title: Characterization and localization of human COX17, a gene involved in mitochondrial copper transport.
abstract: Deficiencies in cytochrome oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, are relatively rare but most often lethal. The underlying causes are beginning to be elucidated, and most mutations are thought to affect the function of proteins involved in assembling the holoenzyme. COX17 is such an assembly protein and is thought to recruit copper to mitochondria for incorporation into the COX apoenzyme. Here we present the gene structure, the expression, and chromosomal localization for COX17, a candidate gene for COX deficiency. The COXI 7 gene spans approximately 8 kb of human genomic DNA and encodes a transcript of approximately 450 bp that is expressed in all tissues tested. Although the COX17 gene was previously mapped to chromosome 13q14-21, our results suggest that a COX17 pseudogene maps to this region. The pseudogene contains several nucleotide changes, including one that would result in an altered amino acid in the putative copper binding domain. We have localized the gene encoding the COX 17 protein to the long arm of chromosome 3 by radiation hybrid mapping. Deciphering of the COX17 genomic structure will allow this gene to be assessed for mutations in COX deficient patients.
authors.affiliation: Department of Medical Genetics, University of Alberta, Edmonton, Canada.
authors.forename: F A
authors.initials: FA
authors.lastname: Punter
authors.forename: D L
authors.initials: DL
authors.lastname: Adams
authors.forename: D M
authors.initials: DM
authors.lastname: Glerum
mesh_terms: D000595:Amino Acid Sequence; D001051:Apoenzymes; D001692:Biological Transport; D015152:Blotting, Northern; D015139:Blotting, Southern; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002460:Cell Line; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003300:Copper / Q000378:metabolism*; D000079922:Copper Transport Proteins; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D011544:Pseudogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: D001051:Apoenzymes; C491006:COX17 protein, human; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D011506:Proteins; D003300:Copper