The HEM Proteins: A Novel Family of Tissue-specific Transmembrane Proteins Expressed from Invertebrates Through Mammals with an Essential Function in Oogenesis

Abstract

We report the identification of a new family of proteins, termed the HEM family, which show distinct expression patterns in blood cells and the central nervous system. Through the isolation and characterization of the corresponding brain-specific Drosophila( dhem-2) and rat orthologues (Hem-2), and through the detection of the Caenorhabditis elegansHem-2 orthologue in the database, we show that this family is conserved throughout evolution. HEM proteins show a conserved length ranging from 1118 to 1126 amino acid residues. Moreover, they are at least 35% identical with each other and harbour several conserved membrane-spanning domains, indicative for their location on the cell surface. One of the members, the Drosophilaorthologue dhem-2, was analysed in detail for its spatial expression pattern during development and for its mutant phenotype. dhem-2is expressed maternally in the oocyte and shows uniform expression during the first half of embryogenesis, but becomes restricted to the brain and the nervous system during late embryogenesis, consistent with the expression of its vertebrate orthologue in the brain. One P-element insertion, located 39 base-pairs downstream from the dhem-2transcription start site, causes female sterility, due to the fact that developmental processes in the oocyte are disturbed. Of the vertebrate HEM family members, the mammalian Hem-1 gene is expressed only in cells of hematopoietic origin, while Hem-2 is preferentially expressed in brain, heart, liver and testis. f1 f1 Correspondence concerning DrosophilaHEM genes should be addressed to S.B. Correspondence concerning the vertebrate HEM genes should be addressed to R.H.