Vacuolar proton pump subunit G2 (ATP6V1G2)

ATP6V1G2 encodes subunit G2 of the V1 domain of vacuolar H+-ATPase (V-ATPase), a multisubunit ATP-dependent proton pump critical for acidifying intracellular compartments such as lysosomes, endosomes, and synaptic vesicles[1][3][5][6]. The V1 sector, where G2 localizes, is responsible for ATP hydrolysis, which energizes proton translocation via the V0 membrane domain. The G2 isoform is selectively expressed in neurons, where it supports neurotransmitter loading into synaptic vesicles—a key step for synaptic transmission. More broadly, V-ATPase-dependent acidification is crucial for protein processing, immune responses, and receptor-mediated endocytosis. Disruption of V-ATPase function, including mutations or altered expression of ATP6V1G2, has been implicated in neurological dysfunction and potentially in immune system modulation[3][5][6]. Essential details: - Subunit G2 is a ~13 kDa protein forming part of the peripheral stalk that connects V1 and V0 domains, contributing to enzyme structural integrity and regulatory dissociation/association cycles[5]. - In mammals, three genes encode G subunit isoforms (ATP6V1G1, ATP6V1G2, ATP6V1G3), with ATP6V1G2 predominantly neuronal[5]. - Mutations or loss of ATP6V1G2 can impact synaptic physiology and may contribute to neurodevelopmental or degenerative diseases[3][5]. - While the entire V-ATPase complex is a validated therapeutic target (e.g., for osteoporosis, cancer, viral infections), subunit-specific targeting has not been achieved as of the available evidence.

Other names

V-type proton ATPase subunit G2ATP6V1G2ATP6GATP6G2NG38Vma10V-ATPase subunit G2V-ATPase 13 kDa subunit 2Vacuolar ATP synthase subunit G2Vacuolar proton pump G subunit 2Em:AC004181.3

General V-ATPase inhibitors decrease acidification of intracellular vesicles, thus interfering with protein degradation, neurotransmitter loading, or viral entry