Human and mouse mitochondrial orthologs of bacterial ClpX.
We have determined the cDNA sequence and exon/intron structure of the human CLPX gene encoding a human ortholog of the E. coli ClpX chaperone and protease subunit. The CLPX gene comprises 14 exons and encodes a 633-amino acid-long precursor polypeptide. The polypeptide contains an N-terminal putative mitochondrial transit peptide, and expression of a full-length ClpX cDNA tagged at its C-terminus (Myc-His) shows that the polypeptide is transported into mitochondria. FISH analysis localized the CLPX gene to human Chromosome (Chr) 15q22.1-22.32. This localization was refined by radiation hybrid mapping placing the CLPX gene 4.6 cR distal to D15S159. Murine ClpX cDNA was sequenced, and the mouse Clpx locus was mapped to a position between 31 and 42 cM offset from the centromere on mouse Chr 9. Experimental observations indicate the presence of a pseudogene in the mouse genome and sequence variability between mouse ClpX cDNAs from different strains. Alignment of the human and mouse ClpX amino acid sequences with ClpX sequences from other organisms shows that they display the typical modular organization of domains with one AAA(+) domain common to a large group of ATPases and several other domains conserved in ClpX orthologs linked by non-conserved sequences. Notably, a C-4 zinc finger type motif is recognized in human and mouse ClpX. This motif of so far unknown function is present only in a subset of the known ClpX sequences.
Corydon
T J
TJ
Institute of Human Genetics, Aarhus University, 8000 Arhus C, Denmark.
Wilsbech
M
M
Jespersgaard
C
C
Andresen
B S
BS
Borglum
A D
AD
Pedersen
S
S
Bolund
L
L
Gregersen
N
N
Bross
P
P
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D004247:DNA / Q000032:analysis; D049071:Endopeptidase Clp; D029968:Escherichia coli Proteins; D015870:Gene Expression; D016678:Genome; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000235:genetics*; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions
D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D004247:DNA; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases; C088072:ClpX protein, E coli; D000074183:ATPases Associated with Diverse Cellular Activities