Amino acid sequence of the murine Mac-1 alpha chain reveals homology with the integrin family and an additional domain related to von Willebrand factor.

Clones encoding the Mac-1 alpha chain were selected from a mouse macrophage cDNA library by screening with oligonucleotide probes based on the sequence of a genomic clone encoding the N-terminus of the mature protein. The sequence of overlapping clones (4282 nt) was determined and translated into a protein of 1137 amino acids and a signal peptide of 15 amino acids. The Mac-1 sequence was found to be related to the alpha chain sequences of three other members of the integrin family of cell adhesion receptors, i.e. the fibroblast receptors for fibronectin and vitronectin and the platelet glycoprotein IIb/IIIa. All four sequences share a number of structural features, like the position of 13 cysteine residues, a transmembrane domain near the C-terminus and the location of three putative binding sites for divalent cations. Furthermore, a conserved sequence motif is repeated seven times in the N-terminal half of the molecule and three of these repeats include putative Ca/Mg-binding sites of the general structure DXDXDGXXD. On the other hand, Mac-1 contains a unique domain of 220 amino acids inserted into the N-terminal part of the integrin structure. This additional domain is homologous to a repeated domain found in von Willebrand factor, cartilage matrix protein and in the complement factors B and C2. In two of these proteins, the homologous domain is likely to be involved in binding to collagen fibrils. Therefore, Mac-1 may also bind to collagen, which could play a role in the interaction of leukocytes with the subendothelial matrix.