Threonylcarbamoyladenosine tRNA methylthiotransferase (CDKAL1)

Threonylcarbamoyladenosine tRNA methylthiotransferase (CDKAL1) is an iron-sulfur cluster-containing methylthiotransferase enzyme responsible for the post-transcriptional modification of tRNA Lys by catalyzing methylthiolation of N6-threonylcarbamoyladenosine at position 37. This modification (ms2t6A37) is crucial for maintaining translational fidelity during decoding of AAA and AAG lysine codons, which is particularly critical for accurate proinsulin translation and normal insulin biosynthesis in pancreatic β-cells. Genetic variants that reduce CDKAL1 function are reproducibly associated with an increased risk of type 2 diabetes, owing to impaired tRNA modification, misincorporation of lysine residues in proinsulin, defective insulin processing, and diminished insulin exocytosis. CDKAL1 also plays a role in adipocyte differentiation, possibly via Wnt/β-catenin signaling, and changes in its activity or expression are increasingly implicated in metabolic disorders[1][2][3][4][5].

Other names

CDKAL1CDK5 regulatory subunit-associated protein 1-like 1tRNA-t(6)A37 methylthiotransferaseFLJ20342

For potential therapeutics: Modulation of CDKAL1 activity may influence tRNA modification, translational accuracy, and insulin production; however, no specific drugs targeting CDKAL1 are currently in clinical use[3][5].