At least three proteins (alpha, beta, and gamma catenin) comprise the cytoplasmic domain of the cadherin cell-cell adhesion complex. We have cloned and sequenced human epithelial alpha(E)-catenin and have identified two distinct transcripts, designated alpha 1- and alpha 2-. The human alpha 1(E)-catenin transcript predicts a 907 aa sequence 97% identical to mouse alpha-catenin. The second transcript, alpha 2(E)-catenin, displays a 24 amino acid insertion after codon 812, yielding a 931 amino acid protein (GenBank #L23805). Analysis by RT-PCR and Northern blotting detects one or both transcripts in epithelial and non-epithelial tissues. Southern blotting indicates that both arise from a single gene. The alternative transcription site in alpha-catenin is analogous to the splice site in vinculin that creates met alpha-vinculin, extending the homology between alpha-catenin and vinculin. These data with the reported structure of other catenin genes suggest that vinculin and alpha-catenin generate a superfamily of proteins mediating membrane-cytoskeletal associations.