Disease relevance of VMA22

• The peptidyl-prolyl cis-trans isomerases cyclophilin A and FKBP12, respectively, mediate CsA and FK506 toxicity in the cev1 mutant strain [1].

High impact information on VMA22

• Vph1p is the 100 kDa membrane subunit of the yeast Saccharomyces cerevisiae V-ATPase, which together with other subunits, assembles into the V-ATPase in the ER, requiring the ER resident protein Vma22p [2].
• Vma12p and Vma22p migrated to fractions separate from Vma21p [3].
• Assembly of the yeast vacuolar H+-ATPase occurs in the endoplasmic reticulum and requires a Vma12p/Vma22p assembly complex [3].
• Similarly, murine mdr3 expression confers resistance to the immunosuppressants cyclosporin A (CsA) and FK506 in a CsA-FK506-sensitive vph6 mutant yeast strain [4].
• The product of the VMA22 gene, Vma22p, is a 21-kDa hydrophilic protein that is not a subunit of the V-ATPase but rather is associated with ER membranes [5].

Biological context of VMA22

• The VPH6 gene was mapped on chromosome VIII and is predicted to encode a 181-amino acid (21 kD) protein with no identity to other known proteins [1].
• A single nuclear mutation, designated cev1 for calcineurin essential for viability, is responsible for the CsA-FK506-sensitive phenotype [1].
• Autophagy delivers glycogen to the vacuole, and we propose that the impaired vacuolar function associated with ATPase mutants (vma10 or vma22) results in reduced degradation and subsequent hyperaccumulation of glycogen [6].

Anatomical context of VMA22

• Three previously identified genes from Saccharomyces cerevisiae, VMA12, VMA21, and VMA22, encode proteins localized to the endoplasmic reticulum (ER) [3].
• Turnover of the 100-kDa integral membrane protein was found to occur in the endoplasmic reticulum (ER) of vma22 delta cells [5].
• The vma22-1 mutation was isolated in a screen for mutants defective in V-ATPase function vma22 delta cells contain no V-ATPase activity due to a failure to assemble the enzyme complex; V1 subunits accumulate in the cytosol, and the V0 100-kDa subunit is rapidly degraded [5].

Physical interactions of VMA22

• The interaction of the Vma12p/Vma22p complex with Vph1p was transient (half-life of approximately 5 min), reflecting trafficking of this V-ATPase subunit through the ER en route to the vacuolar membrane [3].

Other interactions of VMA22

• Subcellular fractionation and chemical cross-linking studies have revealed that Vma12p and Vma22p form a stable membrane associated complex [3].
• Representatives in five complementation groups were identified, including four novel mutant vma5, vma21, vma22, and vma23, all of which were defective in vacuolar ATPase enzyme activity [7].

References