Protein: Methylcytosine dioxygenase TET2 (Q6N021)
Organism: Homo sapiens (Human)
Function: Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT
Subcellular location: Nucleus. Chromosome . Note=Localization to chromatin depends upon monoubiquitination at Lys-1299
InterPro domains:
- IPR024779: 2OGFeDO JBP1/TET, oxygenase domain (domain) [1290-1905]
- IPR046942: Methylcytosine dioxygenase TET1-3, oxygenase domain (domain) [1290-1905]
- IPR040175: Methylcytosine dioxygenase TET1/2/3 (family) [1-2002]
Sequence:
MEQDRTNHVEGNRLSPFLIPSPPICQTEPLATKLQNGSPLPERAHPEVNGDTKWHSFKSYYGIPCMKGSQNSRVSPDFTQESRGYSKCLQNGGIKRTVSEPSLSGLLQIKKLKQDQKANGERRNFGVSQERNPGESSQPNVSDLSDKKESVSSVAQENAVKDFTSFSTHNCSGPENPELQILNEQEGKSANYHDKNIVLLKNKAVLMPNGATVSASSVEHTHGELLEKTLSQYYPDCVSIAVQKTTSHINAINSQATNELSCEITHPSHTSGQINSAQTSNSELPPKPAAVVSEACDADDADNASKLAAMLNTCSFQKPEQLQQQKSVFEICPSPAENNIQGTTKLASGEEFCSGSSSNLQAPGGSSERYLKQNEMNGAYFKQSSVFTKDSFSATTTPPPPSQLLLSPPPPLPQVPQLPSEGKSTLNGGVLEEHHHYPNQSNTTLLREVKIEGKPEAPPSQSPNPSTHVCSPSPMLSERPQNNCVNRNDIQTAGTMTVPLCSEKTRPMSEHLKHNPPIFGSSGELQDNCQQLMRNKEQEILKGRDKEQTRDLVPPTQHYLKPGWIELKAPRFHQAESHLKRNEASLPSILQYQPNLSNQMTSKQYTGNSNMPGGLPRQAYTQKTTQLEHKSQMYQVEMNQGQSQGTVDQHLQFQKPSHQVHFSKTDHLPKAHVQSLCGTRFHFQQRADSQTEKLMSPVLKQHLNQQASETEPFSNSHLLQHKPHKQAAQTQPSQSSHLPQNQQQQQKLQIKNKEEILQTFPHPQSNNDQQREGSFFGQTKVEECFHGENQYSKSSEFETHNVQMGLEEVQNINRRNSPYSQTMKSSACKIQVSCSNNTHLVSENKEQTTHPELFAGNKTQNLHHMQYFPNNVIPKQDLLHRCFQEQEQKSQQASVLQGYKNRNQDMSGQQAAQLAQQRYLIHNHANVFPVPDQGGSHTQTPPQKDTQKHAALRWHLLQKQEQQQTQQPQTESCHSQMHRPIKVEPGCKPHACMHTAPPENKTWKKVTKQENPPASCDNVQQKSIIETMEQHLKQFHAKSLFDHKALTLKSQKQVKVEMSGPVTVLTRQTTAAELDSHTPALEQQTTSSEKTPTKRTAASVLNNFIESPSKLLDTPIKNLLDTPVKTQYDFPSCRCVEQIIEKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVVRRSSSEEKLLCLVRERAGHTCEAAVIVILILVWEGIPLSLADKLYSELTETLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFGCSWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPFSGVTACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREFGGKPEDEQLHVLPLYKVSDVDEFGSVEAQEEKKRSGAIQVLSSFRRKVRMLAEPVKTCRQRKLEAKKAAAEKLSSLENSSNKNEKEKSAPSRTKQTENASQAKQLAELLRLSGPVMQQSQQPQPLQKQPPQPQQQQRPQQQQPHHPQTESVNSYSASGSTNPYMRRPNPVSPYPNSSHTSDIYGSTSPMNFYSTSSQAAGSYLNSSNPMNPYPGLLNQNTQYPSYQCNGNLSVDNCSPYLGSYSPQSQPMDLYRYPSQDPLSKLSLPPIHTLYQPRFGNSQSFTSKYLGYGNQNMQGDGFSSCTIRPNVHHVGKLPPYPTHEMDGHFMGATSRLPPNLSNPNMDYKNGEHHSPSHIIHNYSAAPGMFNSSLHALHLQNKENDMLSHTANGLSKMLPALNHDRTACVQGGLHKLSDANGQEKQPLALVQGVASGAEDNDEVWSDSEQSFLDPDIGGVAVAPTHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKMAEKAREKEEECEKYGPDYVPQKSHGKKVKREPAEPHETSEPTYLRFIKSLAERTMSVTTDSTVTTSPYAFTRVTGPYNRYI
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity), GO:0043167 (ion binding), GO:0005515 (protein binding), GO:0043169 (cation binding), GO:0051213 (dioxygenase activity), GO:0016705 (oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen), GO:0046872 (metal ion binding), GO:0016706 (2-oxoglutarate-dependent dioxygenase activity), GO:0046914 (transition metal ion binding), GO:0005506 (iron ion binding), GO:0008270 (zinc ion binding), GO:0008198 (ferrous iron binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0009058 (biosynthetic process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0070085 (glycosylation), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0070988 (demethylation), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:1901564 (organonitrogen compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0046483 (heterocycle metabolic process), GO:0044248 (cellular catabolic process), GO:0019538 (protein metabolic process), GO:0080111 (DNA demethylation), GO:0060255 (regulation of macromolecule metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0043170 (macromolecule metabolic process), GO:0043413 (macromolecule glycosylation), GO:0009891 (positive regulation of biosynthetic process), GO:1901135 (carbohydrate derivative metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:1901575 (organic substance catabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0030097 (hemopoiesis), GO:0009059 (macromolecule biosynthetic process), GO:0044270 (cellular nitrogen compound catabolic process), GO:0002521 (leukocyte differentiation), GO:1901565 (organonitrogen compound catabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0019439 (aromatic compound catabolic process), GO:0046700 (heterocycle catabolic process), GO:0030099 (myeloid cell differentiation), GO:0010468 (regulation of gene expression), GO:0036211 (protein modification process), GO:1901566 (organonitrogen compound biosynthetic process), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0006486 (protein glycosylation), GO:0043412 (macromolecule modification), GO:0009100 (glycoprotein metabolic process), GO:0090304 (nucleic acid metabolic process), GO:1901361 (organic cyclic compound catabolic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0006259 (DNA metabolic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0034645 (cellular macromolecule biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:1901137 (carbohydrate derivative biosynthetic process), GO:0072527 (pyrimidine-containing compound metabolic process), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0006304 (DNA modification), GO:2001141 (regulation of RNA biosynthetic process), GO:0006493 (protein O-linked glycosylation), GO:0006355 (regulation of DNA-templated transcription), GO:1902680 (positive regulation of RNA biosynthetic process), GO:0009101 (glycoprotein biosynthetic process), GO:0072529 (pyrimidine-containing compound catabolic process), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045893 (positive regulation of DNA-templated transcription), GO:0035510 (DNA dealkylation), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0045944 (positive regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)