Mitochondrial tRNA methylthiotransferase CDK5RAP1 (CDK5RAP1)

Mitochondrial tRNA methylthiotransferase CDK5RAP1 is an enzyme that functions as a radical S-adenosylmethionine (SAM) methylthiotransferase, catalyzing the posttranscriptional modification of mitochondrial tRNAs by converting N6-isopentenyladenosine (i^6A) to 2-methylthio-N6-isopentenyladenosine (ms^2i^6A), an essential modification for accurate mitochondrial protein synthesis and codon-anticodon stabilization[1][3]. In addition to its RNA modification function, CDK5RAP1 also acts as an inhibitor of cyclin-dependent kinase 5 (CDK5) activation, thereby linking mitochondrial RNA modification with protein kinase signaling pathways, particularly in neurons[1][3]. Dysfunction can contribute to mitochondrial deficiency, impaired neuronal differentiation, neurodegenerative disease processes, and certain forms of neuropathy and developmental delay[1][3]. The protein is encoded by the CDK5RAP1 gene (C20orf34), with several protein isoforms showing differential subcellular localization, predominantly mitochondrial but also cytoplasmic and nuclear[1].

Other names

CDK5 regulatory subunit-associated protein 1C20orf34CGI-05HSPC167C42CDK5 activator-binding protein C42mt-tRNA-2-methylthio-N6-dimethylallyladenosine synthasemt-tRNA-N6-(dimethylallyl)adenosine(37) methylthiotransferaseEC 2.8.4.3

Potential mechanisms for experimental inhibitors: inhibition of methylthiotransferase activity, interference with CDK5RAP1-CDK5R1 interaction. No established mechanisms of clinically used drugs due to lack of approved therapeutics.