V-type proton ATPase 116 kDa subunit a1 (ATP6V0A1)

V-type proton ATPase 116 kDa subunit a1 (ATP6V0A1) is a key integral component of the V0 domain of the vacuolar-type H+-ATPase (V-ATPase) complex, a proton pump responsible for ATP-dependent acidification of intracellular organelles such as lysosomes, endosomes, and synaptic vesicles[1][4][6]. The subunit a1 is predominantly expressed in neurons and is essential for assembly and proton transport activity. This acidification underlies numerous cellular processes including receptor-mediated endocytosis, protein degradation, zymogen activation, synaptic vesicle loading, and neuronal signaling pathways. Pathogenic variants in ATP6V0A1 are linked to developmental and epileptic encephalopathies and neurodevelopmental disorders characterized by brain atrophy and epilepsy, underscoring its essential role in neural tissue and potential as a therapeutic target[4][6]. The only known drug-like inhibitors, such as bafilomycin A1, act broadly on the V-ATPase complex and are limited by toxicity. Hence, V-ATPase subunit a1 represents a validated enzymatic and transporter target with significant involvement in cell physiology and human disease.

Other names

ATPase H+ transporting V0 subunit a1ATP6N1ATP6N1AVPP1a1Vph1Stv1Clathrin-coated vesicle/synaptic vesicle proton pump 116 kDa subunitVacuolar adenosine triphosphatase subunit Ac116Vacuolar proton pump subunit 1Vacuolar proton translocating ATPase 116 kDa subunit a isoform 1DEE104NEDEBAVacuolar-type H(+)-ATPase 115 kDa subunitATPase H+ transporting lysosomal V0 subunit a1V-ATPase 116 kDa subunit a1

Inhibitors block ATP-dependent proton translocation by binding to the V0 domain, collapsing proton gradients, altering vesicle acidification, and impairing dependent physiological processes, including neurotransmitter loading[3][4].