UBA-like autoinhibitory domain (AID) found in vertebrate 5'-AMP-activated protein kinase catalytic alpha (AMPKalpha) subunits
The family corresponds to the catalytic subunits of adenosine monophosphate (AMP)-activated protein kinase (AMPK) which includes two isoforms encoded by two distinct genes, AMPKalpha-1 (PRKAA1) and AMPKalpha-2 (PRKAA2). Skeletal muscle predominantly expresses the AMPKalpha-2, whereas the liver expresses approximately equal amounts of both AMPKalpha subunits. One AMPKalpha subunit and two regulatory subunits, beta (beta1, beta2, beta3) and gamma (gamma1, gamma2, gamma3) form a heterotrimeric AMPK complex that plays a central role in the regulation of cellular energy metabolism, activates energy-producing pathways and inhibits energy-consuming processes through responding to a fall in intracellular ATP levels. It is activated in beta-cells at low glucose concentrations, but inhibited as glucose levels increase. AMPKalpha subunits show significant similarity in the catalytic core region, but have divergent COOH-terminal tails, suggesting they may interact with different proteins within this region. Both of AMPKalpha subunits have an N-terminal Ser/Thr kinase domain followed by an ubiquitin-associated (UBA)-like AID, and a C-terminal AMPK regulatory domain. The Ser/Thr kinase domain contains a conserved Thr residue that must be phosphorylated for activity in the activation loop. The AID is responsible for AMPKalpha subunits autoinhibition. The C-terminal regulatory domain of the alpha-subunit is essential for binding the beta- and gamma-subunits.
Jiyao W et al.(2023). "The conserved domain database in 2023.",