Vacuolar-type H+-ATPase subunit c (ATP6V0C) (ATP6V0C)

The Vacuolar-type H+-ATPase (V-ATPase) is a highly conserved, multi-subunit enzyme complex that functions as an ATP-driven proton pump, primarily responsible for the acidification of intracellular compartments such as lysosomes, endosomes, and the Golgi apparatus [UniProt P27449]. The Vo c-subunit is a fundamental component of the membrane-integral Vo domain, where it forms a proteolipid ring that rotates to translocate protons across the lipid bilayer [PubMed: 17203062]. This acidification is essential for diverse biological processes, including the activation of lysosomal hydrolases, receptor-mediated endocytosis, and the coupled transport of neurotransmitters [PubMed: 18606446]. In disease states, V-ATPase is often dysregulated; for example, its overexpression on the plasma membrane of cancer cells facilitates an acidic tumor microenvironment that promotes protease activation and metastasis [PubMed: 25613000]. Additionally, it is critical for bone resorption by osteoclasts and serves as a gateway for the entry of various pH-dependent viruses [PubMed: 20530212]. While the c-subunit is a potent target for inhibitors like bafilomycin A1, the ubiquitous necessity of V-ATPase for cellular viability presents significant challenges for achieving therapeutic selectivity and minimizing systemic toxicity [PubMed: 20433182].

Other names

V-type proton ATPase subunit cV-ATPase 16 kDa proteolipid subunitATP6CATP6LVPATPCVacuolar proton pump subunit cATPase H+ transporting V0 subunit c

Inhibition of the proton-translocating Vo domain by binding to the c-subunit ring, thereby blocking the rotational mechanism required for proton transport across the membrane.