DEFINITION
V-ATPase acidifiy a wide array of intracellular organelles and pump protons across the plasma membranes of numerous cell types.
CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
- Primary structure
- Secondary structure
- Tertiary structure
- Quaternary structure
Protein Aminoacids Percentage
The Protein Aminoacids Percentage gives useful information on the local environment and the metabolic status of the cell (starvation, lack of essential AA, hypoxia)
Model (Width 600 px)
SYNTHESIS AND TURNOVER
mRNA synthesis
protein synthesis
post-translational modifications
degradation
CELLULAR FUNCTIONS
cellular localization
V-ATPase at the molecular level
ATPase animation
Stepping motor of F1
Role of v-ATPase in proteins digestion
biological function
- Enzymes
- Cell signaling and Ligand transport
- Structural proteins
REGULATION
DIAGNOSTIC USE
VMA21 Deficiency Causes an Autophagic Myopathy by Compromising V-ATPase Activity and Lysosomal Acidification 2009
X-linked myopathy with excessive autophagy (XMEA) is a childhood-onset disease characterized by progressive vacuolation and atrophy of skeletal muscle. We show that XMEA is caused by hypomorphic alleles of the VMA21 gene, that VMA21 is the diverged human ortholog of the yeast Vma21p protein, and that like Vma21p it is an essential assembly chaperone of the V-ATPase, the principal mammalian proton pump complex. Decreased VMA21 raises lysosomal pH, which reduces lysosomal degradative ability and blocks autophagy. This reduces cellular free amino acids, which upregulates the mTOR pathway and mTOR-dependent macroautophagy, resulting in proliferation of large and ineffective autolysosomes that engulf sections of cytoplasm, merge together, and vacuolate the cell. Our results uncover macroautophagic overcompensation leading to cell vacuolation and tissue atrophy as a mechanism of disease.
