title: Human peroxisomal L-alanine: glyoxylate aminotransferase. Evolutionary loss of a mitochondrial targeting signal by point mutation of the initiation codon.
abstract: The amino acid sequence of human hepatic peroxisomal L-alanine: glyoxylate aminotransferase 1 (AGTI) deduced from cDNA shows 78% sequence identity with that of rat mitochondrial AGTI, but lacks the N-terminal 22 amino acids (the putative mitochondrial targeting signal). In humans this signal appears to have been deleted during evolution by a point mutation of the initiation codon ATG to ATA. These data suggest that the targeting defect in primary hyperoxaluria type 1, in which AGT1 is diverted from the peroxisomes to the mitochondria, could be due to a point mutation that reintroduces all or part of the mitochondrial signal sequence.
authors.affiliation: Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: N
authors.initials: N
authors.lastname: Kaneko
authors.forename: H
authors.initials: H
authors.lastname: Esumi
authors.forename: P E
authors.initials: PE
authors.lastname: Purdue
authors.forename: C J
authors.initials: CJ
authors.lastname: Danpure
mesh_terms: D000410:Alanine Transaminase / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D003062:Codon; D004272:DNA, Mitochondrial / Q000032:analysis; D004274:DNA, Recombinant / Q000032:analysis; D006801:Humans; D006959:Hyperoxaluria / Q000201:enzymology / Q000235:genetics; D008830:Microbodies / Q000201:enzymology*; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger; D051381:Rats; D000637:Transaminases
chemical_list: D003062:Codon; D004272:DNA, Mitochondrial; D004274:DNA, Recombinant; D012333:RNA, Messenger; D000637:Transaminases; D000410:Alanine Transaminase; C019635:Alanine-glyoxylate transaminase