Organization of the gene for human erythrocyte membrane protein 4.2: structural similarities with the gene for the a subunit of factor XIII.

Human erythrocyte band 4.2 is a major membrane-associated protein with an important, but still undefined, role in erythrocyte survival. We previously sequenced the complete cDNA for band 4.2 and showed that the protein has a strong sequence identity with the transglutaminase family of proteins but lacks transglutaminase activity. Here we have analyzed the genomic organization of band 4.2. The band 4.2 gene is approximately 20 kilobases, consisting of 13 exons and 12 introns. Reticulocytes contain two different sized messages for band 4.2, and our results show that the major, smaller, message is produced by alternative splicing within band 4.2 exon I. The upstream region of the gene has several prospective promoter elements arranged in a pattern similar to that of two other erythroid genes, beta-globin and porphobilinogen deaminase. Alignment of the band 4.2 amino acid sequence with that of the a subunit of human coagulation factor XIII and division of the sequences into exons reveal a remarkable correspondence, and in most cases identity, in the sizes of the paired exons. Moreover, each corresponding intron of the two genes is of an identical splice junction class. These and other similarities suggest that the gene for band 4.2 is closely related to and possibly derived from that for the a subunit of factor XIII and that the proteins may share common structural and functional properties.