Cloning of cDNAs encoding human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Comparison of their deduced amino acid sequences.

Abstract

We have isolated and sequenced cDNA clones corresponding to the entire coding sequences of the human lysosomal membrane glycoproteins, lamp-1 and lamp-2 (h-lamp-1 and h-lamp-2). The deduced amino acid sequences indicate that h-lamp-1 and h-lamp-2 consist of 416 and 408 amino acid residues, respectively, and suggest that 27 and 28 NH2-terminal residues are cleavable signal peptides. The major portions of both h-lamp-1 and h-lamp-2 reside on the luminal side of the lysosome and are heavily glycosylated by N-glycans: h-lamp-1 and h-lamp-2 were found to contain 19 and 16 potential N-glycosylation sites, respectively. The findings are consistent with the results obtained by endo-beta-N-acetylglucosaminidase F treatment of h-lamp-1 and h-lamp-2 precursors, described in the preceding paper (Carlsson, S. R., Roth, J., Piller, F., and Fukuda, M. (1988) J. Biol. Chem. 263, 18911-18919). These N-glycosylation sites are clustered into two domains separated by a hinge-like structure enriched with proline and serine in h-lamp-1 or proline and threonine in h-lamp-2. The two domains of h-lamp-1 on each side of the hinge region are homologous to each other, whereas no such homology was detected between the two domains of h-lamp-2. Both proteins have one putative transmembrane domain consisting of 24 hydrophobic amino acids near the COOH terminus, and contain a short cytoplasmic segment composed of 11 amino acid residues at the COOH-terminal end. Comparison of h-lamp-1 and h-lamp-2 sequences r…