ID A0A158SIU0_HUMAN Unreviewed; 2002 AA. AC A0A158SIU0; DT 08-JUN-2016, integrated into UniProtKB/TrEMBL. DT 08-JUN-2016, sequence version 1. DT 24-JUL-2024, entry version 42. DE RecName: Full=Methylcytosine dioxygenase TET {ECO:0000256|RuleBase:RU367064}; DE EC=1.14.11.80 {ECO:0000256|RuleBase:RU367064}; GN Name=TET2 {ECO:0000313|EMBL:CAX30492.1}; 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 {ECO:0000313|EMBL:CAX30492.1}; RN [1] {ECO:0000313|EMBL:CAX30492.1} RP NUCLEOTIDE SEQUENCE. RA Madupu R., Sebastian Y., Durkin A.S., Torralba M., Methe B., Sutton G.G., RA Strausberg R.L., Nelson K.E.; RL Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000313|EMBL:CAX30492.1} RP NUCLEOTIDE SEQUENCE. RA Delhommeau F., Dupont S., DellaValle V., James C., Trannoy S., Masse A., RA Kosmider O., Le Couedic J.P., Robert F., Alberdi A., Lecluse Y., Plo I., RA Dreyfus F.J., Marzac C., Casadevall N., Lacombe C., Romana S.P., Dessen P., RA Soulier J., Viguie F., Fontenay M., Vainchenker W., Bernard O.A.; RT "TET2 is a tumor suppressor gene inactivated in myeloid malignancies."; RL Submitted (APR-2009) to the EMBL/GenBank/DDBJ databases. 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. {ECO:0000256|RuleBase:RU367064}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + a 5-formyl-2'-deoxycytidine in DNA + O2 = a CC 5-carboxyl-2'-deoxycytidine in DNA + CO2 + H(+) + succinate; CC Xref=Rhea:RHEA:53832, Rhea:RHEA-COMP:13656, Rhea:RHEA-COMP:13657, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:137731, CC ChEBI:CHEBI:137732; EC=1.14.11.80; CC Evidence={ECO:0000256|ARBA:ARBA00034983, CC ECO:0000256|RuleBase:RU367064}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + a 5-hydroxymethyl-2'-deoxycytidine in DNA + CC O2 = a 5-formyl-2'-deoxycytidine in DNA + CO2 + H2O + succinate; CC Xref=Rhea:RHEA:53828, Rhea:RHEA-COMP:13315, Rhea:RHEA-COMP:13656, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:136731, CC ChEBI:CHEBI:137731; EC=1.14.11.80; CC Evidence={ECO:0000256|ARBA:ARBA00034995, CC ECO:0000256|RuleBase:RU367064}; 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=1.14.11.80; Evidence={ECO:0000256|RuleBase:RU367064}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000256|RuleBase:RU367064}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000256|RuleBase:RU367064}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000256|RuleBase:RU367064}; CC Note=The zinc ions have a structural role. CC {ECO:0000256|RuleBase:RU367064}; CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000256|ARBA:ARBA00004286}. CC -!- SIMILARITY: Belongs to the TET family. {ECO:0000256|ARBA:ARBA00007502, CC ECO:0000256|RuleBase:RU367064}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; FM992369; CAX30492.1; -; mRNA. DR RefSeq; NP_001120680.1; NM_001127208.2. DR RefSeq; XP_005263139.1; XM_005263082.2. DR SMR; A0A158SIU0; -. DR Antibodypedia; 45118; 471 antibodies from 38 providers. DR DNASU; 54790; -. DR GeneID; 54790; -. DR KEGG; hsa:54790; -. DR CTD; 54790; -. DR DisGeNET; 54790; -. DR VEuPathDB; HostDB:ENSG00000168769; -. DR OMA; HYSKPAW; -. DR OrthoDB; 5406604at2759; -. DR PhylomeDB; A0A158SIU0; -. DR BioGRID-ORCS; 54790; 8 hits in 1185 CRISPR screens. DR ChiTaRS; TET2; human. DR ExpressionAtlas; A0A158SIU0; baseline and differential. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-UniRule. DR GO; GO:0070579; F:5-methylcytosine dioxygenase activity; IEA:UniProtKB-UniRule. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0006211; P:5-methylcytosine catabolic process; IEA:UniProtKB-UniRule. DR GO; GO:0080111; P:DNA demethylation; IEA:UniProtKB-UniRule. DR GO; GO:0030099; P:myeloid cell differentiation; IEA:TreeGrafter. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:TreeGrafter. DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl. DR CDD; cd18896; TET2; 1. DR InterPro; IPR024779; 2OGFeDO_JBP1/TET_oxygenase_dom. DR InterPro; IPR040175; TET1/2/3. DR InterPro; IPR046942; TET_oxygenase. DR PANTHER; PTHR23358:SF3; METHYLCYTOSINE DIOXYGENASE TET2; 1. DR PANTHER; PTHR23358; UNCHARACTERIZED; 1. DR Pfam; PF12851; Tet_JBP; 1. DR SMART; SM01333; Tet_JBP; 1. PE 2: Evidence at transcript level; KW Chromosome {ECO:0000256|ARBA:ARBA00022454}; KW Dioxygenase {ECO:0000256|RuleBase:RU367064}; KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|RuleBase:RU367064}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, KW ECO:0000256|RuleBase:RU367064}; KW Oxidoreductase {ECO:0000256|RuleBase:RU367064}; KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|RuleBase:RU367064}. FT DOMAIN 1290..1905 FT /note="Methylcytosine dioxygenase TET1-3 oxygenase" FT /evidence="ECO:0000259|SMART:SM01333" FT REGION 1..22 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 113..154 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 266..287 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 349..368 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 390..488 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 703..748 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 930..949 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1075..1095 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1475..1507 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1521..1587 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1932..1961 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 121..154 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 266..286 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 401..417 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 463..488 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 932..946 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1484..1498 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1538..1587 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1932..1959 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 2002 AA; 223811 MW; 6D740305EE2A8D46 CRC64; MEQDRTNHVE GNRLSPFLIP SPPICQTEPL ATKLQNGSPL PERAHPEVNG DTKWHSFKSY YGIPCMKGSQ NSRVSPDFTQ ESRGYSKCLQ NGGIKRTVSE PSLSGLLQIK KLKQDQKANG ERRNFGVSQE RNPGESSQPN VSDLSDKKES VSSVAQENAV KDFTSFSTHN CSGPENPELQ ILNEQEGKSA NYHDKNIVLL KNKAVLMPNG ATVSASSVEH THGELLEKTL SQYYPDCVSI AVQKTTSHIN AINSQATNEL SCEITHPSHT SGQINSAQTS NSELPPKPAA VVSEACDADD ADNASKLAAM LNTCSFQKPE QLQQQKSVFE ICPSPAENNI QGTTKLASGE EFCSGSSSNL QAPGGSSERY LKQNEMNGAY FKQSSVFTKD SFSATTTPPP PSQLLLSPPP PLPQVPQLPS EGKSTLNGGV LEEHHHYPNQ SNTTLLREVK IEGKPEAPPS QSPNPSTHVC SPSPMLSERP QNNCVNRNDI QTAGTMTVPL CSEKTRPMSE HLKHNPPIFG SSGELQDNCQ QLMRNKEQEI LKGRDKEQTR DLVPPTQHYL KPGWIELKAP RFHQAESHLK RNEASLPSIL QYQPNLSNQM TSKQYTGNSN MPGGLPRQAY TQKTTQLEHK SQMYQVEMNQ GQSQGTVDQH LQFQKPSHQV HFSKTDHLPK AHVQSLCGTR FHFQQRADSQ TEKLMSPVLK QHLNQQASET EPFSNSHLLQ HKPHKQAAQT QPSQSSHLPQ NQQQQQKLQI KNKEEILQTF PHPQSNNDQQ REGSFFGQTK VEECFHGENQ YSKSSEFETH NVQMGLEEVQ NINRRNSPYS QTMKSSACKI QVSCSNNTHL VSENKEQTTH PELFAGNKTQ NLHHMQYFPN NVIPKQDLLH RCFQEQEQKS QQASVLQGYK NRNQDMSGQQ AAQLAQQRYL IHNHANVFPV PDQGGSHTQT PPQKDTQKHA ALRWHLLQKQ EQQQTQQPQT ESCHSQMHRP IKVEPGCKPH ACMHTAPPEN KTWKKVTKQE NPPASCDNVQ QKSIIETMEQ HLKQFHAKSL FDHKALTLKS QKQVKVEMSG PVTVLTRQTT AAELDSHTPA LEQQTTSSEK TPTKRTAASV LNNFIESPSK LLDTPIKNLL DTPVKTQYDF PSCRCVEQII EKDEGPFYTH LGAGPNVAAI REIMEERFGQ KGKAIRIERV IYTGKEGKSS QGCPIAKWVV RRSSSEEKLL CLVRERAGHT CEAAVIVILI LVWEGIPLSL ADKLYSELTE TLRKYGTLTN RRCALNEERT CACQGLDPET CGASFSFGCS WSMYYNGCKF ARSKIPRKFK LLGDDPKEEE KLESHLQNLS TLMAPTYKKL APDAYNNQIE YEHRAPECRL GLKEGRPFSG VTACLDFCAH AHRDLHNMQN GSTLVCTLTR EDNREFGGKP EDEQLHVLPL YKVSDVDEFG SVEAQEEKKR SGAIQVLSSF RRKVRMLAEP VKTCRQRKLE AKKAAAEKLS SLENSSNKNE KEKSAPSRTK QTENASQAKQ LAELLRLSGP VMQQSQQPQP LQKQPPQPQQ QQRPQQQQPH HPQTESVNSY SASGSTNPYM RRPNPVSPYP NSSHTSDIYG STSPMNFYST SSQAAGSYLN SSNPMNPYPG LLNQNTQYPS YQCNGNLSVD NCSPYLGSYS PQSQPMDLYR YPSQDPLSKL SLPPIHTLYQ PRFGNSQSFT SKYLGYGNQN MQGDGFSSCT IRPNVHHVGK LPPYPTHEMD GHFMGATSRL PPNLSNPNMD YKNGEHHSPS HIIHNYSAAP GMFNSSLHAL HLQNKENDML SHTANGLSKM LPALNHDRTA CVQGGLHKLS DANGQEKQPL ALVQGVASGA EDNDEVWSDS EQSFLDPDIG GVAVAPTHGS ILIECAKREL HATTPLKNPN RNHPTRISLV FYQHKSMNEP KHGLALWEAK MAEKAREKEE ECEKYGPDYV PQKSHGKKVK REPAEPHETS EPTYLRFIKS LAERTMSVTT DSTVTTSPYA FTRVTGPYNR YI //