CRACC/SLAMF7/CD319 (also known as CS1) is a member of the signaling lymphocytic activation molecule (SLAM) family. It is a single-pass type l transmembrane glycoprotein expressed on NK cells, subsets of mature dendritic cells, activated B and T lymphocytes, but not in promyelocytic B or T cell lines. Expression of this protein has been detected in the spleen, lymph node, peripheral blood leukocytes, bone marrow, small intestine, stomach, appendix, lung, and trachea. Homophilic interactions of CRACC/SLAMF7/CD319 modulate the activity and differentiation of immune cells. CRACC/SLAMF7/CD319 may function as an inhibitory or activating receptor in immune cells depending on cellular context and availability of adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. In the presence of SH2D1B/EAT-2, CRACC/SLAMF7/CD319 activates NK cells and B cells. T cells lack SH2D1B/EAT-2 expression, and therefore CRACC/SLAMF7/CD319 acts as an inhibitory receptor. In LPS-activated monocytes, CRACC/SLAMF7/CD319 negatively regulates production of proinflammatory cytokines. CRACC/SLAMF7/CD319 is upregulated in multiple myeloma and is implicated in the uncontrolled proliferation of these cells, and thus has become the target for therapeutic intervention. Seven isoforms of CRACC/SLAMF7/CD319 produced by alternative splicing have been identified.
