title: The human leukocyte adhesion glycoprotein Mac-1 (complement receptor type 3, CD11b) alpha subunit. Cloning, primary structure, and relation to the integrins, von Willebrand factor and factor B.
abstract: Mac-1 (CD 11b/CD18) is a leukocyte adhesion heterodimeric glycoprotein which functions both as a receptor for iC3b (CR3) and in several cell-cell and cell-substrate adhesive interactions. We describe full-length cDNA clones for the alpha subunit of Mac-1. Mac-1 alpha subunit message was detected in blood monocytes and phorbol-12-myristate acetate-induced myeloid cell lines, but not in cells of the T or B lineages, correlating with Mac-1 protein surface expression. The alpha subunit of Mac-1 is a transmembrane protein of 1137 residues with a long extracellular domain (1092 residues) and a 19-amino acid cytoplasmic tail. The extracellular domain contains three putative divalent cation-binding sequences and 19 potential N-glycosylation sites. The amino acid sequence of Mac-1 alpha shows that it is a member of the integrin superfamily; Mac-1 alpha shows 63% identity to the alpha subunit of the leukocyte adhesion glycoprotein p150.95 and 25% to the alpha subunits of the extracellular matrix receptors platelet glycoprotein IIb/IIIa, the fibronectin receptor, and the vitronectin receptor. The Mac-1 alpha subunit putative divalent cation-binding sites and the flanking regions exhibit a high degree of identity both to the p150.95 alpha subunit (87% identity at the amino acid level) and to the rest of the integrin alpha subunits (38%). The alpha subunit of Mac-1, like the p150.95 alpha subunit, contains a domain of 187 amino acids in the extracellular region which is absent in other integrins. This leukocyte or "L" domain is homologous to the A domains of von Willebrand factor, which in turn are homologous to regions of the C3-binding proteins factor B and C2. These findings draw attention to this region of Mac-1 as a potential binding site for iC3b.
authors: Laboratory of Membrane Immunochemistry, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
authors: A L
authors: AL
authors: Corbi
authors: T K
authors: TK
authors: Kishimoto
authors: L J
authors: LJ
authors: Miller
authors: T A
authors: TA
authors: Springer
mesh_terms: D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000235:genetics*; D001483:Base Sequence; D011415:Complement Factor B / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004274:DNA, Recombinant; D004792:Enzyme Precursors / Q000235:genetics*; D006098:Granulocytes / Q000032:analysis / Q000378:metabolism; D006801:Humans; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000032:analysis / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011951:Receptors, Complement / Q000235:genetics*; D017463:Receptors, Complement 3b; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000235:genetics; D019030:Receptors, Vitronectin; D012689:Sequence Homology, Nucleic Acid; D014357:Trypsin / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D000943:Antigens, Differentiation; D004274:DNA, Recombinant; D004792:Enzyme Precursors; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D019030:Receptors, Vitronectin; D014841:von Willebrand Factor; D004247:DNA; D014357:Trypsin; D011415:Complement Factor B