Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mammalian mitochondrial ATP synthase is composed of at least 16 polypeptides. With the exception of coupling factor F(6), there are likely yeast homologs for each of these polypeptides. There are no obvious yeast homologs of F(6), as predicted from primary sequence comparison of the putative peptides encoded by the open reading frames in the yeast genome. In this manuscript, we demonstrate that expression of bovine F(6) complements a null mutant in ATP14 gene in yeast Saccharomyces cerevisiae. Subunit h of the yeast ATP synthase is encoded by ATP14 and is just 14.5% identical to bovine F(6). Expression of bovine F(6) in an atp14 null mutant strain recovers oxidative phosphorylation, and the ATP synthase is active, although functioning with a lower efficiency than the wild type enzyme. Like subunit h, bovine F(6) is shown to interact mainly with subunit 4 (subunit b), a component of the second stalk of the enzyme. These data indicated the subunit h is the yeast homolog of mammalian coupling factor F(6).
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PMID:Bovine coupling factor 6, with just 14.5% shared identity, replaces subunit h in the yeast ATP synthase. 1108 70

Positional cloning efforts of genes mutated in Batten disease and in the Finnish type of variant late infantile neuronal ceroid lipofuscinosis resulted in the identification of two novel genes, CLN3 and CLN5, and corresponding gene products that proved to be residents of lysosomes. Although the clinical phenotype of these NCL subtypes differs in the age of onset, average life span and EEG findings, the major component of material accumulating in patients' lysosomes is subunit c of mitochondrial ATPase in both these diseases. The CLN3 and CLN5 genes show ubiquitous expression patterns and are targeted to lysosomes in vitro, but the observed synaptosomal localization of the CLN3 protein in neurons would suggest some cell specificity in targeting and function of these proteins. So far, 31 different mutations of the CLN3 gene have been described in Batten patients, with one deletion of 1.02 kb accounting for 75% of disease alleles worldwide. Four CLN5 mutations are known, with one premature stop representing the major founder mutation in the isolated Finnish population. Functional studies of the yeast homolog of CLN3 and increased pH in patients' lysosomes would suggest an involvement of this protein in lysosomal pH homeostasis. Knock-out mouse models for CLN3 have been produced and the histopathology bears a close resemblance to human counterparts with characteristic lysosomal accumulations. Both CLN3 and CLN5 mouse models will provide experimental tools to resolve the pathological cascade in these neurodegenerative diseases.
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PMID:Mutated genes in juvenile and variant late infantile neuronal ceroid lipofuscinoses encode lysosomal proteins. 1212 9