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)

We have sequenced a gene on the right arm near the telomere of chromosome II of Saccharomyces cerevisiae which codes for a putative P-type cation-transporting ATPase (PCA1). The gene codes for a 1216 amino acids protein. The PCA1 gene expresses a 3.5 kb message in both haploid and diploid cells when grown in glucose-based rich medium YPD. The gene product is most similar at the C-terminal region to a human copper-transporting ATPase and Enterococcus hirae copper-transporting ATPases and also an N-terminal dithiol region that was proposed to be a 'metal-binding motif'. Cells lacking PCA1 display no obvious phenotype when tested under standard conditions: whereas they cease growth much earlier than the isogenic wild-type cells in a minimal medium with high copper concentration. Overexpression of PCA1 under GAL1/10 promoter in yeast cells causes poor growth. We also show that yeast strains carrying PCA1 in multiple copies grow slower than isogenic wild-type strains in a minimal synthetic medium containing 0.3 mM-CuSO4.
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PMID:A putative P-type Cu(2+)-transporting ATPase gene on chromosome II of Saccharomyces cerevisiae. 775 11

Yeast cells carrying the CAD2 gene exhibit a resistance to cadmium. We cloned this gene and demonstrated that it was a mutated form derived from the gene of a putative copper-transporting ATPase (PCA1). By site-directed mutagenesis, it appeared that the mutation conferring cadmium resistance was a R970G-substitution in the C-terminal region of Pca1 protein. The intracellular cadmium level of cells carrying CAD2 was lower than that of cells carrying either PAC1 or delta cad2. Furthermore, cells with overexpression of CAD2 showed a much lower intracellular cadmium level than that of cells with a single-copy CAD2. From these results, we conclude that the Cad2 protein controls the intracellular cadmium level through an enhanced cadmium efflux system.
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PMID:The cadmium-resistant gene, CAD2, which is a mutated putative copper-transporter gene (PCA1), controls the intracellular cadmium-level in the yeast S. cerevisiae. 1074 63

The opportunistic fungus Pneumocystis is the etiologic agent of an interstitial plasma cell pneumonia that primarily afflicts immunocompromised individuals. Like other fungi Pneumocystis maintains a H(+) plasma membrane gradient to drive nutrient uptake and regulates intracellular pH by ATP-dependent proton efflux. Previously, we identified a Pneumocystis gene, PCA1, whose predicted protein product was homologous to fungal proton pumps. In this study, we show by functional complementation in a Saccharomyces strain whose endogenous PMA1 proton pump activity is repressed that the Pneumocystis PCA1 encodes a H(+)-ATPase. The properties of PCA1 characterized in this system closely resemble those of yeast PMA1. Yeast expressing PCA1 grow at low pH and are able to acidify the external media. Maximal enzyme activity (V(max)) and efficiency of substrate utilization (K(m)) in plasma membranes were nearly identical for PCA1 and PMA1. PCA1 contains an inhibitory COOH-terminal domain; removal of the final 40 amino acids significantly increased V(max) and growth at pH 6.5. PCA1 activity was inhibited by proton pump inhibitors omeprazole and lansoprazole, but was unaffected by H(+)/K(+)-ATPase inhibitor SCH28080. Thus, H(+) homeostasis in Pneumocystis is likely regulated as in other fungi. This work also establishes a system for screening PCA1 inhibitors to identify new anti-Pneumocystis agents.
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PMID:Functional complementation of the yeast P-type H-ATPase, PMA1, by the Pneumocystis carinii P-type H-ATPase, PCA1. 1667 37

Detoxification and homeostatic acquisition of metal ions are vital for all living organisms. We have identified PCA1 in yeast Saccharomyces cerevisiae as an overexpression suppressor of copper toxicity. PCA1 possesses signatures of a P1B-type heavy metal-transporting ATPase that is widely distributed from bacteria to humans. Copper resistance conferred by PCA1 is not dependent on catalytic activity, but it appears that a cysteine-rich region located in the N terminus sequesters copper. Unexpectedly, when compared with two independent natural isolates and an industrial S. cerevisiae strain, the PCA1 allele of the common laboratory strains we have examined possesses a missense mutation in a predicted ATP-binding residue conserved in P1B-type ATPases. Consistent with a previous report that identifies an equivalent mutation in a copper-transporting P1B-type ATPase of a Wilson disease patient, the PCA1 allele found in laboratory yeast strains is nonfunctional. Overexpression or deletion of the functional allele in yeast demonstrates that PCA1 is a cadmium efflux pump. Cadmium as well as copper and silver, but not other metals examined, dramatically increase PCA1 protein expression through post-transcriptional regulation and promote subcellular localization to the plasma membrane. Our study has revealed a novel metal detoxification mechanism in yeast mediated by a P1B-type ATPase that is unique in structure, substrate specificity, and mode of regulation.
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PMID:A cadmium-transporting P1B-type ATPase in yeast Saccharomyces cerevisiae. 1710 46

Transient cytosolic Ca(2+) ([Ca(2+)](cyt)) elevations are early events in plant signaling pathways including those related to abiotic stress. The restoration of [Ca(2+)](cyt) to prestimulus levels involves ATP-driven Ca(2+) pumps, but direct evidence for an essential role of a plant Ca(2+)-ATPase in abiotic stress adaptation is missing. Here, we report on a stress-responsive Ca(2+)-ATPase gene (PCA1) from the moss Physcomitrella patens. Functional analysis of PCA1 in a Ca(2+) transport-deficient yeast mutant suggests that PCA1 encodes a P(IIB)-type Ca(2+)-ATPase harboring an N-terminal autoinhibitory domain. In vivo localizations identified membranes of small vacuoles as the integration site for a PCA1:GFP fusion protein. PCA1 mRNA levels are up-regulated by dehydration, NaCl, and abscisic acid, and PCA1 loss-of-function mutants (DeltaPCA1) exhibit an enhanced susceptibility to salt stress. The DeltaPCA1 lines show sustained elevated [Ca(2+)](cyt) in response to salt treatment in contrast to WT that shows transient Ca(2+) elevations, indicating a direct role for PCA1 in the restoration of prestimulus [Ca(2+)](cyt). The altered Ca(2+) response of the DeltaPCA1 mutant lines correlates with altered expression levels of stress-induced genes, suggesting disturbance of a stress-associated signaling pathway. We propose that PCA1 is an essential component for abiotic stress adaptation in Physcomitrella involved in the generation of a specific salt-induced Ca(2+) signature.
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PMID:A PIIB-type Ca2+-ATPase is essential for stress adaptation in Physcomitrella patens. 1979 61