CLONING OF THE CDNA FOR A HEMATOPOIETIC CELL-SPECIFIC PROTEIN RELATEDTO CD20 AND THE BETA-SUBUNIT OF THE HIGH-AFFINITY IGE RECEPTOR - EVIDENCE FOR A FAMILY OF PROTEINS WITH 4 MEMBRANE-SPANNING REGIONS

We report the cloning of the cDNA for a human gene whose mRNA is expre ssed specifically in hematopoietic cells. A long open reading frame in the 1.7-kb mRNA encodes a 214-aa protein of 25 kDa with four hydropho bic regions consistent with a protein that traverses the membrane four times. To reflect the structure and expression of this gene in divers e hematopoietic lineages of lymphoid and myeloid origin, we named the gene HTm4. The protein is about 20% homologous to two other ''four-tra nsmembrane'' proteins; the B-cell-specific antigen CD20 and the beta s ubunit of the high-affinity receptor for IgE, Fc(epsilon)RI beta. The highest homologies among the three proteins are found in the transmemb rane domains, but conserved residues are also recognized in the inter- transmembrane domains and in the N and C termini. Using fluorescence i n situ hybridization, we localized HTm4 to human chromosome 11q12-13.1 , where the CD20 and Fc(epsilon)RI beta genes are also located. Both t he murine homologue for CD20, Ly-44, and the murine Fc(epsilon)RI beta gene map to the same region in murine chromosome 19. We propose that the HTm4, CD20, and Fc(epsilon)RI beta genes evolved from the same anc estral gene to form a family of four-transmembrane proteins. It is pos sible that other related members exist. Similar to CD20 and Fc(epsilon )RI beta, it is Likely that HTm4 has a role in signal transduction and , like Fc(epsilon)RI beta, might be a subunit associated with receptor complexes.