Complementary DNA structure and genomic organization of Drosophila menin.

Menin is a protein product of a tumor supressor gene MEN1, mutations of which are responsible for multiple endocrine neoplasia type 1, an autosomal dominant familial cancer syndrome. We determined the nucleotide sequence of the Drosophila menin cDNA using RT-PCR and RACE, and confirmed it by direct sequencing of genomic DNA. Gene expression of Drosophila menin was detected by Northern blot analysis in adult and embryo as two types of transcripts, one identical in size to the cDNA, and the other larger but detected only in embryo. The Drosophila menin gene was composed of five exons in which the protein was encoded in exon 2 through 5, and spanned approximately 6.3 kb. The deduced amino acid (AA) sequence of Drosophila menin consisted of 751 AAs with a calculated molecular mass of 81.7 kDa, and showed 44-47% identity to human, rat, mouse and zebrafish menin over the entire length. Among the AA residue substitutions that have been reported as disease-associated missense mutations and single AA deletions, 53 out of 71 were completely conserved in Drosophila. The presence of menin ortholog in insect indicates that menin is an evolutionally conserved protein with a fundamental role in biological processes.