Structure, expression, and chromosomal localization of the mouse Atox1 gene.
Copper trafficking in eukaryotes involves small proteins termed metallochaperones, which mediate copper delivery to specific intracellular sites. Previous studies in yeast and human cell lines have suggested that Atox1 plays a critical role in copper delivery to the secretory pathway. In the present study, a mouse Atox1 (mAtox1) cDNA was cloned and shown to encode an open reading frame with 85% amino acid identity to human Atox1. RNA blot analysis revealed that mAtox1 was expressed as a single transcript in multiple tissues, and immunoblotting indicated that the relative abundance of mAtox1 mRNA directly correlated with mAtox1 protein. Analysis of the mAtox1 gene locus revealed a genomic structure with four exons encompassing a total of 14.5 kb. RFLP and haplotype analyses indicated that the mAtox1 locus was tightly linked to the Trhr and D15Bir7 loci on mouse chromosome 15. Taken together, these data reveal marked evolutionary conservation of Atox1 structure and provide a genomic organization and localization that will aid in the genetic deciphering of the molecular role of this protein in copper homeostasis.
Hamza
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Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Klomp
L W
LW
Gaedigk
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R
White
R A
RA
Gitlin
J D
JD
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D002874:Chromosome Mapping; D003300:Copper / Q000378:metabolism; D000079922:Copper Transport Proteins; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D056511:Metallochaperones; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009115:Muridae; D009479:Neuropeptides / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
C474500:ATOX1 protein, human; C499247:Atox1 protein, mouse; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D018076:DNA, Complementary; D056511:Metallochaperones; D018832:Molecular Chaperones; D009479:Neuropeptides; D012333:RNA, Messenger; D003300:Copper