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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Wilson disease (WD) is an autosomal recessive disorder characterized by the toxic accumulation of copper in a number of organs, particularly the liver and brain. As shown in the accompanying paper, linkage disequilibrium & haplotype analysis confirmed the disease locus to a single marker interval at 13q14.3. Here we describe a partial cDNA clone (pWD) which maps to this region and shows a particular 76% amino acid homology to the Menkes disease gene, Mc1. The predicted functional properties of the pWD gene together with its strong homology to Mc1, genetic mapping data and identification of four independent disease-specific mutations, provide convincing evidence that pWD is the Wilson disease gene.
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PMID:The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. 829 41

Cellular copper transport processes are required by all organisms for correct utilization in cell biochemical processes and avoidance of the toxicity of copper excess. Copper import into bacterial, yeast, and mammalian cells requires the coordinate function of proteins with both metal-binding and catalytic domains in mediated transport steps. Following entry, detoxification mechanisms found across species include the binding of copper to specific proteins (e.g. metallothioneins) and the transfer of copper into isolated cell compartments (e.g. periplasmic space, lysosome). Multiple proteins mediate intracellular transfers in bacteria, and glutathione may play a major role in cytosolic copper delivery to cuproenzymes in mammalian cells. Study of two human disorders of copper transport, Menkes disease and Wilson disease, led to the identification of an important category of proteins mediating cell copper export. The Menkes and Wilson disease gene products are copper-transporting ATPases of the P type, with ATPase domains and N-terminal metal-binding amino acid motifs that are evolutionarily conserved in unicellular and mammalian organisms. These observations suggest that yeast and bacterial copper transport proteins, or individual domains of these proteins, may generally have homologues in mammalian systems.
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PMID:Cellular copper transport. 852 22

Because copper is an integral component of various enzymes in every cells, it has been known to be essential for cell activities. Copper is also a very toxic ion, so a specific series of copper transport process must exist to carry copper to the sites where it is required, and to ensure copper homeostasis without allowing toxic accumulation. Wilson disease and Menkes disease are the inherited diseases caused by genetic defects in copper metabolism. Wilson disease is related to the toxic effects of copper accumulation in liver, which leads to progressive liver damage and subsequent overflow to brain causing a loss of coordination and involuntary movement. Menkes disease is caused by the deficiency of serum copper and of copper-dependent enzymes, in various tissues except liver which characterized by neurologic degeneration and mental retardation, connective tissue and vascular defects, characteristic brittle and depigmented hair, and death in early childhood.
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PMID:[Inherited neurological disease--relationship between an essential trace elements and Wilson/Menkes disease]. 858 76

In this review, our basic and most recent understanding of copper biochemistry and molecular biology for mammals (including humans) is described. Information is provided on the nutritional biochemistry of copper, including food sources, intestinal absorption, transport, tissue distribution, and excretion, along with descriptions of copper binding proteins and other factors involved and their roles in these processes. The metabolism of copper and its importance for the functions of a roster of vital enzymes is detailed. Its potential toxicology is also addressed. Alterations in copper metabolism associated with genetic and nongenetic diseases are summarized, including potential connections to inflammation, cancer, atherosclerosis, and anemia, and the effects of genetic copper deficiency (Menkes syndrome) and copper overload (Wilson disease). Understanding these diseases suggests new ways of viewing the normal functions of copper and provides new insights into the details of copper transport and distribution in mammals.
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PMID:Copper biochemistry and molecular biology. 861 67

Recent studies resulted in the cloning of the genes responsible for Menkes syndrome and Wilson disease. Despite the distinct clinical phenotypes of these disorders, each gene encodes a highly homologous member of the cation-transport P-type ATPase family. The remarkable evolutionary conservation of these proteins in bacteria, yeast, plants, and mammals reveals a fundamental protein structure essential for copper export in all life forms. Characterization of a molecular defect in the rat homologue of the Wilson ATPase in the Long-Evans Cinnamon rat identifies an animal model of Wilson disease and will permit experimental analysis of the precise role of this ATPase in copper transport, the effects of specific inherited mutations on transport function, and the cellular and molecular mechanisms of tissue injury resulting from copper accumulation. Finally, recent molecular genetic analysis of a distinct group of patients with low serum ceruloplasmin and basal ganglia symptoms identified a series of mutations in the ceruloplasmin gene. The presence of these mutations in conjunction with the clinical and pathologic findings clarifies the essential biological role of this abundant copper protein in metal metabolism and identifies aceruloplasminemia as a novel autosomal recessive disorder of iron metabolism.
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PMID:Genetic and molecular basis for copper toxicity. 861 71

The mouse homologue of the Menkes gene has been shown to span 120 kb of genomic DNA and to be similar in structure to both its human MNK homologue (ATP7A) and the Wilson disease gene (WD; ATP7B). Conservation of the majority of intron/exon boundaries among the three genes was also observed. The high overall conservation of both the Atp7a gene and the direction of transcription of the Atp7a, Pgk1, and Xnp genes between human and mouse is compatible with the evolution of an ancestral gene subject to strong evolutionary constraints lying within a locally relatively conserved region of the X chromosome.
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PMID:Genomic organization of the mottled gene, the mouse homologue of the human Menkes disease gene. 892 75


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