InnateDB Protein
|
IDBP-240925.7
|
Last Modified
|
2014-10-13 [Report errors or provide feedback]
|
Gene Symbol
|
TET2
|
Protein Name
|
tet methylcytosine dioxygenase 2
|
Synonyms
|
|
Species
|
Homo sapiens
|
Ensembl Protein
|
ENSP00000378245
|
InnateDB Gene
|
IDBG-32690 (TET2)
|
Protein Structure
|
|
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:0000269PubMed:19483684, ECO:0000269PubMed:21057493, ECO:0000269PubMed:21817016, ECO:0000269PubMed:23222540, ECO:0000269PubMed:23353889, ECO:0000269PubMed:24315485}.
|
Subcellular Localization |
|
Disease Associations |
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.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 mutations affecting the gene represented in this entry.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.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:0000269PubMed:19372255, ECO:0000269PubMed:19483684, ECO:0000269PubMed:21057493}. Note=The disease is caused by mutations 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.
|
Tissue Specificity |
Broadly expressed. Highly expressed in hematopoietic cells; highest expression observed in granulocytes. Expression is reduced in granulocytes from peripheral blood of patients affected by myelodysplastic syndromes. {ECO:0000269PubMed:12646957, ECO:0000269PubMed:19483684}.
|
Comments |
|
Number of Interactions
|
This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.
Experimentally validated |
Total |
9
[view]
|
Protein-Protein |
8
[view]
|
Protein-DNA |
1
[view]
|
Protein-RNA |
0
|
DNA-DNA |
0
|
RNA-RNA |
0
|
DNA-RNA |
0
|
|
Predicted by orthology |
Total |
7 [view]
|
|
|
Molecular Function |
|
Biological Process |
|
Cellular Component |
|
PDB ID |
|
InterPro |
|
PFAM |
|
PRINTS |
|
PIRSF |
|
SMART |
|
TIGRFAMs |
|
Modification |
|
SwissProt |
Q6N021
|
PhosphoSite |
PhosphoSite-Q6N021
|
TrEMBL |
D6RE87
|
UniProt Splice Variant |
|
Entrez Gene |
54790
|
UniGene |
Hs.740935
|
RefSeq |
|
HUGO |
HGNC:25941
|
OMIM |
612839
|
CCDS |
|
HPRD |
07876
|
IMGT |
|
EMBL |
AB046766
AB075496
AC004069
AC026029
AK000039
AK027819
BC110509
BC110510
BX640738
|
GenPept |
AAI10510
AAI10511
BAA90898
BAB13372
BAB55391
BAE45750
CAE45851
|
|
|