Recombinant Human Tet2 Protein

The protein encoded by this gene is a methylcytosine dioxygenase that catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. The encoded protein is involved in myelopoiesis, and defects in this gene have been associated with several myeloproliferative disorders. Two variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

TET2: Catalyzes the conversion of methylcytosine (5mC) to 5- hydroxymethylcytosine (hmC). Plays an important role in myelopoiesis. The clear function of 5-hydroxymethylcytosine (hmC) is still unclear but it may influence chromatin structure and recruit specific factors or may constitute an intermediate component in cytosine demethylation. 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. Defects in TET2 are a cause of polycythemia vera (PV). 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. 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. Defects in TET2 are a cause of myelodysplastic syndrome (MDS). 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. Myelodysplastic syndromes are considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). 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. Belongs to the TET family. 3 isoforms of the human protein are produced by alternative splicing.

Protein type: Tumor suppressor; EC 1.14.11.n2; Oxidoreductase

Chromosomal Location of Human Ortholog: 4q24

Molecular Function: protein binding; DNA binding; zinc ion binding; ferrous iron binding

Biological Process: spleen development; protein amino acid O-linked glycosylation; hemoglobin metabolic process; cell cycle; regulation of gene expression, epigenetic; post-embryonic development; myeloid progenitor cell differentiation; cytosine metabolic process; 5-methylcytosine catabolic process; gene expression; positive regulation of transcription from RNA polymerase II promoter; myeloid cell differentiation; kidney development

Disease: Myelodysplastic Syndrome