Complementary DNA structure and genomic organization of Drosophila menin

Menin is a protein product of a tumor supressor gene MEN1, mutations of whi ch are responsible for multiple endocrine neoplasia type 1, an autosomal do minant familial cancer syndrome. We determined the nucleotide sequence of t he 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 th e 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% identi ty to human, rat, mouse and zebrafish menin over the entire length. Among t he AA residue substitutions that have been reported as disease-associated m issense mutations and single AA deletions, 53 out of 71 were completely con served in Drosophila. The presence of menin ortholog in insect indicates th at menin is an evolutionally conserved protein with a fundamental role in b iological processes. (C) 2000 Elsevier Science Ireland Ltd. All rights rese rved.