AbstractThe unique LAMMER (or Clk) protein kinase of Drosophila is encoded at the Doa locus. To better understand the pleiotropic effects of Doa mutations, we describe the structure and expression of the multiple RNA and protein products of the locus, as well as their evolutionary conservation among Drosophila. The gene produces at least six different protein isoforms, primarily through alternative promoter usage, generating kinases with virtually identical catalytic domains but variable N‐terminal noncatalytic domains. The single known alternative splicing event generates a kinase with the insertion of six additional amino‐acids in the catalytic domain. Two independent predicted genes nested within Doa introns actually encode additional alternative N‐termini of the locus. An alternative polyadenylation site utilized exclusively during early embryogenesis generates a transcript with a short half‐life, apparently to ensure a “burst” of kinase expression at the onset of development. Ecdysone induction of Doa transcripts affects all isoforms during pupariation. Finally, extensive conservation of amino‐acid sequences of both the catalytic and N‐terminal noncatalytic exons observed in alignments between D. melanogaster exons and the genome sequences of 11 other Drosophila species suggest that the multiple isoforms serve important and nonredundant functions. genesis 46:132–143, 2008. © 2008 Wiley‐Liss, Inc.