V-type proton ATPase catalytic subunit A (ATP6V1A) (ATP6V1A)

V-type proton ATPase catalytic subunit A (ATP6V1A) is a critical component of the V1 domain of the vacuolar-type H+-ATPase (V-ATPase) complex, an ATP-dependent proton pump found in all eukaryotic cells [3, 6, 8]. It serves as the primary site for ATP hydrolysis, providing the energy required to transport protons across membranes to acidify intracellular organelles such as lysosomes, endosomes, and the Golgi apparatus [6, 9, 10]. This acidification is vital for numerous cellular processes, including protein degradation, autophagy, receptor-mediated endocytosis, and the loading of neurotransmitters into synaptic vesicles [2, 9, 12]. Dysregulation of ATP6V1A is implicated in several diseases; for instance, its overexpression on the plasma membrane of cancer cells facilitates an acidic tumor microenvironment that promotes invasion and drug resistance [4, 10]. Mutations in the ATP6V1A gene are also associated with neurodevelopmental disorders, such as developmental and epileptic encephalopathy, and neurodegenerative conditions like Alzheimer's disease [12, 17]. While potent inhibitors like bafilomycin A1 and concanamycin A are widely used in research, their clinical application is hindered by significant systemic toxicity due to the enzyme's ubiquitous role in pH homeostasis [4, 7]. Consequently, current therapeutic strategies focus on identifying isoform-specific inhibitors or modulators that can selectively target disease-associated V-ATPase activity [4, 7, 16].

Other names

ATP6V1AATP6A1ATP6V1A1HO68VA68VPP2Vma1ATPase H+ transporting V1 subunit AARCL2DIECEE3DEE93

Inhibition of ATP hydrolysis, inhibition of proton translocation, and disruption of V-ATPase assembly or interaction with microfilaments [4, 5, 10, 11].