Identification and characterization of AFG3L2, a novel paraplegin-related gene.
We recently identified a gene responsible for an autosomal recessive form of hereditary spastic paraplegia (HSP). This gene encodes paraplegin, a mitochondrial protein highly homologous to the yeast mitochondrial ATPases Afg3p and Rcalp, which have both proteolytic and chaperone-like activities at the inner mitochondrial membrane. By screening the Expressed Sequence Tag database, we identified and characterized a novel human cDNA, ATPase family gene 3-like 2 (AFG3L2, Human Gene Nomenclature Committee-approved symbol), which is closely related to paraplegin. This cDNA encodes a 797-amino-acid predicted protein highly similar to paraplegin as well as to yeast Afg3p and Rca1p. Immunofluorescence studies revealed that AFG3L2 and paraplegin share a similar expression pattern and the same subcellular localization, the mitochondrial compartment. We subsequently mapped AFG3L2 to chromosome 18p11 by radiation hybrid analysis. AFG3L2 may represent a candidate gene for other forms of HSPs and possibly for other neurodegenerative disorders.
Telethon Institute of Genetics and Medicine (TIGEM), San Raffaele Biomedical Science Park, Milan, Italy.
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Banfi
M T
MT
Bassi
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G
Andolfi
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Marchitiello
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Zanotta
A
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Ballabio
G
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Casari
B
B
Franco
D049069:ATP-Dependent Proteases; D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005333:Fetus / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics*; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics*; D008928:Mitochondria / Q000737:chemistry; D008969:Molecular Sequence Data; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018076:DNA, Complementary; D012313:RNA; D049069:ATP-Dependent Proteases; C120699:AFG3L2 protein, human; D008666:Metalloendopeptidases; C112889:SPG7 protein, human; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities