THE GENE ORGANIZATION OF THE HUMAN BETA(7)-SUBUNIT, THE COMMON BETA-SUBUNIT OF THE LEUKOCYTE INTEGRINS HML-1 AND LPAM-1

The integrin beta7 subunit associates with two alternative alpha subunits termed alphaHML-1 and alpha4 to give the lymphocyte activation and homing receptors HML-1 and LPAM-1. Overlapping genomic clones that encoded the human beta7 subunit gene were isolated from cosmid and phage lambda libraries. The coding portion of the gene spanned approximately 10 kb and was composed of 14 exons. Exon 1 (123 bp) encoded 5' untranslated sequences; exon 2 (204 bp) encoded the initiation codon, signal peptide, and 50 amino acid residues of the N-terminus of the mature protein; 7 exons (exons 3 - 9), ranging in size from 90 bp to 242 bp, encoded most of the extracellular domain proximal to the four cysteine-rich repeats; the region corresponding to the beta3 arginine - glycine - aspartic acid (RGD)-binding domain was divided amongst exons 4 and 5; the four cysteine-rich repeats were encoded by 3 exons (exons 10 - 12) with intron insertion into the first and third repeats; exon 13 (209 bp) provided a spacer between the cysteine-rich domains and the transmembrane domain; exon 14 (161 bp) encoded the transmembrane domain and exactly half of the cytoplasmic domain; the remainder of the cytoplasmic domain and most of the 3' untranslated region was contained in the largest 313 bp exon 15. Comparison of integrin beta subunit genes revealed that the gene organization of beta7 was almost identical to that of beta2, but had diverged from that of beta3. Amplification of integrin DNAs directly from genomic DNA, using PCR primers based on beta subunit consensus sequences corresponding to the beta3 RGD-binding domain, yielded partial gene sequences for the beta3, beta5 and beta6 subunits only. Inspection of the amplified sequences revealed that, as for beta3, the regions in beta5 and beta6 corresponding to the beta3 RGD-binding domain lacked the intron present in beta7, beta1, and beta2, which divides this region in beta2 into two subdomains that contribute to subunit assembly. This study provides genetic evidence for at least two major branches to the integrin beta subunit evolutionary tree, with beta7, beta2, and probably beta1 in one branch, and the cytoadhesin beta3 and probably also beta5 and beta6 in the other.