TET2
entrez
54790
canonical
uniprot
Q6N021
canonical
ensembl
ENSG00000168769
resolver
ensp
ENSP00000265149
resolver
ensp
ENSP00000306705
resolver
ensp
ENSP00000369351
resolver
ensp
ENSP00000620454
resolver
genesymbol
TET2
resolver
genesymbol_syn
KIAA1546
resolver
hgnc
HGNC:25941
resolver
uniprot
A0A158SIU0
resolver
uniprot
B5MDU0
resolver
uniprot
Q2TB88
resolver
uniprot
Q3LIB8
resolver
uniprot
Q96JX5
resolver
uniprot
Q9HCM6
resolver
uniprot
Q9NXW0
resolver
uniprot_entry
A0A158SIU0_HUMAN
resolver
uniprot_entry
TET2_HUMAN
resolver
uniprot_sec
B5MDU0
resolver
uniprot_sec
Q2TB88
resolver
uniprot_sec
Q3LIB8
resolver
uniprot_sec
Q96JX5
resolver
uniprot_sec
Q9HCM6
resolver
uniprot_sec
Q9NXW0
resolver
amino_acid_sequence
MEQDRTNHVEGNRLSPFLIPSPPICQTEPLATKLQNGSPLPERAHPEVNGDTKWHSFKSYYGIPCMKGSQNSRVSPDFTQESRGYSKCLQNGGIKRTVSEPSLSGLLQIKKLKQDQKANGERRNFGVSQERNPGESSQPNVSDLSDKKESVSSVAQENAVKDFTSFSTHNCSGPENPELQILNEQEGKSANYHDKNIVLLKNKAVLMPNGATVSASSVEHTHGELLEKTLSQYYPDCVSIAVQKTTSHINAINSQATNELSCEITHPSHTSGQINSAQTSNSELPPKPAAVVSEACDADDADNASKLAAMLNTCSFQKPEQLQQQKSVFEICPSPAENNIQGTTKLASGEEFCSGSSSNLQAPGGSSERYLKQNEMNGAYFKQSSVFTKDSFSATTTPPPPSQLLLSPPPPLPQVPQLPSEGKSTLNGGVLEEHHHYPNQSNTTLLREVKIEGKPEAPPSQSPNPSTHVCSPSPMLSERPQNNCVNRNDIQTAGTMTVPLCSEKTRPMSEHLKHNPPIFGSSGELQDNCQQLMRNKEQEILKGRDKEQTRDLVPPTQHYLKPGWIELKAPRFHQAESHLKRNEASLPSILQYQPNLSNQMTSKQYTGNSNMPGGLPRQAYTQKTTQLEHKSQMYQVEMNQGQSQGTVDQHLQFQKPSHQVHFSKTDHLPKAHVQSLCGTRFHFQQRADSQTEKLMSPVLKQHLNQQASETEPFSNSHLLQHKPHKQAAQTQPSQSSHLPQNQQQQQKLQIKNKEEILQTFPHPQSNNDQQREGSFFGQTKVEECFHGENQYSKSSEFETHNVQMGLEEVQNINRRNSPYSQTMKSSACKIQVSCSNNTHLVSENKEQTTHPELFAGNKTQNLHHMQYFPNNVIPKQDLLHRCFQEQEQKSQQASVLQGYKNRNQDMSGQQAAQLAQQRYLIHNHANVFPVPDQGGSHTQTPPQKDTQKHAALRWHLLQKQEQQQTQQPQTESCHSQMHRPIKVEPGCKPHACMHTAPPENKTWKKVTKQENPPASCDNVQQKSIIETMEQHLKQFHAKSLFDHKALTLKSQKQVKVEMSGPVTVLTRQTTAAELDSHTPALEQQTTSSEKTPTKRTAASVLNNFIESPSKLLDTPIKNLLDTPVKTQYDFPSCRCVEQIIEKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVVRRSSSEEKLLCLVRERAGHTCEAAVIVILILVWEGIPLSLADKLYSELTETLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFGCSWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPFSGVTACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREFGGKPEDEQLHVLPLYKVSDVDEFGSVEAQEEKKRSGAIQVLSSFRRKVRMLAEPVKTCRQRKLEAKKAAAEKLSSLENSSNKNEKEKSAPSRTKQTENASQAKQLAELLRLSGPVMQQSQQPQPLQKQPPQPQQQQRPQQQQPHHPQTESVNSYSASGSTNPYMRRPNPVSPYPNSSHTSDIYGSTSPMNFYSTSSQAAGSYLNSSNPMNPYPGLLNQNTQYPSYQCNGNLSVDNCSPYLGSYSPQSQPMDLYRYPSQDPLSKLSLPPIHTLYQPRFGNSQSFTSKYLGYGNQNMQGDGFSSCTIRPNVHHVGKLPPYPTHEMDGHFMGATSRLPPNLSNPNMDYKNGEHHSPSHIIHNYSAAPGMFNSSLHALHLQNKENDMLSHTANGLSKMLPALNHDRTACVQGGLHKLSDANGQEKQPLALVQGVASGAEDNDEVWSDSEQSFLDPDIGGVAVAPTHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKMAEKAREKEEECEKYGPDYVPQKSHGKKVKREPAEPHETSEPTYLRFIKSLAERTMSVTTDSTVTTSPYAFTRVTGPYNRYI
uniprot
proteins
disease_involvement
DISEASE: Note=TET2 is frequently mutated in myeloproliferative disorders (MPD). These constitute a heterogeneous group of disorders, also known as myeloproliferative diseases or myeloproliferative neoplasms (MPN), characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. Included diseases are: essential thrombocythemia, polycythemia vera, primary myelofibrosis (chronic idiopathic myelofibrosis). Bone marrow samples from patients display uniformly low levels of hmC in genomic DNA compared to bone marrow samples from healthy controls as well as hypomethylation relative to controls at the majority of differentially methylated CpG sites.; DISEASE: Polycythemia vera (PV) [MIM:263300]: A myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=TET2 is frequently mutated in systemic mastocytosis; also known as systemic mast cell disease. A condition with features in common with myeloproliferative diseases. It is a clonal disorder of the mast cell and its precursor cells. The clinical symptoms and signs of systemic mastocytosis are due to accumulation of clonally derived mast cells in different tissues, including bone marrow, skin, the gastrointestinal tract, the liver, and the spleen.; DISEASE: Myelodysplastic syndrome (MDS) [MIM:614286]: A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). {ECO:0000269|PubMed:19372255, ECO:0000269|PubMed:19483684, ECO:0000269|PubMed:21057493}. Note=The disease is caused by variants affecting the gene represented in this entry. Bone marrow samples from patients display uniformly low levels of hmC in genomic DNA compared to bone marrow samples from healthy controls as well as hypomethylation relative to controls at the majority of differentially methylated CpG sites.; DISEASE: Immunodeficiency 75 with lymphoproliferation (IMD75) [MIM:619126]: An autosomal recessive immunologic disorder characterized by recurrent infections, mainly viral and affecting the respiratory tract, immunodeficieny, immune dysregulation, and the development of lymphoproliferative disorders, including lymphoma. {ECO:0000269|PubMed:32518946}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.14.11.80
uniprot
proteins
function
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. {ECO:0000269|PubMed:19483684, ECO:0000269|PubMed:21057493, ECO:0000269|PubMed:21817016, ECO:0000269|PubMed:23222540, ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24315485, ECO:0000269|PubMed:32518946}.
uniprot
proteins
mass_dalton
223811
uniprot
proteins
mutagenesis
MUTAGEN 1261; /note="R->G: Loss of enzyme activity."; /evidence="ECO:0000269|PubMed:24315485"; MUTAGEN 1262; /note="R->A: Slightly reduces enzyme activity."; /evidence="ECO:0000269|PubMed:24315485"; MUTAGEN 1290; /note="S->A: Reduces enzyme activity; when associated with A-1295."; /evidence="ECO:0000269|PubMed:24315485"; MUTAGEN 1291..1296; /note="WSMYYN->GGSGGS: Loss of enzyme activity."; /evidence="ECO:0000269|PubMed:24315485"; MUTAGEN 1292; /note="S->R: No effect on interaction with DCAF1, monoubiquitination, nor on 5-methylcytosine demethylase activity in vivo, when tested in a heterologous system."; /evidence="ECO:0000269|PubMed:25557551"; MUTAGEN 1293..1294; /note="MY->AA: Strongly reduced enzyme activity. Slightly decreased affinity for DNA."; /evidence="ECO:0000269|PubMed:24315485"; MUTAGEN 1295; /note="Y->A: Reduces enzyme activity; when associated with A-1290."; /evidence="ECO:0000269|PubMed:24315485"; MUTAGEN 1298; /note="C->Y: Loss of monoubiquitination and of 5-methylcytosine demethylase activity in vivo. No effect on interaction with DCAF1, when tested in a heterologous system."; /evidence="ECO:0000269|PubMed:25557551"; MUTAGEN 1300; /note="F->S: Loss of interaction with DCAF1, monoubiquitination and of 5-methylcytosine demethylase activity in vivo, when tested in a heterologous system."; /evidence="ECO:0000269|PubMed:25557551"; MUTAGEN 1303; /note="S->N: Loss of enzyme activity; when associated with E-1299."; /evidence="ECO:0000269|PubMed:24315485"; MUTAGEN 1382; /note="H->Y: Loss of enzyme activity. Still able to enhance histone H2BGlcNAcylation by OGT; when associated with A-1384. Loss of enzyme activity; when associated with V-1384."; /evidence="ECO:0000269|PubMed:23222540, ECO:0000269|PubMed:24315485"; MUTAGEN 1384; /note="D->A: Loss of enzyme activity. Still able to enhance histone H2BGlcNAcylation by OGT; when associated with Y-1382."; /evidence="ECO:0000269|PubMed:23222540, ECO:0000269|PubMed:24315485"; MUTAGEN 1384; /note="D->V: Loss of enzyme activity; when associated with Y-1382."; /evidence="ECO:0000269|PubMed:23222540, ECO:0000269|PubMed:24315485"; MUTAGEN 1387; /note="N->A: Near loss of enzyme activity."; /evidence="ECO:0000269|PubMed:24315485"; MUTAGEN 1902; /note="Y->A: Loss of enzyme activity."; /evidence="ECO:0000269|PubMed:24315485"; MUTAGEN 1904; /note="H->R: Loss of enzyme activity."; /evidence="ECO:0000269|PubMed:24315485
uniprot
proteins
post_translational_modification
PTM: May be glycosylated. It is unclear whether interaction with OGT leads to GlcNAcylation. According to a report, it is not GlcNAcylated by OGT (PubMed:23353889). In contrast, another group reports GlcNAcylation by OGT in mouse ortholog. {ECO:0000269|PubMed:23353889}.; PTM: Monoubiquitinated at Lys-1299 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}.; PTM: Acetylated (PubMed:39567688). Deacetylase HDAC6 acts as a valine sensor by binding to valine through its primate-specific SE14 repeat region and deacetylates TET2 following valine deprivation which promotes TET2-dependent DNA demethylation (PubMed:39567688). {ECO:0000269|PubMed:39567688}.
uniprot
proteins
protein_family
TET family
uniprot
proteins
pubmed
10997877
uniprot
proteins
pubmed
12646957
uniprot
proteins
pubmed
12880961
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19262599
uniprot
proteins
pubmed
19262601
uniprot
proteins
pubmed
19372255
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19420352
uniprot
proteins
pubmed
19474426
uniprot
proteins
pubmed
19483684
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
21057493
uniprot
proteins
pubmed
21817016
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23222540
uniprot
proteins
pubmed
23353889
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24315485
uniprot
proteins
pubmed
24357321
uniprot
proteins
pubmed
25557551
uniprot
proteins
pubmed
32518946
uniprot
proteins
pubmed
34667079
uniprot
proteins
pubmed
39567688
uniprot
proteins
sequence_length
2002
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25557551}. Chromosome {ECO:0000269|PubMed:25557551}. Note=Localization to chromatin depends upon monoubiquitination at Lys-1299. {ECO:0000269|PubMed:25557551}.
uniprot
proteins