IDENTIFICATION AND CHARACTERIZATION OF A CDNA AND THE STRUCTURAL GENEENCODING THE MOUSE EPITHELIAL MEMBRANE PROTEIN-1

The PMP22/EMP/MP20 gene family includes four closely related proteins, peripheral myelin protein-22 (PMP22), epithelial membrane protein-1 ( EMP-1), epithelial membrane protein-2 (EMP-2), and epithelial membrane protein-3 (EMP-3), which share amino acid identities ranging from 33 to 43%. In addition, the lens-specific membrane protein MP20 represent s a more distant relative. Functionally, this family of proteins is li kely to play important roles in the control of cell proliferation, cel l differentiation, and cell death. In particular, mutations affecting the PMP22 gene are responsible for various hereditary peripheral neuro pathies in humans and mice. We report the isolation and characterizati on of a mouse EMP-1 cDNA and the corresponding emp-1 gene. Mouse EMP-1 displays 93% amino acid identity to rat EMP-1 and 39% identity to mou se PMP22. The cDNA-predicted EMP-1 protein contains four putative memb rane-associated domains and can be N-linked glycosylated in vitro. EMP -1 is encoded by a single-copy gene with the positions of introns exac tly conserved between emp-1 and PMP22, corroborating the hypothesis th at both genes belong to the same family. Computer-predicted structural domains of EMP-1 are partially mirrored by the exon/intron structure of emp-1. Most interestingly, exon 4, which covers the potential secon d transmembrane domain, a small intracellular loop, and half of the th ird transmembrane domain, encodes the most highly conserved regions be tween the EMP-1 and PMP22 proteins and is also remarkably conserved in the MP20 gene, indicating some shared functional significance for thi s module in the PMP22/EMP/MP20 family. (C) 1996 Academic Press, Inc.