Protein: Methylcytosine dioxygenase TET1 (EC 1.14.11.80) (CXXC-type zinc finger protein 6) (Ten-eleven translocation 1 gene protein homolog) (Q3URK3)
Organism: Mus musculus (Mouse)
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. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). In addition to its role in DNA demethylation, plays a more general role in chromatin regulation by recruiting histone modifying protein complexes to alter histone marks and chromatin accessibility, leading to both activation and repression of gene expression. Plays therefore a role in many biological processes and diseases, including stem cell maintenance, T and B-cell development, inflammation regulation, iron homeostasis, neural activity or DNA repair. Involved in the balance between pluripotency and lineage commitment of cells it plays a role in embryonic stem cells maintenance and inner cell mass cell specification. Plays an important role in the tumorigenicity of glioblastoma cells. TET1-mediated production of 5hmC acts as a recruitment signal for the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of genes involved in glioblastomagenesis. Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (By similarity). Plays an essential role in the protection and maintenance of transcriptional and developmental programs together with QSER1 to inhibit the binding of DNMT3A/3B and therefore de novo methylation (By similarity).
Subcellular location: Nucleus {ECO:0000269|PubMed:25557551}. Chromosome {ECO:0000269|PubMed:32286661}.; SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:27916660, ECO:0000269|PubMed:36056023}. Chromosome {ECO:0000269|PubMed:27916660}. Note=Contrary to isoform 2, which accumulates at sites of ongoing DNA replication in heterochromatin, isoform 1 shows a homogenous nuclear pattern during mitotic S phase. {ECO:0000269|PubMed:36056023}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:27916660, ECO:0000269|PubMed:36056023}. Chromosome {ECO:0000269|PubMed:27916660}. Note=During DNA replication, localizes to sites of ongoing DNA replication in heterochromatin (in late S phase) in an UHRF1- and CRL4(VprBP)-dependent manner, by ubiquitination of the conserved residue Lys-1537. Localization to heterochromatin is independent of catalytic activity. {ECO:0000269|PubMed:36056023}.
Interaction partners:
- Homeobox protein NANOG
- Paired amphipathic helix protein Sin3a
- Growth arrest and DNA damage-inducible protein GADD45 alpha
- Histone deacetylase 1
- UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit
- Histone deacetylase 2
- AT-rich interactive domain-containing protein 4B
- DNA
- Methylcytosine dioxygenase TET2
- DNA
Sequence:
MSRSRPAKPSKSVKTKLQKKKDIQMKTKTSKQAVRHGASAKAVNPGKPKQLIKRRDGKKETEDKTPTPAPSFLTRAGAARMNRDRNQVLFQNPDSLTCNGFTMALRRTSLSWRLSQRPVVTPKPKKVPPSKKQCTHNIQDEPGVKHSENDSVPSQHATVSPGTENGEQNRCLVEGESQEITQSCPVFEERIEDTQSCISASGNLEAEISWPLEGTHCEELLSHQTSDNECTSPQECAPLPQRSTSEVTSQKNTSNQLADLSSQVESIKLSDPSPNPTGSDHNGFPDSSFRIVPELDLKTCMPLDESVYPTALIRFILAGSQPDVFDTKPQEKTLITTPEQVGSHPNQVLDATSVLGQAFSTLPLQWGFSGANLVQVEALGKGSDSPEDLGAITMLNQQETVAMDMDRNATPDLPIFLPKPPNTVATYSSPLLGPEPHSSTSCGLEVQGATPILTLDSGHTPQLPPNPESSSVPLVIAANGTRAEKQFGTSLFPAVPQGFTVAAENEVQHAPLDLTQGSQAAPSKLEGEISRVSITGSADVKATAMSMPVTQASTSSPPCNSTPPMVERRKRKACGVCEPCQQKANCGECTYCKNRKNSHQICKKRKCEVLKKKPEATSQAQVTKENKRPQREKKPKVLKTDFNNKPVNGPKSESMDCSRRGHGEEEQRLDLITHPLENVRKNAGGMTGIEVEKWAPNKKSHLAEGQVKGSCDANLTGVENPQPSEDDKQQTNPSPTFAQTIRNGMKNVHCLPTDTHLPLNKLNHEEFSKALGNNSSKLLTDPSNCKDAMSVTTSGGECDHLKGPRNTLLFQKPGLNCRSGAEPTIFNNHPNTHSAGSRPHPPEKVPNKEPKDGSPVQPSLLSLMKDRRLTLEQVVAIEALTQLSEAPSESSSPSKPEKDEEAHQKTASLLNSCKAILHSVRKDLQDPNVQGKGLHHDTVVFNGQNRTFKSPDSFATNQALIKSQGYPSSPTAEKKGAAGGRAPFDGFENSHPLPIESHNLENCSQVLSCDQNLSSHDPSCQDAPYSQIEEDVAAQLTQLASTINHINAEVRNAESTPESLVAKNTKQKHSQEKRMVHQKPPSSTQTKPSVPSAKPKKAQKKARATPHANKRKKKPPARSSQENDQKKQEQLAIEYSKMHDIWMSSKFQRFGQSSPRSFPVLLRNIPVFNQILKPVTQSKTPSQHNELFPPINQIKFTRNPELAKEKVKVEPSDSLPTCQFKTESGGQTFAEPADNSQGQPMVSVNQEAHPLPQSPPSNQCANIMAGAAQTQFHLGAQENLVHQIPPPTLPGTSPDTLLPDPASILRKGKVLHFDGITVVTEKREAQTSSNGPLGPTTDSAQSEFKESIMDLLSKPAKNLIAGLKEQEAAPCDCDGGTQKEKGPYYTHLGAGPSVAAVRELMETRFGQKGKAIRIEKIVFTGKEGKSSQGCPVAKWVIRRSGPEEKLICLVRERVDHHCSTAVIVVLILLWEGIPRLMADRLYKELTENLRSYSGHPTDRRCTLNKKRTCTCQGIDPKTCGASFSFGCSWSMYFNGCKFGRSENPRKFRLAPNYPLHNYYKRITGMSSEGSDVKTGWIIPDRKTLISREEKQLEKNLQELATVLAPLYKQMAPVAYQNQVEYEEVAGDCRLGNEEGRPFSGVTCCMDFCAHSHKDIHNMHNGSTVVCTLIRADGRDTNCPEDEQLHVLPLYRLADTDEFGSVEGMKAKIKSGAIQVNGPTRKRRLRFTEPVPRCGKRAKMKQNHNKSGSHNTKSFSSASSTSHLVKDESTDFCPLQASSAETSTCTYSKTASGGFAETSSILHCTMPSGAHSGANAAAGECTGTVQPAEVAAHPHQSLPTADSPVHAEPLTSPSEQLTSNQSNQQLPLLSNSQKLASCQVEDERHPEADEPQHPEDDNLPQLDEFWSDSEEIYADPSFGGVAIAPIHGSVLIECARKELHATTSLRSPKRGVPFRVSLVFYQHKSLNKPNHGFDINKIKCKCKKVTKKKPADRECPDVSPEANLSHQIPSRVASTLTRDNVVTVSPYSLTHVAGPYNRWV