TET1
entrez
80312
canonical
uniprot
Q8NFU7
canonical
ensembl
ENSG00000138336
resolver
ensp
ENSP00000362748
resolver
ensp
ENSP00000599822
resolver
ensp
ENSP00000599823
resolver
genesymbol
TET1
resolver
genesymbol_syn
CXXC6
resolver
genesymbol_syn
KIAA1676
resolver
genesymbol_syn
LCX
resolver
hgnc
HGNC:29484
resolver
uniprot
A0A023HHK9
resolver
uniprot
A0A023HHL0
resolver
uniprot
Q5VUP7
resolver
uniprot
Q7Z6B6
resolver
uniprot
Q8TCR1
resolver
uniprot
Q9C0I7
resolver
uniprot_entry
TET1_HUMAN
resolver
uniprot_sec
A0A023HHK9
resolver
uniprot_sec
A0A023HHL0
resolver
uniprot_sec
Q5VUP7
resolver
uniprot_sec
Q7Z6B6
resolver
uniprot_sec
Q8TCR1
resolver
uniprot_sec
Q9C0I7
resolver
amino_acid_sequence
MSRSRHARPSRLVRKEDVNKKKKNSQLRKTTKGANKNVASVKTLSPGKLKQLIQERDVKKKTEPKPPVPVRSLLTRAGAARMNLDRTEVLFQNPESLTCNGFTMALRSTSLSRRLSQPPLVVAKSKKVPLSKGLEKQHDCDYKILPALGVKHSENDSVPMQDTQVLPDIETLIGVQNPSLLKGKSQETTQFWSQRVEDSKINIPTHSGPAAEILPGPLEGTRCGEGLFSEETLNDTSGSPKMFAQDTVCAPFPQRATPKVTSQGNPSIQLEELGSRVESLKLSDSYLDPIKSEHDCYPTSSLNKVIPDLNLRNCLALGGSTSPTSVIKFLLAGSKQATLGAKPDHQEAFEATANQQEVSDTTSFLGQAFGAIPHQWELPGADPVHGEALGETPDLPEIPGAIPVQGEVFGTILDQQETLGMSGSVVPDLPVFLPVPPNPIATFNAPSKWPEPQSTVSYGLAVQGAIQILPLGSGHTPQSSSNSEKNSLPPVMAISNVENEKQVHISFLPANTQGFPLAPERGLFHASLGIAQLSQAGPSKSDRGSSQVSVTSTVHVVNTTVVTMPVPMVSTSSSSYTTLLPTLEKKKRKRCGVCEPCQQKTNCGECTYCKNRKNSHQICKKRKCEELKKKPSVVVPLEVIKENKRPQREKKPKVLKADFDNKPVNGPKSESMDYSRCGHGEEQKLELNPHTVENVTKNEDSMTGIEVEKWTQNKKSQLTDHVKGDFSANVPEAEKSKNSEVDKKRTKSPKLFVQTVRNGIKHVHCLPAETNVSFKKFNIEEFGKTLENNSYKFLKDTANHKNAMSSVATDMSCDHLKGRSNVLVFQQPGFNCSSIPHSSHSIINHHASIHNEGDQPKTPENIPSKEPKDGSPVQPSLLSLMKDRRLTLEQVVAIEALTQLSEAPSENSSPSKSEKDEESEQRTASLLNSCKAILYTVRKDLQDPNLQGEPPKLNHCPSLEKQSSCNTVVFNGQTTTLSNSHINSATNQASTKSHEYSKVTNSLSLFIPKSNSSKIDTNKSIAQGIITLDNCSNDLHQLPPRNNEVEYCNQLLDSSKKLDSDDLSCQDATHTQIEEDVATQLTQLASIIKINYIKPEDKKVESTPTSLVTCNVQQKYNQEKGTIQQKPPSSVHNNHGSSLTKQKNPTQKKTKSTPSRDRRKKKPTVVSYQENDRQKWEKLSYMYGTICDIWIASKFQNFGQFCPHDFPTVFGKISSSTKIWKPLAQTRSIMQPKTVFPPLTQIKLQRYPESAEEKVKVEPLDSLSLFHLKTESNGKAFTDKAYNSQVQLTVNANQKAHPLTQPSSPPNQCANVMAGDDQIRFQQVVKEQLMHQRLPTLPGISHETPLPESALTLRNVNVVCSGGITVVSTKSEEEVCSSSFGTSEFSTVDSAQKNFNDYAMNFFTNPTKNLVSITKDSELPTCSCLDRVIQKDKGPYYTHLGAGPSVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKSSHGCPIAKWVLRRSSDEEKVLCLVRQRTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELTENLKSYNGHPTDRRCTLNENRTCTCQGIDPETCGASFSFGCSWSMYFNGCKFGRSPSPRRFRIDPSSPLHEKNLEDNLQSLATRLAPIYKQYAPVAYQNQVEYENVARECRLGSKEGRPFSGVTACLDFCAHPHRDIHNMNNGSTVVCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDEFGSKEGMEAKIKSGAIEVLAPRRKKRTCFTQPVPRSGKKRAAMMTEVLAHKIRAVEKKPIPRIKRKNNSTTTNNSKPSSLPTLGSNTETVQPEVKSETEPHFILKSSDNTKTYSLMPSAPHPVKEASPGFSWSPKTASATPAPLKNDATASCGFSERSSTPHCTMPSGRLSGANAAAADGPGISQLGEVAPLPTLSAPVMEPLINSEPSTGVTEPLTPHQPNHQPSFLTSPQDLASSPMEEDEQHSEADEPPSDEPLSDDPLSPAEEKLPHIDEYWSDSEHIFLDANIGGVAIAPAHGSVLIECARRELHATTPVEHPNRNHPTRLSLVFYQHKNLNKPQHGFELNKIKFEAKEAKNKKMKASEQKDQAANEGPEQSSEVNELNQIPSHKALTLTHDNVVTVSPYALTHVAGPYNHWV
uniprot
proteins
disease_involvement
DISEASE: Note=A chromosomal aberration involving TET1 may be a cause of acute leukemias (PubMed:12646957). Translocation t(10;11)(q22;q23) with KMT2A/MLL1. This is a rare chromosomal translocation 5' KMT2A/MLL1-TET1 3' (PubMed:12124344, PubMed:12646957). 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 (PubMed:25284789). {ECO:0000269|PubMed:12124344, ECO:0000269|PubMed:12646957, 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:19372391, PubMed:21496894, PubMed:21778364, PubMed:35798741). 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:33833093). Plays therefore a role in many biological processes, including stem cell maintenance, T- and B-cell development, inflammation regulation, genomic imprinting, neural activity or DNA repair (PubMed:31278917). Involved in the balance between pluripotency and lineage commitment of cells and plays a role in embryonic stem cells maintenance and inner cell mass cell specification. 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 (PubMed:33833093). May play a role in 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 (PubMed:35798741). 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 (By similarity). During embryonic development, may be required for normal meiotic progression in oocytes and meiotic gene activation (By similarity). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (PubMed:29276034). {ECO:0000250|UniProtKB:Q3URK3, ECO:0000269|PubMed:12124344, ECO:0000269|PubMed:19372391, ECO:0000269|PubMed:19372393, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:29276034, ECO:0000269|PubMed:31278917, ECO:0000269|PubMed:33833093, ECO:0000269|PubMed:35798741}.; FUNCTION: [Isoform 1]: Dioxygenase that plays a key role in active DNA demethylation (PubMed:28531272). Binds to promoters, particularly to those with high CG content (By similarity). In hippocampal neurons, isoform 1 regulates the expression of a unique subset of genes compared to isoform 2, although some overlap exists between both isoforms, hence differentially regulates excitatory synaptic transmission (By similarity). In hippocampal neuron cell cultures, isoform 1 controls both miniature excitatory postsynaptic current amplitude and frequency (By similarity). Isoform 1 may regulate genes involved in hippocampal-dependent memory, leading to positive regulation of memory, contrary to isoform 2 that may decrease memory (By similarity). {ECO:0000250|UniProtKB:Q3URK3, ECO:0000269|PubMed:28531272}.; FUNCTION: [Isoform 2]: Dioxygenase that plays a key role in active DNA demethylation (PubMed:28531272). 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 (By similarity). 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 (By similarity). In hippocampal neurons, isoform 2 regulates the expression of a unique subset of genes compared to isoform 1, although some overlap between both isoforms, hence differentially regulates excitatory synaptic transmission (By similarity). In hippocampal neuron cell cultures, isoform 2 controls miniature excitatory postsynaptic current frequency, but not amplitude (By similarity). Isoform 2 may regulate genes involved in hippocampal-dependent memory, leading to negative regulation of memory, contrary to isoform 1 that may improve memory (By similarity). In immature and partially differentiated gonadotrope cells, directly represses luteinizing hormone gene LHB expression and does not catalyze 5hmC at the gene promoter (By similarity). {ECO:0000250|UniProtKB:Q3URK3, ECO:0000269|PubMed:28531272}.
uniprot
proteins
mass_dalton
235309
uniprot
proteins
mutagenesis
MUTAGEN 1672; /note="H->Y: Loss of catalytic activity and loss of the ability to induce DNA demethylation; when associated with A-1674. When transfected in knockout cells, fails to restore pancreatic beta-cell specification, as shown by impaired NKX6.1, PAX6, PDX1 and INS expression; when associated with A-1674."; /evidence="ECO:0000269|PubMed:19372391, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:35798741"; MUTAGEN 1674; /note="D->A: Loss of catalytic activity and loss of the ability to induce DNA demethylation; when associated with Y-1672. When transfected in knockout cells, fails to restore pancreatic beta-cell specification, as shown by impaired NKX6.1, PAX6, PDX1 and INS expression; when associated with Y-1672."; /evidence="ECO:0000269|PubMed:19372391, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:35798741
uniprot
proteins
post_translational_modification
PTM: Glycosylated. Interaction with OGT leads to GlcNAcylation (By similarity). {ECO:0000250|UniProtKB:Q3URK3}.; PTM: Monoubiquitinated at Lys-1589 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
11214970
uniprot
proteins
pubmed
12124344
uniprot
proteins
pubmed
12646957
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19372391
uniprot
proteins
pubmed
19372393
uniprot
proteins
pubmed
21490601
uniprot
proteins
pubmed
21496894
uniprot
proteins
pubmed
21778364
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24357321
uniprot
proteins
pubmed
25284789
uniprot
proteins
pubmed
25557551
uniprot
proteins
pubmed
28397838
uniprot
proteins
pubmed
28531272
uniprot
proteins
pubmed
29276034
uniprot
proteins
pubmed
31278917
uniprot
proteins
pubmed
33833093
uniprot
proteins
pubmed
35798741
uniprot
proteins
pubmed
36056023
uniprot
proteins
sequence_length
2136
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q3URK3}. Chromosome {ECO:0000269|PubMed:33833093}. Note=Localization to chromatin is promoted by monoubiquitination on Lys-1589. {ECO:0000269|PubMed:25557551}.; SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000269|PubMed:36056023}. Chromosome {ECO:0000250|UniProtKB:Q3URK3}. 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:0000250|UniProtKB:Q3URK3}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:36056023}. Chromosome {ECO:0000250|UniProtKB:Q3URK3}. 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, as a consequence of ubiquitination of the conserved residue Lys-1589. Localization to heterochromatin is independent of catalytic activity. {ECO:0000269|PubMed:36056023}.
uniprot
proteins