title: Molecular and functional analyses of the human and mouse genes encoding AFG3L1, a mitochondrial metalloprotease homologous to the human spastic paraplegia protein.
abstract: The identification of SPG7 as the gene defective in a recessive form of spastic paraplegia has drawn attention to the yeast protein family of ATP-dependent zinc metalloproteases. The protein encoded by SPG7, paraplegin, shows high homology to members of this protein family. Recently, many mammalian ATP-dependent zinc metalloproteases have been identified and considered as possible candidates for defects in other forms of hereditary spastic paraplegia and possibly other neurodegenerative disorders. So far only a partial sequence has been available for one of those genes, ATPase family gene-3, yeast-like-1 (AFG3L1). We have carried out detailed molecular analysis of this gene and identified and characterized its mouse orthologue, Afg3l1. Our data indicate that AFG3L1 is transcribed into four mRNA isoforms that are not translated in humans. Afg3l1 encodes a protein with high homology to paraplegin and the other members of the ATP-dependent zinc metalloprotease family. Like the other ATP-dependent zinc metalloproteases, Afg3l1 localizes to the mitochondria.
authors.affiliation: Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, South Australia, Australia. gkremmid@wch.bionomics.com.au
authors.forename: G
authors.initials: G
authors.lastname: Kremmidiotis
authors.forename: A E
authors.initials: AE
authors.lastname: Gardner
authors.forename: C
authors.initials: C
authors.lastname: Settasatian
authors.forename: A
authors.initials: A
authors.lastname: Savoia
authors.forename: G R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: D F
authors.initials: DF
authors.lastname: Callen
mesh_terms: D016475:3T3 Cells; D000074183:ATPases Associated with Diverse Cellular Activities; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015419:Spastic Paraplegia, Hereditary / Q000201:enzymology / Q000235:genetics; D015032:Zinc / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; C112311:AFG3L1P protein, human; D008666:Metalloendopeptidases; C112889:SPG7 protein, human; C491813:Spg7 protein, mouse; D000074183:ATPases Associated with Diverse Cellular Activities; D015032:Zinc