Macrosialin, a mouse macrophage-restricted glycoprotein, is a member of the lamp/lgp family.
Macrosialin is a heavily glycosylated transmembrane protein of 87-115 kDa, highly and specifically expressed by mouse tissue macrophages, and to a lesser extent by dendritic cells. We have isolated cDNA clones encoding macrosialin from a thioglycollate-elicited peritoneal macrophage cDNA library by transient expression in COS cells and panning with the anti-macrosialin monoclonal antibody FA/11. A single 1.3-kilobase macrosialin transcript was detected in both untreated and phorbol 12-myristate 13-acetate-stimulated RAW cells. The cDNA sequence predicts a type I integral membrane protein of 326 residues with a heavily glycosylated extracellular domain of 306 residues containing nine potential N-linked glycosylation sites and numerous potential O-linked glycosylation sites. The extracellular domain consists of two distinct regions, separated by an extended 12 residue proline-rich hinge; a membrane-distal mucin-like domain of 89 residues containing short peptide repeats and consisting of 44% serine and threonine residues; and a membrane proximal domain of 170 residues, which has significant sequence homology to a family of lysosomal associated glycoproteins known as the lamp-1 group. Macrosialin is the murine homologue of the human macrophage glycoprotein CD68 (72% identity, 80% similarity). Both proteins are preferentially expressed by macrophages and share the same bipartite structure having a mucin-like domain and a domain common to the lamp family. Macrosialin and CD68 are the first examples of a lamp family protein with a restricted cell-type-specific expression. They may have evolved from the lamps to carry out specialized functions in dedicated phagocytic cells.
Holness
C L
CL
Cell Adhesion Laboratory, Imperial Cancer Research Fund, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
da Silva
R P
RP
Fawcett
J
J
Gordon
S
S
Simmons
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D015723:Gene Library; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D016133:Polymerase Chain Reaction / Q000379:methods; D011487:Protein Conformation; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004247:DNA; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C081026:CD68 protein, mouse