SET domain containing 2 is an enzyme that in humans is encoded by the SETD2 gene. [5] [6] [7]
SETD2 protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyperphosphorylated RNA polymerase II. [7]
The trimethylation of lysine-36 of histone H3 (H3K36me3) is required in human cells for homologous recombinational repair and genome stability. [8] Depletion of SETD2 increases the frequency of deletion mutations that arise by the alternative DNA repair process of microhomology-mediated end joining.
The SETD2 gene is located on the short arm of chromosome 3 and has been shown to play a tumour suppressor role in human cancer. [9]
SETD2 has been shown to interact with Huntingtin. [10] Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. SETD2 belongs to a class of huntingtin interacting proteins characterized by WW motifs. [7]