Vacuolar-type H+-ATPase catalytic subunit A (ATP6V1A) (ATP6V1A)

Vacuolar-type H+-ATPase catalytic subunit A (ATP6V1A) is a core component of the V1 domain of the V-ATPase complex, a multi-subunit rotary enzyme that functions as a primary proton pump in eukaryotic cells [1, 2]. This subunit is responsible for the hydrolysis of ATP, which provides the energy necessary to transport protons across biological membranes to acidify intracellular organelles such as lysosomes and endosomes [2, 19]. Such acidification is critical for essential cellular processes, including protein degradation, receptor-mediated endocytosis, and nutrient sensing through the mTORC1 pathway [8, 20]. In disease states, ATP6V1A is often dysregulated; for instance, its recruitment to the plasma membrane in cancer cells facilitates the acidification of the tumor microenvironment, promoting invasion and metastasis [14, 20]. Furthermore, mutations in the ATP6V1A gene are linked to severe conditions such as cutis laxa and developmental and epileptic encephalopathy [7]. While numerous experimental inhibitors like bafilomycin A1 and salicylihalamides target this enzyme, their clinical utility is currently limited by potential systemic toxicity given the ubiquitous role of V-ATPases in cellular homeostasis [15, 18]. Recent therapeutic efforts focus on identifying isoform-specific interactions or targeting specialized V-ATPase populations to treat osteoporosis and metastatic cancers more selectively [15, 16].

Other names

V-ATPase subunit AATP6V1AVacuolar proton pump subunit alphaV-ATPase 69 kDa subunitV-type proton ATPase catalytic subunit AATPase H+ transporting V1 subunit AVA68ATP6A1

Inhibition of ATP hydrolysis within the V1 domain; Prevention of the rotational mechanism of the V-ATPase complex; Disruption of the coupling between ATP hydrolysis and proton translocation; Interference with subunit-subunit interactions within the V1 domain