Molecular cloning and expression of the cDNA for α₃ subunit of human α₃β₁ (VLA-3), an integrin receptor for fibronectin, laminin, and collagen

α₃β₁ (VLA-3), a member of the integrin family of cell adhesion receptors, may function as a receptor for fibronectin, laminin, and collagen. A partial cDNA clone (2.4 kb) for the human α₃ subunit was selected from an endothelial cell λgt11 cDNA library by specific antibody screening. Several overlapping cDNA clones were subsequently obtained, of a total length of 4.6 kb from various cDNA libraries. The reconstructed α₃ cDNA was expressed on the surface of chinese hamster ovary cells as detected by an α₃-specific mAb after transfection, suggesting that the cDNA is authentic. Within this sequence was an open reading frame, encoding for 1,051 amino acids, including a signal peptide of 32 residues, a long extracellular domain (959 residues), a transmembrane domain (28 residues), and a short cytoplasmic segment (32 residues). Overall, the α₃ amino acid sequence was 25-37% similar to the other integrin α subunits that are cleaved, with most similarity to the α₆ sequence (37%), and less similarity to those α subunits that have I domains (15-20%, excluding the I domain sequence itself). Features most like those in other α subunits are (a) the positions of 18/19 cysteine residues, (b) three potential metal binding domains of the general structure DX(D/N)X(D/N)GXXD, and (c) the predicted transmembrane domain. The mass of α₃ calculated from its amino acid sequence is 113,505. The human α₃ sequence was 89% identical to hamster galactoprotein b3, and 70% similar to the chicken CSAT antigen band 2 protein partial sequence, suggesting that these two polypeptides are homologues of human α₃.