Disease relevance of CUP5

• Moreover, in the vma3 background, toxicity caused by the cls2 mutation is greatly enhanced by FK506 [1].
• Of three mutants examined (vps45, vma3, and rcy1), all were found to have defective calcium homeostasis, supporting a correlation with amiodarone hypersensitivity [2].

High impact information on CUP5

• Since disruption of GEF2, a subunit of the vacuolar H+-ATPase, leads to a similar phenotype, it was previously suggested that the chloride conductance provided by Gef1p is necessary for vacuolar acidification [3].
• We report here that the immunosuppressants FK506 and cyclosporin A cause general growth inhibition of the vma3 mutant [4].
• Ca(2+)-sensitive mutants of the yeast Saccharomyces cerevisiae showing a Pet- phenotype (cls7-cls11) have lesions in a system for maintaining intracellular Ca2+ homeostasis (Ohya, Y., Ohsumi, Y., and Anraku, Y. (1986) J. Gen. Microbiol. 132, 979-988) [5].
• The deduced amino acid sequence shows 56.7% identity, and significant coincidence in amino acid composition with the 16-kDa subunit c (a VMA3 gene product) of the yeast vacuolar membrane H(+)-ATPase [6].
• To investigate functional and structural roles of the subunit c for vacuolar acidification and protein transport to the vacuole, haploid mutants with the disrupted VMA3 gene were constructed [7].

Biological context of CUP5

• One CLS gene, CLS7, was located on the left arm of chromosome V [8].
• Cloning of structural genes for the three subunits of the H+-ATPase (VMA1, VMA2, and VMA3) and their nucleotide sequence determination have been accomplished, which provide greater advantages for molecular biological studies on the structure-function relationship and biogenesis of the enzyme complex [9].
• The cDNA for the Nephrops proteolipid complements a mutation in the yeast VMA3 gene, resulting in assembly of a hybrid H(+)-ATPase comprising yeast catalytic subunits and Nephrops integral membrane components [10].
• A defect in mitochondrial function may be the cause of the petite phenotype: the rate of oxygen consumption by intact gef2 cells and by mitochondrial fractions isolated from gef2 mutants was reduced 60%-75% relative to wild type [11].

Anatomical context of CUP5

• Using a vma3 mutation that impairs the Ca2+ sequestering activity into the vacuole, we have shown that the cls2 mutation results in 3.4-fold increase in the Ca2+ pool that is not exchangeable with extracellular Ca2+ [1].
• Functional expression of Acetabularia acetabulum vacuolar H(+)-pyrophosphatase in a yeast VMA3-deficient strain [12].
• Two translation products from the other two cDNAs were demonstrated not to be localized in vacuolar membranes, and thus could not complement the function of the VMA3-deficient strain [13].

Associations of CUP5 with chemical compounds

• Peptide sequence analysis indicated that the VMA3 gene product lacks N-terminal methionine and does not have a cleavable signal sequence [7].

Other interactions of CUP5

• In this study we demonstrate that proteins encoded by genes previously demonstrated to play critical roles in vacuole assembly for acidification, PEP3, PEP5 and VMA3, are also required for normal copper and iron metal ion homeostasis [14].
• A vma3 mutant defective in vacuolar acidification showed no reduction of vacuolar pH after application of hydrostatic pressure, indicating that the transient acidification is mediated through the function of vacuolar H(+)-ATPase [15].

References