Bovine milk fat globule membranes are a rich source of glycoproteins PAS-6 (52 kDa) and PAS-7 (47 kDa). They are glycosylation variants sharing a common polypeptide core. The PAS-6/7 protein consists of two EGF-like domains and a tandem repeated structure with a high degree of similarity to the C1 and C2 domains found in blood-clotting factors V and VIII. The second EGF- like domain contains an RGD cell adhesion sequence with the possibility of binding integrins, while the C-terminal end of the C2-like domain contains a probable amphipathic α-helix. Using a PAS-6/7 column, bovine α(v)β5 integrin was purified from mammary gland tissue by affinity chromatography and characterized by Western blotting and N-terminal sequencing. The interaction between PAS-6/7 and the α(v)β5 integrin was shown to be RGD dependent. Lipid binding assays showed that PAS-6/7 binds to surfaces of phosphatidylserine, -inositol, and -glycerol, and their precursor, phosphatidic acid, but not phosphatidylcholine. Furthermore, PAS-6/7 displayed the highest affinity toward a total lipid fraction derived from the milk fat globule membrane as compared to pure phospholipids. Using Western blotting technique, PAS-6/7 was shown to be widely expressed in a number of tissues. These results show that PAS-6/7 is a common protein which can bind to membranes by two distinct mechanisms, one through affinity to integrin α(v)β5 and another by direct binding to phospholipids.