A review of the molecular and cellular biology of butyrophilin, the major protein of bovine milk fat globule membrane.

The molecular and cellular biology of the milk protein butyrophilin is reviewed. Butyrophilin constitutes more than 40% by weight of the total protein associated with the fat globule membrane of bovine milk. Closely related proteins are abundant in the fat globule membranes of many other species. Butyrophilin is synthesized as a peptide of 526 amino acids with an amino-terminal hydrophobic signal sequence of 26 amino acids, which is cleaved before secretion in association with the fat globule membrane. Hydropathy analysis and in vitro translation of butyrophilin mRNA indicate that the protein associates with membranes in a type I orientation via a single stretch of 27 hydrophobic amino acids in the approximate middle of the sequence. Evidence that butyrophilin is incorporated into fat globule membrane as a transmembrane protein and as a cytoplasmically oriented peripheral component is discussed. The carboxy-terminal sequence of butyrophilin is significantly homologous to two other proteins: ret finger protein and the 52-kDa nuclear antigen A of Sjögren's syndrome. Expression of bovine butyrophilin mRNA correlates with the onset of milk fat secretion toward the end of pregnancy and is maintained throughout lactation. The possible function of butyrophilin in the secretion of milk lipid droplets is discussed.