TET3A_XENLA
ID TET3A_XENLA Reviewed; 1925 AA.
AC A0A1L8GSA2; K9JHZ7;
DT 22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Methylcytosine dioxygenase tet3-A;
DE EC=1.14.11.n2 {ECO:0000269|PubMed:23217707};
GN Name=tet3-a {ECO:0000312|Xenbase:XB-GENE-17338508};
GN ORFNames=XELAEV_18020377mg {ECO:0000312|EMBL:OCT86689.1};
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|Proteomes:UP000186698};
RN [1] {ECO:0000312|EMBL:ADU77105.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, DEVELOPMENTAL
RP STAGE, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
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|Proteomes:UP000186698}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=J {ECO:0000312|Proteomes:UP000186698};
RX PubMed=27762356; DOI=10.1038/nature19840;
RA Session A.M., Uno Y., Kwon T., Chapman J.A., Toyoda A., Takahashi S.,
RA Fukui A., Hikosaka A., Suzuki A., Kondo M., van Heeringen S.J., Quigley I.,
RA Heinz S., Ogino H., Ochi H., Hellsten U., Lyons J.B., Simakov O.,
RA Putnam N., Stites J., Kuroki Y., Tanaka T., Michiue T., Watanabe M.,
RA Bogdanovic O., Lister R., Georgiou G., Paranjpe S.S., van Kruijsbergen I.,
RA Shu S., Carlson J., Kinoshita T., Ohta Y., Mawaribuchi S., Jenkins J.,
RA Grimwood J., Schmutz J., Mitros T., Mozaffari S.V., Suzuki Y., Haramoto Y.,
RA Yamamoto T.S., Takagi C., Heald R., Miller K., Haudenschild C., Kitzman J.,
RA Nakayama T., Izutsu Y., Robert J., Fortriede J., Burns K., Lotay V.,
RA Karimi K., Yasuoka Y., Dichmann D.S., Flajnik M.F., Houston D.W.,
RA Shendure J., DuPasquier L., Vize P.D., Zorn A.M., Ito M., Marcotte E.M.,
RA Wallingford J.B., Ito Y., Asashima M., Ueno N., Matsuda Y., Veenstra G.J.,
RA Fujiyama A., Harland R.M., Taira M., Rokhsar D.S.;
RT "Genome evolution in the allotetraploid frog Xenopus laevis.";
RL Nature 538:336-343(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 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, neural tube 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; CM004471; OCT86689.1; -; Genomic_DNA.
DR EMBL; HQ220207; ADU77105.1; -; mRNA.
DR RefSeq; XP_018110686.1; XM_018255197.1.
DR RefSeq; XP_018110687.1; XM_018255198.1.
DR AlphaFoldDB; A0A1L8GSA2; -.
DR SMR; A0A1L8GSA2; -.
DR STRING; 8355.A0A1L8GSA2; -.
DR GeneID; 108712780; -.
DR KEGG; xla:108712780; -.
DR CTD; 108712780; -.
DR Xenbase; XB-GENE-17338508; tet3.S.
DR OMA; PDSQWGL; -.
DR OrthoDB; 29059at2759; -.
DR Proteomes; UP000186698; Chromosome 3S.
DR Bgee; 108712780; Expressed in blastula and 8 other tissues.
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..1925
FT /note="Methylcytosine dioxygenase tet3-A"
FT /id="PRO_0000442315"
FT ZN_FING 62..103
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT REGION 457..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 630..685
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 774..812
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 833..892
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1307..1364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1474..1513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1556..1600
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1722..1769
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1837..1870
FT /evidence="ECO:0000255"
FT COMPBIAS 655..676
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 774..808
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 838..852
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 866..892
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1307..1346
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1347..1364
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1556..1595
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1725..1746
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1747..1764
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 69
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 72
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 75
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 81
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 87
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 102
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 982
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
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 1042
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1068
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1070
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1110
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1120
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1138
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1223
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1229
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1231
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1233
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1265
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1804
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT BINDING 1819..1821
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q6N021"
FT CONFLICT 1
FT /note="Missing (in Ref. 1; ADU77105)"
FT /evidence="ECO:0000305"
FT CONFLICT 598
FT /note="A -> V (in Ref. 1; ADU77105)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1925 AA; 213144 MW; 5A1C1757BF9BAEAC CRC64;
MMETQPTSLP HVLPQDVYEF CDDRKSLGRL RVSEMPAESN GDGGGSKGDG AAVVAKEVPE
QSNKKRKRCG VCVPCLRKEP CGACYNCVNR STSHQICKMR KCEQLKKKRV VPLKGVEAVN
KDDSKNQAKE QVPNVKNCSE SILVDGPKTD QMEAGPVNHV QEGRLKKECD STLPSKACED
LANQLLMEAN SWLSNTAAPQ DPCNKLNWDK PTIPNHTAAT NNSNLEDAKN LVAFSAVAEA
MSNYGMPASG TPSSVSMQLY EKFNYETNRD SSGHPEGNAP SCPEDLNTLK TALALAKHGV
KPPNCNCDGP ECPDYLEWLE NKIKSSQKDS QESSFPGLGQ VSKELVQKSY PKEEVLNLEN
KNLCPSGNLP FSQNALSLAK EKNISLQTAI AIEALTQLSS ALPQTNNECP NSSSQPLINT
CDQLTHFPTA KGNQLPIFPM ACNELFQNQQ SQLYTGKNAL PVPQSPRQTS WEQNKKPSYQ
EGQYIPENLS QSSSVLPSDA STPQKTEFLQ QWIQNADLLK SPSDPMTGLK QLLGNTDEYI
KSVFKGPEAL PNKIKHVKTK RTIKSIKKKS SDFLKMSPDQ QLSQLLQEND FHHNAQAALQ
QHLHHKRNLF VDPNTMEACA QEQQNWWVPK SQKLPVSKTT ENPVKERKKR RQRSPSQKQV
EPKPKPPRKQ VQIKKPRMKE GNAVFMPVSQ ISLDAFRGAE KEENQLKEMN LEKSLSNNIQ
PDLLESQSIL VTGSQANIEN RKTVNTQETC NENQASNGKA SNFALCVNQA NSLGAKDSCP
TPSTDDASSS SGQGDSANQH TNVGDVPGQN DLSCLDDKFE DLLRQFEAEF GEDFSLPGSE
APSQNGVGPP KQQISGDPQF KMPFPSQLLP SENSTRPDAH SNPALSNNPI SHNVSHNLDS
LFSSKSPKKI KIESSGAITV VSTTCFYSEE NQHLDGTPTK SDLPFNPTLS GFLESPLKYL
TSPTKSLIDT PAKMAQAEFP TCDCVEQINE KDEGPYYTHL GSGPTVASIR ELMEDRFGEK
GEAIRIEKVI YTGKEGKSSR GCPIAKWVIR RQSEDEKLMC LVRQRAGHHC ENAVIIILIM
AWEGIPRALG DSLYSDITET ITKYGNPTSR RCGLNDDRTC ACQGKDPNTC GASFSFGCSW
SMYFNGCKYA RSKTPRKFRL IGDNPKEEEF LNDNFQDLAT KVAPVYQMLA PQSYENQVNN
EEVAIDCRLG LKEGRPFSGV TACMDFCAHA HKDQHNLYNG CTVVCTLTKE DNRTIGRIPE
DEQLHVLPLY KVSSTDEFGS EDGQAEKIRK GGIQVLASFP REVRKLSEPA KSCRQRQLDA
KKAAAEKKKL QKEKLVSPDK TKQEPADTKM CQQNPGVPQQ QTKPCVKVEP SNHYNTYKYN
GNGVVESYSV LGSCRPSDPY SMNSVYSYHS FYAQPNLPSV NGFHSKFALP PFGFYGFPNN
PVVPNQFMNY GTSDARNSGW MNNSFEKKPD VQSLADGMNQ SYGSELPEQS YRRSSEVPHH
YSLQNPNSQK SFNISHRTTP SPMETTPYSN LPCYNKVIKK EPVCDPLVDP FQRANSVHSQ
SPGVNHSLQT SDLPFKANGA LPSSGRSNAE GPCSMSLPND KSGLEKRDYF GVHSNVPALK
DKQWTPYGTD VPVGQRDSLD AQSPGKVWSS CKLSDSPAVL PSFASTQTKN WNGRQASLNQ
GLKEPMPFQE KLWNSVAASD RCSVTPSDRS SVTPCAELQD KNWASFPNPV GNSLKTESSQ
NHWDPYSLDD NMDDGQSKSV KEEEDEEEIW SDSEHNFLDK NIGGVAVAPG HGSILIECAR
RELHATTPLK KPNRCHPARI SLVFYQHKNL NQPNHGLALW EAKMKLLAER ARVKEEEAAR
LGIKQEVKSL GKKRKWGGAA TTETPPVEKK DFIPTRQATT ILTDSATTAF SYAYTKVTGP
YSRFI
