Methionine adenosyltransferase 2A (MAT2A)

Methionine adenosyltransferase 2A (MAT2A) is a cytosolic enzyme that catalyzes the formation of S-adenosylmethionine (SAM) from methionine and ATP. SAM acts as a critical methyl donor for DNA, RNA, protein, and other small molecule methylation reactions essential for epigenetic regulation, gene expression, and cellular homeostasis. MAT2A is highly expressed in many tissues and is upregulated in various cancers, serving as a key node in the methionine cycle. Notably, MAT2A has emerged as a synthetic lethal therapeutic target in cancers lacking methylthioadenosine phosphorylase (MTAP), which comprise about 15% of all cancers. In these tumors, MAT2A inhibition selectively induces cancer cell death by depleting cellular SAM and enhancing PRMT5 inhibition, which is exploited by several MAT2A inhibitors now in clinical development for MTAP-deleted tumors[1][2][3][4][5][6].

Other names

S-adenosylmethionine synthase isoform type-2MAT2A protein, humanMethionine adenosyltransferase II

Enzyme inhibition, leading to reduced intracellular S-adenosylmethionine and selective cell death in MTAP-deleted cancers Synthetic lethality in MTAP-deleted cancers when combined with protein arginine N-methyltransferase 5 (PRMT5) inhibitors