Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atp11p (Atpaf1p; F(1)-ATPase assembly factor 1) and Atp12p (Atpaf2p; F(1)-ATPase assembly factor 2) are proteins required for the assembly of beta (F(1)-beta) and alpha (F(1)-alpha) subunits into the mitochondrial ATPase. Here we report about 100 times lower levels of ATPAF1 and ATPAF2 transcripts in relation to the mRNA levels of F(1)-alpha and F(1)-beta in a range of mouse tissues. Quantitative reverse-transcription polymerase chain reaction revealed nearly constant ATPAF1 expression in all tissues in both adult and 5-day-old mice (up to two-fold differences), indicating that ATPAF1 rather behaves like a maintenance gene. In contrast, ATPAF2 expression differed up to 30-fold in the tissues analysed. ATPAF2 tissue-specific expression was also found to correlate well with mRNA levels of both F(1)-alpha and F(1)-beta (BATz.Gt;kidney, liver>heart, brain>skeletal muscle), showing the highest mRNA level in the thermogenic, ATPase-poor brown adipose tissue, which is characterised by a 10-fold decrease in ATPase/respiratory chain stoichiometry relative to the other tissues.
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PMID:Differential expression of ATPAF1 and ATPAF2 genes encoding F(1)-ATPase assembly proteins in mouse tissues. 1296 2

The ATP synthase of yeast mitochondria is composed of 17 different subunit polypeptides. We have screened a panel of ATP synthase mutants for impaired expression of Atp6p, Atp8p, and Atp9p, the only mitochondrially encoded subunits of ATP synthase. Our results show that translation of Atp6p and Atp8p is activated by F(1) ATPase (or assembly intermediates thereof). Mutants lacking the alpha or beta subunits of F(1), or the Atp11p and Atp12p chaperones that promote F(1) assembly, have normal levels of the bicistronic ATP8/ATP6 mRNAs but fail to synthesize Atp6p and Atp8p. F(1) mutants are also unable to express ARG8(m) when this normally nuclear gene is substituted for ATP6 or ATP8 in mitochondrial DNA. Translational activation by F(1) is also supported by the ability of ATP22, an Atp6p-specific translation factor, to restore Atp6p and to a lesser degree Atp8p synthesis in the absence of F(1). These results establish a mechanism by which expression of ATP6 and ATP8 is translationally regulated by F(1) to achieve a balanced output of two compartmentally separated sets of ATP synthase genes.
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PMID:F1-dependent translation of mitochondrially encoded Atp6p and Atp8p subunits of yeast ATP synthase. 1984 Dec 66

Studies in yeast have shown that a deficiency in Atp12p prevents assembly of the extrinsic domain (F(1)) of complex V and renders cells unable to make ATP through oxidative phosphorylation. De Meirleir et al. (De Meirleir, L., Seneca, S., Lissens, W., De Clercq, I., Eyskens, F., Gerlo, E., Smet, J., and Van Coster, R. (2004) J. Med. Genet. 41, 120-124) have reported that a homozygous missense mutation in the gene for human Atp12p (HuAtp12p), which replaces Trp-94 with Arg, was linked to the death of a 14-month-old patient. We have investigated the impact of the pathogenic W94R mutation on Atp12p structure/function. Plasmid-borne wild type human Atp12p rescues the respiratory defect of a yeast ATP12 deletion mutant (Deltaatp12). The W94R mutation alters the protein at the most highly conserved position in the Pfam sequence and renders HuAtp12p insoluble in the background of Deltaatp12. In contrast, the yeast protein harboring the corresponding mutation, ScAtp12p(W103R), is soluble in the background of Deltaatp12 but not in the background of Deltaatp12Deltafmc1, a strain that also lacks Fmc1p. Fmc1p is a yeast mitochondrial protein not found in higher eukaryotes. Tryptophan 94 (human) or 103 (yeast) is located in a positively charged region of Atp12p, and hence its mutation to arginine does not alter significantly the electrostatic properties of the protein. Instead, we provide evidence that the primary effect of the substitution is on the dynamic properties of Atp12p.
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PMID:Defining the pathogenesis of the human Atp12p W94R mutation using a Saccharomyces cerevisiae yeast model. 1993 71

F₁-ATPase (F₁) is a multisubunit water-soluble domain of F_oF_1- ATP synthase and is a rotary enzyme by itself. Earlier genetic studies using yeast suggested that two factors, Atp11p and Atp12p, contribute to F₁ assembly. Here, we show that their mammalian counterparts, AF1 and AF2, are essential and sufficient for efficient production of recombinant bovine mitochondrial F₁ in Escherichia coli cells. Intactness of the function and conformation of the E. coli-expressed bovine F₁ was verified by rotation analysis and crystallization. This expression system opens a way for the previously unattempted mutation study of mammalian mitochondrial F₁.
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PMID:Expression of mammalian mitochondrial F₁-ATPase in Escherichia coli depends on two chaperone factors, AF1 and AF2. 2820 26

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