Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuromedin C is a bombesin-like neuropeptide of the sequence Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2. Characterization of the amino terminal Cu(II), Ni(II) binding motif in albumins led us to predict that any other peptides or proteins with the same motif would also bind Cu(II) and Ni(II) specifically (1). The primary sequence of neuromedin C contains the motif in the form Gly-Asn-His. Neuromedin C was therefore predicted to bind Cu(II) and Ni(II) specifically. The studies presented here confirm that prediction. These findings may have implications for the transport of Cu(II) within the central nervous system as well as both Menkes disease and Wilson disease. Both are genetic copper metabolism disorders which are characterized by severe neurological symptoms. In addition, Cu(II) may interfere with the neurotransmission or growth factor effects of neuromedin C.
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PMID:Neuromedin C binds Cu(II) and Ni(II) via the ATCUN motif: implications for the CNS and cancer growth. 773 79

The full-length cDNA coding for a putative copper transporting P-type ATPase (Cu2+-ATPase) was cloned from Caenorhabditis elegans. The putative Cu2+-ATPase is a 1,238-amino acid protein, and highly homologous to the Menkes and Wilson disease gene products mutations of which are responsible for human defects of copper metabolism. The Saccharomyces cerevisiae mutant with a disrupted CCC2 gene (yeast Menkes/Wilson disease gene homologue) was rescued by the cDNA for the C. elegans Cu2+-ATPase but not by the cDNA with an Asp-786 (an invariant phosphorylation site) to Asn mutation, suggesting that the C. elegans Cu2+-ATPase functions as a copper transporter in yeast. The expressed C. elegans protein was detected in yeast vacuolar membranes by immunofluorescence microscopy. The yeast expression system may facilitate further studies on copper transporting P-type ATPases.
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PMID:Caenorhabditis elegans cDNA for a Menkes/Wilson disease gene homologue and its function in a yeast CCC2 gene deletion mutant. 935 93

P(1B)-type ATPases transport heavy metals (Cu+, Cu2+, Zn2+, Co2+, Cd2+, Pb2+) across membranes. Present in most organisms, they are key elements for metal homeostasis. P(1B)-type ATPases contain 6-8 transmembrane fragments carrying signature sequences in segments flanking the large ATP binding cytoplasmic loop. These sequences made possible the differentiation of at least four P(1B)-ATPase subgroups with distinct metal selectivity: P(1B-1): Cu+, P(1B-2): Zn2+, P(1B-3): Cu2+, P(1B-4): Co2+. Mutagenesis of the invariant transmembrane Cys in H6, Asn and Tyr in H7 and Met and Ser in H8 of the Archaeoglobus fulgidus Cu+-ATPase has revealed that their side chains likely coordinate the metals during transport and constitute a central unique component of these enzymes. The structure of various cytoplasmic domains has been solved. The overall structure of those involved in enzyme phosphorylation (P-domain), nucleotide binding (N-domain) and energy transduction (A-domain), appears similar to those described for the SERCA Ca2+-ATPase. However, they show different features likely associated with singular functions of these proteins. Many P(1B)-type ATPases, but not all of them, also contain a diverse arrangement of cytoplasmic metal binding domains (MBDs). In spite of their structural differences, all N- and C-terminal MBDs appear to control the enzyme turnover rate without affecting metal binding to transmembrane transport sites. In addition, eukaryotic Cu+-ATPases have multiple N-MBD regions that participate in the metal dependent targeting and localization of these proteins. The current knowledge of structure-function relationships among the different P(1B)-ATPases allows for a description of selectivity, regulation and transport mechanisms. Moreover, it provides a framework to understand mutations in human Cu+-ATPases (ATP7A and ATP7B) that lead to Menkes and Wilson diseases.
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PMID:The structure and function of heavy metal transport P1B-ATPases. 1721 55