Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase.
Menkes disease is an X-linked disorder of copper transport characterized by progressive neurological degeneration and death in early childhood. We have isolated a candidate gene (Mc1) for Menkes disease and find qualitative or quantitative abnormalities in the mRNA in sixteen of twenty-one Menkes patients. Four patients lacking Mc1RNA showed rearrangements of the Menkes gene. The gene codes for a 1,500 amino acid protein, predicted to be a P-type cation-transporting ATPase. The gene product is most similar to a bacterial copper-transporting ATPase and additionally contains six putative metal-binding motifs at the N-terminus. The gene is transcribed in all cell types tested except liver, consistent with the expression of the Menkes defect.
Vulpe
C
C
Department of Biochemistry, Howard Hughes Medical Institute, San Francisco, California.
Levinson
B
B
Whitney
S
S
Packman
S
S
Gitschier
J
J
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001693:Biological Transport, Active; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D004247:DNA / Q000302:isolation & purification; D015870:Gene Expression; D015321:Gene Rearrangement; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D011993:Recombinant Fusion Proteins; D014178:Translocation, Genetic; D014960:X Chromosome
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D011993:Recombinant Fusion Proteins; D003300:Copper; D004247:DNA; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases