BioPAX pathway converted from "SLAMF6 binds SLAMF6" in the Reactome database.SLAMF6 binds SLAMF6SLAMF6 binds SLAMF6Members of the signaling lymphocytic-activation molecule (SLAM) family, are all encoded in the SLAM locus, and are mostly homotypic self-associating receptors expressed by cells of hemopoietic origin (Veillette et al. 2006). SLAMF6 (also called as NTB-A) is a homophilic receptor that stimulates cytotoxicity in natural killer (NK) cells, regulates bactericidal activities in neutrophils, and potentiates T helper 2 (Th2) responses (Cao et al. 2006).Authored: Garapati, Phani Vijay, 2015-03-27Reviewed: Barrow, Alexander D, 2015-05-12Edited: Garapati, Phani Vijay, 2015-03-27Reactome DB_ID: 1978482plasma membraneGO0005886UniProt:Q96DU3 SLAMF6SLAMF6KALIUNQ6123/PRO20080SLAMF6FUNCTION 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).SUBUNIT Homodimer. Interacts with PTN6. Interacts (phosphorylated) with PTN11. Interacts (phosphorylated on tyrosine residues) with SH2D1A/SAP and SH2D1B/EAT2; SH2D1A and SH2D1B can associate with the same SLAMF6 molecule; interaction with SH2D1B is mediated by ITSM 2.TISSUE SPECIFICITY Expressed by all (resting and activated) natural killer cells (NK), T- and B-lymphocytes (PubMed:11489943). Increased surface expression on T-cells of systemic lupus erythematosus (SLE) patients (PubMed:22184727).DOMAIN The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containingbinding partners. Especially they mediate the with the SH2 domain of SH2D1A and SH2D1B. A 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3).PTM Phosphorylation in NK cells upon engagment by SLAMF6-expressing target cells is leading to receptor activation.Reactomehttp://www.reactome.orgHomo sapiensNCBI Taxonomy9606UniProtQ96DU3Chain Coordinates22EQUAL332EQUALReactome DB_ID: 56852291SLAMF6 dimer [plasma membrane]SLAMF6 dimerSLAMF6:SLAMF6Reactome DB_ID: 197848222EQUAL332EQUALReactome Database ID Release 755685229Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5685229ReactomeR-HSA-56852292Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5685229.2Reactome Database ID Release 755685604Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5685604ReactomeR-HSA-56856041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5685604.117045824Pubmed2006NTB-A receptor crystal structure: insights into homophilic interactions in the signaling lymphocytic activation molecule receptor familyCao, ErhuRamagopal, Udupi AFedorov, AlexanderFedorov, ElenaYan, QingrongLary, Jeffrey WCole, James LNathenson, Stanley GAlmo, Steven CImmunity 25:559-7018031695Pubmed2007Homotypic interactions mediated by Slamf1 and Slamf6 receptors control NKT cell lineage developmentGriewank, KlausBorowski, ChristineRietdijk, SvendWang, NinghaiJulien, AimeeWei, Datsen GMamchak, Alusha ATerhorst, CoxBendelac, AlbertImmunity 27:751-6216493427Pubmed2006Immune regulation by SLAM family receptors and SAP-related adaptorsVeillette, AndréNat. Rev. Immunol. 6:56-66