a mitochondrial oxidoreductase that catalyzes the third step of the citric acid cycle: the oxidative decarboxylation of isocitrate, consuming NADP(+), and producing alpha-ketoglutarate (alpha-KG) and CO2. Can also use oxalosuccinate as a substrate. Alpha-KG is an activator the dioxygenases that hydroxylate the transcription factor HIF and lead to its degradation by VHL. Since HIF turns on oncogenic pathways, IDH2 has apparent tumor suppressor activity. Homo-dimerization is required for activity. Each subunit binds 1 magnesium or manganese ion. May tightly associate or interact with the pyruvate dehydrogenase complex. A somatic mutation resulting in the R172K conversion results in a neomorphic enzyme activity that converts isocitrate to R(-)-2-hydroxyglutarate (2HG) occurs in a significant percentage of patients with cytogenetically normal acute myeloid leukemia (AML). Elevated levels of 2HG are also correlated with an elevated risk of malignant brain tumors. Note: This description may include information from UniProtKB.
Protein type: Mitochondrial; Oxidoreductase; Carbohydrate Metabolism - citrate (TCA) cycle; EC 126.96.36.199; Other Amino Acids Metabolism - glutathione
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.