tRNA wybutosine-synthesizing protein 4 (TYW4)

tRNA wybutosine-synthesizing protein 4 (TYW4, also known as LCMT2) is a probable S-adenosyl-L-methionine-dependent methyltransferase involved in the final steps of wybutosine (yW) biosynthesis, specifically modifying the phenylalanine tRNA (tRNA^Phe^). Wybutosine is a hypermodified guanosine residue adjacent to the anticodon, critical for accurate translation and tRNA stability. TYW4 catalyzes methylation and methoxycarbonylation of the α-amino-α-carboxypropyl side chain on yW, operating as a bifunctional enzyme. It is a member of the highly variable methyltransferase superfamily and contains an N-terminal class I methyltransferase domain and a C-terminal β-propeller domain. Genetic variants in this gene are associated with rare intellectual disabilities and creatine deficiency syndromes[1][2][3][5]. No therapeutic agents currently target this protein, and its primary biological role is in RNA modification.

Other names

Leucine carboxyl methyltransferase 2 (LCMT2)KIAA0547PPM2tRNA(Phe) (7-(3-amino-3-(methoxycarbonyl)propyl)wyosine(37)-N)-methoxycarbonyltransferasetRNA(Phe) (7-(3-amino-3-carboxypropyl)wyosine(37)-O)-methyltransferaseMGC9534tRNA wybutosine-synthesizing protein 4tRNA-yW synthesizing protein 4tRNA-Wybutosine-synthesizing protein 4p21WAF1/CIP1 promoter-interacting protein

Not established for clinical drugs, as no drugs are known to interact with TYW4. For related enzymes: methyltransferase inhibitors often function by competing for the SAM binding site or by direct inhibition of substrate binding[4] (not known for TYW4).