The gp49A gene has extensive sequence conservation with the gp49B gene andprovides gp49A protein, a unique member of a large family of activating and inhibitory receptors of the immunoglobulin superfamily

Members of the gp49-related family of mouse and human immunoglobulin (Ig) s uperfamily receptors have significant amino acid sequence homology in their C2-type, Ig-like domains and include the killer cell Ig-like receptors (KI Rs) for major histocompatibility complex class I molecules. We now report t he cloning, complete sequence, and organization of the mouse gp49A gene tha t encodes the only member of this newly-appreciated family without either o f two mutually exclusive functional motifs, namely, immunoreceptor tyrosine -based inhibitory motifs (ITIMs) or a charged transmembrane amino acid for heterodimerization with activation molecules. The gp49A and gp49B genes are 94% identical over 5.6 kilobases, the 5' flanking regions are 94% identica l over 1900 nucleotides, and the 3' flanking regions are 97% identical for 121 nucleotides and then diverge completely; the gp49B gene encodes gp49B1 bearing two ITIMs. As measured by flow cytometry with specific antibody, gp 49A is expressed on immature bone-marrow-derived mast cells, mature serosal mast cells, and several mouse mast cell lines. The substantial sequence id entity of the introns of the gp49A and gp49B genes is comparable to that of the exons, establishing the gene pair as the most homologous of the gp49-r elated family and suggesting that the gp49A and gp49B genes arose by duplic ation with relatively little subsequent mutation. The findings also represe nt the first demonstration that gp49A is expressed on mast cells in tandem with inhibitory gp49B1, and establish that the gp49A gene is not a pseudoge ne, but rather encodes a protein product with characteristics different fro m the other family members.