SLAMF6

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 functions as a coreceptor in the process of NK cell activation. It can also mediate inhibitory signals in NK cells from X-linked lymphoproliferative patients. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

SLAM Family Member 6

Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors (PubMed:11489943, PubMed:16920955).
Positive signaling in NK cells implicates phosphorylation of VAV1. NK cell activation seems to depend on SH2D1B and not on SH2D1A (PubMed:16920955).
In conjunction with SLAMF1 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage (By similarity).
Promotes T-cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A (PubMed:22184727, PubMed:16920955).
Promotes recruitment of RORC to the IL-17 promoter (PubMed:22989874).
In conjunction with SLAMF1 and CD84/SLAMF5 may be a negative regulator of the humoral immune response. In the absence of SH2D1A/SAP can transmit negative signals to CD4+ T-cells and NKT cells. Negatively regulates germinal center formation by inhibiting T-cell:B-cell adhesion; the function probably implicates increased association with PTPN6/SHP-1 via ITSMs in absence of SH2D1A/SAP. However, reported to be involved in maintaining B-cell tolerance in germinal centers and in preventing autoimmunity (By similarity).

Biological Process innate immune responseIEA:UniProtKB-KW
Biological Process positive regulation of interferon-gamma productionManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of interleukin-17 productionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of natural killer cell mediated cytotoxicityManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process T cell activationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process T-helper 17 cell lineage commitmentManual Assertion Based On ExperimentIDA:UniProtKB

Cell membrane

Extracellular: 22-226
Helical: 227-247
Cytoplasmic: 248-331

Phosphorylation in NK cells upon engagment by SLAMF6-expressing target cells is leading to receptor activation.