Bud32

Bud32 is a conserved protein that serves as a subunit of the KEOPS (also known as EKC) complex in archaea and eukaryotes. The KEOPS complex is responsible for the universal t6A modification of transfer RNAs, specifically the addition of N6-threonylcarbamoyladenosine at position 37 of many tRNA species, a modification important for accurate translation.

Bud32 belongs to the protein kinase-like family and is believed to contribute to the activity of the KEOPS complex through ATP binding and hydrolysis. Although it shares structural features with kinases, Bud32 often shows only weak or no canonical protein kinase activity in vitro, and its essential role appears to be more related to ATP-dependent regulation and complex stability than to phosphorylation of conventional substrates. Its ATPase-like function is thought to drive conformational changes that promote t6A synthesis by the catalytic subunit Kae1.

In the KEOPS assembly, Bud32 interacts with Kae1 as well as other subunits such as Cgi121 and Pcc1, forming a stable complex required for proper tRNA modification. Disruption of Bud32 or perturbation of KEOPS compromises t6A formation, leading to translational defects, slower growth, and heightened sensitivity to cellular stress in model organisms.

Bud32 is evolutionarily conserved from archaea to humans. In humans, the Bud32/KEOPS orthologs include a kinase-like protein known as PRPK, which associates with the KEOPS complex and shares a conserved role in tRNA modification and complex integrity.