ASH2L is the human homolog of the Drosophila absent, small or homeotic discs 2 (ash2) gene product, a member of the trithorax group (TrxG) of proteins. The TrxG gene products in Drosophila and their mammalian homologs are responsible for controlling gene transcription. The ASH2L protein is a component of various multisubunit protein complexes, including the large complex of proteins associated with the SET1 (MLL) family of lysine methyltransferases. ASH2L, along with WDR5 and RbBP5, form the human MLL1 core protein complex. MLL1-5 protein complexes catalyze the di- and trimethylation of histone H3 at lysine 4 (H3K4me2/me3), leading to the maintenance of global H3K4 trimethylation. Post-translational modifications of ASH2L have also been described showing methylation of Arg-296 by protein-arginine methyltransferease 1 (PRMT1) in vitro and in cells and by PRMT5 in vitro. Further experimental evidence in rats suggests that ASH2L cooperates with Ha-RAS to transform rat embryonic fibroblasts, implicating ASH2L as a novel oncoprotein.
