Cloning, Primary Structure, and Relation to the Integrins, Von Willebrand Factor

Mac-1 (CD llb/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 fulllength cDNA clones for the a subunit of Mac1. Mac-1 a subunit message was detected in blood monocytes and phorbol12-myristate acetate-induced myeloid cell lines, but not in cells of the T or B lineages, correlating with Mac-1 protein surface expression. The a subunit of Mac1 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 a shows that it is a member of the integrin superfamily; Mac-1 a shows 63% identity to the a subunit of the leukocyte adhesion glycoprotein pl50,95 and 25% to the a subunits of the extracellular matrix receptors platelet glycoprotein IIb/IIIa, the fibronectin receptor, and the vitronectin receptor. The Mac-1 a subunit putative divalent cation-binding sites and the flanking regions exhibit a high degree of identity both to the p150,95 a subunit (87% identity at the amino acid level) and to the rest of the integrin a subunits (38%). The a subunit of Mac1, like the p150,95 a 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 C3binding proteins factor B and C2. These findings draw attention to this region of Mac-1 as a potential binding site for iC3b.