SET domain containing 3, actin N3-histidine methyltransferase (SETD3)

SET domain containing 3, actin N3-histidine methyltransferase (SETD3) is an evolutionarily conserved enzyme responsible for the methylation of histidine 73 (H73) of β-actin by transferring a methyl group from S-adenosyl-L-methionine (AdoMet/SAM) to the imidazole ring of actin[1][5][3]. This modification is crucial for maintaining actin filament stability and cytoskeletal integrity[1][5]. Structurally, SETD3 possesses a catalytic SET domain and a RuBisCO LSMT substrate-binding domain, providing specificity for actin and potentially other protein substrates[5]. Initially thought to act on histones, current evidence supports actin H73 as its primary physiological substrate[5][3]. Beyond cytoskeletal roles, SETD3 also impacts cell cycle, apoptosis, smooth muscle contractility, and has been implicated as a host factor in enterovirus replication[3][5][8]. Loss of SETD3 leads to cytoskeletal alterations, increased glycolytic activity, and impaired smooth muscle contraction, and may contribute to tumorigenesis and resistance to viral infection[1][3][8].

Other names

Actin-histidine N-methyltransferaseC14orf154hSETD3FLJ23027Protein-L-histidine N-tele-methyltransferaseSET domain-containing protein 3histone-lysine N-methyltransferase setd3