Conserved cassette structure of vertebrate M-r 300 kDa mannose 6-phosphatereceptors: partial cDNA sequence of fish MPR 300

The existence of two homologous mannose 6-phosphate receptors (MPRs) with o verlapping, but distinct functions has raised the question of at what stage in the phylogenetic tree the two receptors have occurred for the first tim e. In this paper, we present a partial cDNA sequence of M-r 300 kDa MPR (MP R 300) from poeciliid fish (Xiphophorus). It contains a 5'-untranslated reg ion followed by the initiator ATG, and an open reading frame that correspon ds to cassettes 1-5 and part of cassette 6 of mammalian MPR 300. The size o f the mRNA transcript for fish MPR 300 was comparable with that of other ve rtebrates. The amino acid sequence of fish MPR 300 displays 48-52% similari ty with mammalian and chicken MPR 300. In particular, all the cysteine resi dues involved in disulfide bonding and an arginine residue, which is consid ered to be part of the mannose 6-phosphate binding site in cassette 3 of ma mmalian MPR 300, are conserved. Sequence similarities were significantly hi gher within cassette 3 and within cassette 5, to which a ligand-binding fun ction has not yet been ascribed. Sequence similarities of the internal cass ettes of MPR 300 are discussed with regard to the multifunctional nature of MPR 300. (C) 2000 Elsevier Science Inc. All rights reserved.