NUCLEOTIDE-SEQUENCE OF HUMAN ALKYL-DIHYDROXYACETONEPHOSPHATE SYNTHASECDNA REVEALS THE PRESENCE OF A PEROXISOMAL TARGETING SIGNAL 2

Two overlapping clones were isolated from a human liver cDNA library i n lambda gt11 that coded for human alkyl-dihydroxyacetonephosphate syn thase using guinea pig and PCR-derived human cDNA probes. The open rea ding frame encodes a protein of 658 amino acids that shows a homology of 92% with the guinea pig homolog and a similarity of 98%. The peroxi somal targeting signal 2 that was recently identified in the presequen ce of the guinea pig enzyme appeared to be completely preserved in the human enzyme. Supportive confirmation for parts of the sequence of th e mature protein was obtained from the Expressed Sequence Tags databas e of the National Center for Biotechnology Information. This database contained nine cDNA sequences, derived from seven independent clones, that correspond exactly to parts of the cDNA of human alkyl-dihydroxya cetonephosphate synthase. One of these clones most likely represents a not fully processed RNA with a putative intron containing an Alu sequ ence. An unexpected homology with D-lactate dehydrogenase (cytochrome C) precursor from Saccharomyces cerevisiae and with glycolate oxidase subunit D from Escherichia coli was also revealed. (C) 1997 Elsevier S cience B.V.