Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome predisposing to multiple tumors. The responsible gene, MEN1, has been identified and inactivating mutations reported. It encodes a protein named menin, which lacks homology to any known proteins. Comparative genomics is used to ascertain important functional domains via the identification of evolutionary conserved regions. Here we report the sequencing and characterization of the MEN1 gene in zebrafish (Danio rerio) at the cDNA level. Zebrafish menin is a 617 amino acid protein and, when compared with human and rodent proteins, shows 75% and 76% similarity, respectively. The most conserved region is amino acid residues 41-322 which shows a human/zebrafish similarity of 83%. Amino acids affected by inactivating missense mutations in MEN1 patients in this region are completely conserved between human and zebrafish. Such high correlation between conservation throughout evolution and mutation position strongly emphasizes the importance of this region.
Copyright 1999 Academic Press.