AMINO-ACID-SEQUENCE OF A NOVEL INTEGRIN BETA-4 SUBUNIT AND PRIMARY EXPRESSION OF THE MESSENGER-RNA IN EPITHELIAL-CELLS

Using the polymerase chain reaction, we have isolated cDNA clones that encode a new integrin β subunit -β4. Its cDNA, which is 5676 bp in length, has one long coding sequence (5256 bp), a polyadenylation signal and a poly(A) tail. The deduced sequence of 1752 amino acids is unique among the integrin β subunits. It contains a putative signal sequence as well as a transmembrane domain that divides the molecule into an extracellular domain at the N-terminal side and a cytoplasmic domain at the C-terminal side. The extracellular domain exhibits a 4-fold repeat of cysteine-rich motif similar to those of other integrin β subunits. Certain features of the extracellular domain, however, are unique to the β4 subunit sequence. Of the 56 conserved cysteine residues found within the extracellular domain of other mature β subunits, eight such residues are deleted from the β4 subunit sequence. The cytoplasmic domain is much larger (~ 1000 amino acids) than those of other β subunits (~ 50 amino acids) and has no significant homology with them. A protein homology search revealed that the β4 subunit smic domain has four repeating units that are homologous to the type III repetition exhibited by fibronectin. The β4 subunit mRNA was expressed primarily in epithelial cells. The restricted expression and the new structural features distinguish the integrin β4 subunit from other integrin β subunits.