Tet1
entrez
52463
canonical
uniprot
Q3URK3
canonical
ensembl
ENSMUSG00000047146
resolver
ensp
ENSMUSP00000133279
resolver
genesymbol
Tet1
resolver
genesymbol_syn
Cxxc6
resolver
genesymbol_syn
Kiaa1676
resolver
uniprot
D0VLQ4
resolver
uniprot
E9Q9Y4
resolver
uniprot
Q6ZPK2
resolver
uniprot
Q9CY36
resolver
uniprot_entry
TET1_MOUSE
resolver
uniprot_sec
D0VLQ4
resolver
uniprot_sec
E9Q9Y4
resolver
uniprot_sec
Q6ZPK2
resolver
uniprot_sec
Q9CY36
resolver
amino_acid_sequence
MSRSRPAKPSKSVKTKLQKKKDIQMKTKTSKQAVRHGASAKAVNPGKPKQLIKRRDGKKETEDKTPTPAPSFLTRAGAARMNRDRNQVLFQNPDSLTCNGFTMALRRTSLSWRLSQRPVVTPKPKKVPPSKKQCTHNIQDEPGVKHSENDSVPSQHATVSPGTENGEQNRCLVEGESQEITQSCPVFEERIEDTQSCISASGNLEAEISWPLEGTHCEELLSHQTSDNECTSPQECAPLPQRSTSEVTSQKNTSNQLADLSSQVESIKLSDPSPNPTGSDHNGFPDSSFRIVPELDLKTCMPLDESVYPTALIRFILAGSQPDVFDTKPQEKTLITTPEQVGSHPNQVLDATSVLGQAFSTLPLQWGFSGANLVQVEALGKGSDSPEDLGAITMLNQQETVAMDMDRNATPDLPIFLPKPPNTVATYSSPLLGPEPHSSTSCGLEVQGATPILTLDSGHTPQLPPNPESSSVPLVIAANGTRAEKQFGTSLFPAVPQGFTVAAENEVQHAPLDLTQGSQAAPSKLEGEISRVSITGSADVKATAMSMPVTQASTSSPPCNSTPPMVERRKRKACGVCEPCQQKANCGECTYCKNRKNSHQICKKRKCEVLKKKPEATSQAQVTKENKRPQREKKPKVLKTDFNNKPVNGPKSESMDCSRRGHGEEEQRLDLITHPLENVRKNAGGMTGIEVEKWAPNKKSHLAEGQVKGSCDANLTGVENPQPSEDDKQQTNPSPTFAQTIRNGMKNVHCLPTDTHLPLNKLNHEEFSKALGNNSSKLLTDPSNCKDAMSVTTSGGECDHLKGPRNTLLFQKPGLNCRSGAEPTIFNNHPNTHSAGSRPHPPEKVPNKEPKDGSPVQPSLLSLMKDRRLTLEQVVAIEALTQLSEAPSESSSPSKPEKDEEAHQKTASLLNSCKAILHSVRKDLQDPNVQGKGLHHDTVVFNGQNRTFKSPDSFATNQALIKSQGYPSSPTAEKKGAAGGRAPFDGFENSHPLPIESHNLENCSQVLSCDQNLSSHDPSCQDAPYSQIEEDVAAQLTQLASTINHINAEVRNAESTPESLVAKNTKQKHSQEKRMVHQKPPSSTQTKPSVPSAKPKKAQKKARATPHANKRKKKPPARSSQENDQKKQEQLAIEYSKMHDIWMSSKFQRFGQSSPRSFPVLLRNIPVFNQILKPVTQSKTPSQHNELFPPINQIKFTRNPELAKEKVKVEPSDSLPTCQFKTESGGQTFAEPADNSQGQPMVSVNQEAHPLPQSPPSNQCANIMAGAAQTQFHLGAQENLVHQIPPPTLPGTSPDTLLPDPASILRKGKVLHFDGITVVTEKREAQTSSNGPLGPTTDSAQSEFKESIMDLLSKPAKNLIAGLKEQEAAPCDCDGGTQKEKGPYYTHLGAGPSVAAVRELMETRFGQKGKAIRIEKIVFTGKEGKSSQGCPVAKWVIRRSGPEEKLICLVRERVDHHCSTAVIVVLILLWEGIPRLMADRLYKELTENLRSYSGHPTDRRCTLNKKRTCTCQGIDPKTCGASFSFGCSWSMYFNGCKFGRSENPRKFRLAPNYPLHNYYKRITGMSSEGSDVKTGWIIPDRKTLISREEKQLEKNLQELATVLAPLYKQMAPVAYQNQVEYEEVAGDCRLGNEEGRPFSGVTCCMDFCAHSHKDIHNMHNGSTVVCTLIRADGRDTNCPEDEQLHVLPLYRLADTDEFGSVEGMKAKIKSGAIQVNGPTRKRRLRFTEPVPRCGKRAKMKQNHNKSGSHNTKSFSSASSTSHLVKDESTDFCPLQASSAETSTCTYSKTASGGFAETSSILHCTMPSGAHSGANAAAGECTGTVQPAEVAAHPHQSLPTADSPVHAEPLTSPSEQLTSNQSNQQLPLLSNSQKLASCQVEDERHPEADEPQHPEDDNLPQLDEFWSDSEEIYADPSFGGVAIAPIHGSVLIECARKELHATTSLRSPKRGVPFRVSLVFYQHKSLNKPNHGFDINKIKCKCKKVTKKKPADRECPDVSPEANLSHQIPSRVASTLTRDNVVTVSPYSLTHVAGPYNRWV
uniprot
proteins
disease_involvement
DISEASE: Note=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 glioblastoma genesis. {ECO:0000269|PubMed:25284789}.
uniprot
proteins
ec_number
1.14.11.80
uniprot
proteins
function
FUNCTION: Dioxygenase that plays a key role in active DNA demethylation, by catalyzing the sequential oxidation of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) (PubMed:20639862, PubMed:21496894, PubMed:21778364). 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 (PubMed:28504700, PubMed:32286661). Plays therefore a role in many biological processes, including stem cell maintenance, T- and B-cell development, inflammation regulation, iron homeostasis, neural activity or DNA repair (PubMed:20639862, PubMed:31089182, PubMed:32855402, PubMed:33895792). 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 (PubMed:20639862, PubMed:28504700). Together with QSER1, plays an essential role in the protection and maintenance of transcriptional and developmental programs to inhibit the binding of DNMT3A/3B and therefore de novo methylation (By similarity). May play a role in the pancreatic beta-cell specification during development. In this context, may function as an upstream epigenetic regulator of PAX4 presumably through direct recruitment by FOXA2 to a PAX4 enhancer to preserve its unmethylated status, thereby potentiating PAX4 expression to adopt beta-cell fate during endocrine lineage commitment (By similarity). Under DNA hypomethylation conditions, such as in female meiotic germ cells, may induce epigenetic reprogramming of pericentromeric heterochromatin (PCH), the constitutive heterochromatin of pericentromeric regions. PCH forms chromocenters in the interphase nucleus and chromocenters cluster at the prophase of meiosis. In this context, may also be essential for chromocenter clustering in a catalytic activity-independent manner, possibly through the recruitment polycomb repressive complex 1 (PRC1) to the chromocenters (PubMed:34166371). During embryonic development, may be required for normal meiotic progression in oocytes and meiotic gene activation (PubMed:23151479). 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). {ECO:0000250|UniProtKB:Q8NFU7, ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:21451524, ECO:0000269|PubMed:21490601, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21514197, ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:23151479, ECO:0000269|PubMed:23352454, ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:28504700, ECO:0000269|PubMed:31089182, ECO:0000269|PubMed:32286661, ECO:0000269|PubMed:32855402, ECO:0000269|PubMed:33895792, ECO:0000269|PubMed:34166371}.; FUNCTION: [Isoform 1]: Dioxygenase that plays a key role in active DNA demethylation (PubMed:27916660, PubMed:36056023). Binds to promoters, particularly to those with high CG content (PubMed:27916660). In hippocampal neurons, isoform 1 regulates the expression of a unique subset of genes compared to isoform 2, although some overlap between both isoforms, hence differentially regulates excitatory synaptic transmission (PubMed:33262245). In hippocampal neuron cell cultures, isoform 1 controls both miniature excitatory postsynaptic current amplitude and frequency (PubMed:33262245). Isoform 1 may regulate genes involved in hippocampal-dependent memory, leading to positive regulation of memory, contrary to isoform 2 that may decrease memory (PubMed:33262245). {ECO:0000269|PubMed:27916660, ECO:0000269|PubMed:33262245, ECO:0000269|PubMed:36056023}.; FUNCTION: [Isoform 2]: Dioxygenase that plays a key role in active DNA demethylation (PubMed:27916660, PubMed:36056023). As isoform 1, binds to promoters, particularly to those with high CG content, however displays reduced global chromatin affinity compared with isoform 1, leading to decreased global DNA demethylation compared with isoform 1 (PubMed:27916660). Contrary to isoform 1, isoform 2 localizes during S phase to sites of ongoing DNA replication in heterochromatin, causing a significant de novo 5hmC formation, globally, and more so in heterochromatin, including LINE 1 interspersed DNA repeats leading to their activation (PubMed:36056023). In hippocampal neurons, isoform 2 regulates the expression of a unique subset of genes compared with isoform 1, although some overlap between both isoforms, hence differentially regulating excitatory synaptic transmission (PubMed:33262245). In hippocampal neuron cell cultures, isoform 2 controls miniature excitatory postsynaptic current frequency, but not amplitude (PubMed:33262245). Isoform 2 may regulate genes involved in hippocampal-dependent memory, leading to negative regulation of memory, contrary to isoform 1 that may improve memory (PubMed:33262245). In immature and partially differentiated gonadotrope cells, represses luteinizing hormone gene LHB expression directly and does not catalyze 5hmC at the gene promoter (PubMed:28855337). {ECO:0000269|PubMed:27916660, ECO:0000269|PubMed:28855337, ECO:0000269|PubMed:33262245, ECO:0000269|PubMed:36056023}.
uniprot
proteins
mass_dalton
222945
uniprot
proteins
mutagenesis
MUTAGEN 1537; /note="K->E: Decreased levels of ubiquitination in isoform 2; loss of isoform 2 localization to sites of ongoing DNA replication in heterochromatic regions; does not affect interaction with CRL4(VprBP) ubiquitin ligase complex. Loss of DNA-binding and of 5-methylcytosine demethylase activity in vivo. Does not affect nuclear localization."; /evidence="ECO:0000269|PubMed:25557551, ECO:0000269|PubMed:36056023"; MUTAGEN 1537; /note="K->N: Strongly reduces ubiquitination, loss of DNA-binding and of 5-methylcytosine demethylase activity in vivo. Does not affect nuclear localization."; /evidence="ECO:0000269|PubMed:25557551"; MUTAGEN 1537; /note="K->R: Decreased levels of ubiquitination in isoform 2; loss of isoform 2 localization to sites of ongoing DNA replication in heterochromatic regions; does not affect interaction with CRL4(VprBP) ubiquitin ligase complex."; /evidence="ECO:0000269|PubMed:36056023"; MUTAGEN 1652; /note="H->Y: Loss of catalytic activity; when associated with A-1654. Does not affect chromocenter clustering; when associated with A-1654. Does not affect interaction with DCAF1; when associated with A-1654. In isoform 2, does not affect localization to heterochromatin in late S-phase; when associated with A-1654."; /evidence="ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:25557551, ECO:0000269|PubMed:34166371"; MUTAGEN 1654; /note="D->A: Loss of catalytic activity; when associated with Y-1652. Does not affect chromocenter clustering; when associated with A-1654; when associated with Y-1652. Does not affect interaction with DCAF1; when associated with Y-1652. In isoform 2, does not affect localization to heterochromatin in late S-phase; when associated with Y-1652."; /evidence="ECO:0000269|PubMed:20639862, ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:25557551, ECO:0000269|PubMed:34166371
uniprot
proteins
post_translational_modification
PTM: Glycosylated. Interaction with OGT leads to GlcNAcylation. {ECO:0000269|PubMed:23352454}.; PTM: [Isoform 2]: Monoubiquitinated by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex. {ECO:0000269|PubMed:36056023}.; PTM: Monoubiquitinated by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex; this modification promotes binding to DNA. {ECO:0000269|PubMed:25557551}.
uniprot
proteins
protein_family
TET family
uniprot
proteins
pubmed
14621295
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20639862
uniprot
proteins
pubmed
21451524
uniprot
proteins
pubmed
21490601
uniprot
proteins
pubmed
21496894
uniprot
proteins
pubmed
21514197
uniprot
proteins
pubmed
21778364
uniprot
proteins
pubmed
21816367
uniprot
proteins
pubmed
23151479
uniprot
proteins
pubmed
23352454
uniprot
proteins
pubmed
23352810
uniprot
proteins
pubmed
24357321
uniprot
proteins
pubmed
25284789
uniprot
proteins
pubmed
25557551
uniprot
proteins
pubmed
27916660
uniprot
proteins
pubmed
28504700
uniprot
proteins
pubmed
28531272
uniprot
proteins
pubmed
28554894
uniprot
proteins
pubmed
28855337
uniprot
proteins
pubmed
31089182
uniprot
proteins
pubmed
32286661
uniprot
proteins
pubmed
32855402
uniprot
proteins
pubmed
33262245
uniprot
proteins
pubmed
33895792
uniprot
proteins
pubmed
34166371
uniprot
proteins
pubmed
36056023
uniprot
proteins
sequence_length
2039
uniprot
proteins
subcellular_location
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 homogeneous 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}.
uniprot
proteins