The gene encoding the immunoregulatory signaling molecule CMRF-35A localized to human chromosome 17 in close proximity to other members of the CMRF-35 family

The immunoregulatory signaling (IRS) family includes several molecules, whi ch play major roles in the regulation of the immune response. The CMRF-35A and CMRF-35H molecules are two new members of the IRS family of molecules, that are found on a wide variety of haemopoietic lineages. The extracellula r functional interactions of these molecules is presently unknown, although CMRF-35H on initiate an inhibitory signal and is internalized when cross-l inked. In this paper, we described the gene structure for the CMRF-35A gene and its localization to human chromosome 17. The gene consists of four exo ns spanning approximately 4.5 kb. Exon 1 encodes the 5' untranslated region and leader sequence, exon 2 encodes the immunoglobulin (Ig)-like domain, e xon 3 encodes the membrane proximal region and exon 4 encodes the transmemb rane region, the cytoplasmic tail and the 3' untranslated region. A region in the 5' flanking sequence of the CMRF-35A gene, that promoted expression of a reporter gene was identified. The genes for the CMRF-35A and CMRF-35H molecules are closely linked on chromosome 17. Similarity between the Ig-li ke exons and the preceding intron of the two genes suggests exon duplicatio n was involved in their evolution. We also identified a further member of t he CMRF-35 family, the CMRF-35J pseudogene. This gene appears to have arise n by gene duplication of the CMRF-35A gene. These three loci-the CMRF-35A, CMRF-35J and CMRF-35H genes-form a new complex of IRS genes on chromosome 1 7.