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)

ATP7B, the gene altered in Wilson disease (WD) patients, lies in a block of homology shared between human chromosome 13q14 and the central region of mouse chromosome 14. However, we have mapped the murine homologue of ATP7B (Atp7b) to mouse chromosome 8 by somatic cell hybrid analysis. Analysis of 80 interspecific backcross offspring was used to position Atp7b close to D8Mit3 and another ATPase locus, Atp4b, on mouse chromosome 8. ATP4B lies in 13q34 and is separated from ATP7B by several loci whose mouse homologues map to mouse chromosome 14. The assignment of Atp7b to mouse chromosome 8 identifies a previously unrecognized region of homology between this chromosome and human chromosome 13. This assignment suggests a possible location for the toxic milk mutation in the mouse, which has been proposed as a homologue of WD.
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PMID:Mapping of the mouse homologue of the Wilson disease gene to mouse chromosome 8. 749 97

The gene defective in Menkes disease, an X-linked recessive disturbance of copper metabolism, has been isolated and predicted to encode a copper-binding P-type ATPase. We determined the complete exon-intron structure of the Menkes disease gene, which spans about 150 kb of genomic DNA. The gene contains 23 exons, and the ATG start codon is in the second exon. All of the exon-intron boundaries were sequenced and conformed to the GT/AT rule, except for the 5' splice site of intron 9. A preliminary comparison demonstrated a striking similarity between the exon structures of the Menkes and Wilson disease genes, giving insight into their evolution.
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PMID:Characterization of the exon structure of the Menkes disease gene using vectorette PCR. 760 65

Wilson disease is a disorder of copper transport, resulting in neurological and hepatic damage due to copper toxicity. We have recently identified > 20 mutations in the copper-transporting ATPase defective in this disease. Given the difficulties of searching for mutations in a gene spanning > 80 kb of genomic DNA, haplotype data are important as a guide to mutation detection. Here we examine the haplotypes associated with specific mutations. We have extended previous studies of DNA haplotypes of dinucleotide-repeat polymorphisms (CA repeats) in the Wilson disease region to include an additional marker, in 58 families. These haplotypes, combining three markers (D13S314, D13S316, and D13S301), are usually specific for each different mutation, even though highly polymorphic CA repeat markers have been used. Haplotypes, as well as their accompanying mutations, differ between populations. In the patients whom we have studied, the haplotype data indicate that as many as 20 mutations may still be unidentified. The use of the haplotypes that we have identified provides an important guide for the identification of known mutations and can facilitate future mutation searches.
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PMID:Haplotypes and mutations in Wilson disease. 776 53

We have isolated, sequenced, mapped and disrupted a gene, CCC2, from Saccharomyces cerevisiae. This gene displays non-allelic complementation of the Ca(2+)-sensitive phenotype conferred by the csg1 mutation. Analysis of the CCC2p amino acid sequence reveals that it encodes a member of the P-type ATPase family and is most similar to a subfamily thought to consist of Cu2+ transporters, including the human genes that mutate to cause Wilson disease and Menkes disease. The ability of this gene, in two or more copies, to reverse the csg1 defect suggests that Ca(2+)-induced death of csg1 mutant cells is related to Cu2+ metabolism. Cells without CCC2 require increased Cu2+ concentrations for growth. Therefore CCC2p may function to provide Cu2+ to a cellular compartment rather than in removal of excess Cu2+.
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PMID:Sequence, mapping and disruption of CCC2, a gene that cross-complements the Ca(2+)-sensitive phenotype of csg1 mutants and encodes a P-type ATPase belonging to the Cu(2+)-ATPase subfamily. 778 28

Menkes disease and Wilson disease are human disorders of copper metabolism. It has recently been shown that both are due to mutations in P-type ATPase copper transport molecules. Related heavy metal transporting ATPases have been described in several strains of bacteria. In an effort to isolate other mammalian metal transporters, we screened a human small intestine library with probes homologous to conserved sequences in the known proteins. Two novel cDNAs were isolated, which encode new members of this family. Surprisingly, they were both of bacterial origin, most likely derived from E. coli sequences transduced during library construction.
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PMID:Novel bacterial P-type ATPases with histidine-rich heavy-metal-associated sequences. 781 Dec 48

The process of hepatobiliary copper (Cu) secretion is still poorly understood: Cu secretion as a complex with glutathione and transport via a lysosomal pathway have been proposed. The recent cloning and sequencing of the gene for Wilson disease indicates that Cu transport in liver cells may be mediated by a Cu transporting P-type ATPase. Biochemical evidence for ATP-dependent Cu transport in mammalian systems, however, has not been reported so far. We have investigated Cu transport in rat liver plasma membrane vesicles enriched in canalicular or basolateral membranes in the presence and absence of ATP (4 mM) and an ATP-regenerating system. The presence of ATP clearly stimulated uptake of radiolabeled Cu (64Cu, 10 microM) into canalicular plasma membrane vesicles and, to a lesser extent, also into basolateral plasma membrane vesicles. ATP-dependent Cu transport was dose-dependently inhibited by the P-type ATPase inhibitor vanadate, and showed saturation kinetics with an estimated Km of 8.6 microM and a Vmax of 6.9 nmol/min/mg protein. ATP-stimulated Cu uptake was similar in canalicular membrane vesicles of normal Wistar rats and those of mutant GY rats, expressing a congenital defect in the activity of the ATP-dependent canalicular glutathione-conjugate transporter (cMOAT). These studies demonstrate the presence of an ATP-dependent Cu transporting system in isolated plasma membrane fractions of rat liver distinct from cMOAT.
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PMID:Adenosine triphosphate-dependent copper transport in isolated rat liver plasma membranes. 781 42

DNA encoding a P-type ATPase was cloned from the cyanobacterium Synechococcus 7942. The cloned ctaA gene encodes a 790-amino acid polypeptide related to the CopA Cu(2+)-uptake ATPase of Enterococcus hirae, to other known P-type ATPases, and to the candidate gene products for the human diseases of copper metabolism, Menkes disease and Wilson disease. Disruption of the single chromosomal gene in Synechococcus 7942 by insertion of an antibiotic-resistance cassette results in a mutant cell line with increased tolerance to Cu2+ compared with the wild type.
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PMID:P-type ATPase from the cyanobacterium Synechococcus 7942 related to the human Menkes and Wilson disease gene products. 793 23

Little is known at the molecular level about the homeostatic control of heavy-metal concentrations in mammals. Recently, however, two human diseases that disrupt copper transport, Menkes disease and Wilson disease, were found to be caused by mutations in two closely related genes, MNK and WND, which encode proteins belonging to the P-type ATPase family of cation transporters. The MNK and WND proteins are unique in having at their amino termini six copies of a sequence that is remarkably similar to sequences previously found in bacterial heavy-metal-resistance proteins and in a P-type ATPase that appears to form part of a bacterial copper homeostatic system. These two human ATPases are the first putative heavy-metal transporters to be discovered in eukaryotes.
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PMID:Wilson disease and Menkes disease: new handles on heavy-metal transport. 809 5

The putative copper and ATP-binding domains of the human Menkes disease gene were used as probes to screen a human liver cDNA library at reduced stringency. Sixty-five clones which remained positive after tertiary screening were subcloned and sequenced. One of these cDNA clones contains an open reading frame with 65% amino acid homology to the Menkes protein. Southern blot analysis localizes this cDNA to the region of the Wilson disease locus on chromosome 13. This cDNA detects a 7.5 kB transcript which is present in human liver and cell lines devoid of the Menkes transcript and which is absent in liver from a patient with Wilson disease. These data suggest that this cDNA is a candidate gene for Wilson disease and that the protein encoded at this locus is a member of the P-type ATPase family.
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PMID:Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease. 825 Sep 34

Wilson disease (WD) is an autosomal recessive disorder of copper transport, resulting in copper accumulation and toxicity to the liver and brain. The gene (WD) has been mapped to chromosome 13 q14.3. On yeast artificial chromosomes from this region we have identified a sequence, similar to that coding for the proposed copper binding regions of the putative ATPase gene (MNK) defective in Menkes disease. We show that this sequence forms part of a P-type ATPase gene (referred to here as Wc1) that is very similar to MNK, with six putative metal binding regions similar to those found in prokaryotic heavy metal transporters. The gene, expressed in liver and kidney, lies within a 300 kb region likely to include the WD locus. Two WD patients were found to be homozygous for a seven base deletion within the coding region of Wc1. Wc1 is proposed as the gene for WD.
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PMID:The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. 829 39


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