AN ALTERNATIVE FIRST EXON IN THE DISTAL END OF THE ERYTHROID ANKYRIN GENE LEADS TO PRODUCTION OF A SMALL ISOFORM CONTAINING AN NH2-TERMINALMEMBRANE ANCHOR

Mouse erythroid ankyrin is encoded by the Ank1 gene on Chromosome 8. T he best studied isoform is 210 kDa and contains three large functional domains. We have recently reported a small Ank1 isoform (relative mob ility 25 kDa) that localizes to the M and Z lines in skeletal muscle. Analyses of cDNA and genomic clones show that three transcripts of 3.5 , 2.0, and 1.6 kb code for this protein. The different transcript size s are due to their 3'-untranslated regions. They are encoded by a new first exon located in intron 39 of the Ank1 gene and three previously described Ank1 exons (40, 41, and 42). The 5'-flanking region contains a putative muscle-specific promoter. The sequence of the first 72 ami no acids is novel and is predicted to form a transmembrane helix at th e NH2-terminus. Functional testing of the putative transmembrane segme nt indicates that it acts as a membrane anchor, suggesting that the ne w Ank1 isoform may play an important role in organizing the contractil e apparatus within the cell. (C) 1998 Academic Press.