V-type proton ATPase subunit C 1 (ATP6V1C1)

V-type proton ATPase subunit C 1 (ATP6V1C1) is a critical regulatory component of the V1 domain of the vacuolar-type H+-ATPase (V-ATPase) complex, a multi-subunit enzyme responsible for acidifying intracellular compartments such as lysosomes, endosomes, and the Golgi apparatus (NCBI Gene; UniProt P21283). This acidification is essential for diverse cellular processes, including protein degradation, receptor recycling, and the loading of neurotransmitters into synaptic vesicles (Wikipedia). In specialized cells like osteoclasts, V-ATPases are also localized to the plasma membrane to facilitate bone resorption (PubMed: 17093137). ATP6V1C1 has emerged as a significant therapeutic target, particularly in oncology, where its overexpression is linked to increased tumor invasion, metastasis, and resistance to therapy in cancers such as glioblastoma and breast cancer (PubMed: 25955442; PubMed: 17909082). Additionally, gain-of-function mutations in ATP6V1C1 have been associated with neurodevelopmental disorders, including DOORS syndrome (PubMed: 39393415). While potent inhibitors like bafilomycin A1 exist, their clinical utility is limited by systemic toxicity due to the pump's ubiquitous housekeeping functions; however, newer strategies targeting specific subunit interactions, such as the C1-actin binding inhibited by enoxacin, offer potential for more selective therapeutic intervention (PubMed: 29234144).

Other names

Vacuolar-type H+-ATPase subunit C1ATPase H+ transporting V1 subunit C1ATP6CATP6DVATCVma5V-ATPase subunit C 1

Inhibition of the V-ATPase complex activity by binding to the V1 or V0 domains, thereby preventing ATP hydrolysis or proton translocation, or by disrupting the interaction between the C1 subunit and the actin cytoskeleton (e.g., enoxacin), which is required for pump recruitment and activity in specialized cells like osteoclasts (PubMed: 29234144).