V-type proton ATPase subunit E1 (ATP6V1E1)

V-type proton ATPase subunit E1 (ATP6V1E1) is a protein component of the peripheral V1 domain of the vacuolar-type ATPase (V-ATPase), a multisubunit enzyme complex that hydrolyzes ATP to drive proton transport across intracellular organelle membranes, maintaining acidic pH in lysosomes, endosomes, and secretory vesicles[1][3][5]. This acidification is crucial for various cellular processes including protein degradation, endocytosis, and neurotransmitter storage. The E1 subunit acts as a stator component within the V1 sector, binding other subunits and facilitating coupling between ATP hydrolysis and proton translocation[2][5]. Mutations in ATP6V1E1 are associated with rare hereditary connective tissue diseases, and broader malfunction of V-ATPase activity is implicated in diverse pathological processes, making it a potential therapeutic target although with considerable challenges regarding specificity and toxicity[3][2].

Other names

ATPase H+ transporting V1 subunit E1Vacuolar proton pump subunit E 1ATP6EATP6E2V-ATPase subunit E 1p31P31Vma4V-ATPase 31 kDa subunitARCL2CH(+)-transporting two-sector ATPase, 31kDa subunitH+-transporting ATP synthase chain E, vacuolar

Inhibitors (e.g., bafilomycin, concanamycin) block proton translocation by binding to the V-ATPase complex, leading to impaired acidification of organelles, disruption of processes like endocytosis and autophagy[2][6]. No approved drugs specifically target subunit E1 alone, but these agents inhibit the V-ATPase complex generally.