Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to CD97

The epidermal growth factor (EGF)-TM7 proteins [EMR1, (EGF-like molecule co ntaining mucin-like hormone receptor 1) F4/80, and CD97] constitute a recen tly defined class B GPCR subfamily and are predominantly expressed on leuko cytes. These molecules possess N-terminal EGF-like domains coupled to a sev en-span transmembrane (7TM) moiety via a mucin-like spacer domain. Genomic mapping analysis has suggested a possible EGF-TM7 gene family on the human chromosome 19p13 region. In this study, a new member of the EGF-TM7 family, EMR2, which shares strikingly similar molecular characteristics with CD97, is described. In addition to mapping closely to CD97 on human chromosome 1 9p13.1, EMR2 contains a total of five tandem EG;F-like domains and expresse s similar protein isoforms consisting of various numbers of EGF-Like domain s as a result of alternative RNA splicing. Furthermore, EMR2 and CD97 exhib it highly homologous EGF-like domains and share identical gene organization , indicating that both genes are the products of a recent gene duplication event. The homologous EGF-like domains enable the identification of both EM R2 and CD97 by monoclonal antibodies (mAbs) raised against the first EGF-li ke domain of CD97, whereas mAbs directed against the extracellular spacer d omain of CD97 are able to differentiate these two proteins. Both EMR2 and C D97 are highly expressed in immune tissues; however, unlike CD97, which is ubiquitously expressed in most cell types, EMR2 expression is restricted to monocytes/M phi and granulocytes. EMR2 fails to interact with CD55, the ce llular ligand for CD97, suggesting the possibility of a different cellular ligand(s). EMR2 may therefore have a unique function in cells of monocyte/M phi and granulocyte lineages. (C) 2000 Academic Press.