| Primary Identifier | IPR044437 | Type | Domain |
| Short Name | SETD2/Set2_SET |
| description | This entry represents the SET domain found in SETD2 from animals, ASHH2 from plants and Set2 from fungi. Proteins containing this domain are a group of histone methyltransferases that methylates histone H3 to form H3K36me [, ].Yeast Set2 is involved in transcription elongation as well as in transcription repression []. The methyltransferase activity of budding yeast Set2 requires the recruitment to the RNA polymerase II, which is CTK1 dependent [, , , , , , ]. Plant ASHH2 is required for the correct expression of genes essential to reproductive development [].SETD2 acts as histone-lysine N-methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using demethylated 'Lys-36' (H3K36me2) as substrate [, ]. SETD2 is also required for DNA double-strand break repair and activation of the p53-mediated checkpoint []. SETD2-inactivation has been linked to tumour development []. SETD2 also methylates alpha-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy []. Moreover, SETD2 is also involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription [].SETD2 has been linked to several human diseases, including Renal cell carcinoma (RCC) [], Luscan-Lumish syndrome (LLS) [], Leukemia, acute lymphoblastic (ALL) []and Leukemia, acute myelogenous (AML) [, ]. |
