SLAMF6
Description
The SLAMF6 (SLAM family member 6) is a protein-coding gene located on chromosome 1.
SLAM family member 6 is a protein that in humans is encoded by the SLAMF6 gene. The protein encoded by this gene is a type I transmembrane protein, belonging to the CD2 subfamily of the immunoglobulin superfamily. This encoded protein is expressed on natural killer (NK), T, and B lymphocytes. It undergoes tyrosine phosphorylation and associates with the Src homology 2 domain-containing protein (SH2D1A) as well as with SH2 domain-containing phosphatases (SHPs). It may function as a coreceptor in the process of NK cell activation. It can also mediate inhibitory signals in NK cells from X-linked lymphoproliferative patients.
SLAMF6, also known as Activating NK receptor, NK-T-B-antigen, is a self-ligand receptor belonging to the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors, triggered by cell-cell interactions, modulate the activation and differentiation of various immune cells, regulating both innate and adaptive immune responses. The presence or absence of adapter proteins SH2D1A/SAP and SH2D1B/EAT-2 controls SLAMF6 activity. It triggers cytolytic activity specifically in natural killer cells (NK) expressing high levels of natural cytotoxicity receptors, mediated by phosphorylation of VAV1 and requiring SH2D1B. In conjunction with SLAMF1, it controls the development of thymocytic natural killer T (NKT) cells. SLAMF6 promotes T-cell differentiation into Th17 helper cells, enhancing IL-17 secretion, a process requiring SH2D1A and involving RORC recruitment to the IL-17 promoter. Along with SLAMF1 and CD84/SLAMF5, it may negatively regulate humoral immune response. In the absence of SH2D1A/SAP, SLAMF6 transmits negative signals to CD4(+) T-cells and NKT cells, inhibiting germinal center formation by disrupting T-cell:B-cell adhesion. This inhibition likely involves increased association with PTPN6/SHP-1 via ITSMs when SH2D1A/SAP is absent. However, SLAMF6 is also suggested to maintain B-cell tolerance in germinal centers and prevent autoimmunity. SLAMF6 forms homodimers and interacts with PTN6, PTN11 (phosphorylated), SH2D1A/SAP, and SH2D1B/EAT2 (phosphorylated on tyrosine residues). Interestingly, SH2D1A and SH2D1B can bind to the same SLAMF6 molecule, with SH2D1B interaction mediated by ITSM 2.
SLAMF6 is also known as CD352, KALI, KALIb, Ly108, NTB-A, NTBA, SF2000.
