title: 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 reveal strong homology between the two molecules, particularly in the proximity to the COOH-terminal end. It is possible that this portion is important for targeting the molecules to lysosomes. These results also suggest that lamp-1 and lamp-2 are evolutionarily related. Comparison of known lamp-1 sequences among different species, on the other hand, show that human lamp-1 has more similarity to lamp-1 from other species than to human lamp-2. This fact, taken together with the finding that h-lamp-2 lacks repeating domains, suggests that lamp-1 and lamp-2 diverged from a putative ancestor gene in early stages of evolution. These results also suggest that lamp-1 and lamp-2 probably have distinctly separate functions despite the fact that they share many structural features.
authors.affiliation: La Jolla Cancer Research Foundation, California 92037.
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: J
authors.initials: J
authors.lastname: Viitala
authors.forename: J
authors.initials: J
authors.lastname: Matteson
authors.forename: S R
authors.initials: SR
authors.lastname: Carlsson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D002645:Chickens; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis*; D006031:Glycosylation; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000032:analysis*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data
chemical_list: D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D004247:DNA