
KW Dioxygenase; DNA-binding; Iron; Metal-binding; Nucleus; Oxidoreductase;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..1915
FT /note="Methylcytosine dioxygenase tet3-B"
FT /id="PRO_0000442316"
FT ZN_FING 61..102
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT REGION 28..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 629..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 776..806
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 831..880
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1298..1356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1469..1516
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1719..1753
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1827..1860
FT /evidence="ECO:0000255"
FT COMPBIAS 640..675
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 835..880
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1298..1338
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1339..1356
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1469..1507
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1719..1736
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1737..1753
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 74
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
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 86
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 974
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 976
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1034
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1060
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1062
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1102
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1130
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1215
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1221
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1223
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1225
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1257
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1794
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1809..1811
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
SQ SEQUENCE 1915 AA; 212099 MW; 49CC646926FBE86C CRC64;
METQPASVPC VLPQDVYEFS EDRESLGRLR VSEMPSELNG GGDGSKGDGA AVVATEVSQQ
SNKKRKRCGV CVPCLRKEPC GTCYNCVNRS TSHQICKMRK CEQLKKKRVV PMKGVEAVDK
DDAKNQAKEQ VPSVKNCSES ILVDGPKTDQ MEAGPVNHVQ EGRLKQECDS TLPSKGSEDL
ANQLLMEANS WLSNTAAPQD PCNKLNWDKP IIPNHIAANN NSNLEDAKNL VAFSAVAEAM
SNYGMPASGT PSSISMQLYE KFNYETNQDN SGHSEGNAPS CPEDLNTLKE ALALAKHGVK
PPNCNCDGPE CPDYLEWLEN KIKSTGKGSQ ESPFPSLGQV SKKLVQKSYH KEQVLNLENT
NVTCPSGNLP FSQNALSLAK EKNISLQTAI AIEALTQLSS ALPQTNNEYP NAPSQPLINH
NDQLTHFPTA KGNQLPMLPL SCNELFQNQQ AQLYTGKNAL PVPQSPRQAS WEQNKKPGYQ
ESEYIPENLS QSSSVLPSDA STPQKKEFLQ QWVQNADLLK SPSDPMTGLK QLLGNTDEYI
KSAFKGPEGL SKKIKNVKSK HTIKSIKKES ADFTKMSPDQ QLSQLLQGND FHRNTQAALQ
QHLHHKRNLF VDSNTMEACT QEQQNWWVPN SQQAPVSKTT EKPVKERKKR RQSPSQKQVE
PKPKPPRKQV QIKKPRVKEG NAVFMPVSQI SLDSFRRVEK EENQVKELDL ENSLPINVQP
DLLGSQSIQL TGSQANLENQ KTVNTQETCN ENQTSIGKAN NFALCVNKTN SLVAKGRCPT
PSTGDSSSGQ GDSANQHTNL TDVPGQNDLS CIDDKFEDLI KQFAAEFGED FSLPGSEVPS
QNGERPPKQQ TSGVPQFKMP FPSQLPSENA THSNPALSNN LLTHNASHKF DSLFSSKSPK
QIKIESSGAI TVVSTTCSYS EENQHLDGTP TKSELPFNPT LSGFLESPLK YLTSPTKSLI
DTPAKMAQAE FPTCDCVEQI NEKDEGPYYT HLGSGPTVAS IRELMEERFG EKGEAIRIEK
VIYTGKEGKS SRGCPIAKWV IRRQSEDEKL MCLVRQRAGH HCENAVIIIL IMAWEGIPRA
LGDSLYDDIS GTITKYGNPT SRRCGLNDDR TCACQGKDPN TCGASFSFGC SWSMYFNGCK
YARSKTPRKF RLIGDNPKEE EFLKDSFQDL ATKVAPVYKM LAPQAYQNQA NNEDVAIDCR
LGLEEGRPFS GVTACMDFCA HAHKDQHNLY NGCTVVCTLT KEDNRMIGKI AEDEQLHVLP
LYKVSTTDEF GSEERQLEKI RKGGIQVLSS FPREVRKLSE PAKSCRQRQL DAKKATAEKK
KLQKEKLVSP DKTKQEPSDT KTCQQNPGVP QQQTKPCVKV EPSNHYNTFK YNGNGVVESY
SVLGSCRPSD PYSMNSVYSY HSFYAQPNLP SVNGFHSKFA LPPFGFYSFP NNPVVPNQFM
NYGTGDARNS GWMNNSFEKK PELQSLADGM NQSYGSELPE QNYRRSSEVP HHYSLQNSNS
QKSVGVPHRT TPAPMETTPY SNVPCYNKVI KKEPVCDPLV DPFQRSNSVH SQSPGVNHSL
QTNDLSYKAN GALPSSGRTN KEGPCSMFLP SDKNGLEKRD YFGVHSNVPG LKEKQWTPYG
IDVPVGQRDS LDSQCSGKVW SSCKLSDSPA VMPSTVQDKN WTGRQASLNQ GVKEPMPFQE
KLWNSVAASG RCSTTPNDRS SVTPCAELQD KNWMSFPNPA VNSLKTDSSQ NHWDPYSLDD
NMDDGQSKSV KEEEDEEEIW SDSEHNFLDG NIGGVAVAPG HGSILIECAR RELHATTPLK
KPNRCHPTRI SLVFYQHKNL NQPNHGLALW EAKMKQLAER ARVKEEEAAK LGIKQEVKSL
GKKRKWGGAA TTETPPVEKK DFIPTRQAAT SLTDSTTTAF SYAYTKVTGP YSRFI
