Vacuolar-type H+-ATPase subunit a isoform 2 (ATP6V0A2)

Vacuolar-type H+-ATPase subunit a isoform 2 (ATP6V0A2) is a critical component of the V0 domain of the V-type ATPase, a multi-subunit enzyme complex responsible for acidifying intracellular compartments (UniProt: P21271). This specific isoform is predominantly localized to the Golgi apparatus and early endosomes, where it maintains the acidic environment necessary for proper protein processing and glycosylation (PubMed: 18157129). Mutations in the ATP6V0A2 gene are the primary cause of autosomal recessive cutis laxa type IIA (ARCL2A), a disorder characterized by skin hyperelasticity and developmental delays due to impaired glycosylation pathways (OMIM: 611716). While V-ATPases are broad therapeutic targets in cancer and osteoporosis, the a2 isoform specifically is being investigated for its role in tumor microenvironment acidification and viral entry (PubMed: 22561081). Pharmacological inhibition of this target, typically via macrolide antibiotics like bafilomycin, disrupts the proton gradient, leading to defects in vesicular trafficking and protein maturation (PubMed: 28330603). Targeting this isoform specifically is of interest to minimize the off-target effects associated with pan-V-ATPase inhibition in non-target tissues.

Other names

V-type proton ATPase 116 kDa subunit a isoform 2ATP6V0A2TJ6WSSARCL2ASTV1V-ATPase subunit a2

Inhibition of the V0 domain of the V-type ATPase complex, preventing the translocation of protons across the membrane and thereby inhibiting the acidification of intracellular compartments such as the Golgi apparatus and endosomes.