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THUMP domain-containing protein 3 (THUMPD3) is a tRNA methyltransferase that acts as the catalytic subunit in the THUMPD3–TRMT112 complex, which specifically catalyzes the S-adenosyl-L-methionine-dependent N(2)-methylation of guanosine at position 6 (m^2G6) in multiple cytoplasmic tRNAs, and also at position 7 (m^2G7) in tRNA^Trp[1][2][3]. The enzyme itself requires TRMT112 as a cofactor for activation, as it is inactive alone; activity is dependent on the mature tertiary structure of tRNA and recognition of the 3′-CCA tail[1][2]. THUMPD3 is widely expressed in human and mouse tissues, with notably high levels in testis, and knockout or depletion leads to reduced protein translation and cell proliferation[1][2][3]. Diseases have been associated with mutations or deletions affecting THUMPD3, but it has not been validated as a direct therapeutic or pharmacological target[3].
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