Identification and characterization of AFG3L2, a novel paraplegin-related gene

We recently identified a gene responsible for an autosomal recessive form o f hereditary spastic paraplegia (HSP). This gene encodes paraplegin, a mito chondrial protein highly homologous to the yeast mitochondrial ATPases Afg3 p and Rca1p, which have both proteolytic and chaperone-like activities at t he inner mitochondrial membrane. By screening the Expressed Sequence Tag da tabase, we identified and characterized a novel human cDNA, ATPase family g ene 3-like 2 (AFG3L2, Human Gene Nomenclature Committee-approved symbol), w hich is closely related to paraplegin. This cDNA encodes a 797-amino-acid p redicted protein highly similar to paraplegin as well as to yeast Afg3p and Rca1p. Immunofluorescence studies revealed that AFG3L2 and paraplegin shar e a similar expression pattern and the same subcellular localization, the m itochondrial compartment. We subsequently mapped AFG3L2 to chromosome 18p11 by radiation hybrid analysis. AFG3L2 may represent a candidate gene for ot her forms of HSPs and possibly for other neurodegenerative disorders. (C) 1 999 Academic Press.