{"gene":"SLAMF1","run_date":"2026-04-28T20:42:07","timeline":{"discoveries":[{"year":2000,"finding":"SLAMF1 (CD150/SLAM) functions as a cellular receptor for measles virus; transfection of human SLAMF1 cDNA into non-susceptible cell lines enabled measles virus binding, replication, and cytopathic effects, establishing SLAMF1 as the entry receptor for wild-type measles virus strains.","method":"Transfection of SLAMF1 cDNA into resistant cell lines followed by virus binding and infection assays","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 — reconstituted receptor function in heterologous cells, replicated by multiple labs","pmids":["10972291"],"is_preprint":false},{"year":1998,"finding":"SAP (SLAM-associated protein) binds to the SLAMF1 cytoplasmic region via its SH2 domain, acting as an inhibitor that blocks recruitment of SHP-2 to SLAMF1, thereby regulating SLAM-mediated signaling; SAP gene mutations were found in XLP patients, linking defective SLAMF1 signaling regulation to the disease.","method":"Co-immunoprecipitation, SH2 domain binding assays, patient mutational analysis","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1–2 — direct binding demonstrated, replicated and foundational paper with >700 citations","pmids":["9774102"],"is_preprint":false},{"year":2001,"finding":"SLAMF1 receptor engagement triggers protein tyrosine phosphorylation signaling in T cells strictly dependent on SAP expression; this signal involves SHIP, Dok2, Dok1, Shc, and RasGAP, with SAP facilitating selective recruitment and activation of Src-related kinase FynT to SLAMF1; signaling via this pathway alters cytokine production profile during T cell activation.","method":"T cell signaling assays with SAP-deficient and reconstituted cell lines, phosphorylation assays, cytokine production measurement","journal":"Nature immunology","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal biochemical methods, specific pathway components identified","pmids":["11477403"],"is_preprint":false},{"year":2003,"finding":"SAP couples FynT to SLAMF1 by binding the SH3 domain of FynT through the SAP SH2 domain via a non-canonical surface-surface interaction; a crystal structure of a ternary SLAM-SAP-Fyn-SH3 complex revealed this interaction mode and showed that SAP binding precludes the auto-inhibited conformation of Fyn, promoting kinase activation after recruitment.","method":"Crystal structure determination of ternary complex, in vitro binding assays","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1 — crystal structure with functional validation of interaction mechanism","pmids":["12545174"],"is_preprint":false},{"year":2001,"finding":"SLAMF1 (CD150) is used as a cellular receptor by canine distemper virus and rinderpest virus (acting on their respective host species SLAM orthologs), demonstrating that SLAM usage as a receptor is a common property of morbilliviruses; virus entry via SLAM was confirmed by pseudotype assays.","method":"Expression of species-specific SLAM in CHO cells, infection assays, VSV pseudotype entry assays","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 1 — reconstituted receptor function across multiple morbilliviruses","pmids":["11390585"],"is_preprint":false},{"year":2007,"finding":"Homotypic interactions mediated by Slamf1 (SLAM) and Slamf6 (Ly108) between thymocytes provide 'second signals' during TCR engagement that recruit SAP and Fyn kinase, which are essential for NKT cell lineage expansion and differentiation; this cosignaling pathway is only available when selecting ligands are presented by thymocytes (not epithelial cells) because stromal cells do not express Slamf1/Slamf6.","method":"Genetic knockout mice, bone marrow chimeras, flow cytometric analysis of NKT development, epistasis experiments","journal":"Immunity","confidence":"High","confidence_rationale":"Tier 2 — genetic epistasis with multiple knockout combinations and defined phenotypic readout","pmids":["18031695"],"is_preprint":false},{"year":2010,"finding":"SLAMF1 (CD150) receptor ligation on germinal center T follicular helper (GC TFH) cells is specifically required for IL-4 production by these cells, as demonstrated by SLAM-deficient mice that lacked IL-4 production in GC TFH cells despite only a moderate defect in TFH differentiation.","method":"SLAM knockout mouse analysis, flow cytometry, intracellular cytokine staining","journal":"Journal of immunology","confidence":"High","confidence_rationale":"Tier 2 — clean KO with specific functional readout and mechanistic distinction from TFH differentiation","pmids":["20525889"],"is_preprint":false},{"year":2002,"finding":"The measles virus hemagglutinin (H protein) is responsible for downregulating SLAMF1 from the cell surface after infection; transfection of hemagglutinin expression plasmid alone induced SLAM downregulation in cells expressing or coming in contact with hemagglutinin-expressing cells, while the fusion protein had no such effect.","method":"Transfection of individual MV envelope proteins, flow cytometric measurement of surface SLAM expression","journal":"Archives of virology","confidence":"Medium","confidence_rationale":"Tier 2 — clean dissection of hemagglutinin vs. fusion protein role, single lab","pmids":["11855632"],"is_preprint":false},{"year":2008,"finding":"Measles virus hemagglutinin isoleucine 194 is essential for primary binding to SLAMF1 (measured by surface plasmon resonance); after binding, a quartet of residues on propeller blade 5 mediates receptor-specific conformational changes required for membrane fusion, establishing distinct binding and fusion-triggering sites on the hemagglutinin-SLAMF1 interface.","method":"Site-directed mutagenesis, surface plasmon resonance, receptor-specific fusion assays, crystal structure localization of residues","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — mutagenesis combined with biophysical binding measurement and functional fusion assay","pmids":["18292085"],"is_preprint":false},{"year":2004,"finding":"CD150 (SLAMF1) ligation in DT40 B cells induces ERK signaling requiring SHIP but not SH2D1A, while CD150-mediated Akt phosphorylation requires Syk and SH2D1A and is negatively regulated by Lyn and Btk; Lyn directly phosphorylates Y327 in the SLAMF1 cytoplasmic tail, demonstrating SH2D1A-dependent switching of SLAMF1 downstream signaling pathways.","method":"DT40 B cell knockout sublines, phosphorylation assays, kinase-specific inhibitors, direct kinase phosphorylation assay","journal":"Blood","confidence":"High","confidence_rationale":"Tier 1–2 — multiple genetic knockouts and biochemical assays in defined cell system","pmids":["15315965"],"is_preprint":false},{"year":2015,"finding":"SLAMF1 ligation in CLL cells with an agonistic monoclonal antibody induces ROS accumulation, phosphorylation of p38, JNK1/2, and BCL2, and promotes autophagic flux; mechanistically, Beclin1 dissociates from BCL2 upon SLAMF1 ligation, leading to formation of an autophagy macrocomplex containing SLAMF1, Beclin1, and VPS34; SLAMF1-silenced cells showed increased CXCR4, CD38, and CD44 expression and enhanced chemotactic responses to CXCL12.","method":"SLAMF1 silencing (RNAi), agonistic antibody ligation, co-immunoprecipitation, immunoblotting, autophagy flux assays, migration assays","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (Co-IP, KD, functional assays) in primary CLL and cell lines","pmids":["26619119"],"is_preprint":false},{"year":2015,"finding":"Slamf1 and Slamf8 differentially regulate NADPH-oxidase (Nox2)-dependent reactive oxygen species (ROS) production by myeloid cells in response to bacteria; Slamf1 is required for optimal ROS production and promotes myeloid cell migration in vivo, while Slamf8 negatively regulates ROS production and its absence accelerates myeloid cell migration; inhibiting ROS in Slamf8-deficient macrophages blocked enhanced in vitro migration.","method":"Knockout mice, in vivo migration assays (peritonitis, skin sensitization, intestinal repopulation), in vitro transwell migration assays, ROS production measurement with DPI inhibition","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 — clean KO phenotypes with in vivo and in vitro mechanistic dissection and pharmacological rescue","pmids":["25799045"],"is_preprint":false},{"year":2012,"finding":"SLAMF1 (and related family members Ly108 and 2B4) regulate immunological synapse organization between cytotoxic lymphocytes and B cell targets; in the absence of SAP, signaling through Ly108 and 2B4 results in increased SHP-1 phosphatase recruitment, altered SHP-1 localization, and decreased activation of Src kinases at the synapse, leading to impaired actin clearance and defective killing of B cell targets.","method":"SAP-deficient mouse CD8+ T cells, cytotoxicity assays against different targets, confocal imaging of immunological synapses, phosphatase recruitment assays","journal":"Immunity","confidence":"High","confidence_rationale":"Tier 2 — mechanistic dissection with imaging, biochemistry, and functional readouts","pmids":["22683123"],"is_preprint":false},{"year":2017,"finding":"SLAMF1 engagement by measles virus induces MeV endocytosis via a macropinocytosis-like pathway; MeV engagement of SLAMF1 triggers membrane blebbing, actin cytoskeleton rearrangement, and the RhoA-ROCK-myosin II signaling axis to mediate viral particle internalization; chemical inhibition of macropinocytosis or actin dynamics blocked MeV entry.","method":"Live-cell imaging, chemical inhibitors (RhoA-ROCK-myosin II pathway, macropinocytosis inhibitors), colocalization studies, infection assays in SLAMF1+ vs SLAMF1- cells","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 2 — multiple pharmacological dissections with imaging and functional infection assays","pmids":["28100610"],"is_preprint":false},{"year":2012,"finding":"Slamf1 is required on myeloid cells for efficient intracellular replication of Trypanosoma cruzi; Slamf1-deficient mice were completely protected from lethal parasite challenge, with Slamf1-deficient myeloid cells impaired in parasite replication and showing altered cytokine production; anti-Slamf1 monoclonal antibody treatment also reduced cardiac parasites.","method":"Slamf1 knockout mice, in vivo and in vitro infection assays, anti-Slamf1 antibody blockade, cytokine production assays","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 — clean KO with defined cellular phenotype, confirmed with antibody blockade","pmids":["22807679"],"is_preprint":false},{"year":2020,"finding":"Brucella abortus outer membrane protein Omp25 specifically binds SLAMF1 on dendritic cells; this Omp25-SLAMF1 engagement limits NF-κB translocation, decreases pro-inflammatory cytokine secretion, and impairs DC activation without affecting Brucella intracellular trafficking; at chronic infection stage, the Omp25-SLAMF1 axis is essential for bacterial persistence in vivo.","method":"In vitro binding assays (Omp25-SLAMF1 interaction), NF-κB translocation assays, cytokine measurement, mouse infection models (acute and chronic stages)","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 — direct protein-protein interaction established with in vivo functional validation","pmids":["31953913"],"is_preprint":false},{"year":2020,"finding":"SLAMF1 is expressed on human neutrophils upon Mycobacterium tuberculosis stimulation; SLAMF1 colocalizes with LC3B+ vesicles, and SLAMF1 activation increases neutrophil autophagy induced by Mtb; tuberculosis patients' neutrophils display reduced SLAMF1 levels and lower autophagy against Mtb.","method":"Flow cytometry, confocal microscopy (SLAMF1-LC3B colocalization), SLAMF1 agonistic antibody stimulation, autophagy assays","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 3 — colocalization and antibody activation with functional readout, single lab, limited mechanistic depth","pmids":["32954947"],"is_preprint":false},{"year":2001,"finding":"SLAMF1 (CD150) is downregulated from the cell surface after measles virus infection or contact with MV envelope proteins; anti-SLAM antibodies block virus binding but do not interfere with contact-mediated proliferation inhibition, demonstrating that MV-induced proliferation inhibition is independent of SLAMF1 and CD46 receptor engagement.","method":"Anti-SLAM antibody blocking assays, flow cytometric measurement of surface SLAM after infection/contact, cell proliferation assays","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 — functional dissection with antibody blocking and receptor downregulation measurement","pmids":["11312320"],"is_preprint":false},{"year":2001,"finding":"SLAMF1 (CD150) expression is induced on monocytes by phytohaemagglutinin, bacterial lipopolysaccharide, or measles virus itself (which do not constitutively express SLAM); once induced, SLAM serves as the functional MV receptor on activated monocytes, as confirmed by anti-SLAM antibody blocking of infection.","method":"Flow cytometry of monocyte SLAM expression under various stimuli, anti-SLAM antibody blocking of MV infection","journal":"The Journal of general virology","confidence":"Medium","confidence_rationale":"Tier 2 — direct receptor induction and functional blocking demonstrated","pmids":["11714966"],"is_preprint":false},{"year":1997,"finding":"SLAMF1 acts as a self-ligand (homophilic interaction) that promotes B cell proliferation and Ig synthesis; soluble SLAMF1 and L cells transfected with membrane SLAMF1 both enhanced proliferation and IgM, IgG, IgA production by activated human B cells, establishing SLAMF1-SLAMF1 homotypic interaction as a costimulatory signal for B cells.","method":"Recombinant soluble SLAMF1, SLAMF1-transfected L cells, B cell proliferation assays, Ig production measurement by ELISA","journal":"The Journal of experimental medicine","confidence":"Medium","confidence_rationale":"Tier 2 — reconstituted homophilic interaction with functional B cell readout","pmids":["9091591"],"is_preprint":false},{"year":2015,"finding":"SLAMF1, SLAMF5, and SLAMF6 act as negative regulators of humoral immune responses; combined knockout of all three genes resulted in enhanced T-dependent and T-independent antibody responses, with B-cell-intrinsic effects being more pronounced than T-cell effects as established by adoptive co-transfer experiments.","method":"Single and triple knockout mice, adoptive co-transfer of B and T cells, T-dependent and T-independent antibody response assays","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis with adoptive transfer dissection, but mechanism downstream not fully defined","pmids":["25926831"],"is_preprint":false},{"year":2001,"finding":"SLAMF1 engagement promotes T cell-mediated cytotoxicity; in CD4+ and CD8+ T cells SLAM enhanced TCR-mediated killing, and in Herpesvirus saimiri-transformed T cells SLAM engagement alone triggered cytotoxicity requiring release of lytic granules, extracellular Ca2+, cytoskeletal rearrangements, and MEK1/2 signaling in a CD95-independent manner.","method":"Cytotoxicity assays, pharmacological inhibition (MEK1/2, Ca2+, cytoskeletal), granule release assays","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 — pharmacological dissection of signaling requirements for SLAMF1-mediated cytotoxicity","pmids":["11536173"],"is_preprint":false},{"year":2019,"finding":"SLAM family receptors (SFRs), with SLAMF6 alone being sufficient, promote iNKT cell development by reducing TCR signal strength after positive selection, improving iNKT cell survival; this involves the SAP-Fyn complex and the phosphatase SHP-1; loss of SFRs upregulated PD-1 expression on iNKT cells as a compensatory mechanism.","method":"SFR-deficient mice (seven simultaneous SFR knockouts), SLAMF6 single rescue in SFR-deficient background, epistasis with SAP-Fyn and SHP-1, TCR signaling measurement","journal":"Nature immunology","confidence":"High","confidence_rationale":"Tier 2 — comprehensive genetic rescue experiments with pathway component dissection","pmids":["30833791"],"is_preprint":false},{"year":2008,"finding":"Impaired SLAMF1 (SLAM) homotypic interaction between iNKT cells and mature dendritic cells from NOD mice results in defective GATA-3 upregulation and reduced IL-4/IL-10 (NKT2) cytokine production; NOD mDC express significantly lower levels of SLAMF1 due to the Slamf1 genetic defect, impairing peripheral NKT2 polarization.","method":"Cross-strain iNKT-DC co-culture assays, GATA-3 expression analysis, cytokine production measurement, flow cytometric SLAM expression on NOD vs C57BL/6 DCs","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 3 — cross-strain comparison with functional readout but mechanism not fully biochemically dissected","pmids":["18606638"],"is_preprint":false},{"year":2007,"finding":"CD150 (SLAMF1) co-localizes with lipid rafts in specific membrane compartments on CD8+ T cells after activation; overexpression of CD150 enhanced cytotoxic activity and IFN-γ secretion in vitro and anti-tumor activity in vivo, while siRNA silencing of CD150 reduced effector functions.","method":"Lipid raft fractionation/co-localization, CD150 overexpression and siRNA knockdown, cytotoxicity assays, IFN-γ ELISpot, xenograft tumor model","journal":"Molecular immunology","confidence":"Medium","confidence_rationale":"Tier 2–3 — functional gain/loss-of-function with lipid raft localization, but mechanistic link not deeply characterized","pmids":["17692919"],"is_preprint":false}],"current_model":"SLAMF1 (CD150) is a homophilic cell-surface receptor on immune cells that acts as the primary entry receptor for morbilliviruses (including measles virus) via direct binding of viral hemagglutinin at specific interface residues, and that signals through immunoreceptor tyrosine-based switch motifs (ITSMs) in its cytoplasmic tail; SAP binds these ITSMs and couples SLAMF1 to FynT (via a non-canonical SH2-SH3 interaction), driving downstream phosphorylation cascades involving SHIP, Dok proteins, and RasGAP to regulate T and B cell activation, cytokine production (including IL-4 and IFN-γ), NKT cell development, cytotoxicity, and autophagy, while also functioning as a microbial sensor on myeloid cells to control ROS production, migration, and intracellular pathogen replication."},"narrative":{"teleology":[{"year":1997,"claim":"Establishing that SLAMF1 undergoes homophilic (self-ligand) interaction and that this engagement costimulates B cell proliferation and immunoglobulin production resolved the question of the receptor's natural ligand and placed SLAMF1 as a lymphocyte costimulatory molecule.","evidence":"Recombinant soluble SLAMF1 and SLAMF1-transfected L cells in B cell proliferation/Ig secretion assays","pmids":["9091591"],"confidence":"Medium","gaps":["Structural basis of homophilic interaction not defined","Signaling events downstream of B cell engagement not characterized"]},{"year":1998,"claim":"Identification of SAP as an SH2-domain adaptor that binds the SLAMF1 cytoplasmic tail and blocks SHP-2 recruitment—and its mutational loss in XLP patients—established the first signaling mechanism downstream of SLAMF1 and linked it to human immunodeficiency.","evidence":"Co-immunoprecipitation, SH2 domain binding assays, and patient mutational analysis","pmids":["9774102"],"confidence":"High","gaps":["Kinase effectors downstream of SAP–SLAMF1 unknown","Whether SAP loss rewires rather than merely ablates signaling was unresolved"]},{"year":2000,"claim":"Demonstrating that SLAMF1 cDNA transfection confers measles virus susceptibility to resistant cells resolved the identity of the primary wild-type measles virus entry receptor, a long-standing question in morbillivirus biology.","evidence":"Heterologous expression of SLAMF1 in non-susceptible cell lines followed by MV binding and infection assays","pmids":["10972291"],"confidence":"High","gaps":["Molecular interface between hemagglutinin and SLAMF1 undefined","Whether other morbilliviruses share SLAM usage unknown at this point"]},{"year":2001,"claim":"Multiple studies established that SLAMF1 signaling proceeds through a SAP-dependent phosphorylation cascade (FynT, SHIP, Dok1/2, RasGAP) that controls cytokine production and T cell cytotoxicity, and that SLAMF1 serves as a shared morbillivirus receptor across species.","evidence":"SAP-deficient/reconstituted T cell signaling assays, pharmacological inhibition of MEK1/2 and calcium, pseudotype entry assays with species-specific SLAM orthologs","pmids":["11477403","11536173","11390585","11312320","11714966"],"confidence":"High","gaps":["How SAP couples to FynT mechanistically remained unclear","Contribution of individual downstream effectors (e.g., Dok vs SHIP) not dissected in vivo"]},{"year":2003,"claim":"The crystal structure of the ternary SLAM–SAP–Fyn-SH3 complex revealed a non-canonical SH2–SH3 surface interaction through which SAP recruits and activates FynT, explaining how an adaptor lacking enzymatic activity transduces SLAMF1 signals.","evidence":"X-ray crystallography of ternary complex with in vitro binding validation","pmids":["12545174"],"confidence":"High","gaps":["Ternary complex formation not demonstrated in intact cells with endogenous proteins at that time","Whether the same mechanism applies at all SLAM-family receptors not tested"]},{"year":2004,"claim":"Dissection of SLAMF1 signaling in B cells showed SH2D1A-dependent switching between ERK (via SHIP) and Akt (via Syk) pathways, with Lyn phosphorylating SLAMF1 Y327, demonstrating that SLAMF1 operates as a signaling platform whose output depends on adapter availability.","evidence":"DT40 B cell knockout sublines for individual kinases/adaptors with phosphorylation and pathway-specific readouts","pmids":["15315965"],"confidence":"High","gaps":["Relevance of Y327 phosphorylation in primary B cells not validated","Integration of ERK vs Akt branches in physiological B cell responses unclear"]},{"year":2007,"claim":"Genetic epistasis in knockout mice demonstrated that SLAMF1 (with SLAMF6) provides essential thymocyte-derived costimulatory signals for NKT cell lineage development via SAP-Fyn recruitment, and that SLAMF1 lipid-raft localization in CD8+ T cells enhances cytotoxicity and IFN-γ production.","evidence":"Multiple knockout/chimeric mice for NKT analysis; lipid raft fractionation, overexpression/siRNA, and xenograft models for CD8+ T cells","pmids":["18031695","17692919"],"confidence":"High","gaps":["Relative contributions of SLAMF1 vs SLAMF6 to NKT development not fully separated","Mechanism linking lipid raft localization to enhanced signaling not biochemically defined"]},{"year":2008,"claim":"Identification of hemagglutinin residue I194 as the primary SLAMF1-binding determinant and a distinct fusion-triggering site on blade 5 established a two-step model of MV entry (binding then conformational change), while NOD mouse studies showed that reduced SLAMF1 on dendritic cells impairs NKT2 polarization via defective GATA-3 induction.","evidence":"Site-directed mutagenesis with SPR and fusion assays for MV entry; cross-strain DC–NKT co-culture for NOD phenotype","pmids":["18292085","18606638"],"confidence":"High","gaps":["Full atomic structure of SLAMF1–hemagglutinin complex not yet solved","Whether NOD SLAMF1 defect is solely expression-level or includes functional polymorphism unclear"]},{"year":2012,"claim":"SLAMF1 was shown to regulate immunological synapse organization in cytotoxic lymphocytes: in the absence of SAP, SLAM-family signaling recruits SHP-1 instead of Fyn, impairing actin clearance and B cell killing; separately, SLAMF1 on myeloid cells was found essential for intracellular Trypanosoma cruzi replication, with knockout mice fully protected from lethal challenge.","evidence":"SAP-deficient mouse CD8+ T cell synapse imaging and cytotoxicity assays; Slamf1 KO mice and anti-SLAMF1 antibody blockade in T. cruzi infection","pmids":["22683123","22807679"],"confidence":"High","gaps":["How SLAMF1 promotes parasite replication at the molecular level unknown","Relative contribution of SHP-1 vs loss of Fyn to cytotoxic defect not separated"]},{"year":2015,"claim":"SLAMF1 was placed as a positive regulator of autophagy (via a Beclin-1–VPS34 macrocomplex and ROS/p38/JNK signaling) and Nox2-dependent ROS production in myeloid cells, while triple SLAM-family knockout studies revealed SLAMF1 as a negative regulator of humoral responses, adding B-cell-intrinsic suppressive function to its portfolio.","evidence":"RNAi/agonistic antibody in CLL cells with co-IP of SLAMF1–Beclin-1–VPS34; Slamf1 KO myeloid ROS and migration assays; triple KO adoptive transfer for antibody responses","pmids":["26619119","25799045","25926831"],"confidence":"High","gaps":["How Beclin-1 is recruited to SLAMF1 (direct vs indirect) not established","Mechanism by which SLAMF1 restrains antibody responses at the molecular level unresolved"]},{"year":2017,"claim":"Demonstrating that MV engagement of SLAMF1 triggers a macropinocytosis-like entry pathway via RhoA–ROCK–myosin II defined the cell-biological mechanism of SLAMF1-mediated viral internalization, beyond simple receptor binding.","evidence":"Live-cell imaging and pharmacological inhibition of actin dynamics and RhoA–ROCK–myosin II pathway in SLAMF1+ cells during MV infection","pmids":["28100610"],"confidence":"High","gaps":["Whether this entry pathway is shared by all morbilliviruses not tested","SLAMF1 cytoplasmic domain signaling events that trigger macropinocytosis not defined"]},{"year":2019,"claim":"Comprehensive SFR-knockout and single-gene rescue experiments showed that SLAMF6, more than SLAMF1, is the critical family member reducing TCR signal strength to permit iNKT survival after positive selection, refining the earlier model of redundant SLAMF1/SLAMF6 roles in NKT development.","evidence":"Seven-SFR-deficient mice with SLAMF6 single rescue, epistasis with SAP-Fyn and SHP-1","pmids":["30833791"],"confidence":"High","gaps":["Whether SLAMF1 has any non-redundant role in iNKT development beyond SLAMF6 remains unclear","Cell-type-specific redundancy among SFRs in humans not addressed"]},{"year":2020,"claim":"SLAMF1 was identified as a direct target of bacterial immune evasion (Brucella Omp25 binds SLAMF1 to suppress NF-κB and DC activation) and as a promoter of neutrophil autophagy during M. tuberculosis infection, extending its microbial-sensor role to chronic bacterial pathogens.","evidence":"In vitro Omp25–SLAMF1 binding assays and in vivo Brucella persistence models; SLAMF1–LC3B colocalization and agonistic antibody stimulation in Mtb-exposed neutrophils","pmids":["31953913","32954947"],"confidence":"High","gaps":["Omp25–SLAMF1 binding interface not structurally defined","Whether SLAMF1-driven autophagy in neutrophils restricts Mtb growth in vivo unknown"]},{"year":null,"claim":"Key unresolved questions include: the atomic structure of the SLAMF1 homophilic interface, the mechanism by which SLAMF1 cytoplasmic signals trigger macropinocytosis and autophagy complex assembly, and how SLAMF1 restrains humoral immune responses at the molecular level.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of SLAMF1 homophilic complex","Mechanism linking SLAMF1 cytoplasmic domain to Beclin-1–VPS34 recruitment unknown","Molecular basis of B-cell-intrinsic antibody suppression undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,4,8,19]},{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[19,5,12]},{"term_id":"GO:0001618","term_label":"virus receptor activity","supporting_discovery_ids":[0,4,13]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,7,17,18,24]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[13,16]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1,2,5,6,12,20,21,22]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,3,9,10]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[10,16]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[0,4,14,15]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[10]}],"complexes":["SLAMF1–SAP–FynT ternary signaling complex","SLAMF1–Beclin-1–VPS34 autophagy macrocomplex"],"partners":["SH2D1A","FYN","SHIP1","DOK1","DOK2","BECN1","PIK3C3","LYN"],"other_free_text":[]},"mechanistic_narrative":"SLAMF1 (CD150) is a homophilic immunoglobulin-superfamily receptor that orchestrates adaptive and innate immune responses by coupling antigen receptor signaling to cytokine polarization, cytotoxicity, autophagy, and pathogen handling on T cells, B cells, NKT cells, and myeloid cells. Homotypic SLAMF1–SLAMF1 engagement recruits the adaptor SAP, whose SH2 domain binds cytoplasmic immunoreceptor tyrosine-based switch motifs (ITSMs) and simultaneously docks FynT via a non-canonical SH2–SH3 interaction, activating a downstream phosphorylation cascade involving SHIP, Dok1/2, Shc, and RasGAP that drives IL-4 and IFN-γ production, granule-dependent cytotoxicity, and NKT cell lineage development [PMID:9774102, PMID:11477403, PMID:12545174, PMID:18031695, PMID:20525889]. In myeloid cells, SLAMF1 promotes Nox2-dependent ROS production and autophagy through a Beclin-1–VPS34 macrocomplex, regulates intracellular replication of pathogens such as Trypanosoma cruzi and Brucella abortus, and is exploited by morbilliviruses—including measles, canine distemper, and rinderpest viruses—as the primary entry receptor via direct hemagglutinin binding that triggers macropinocytosis-like internalization [PMID:10972291, PMID:11390585, PMID:26619119, PMID:25799045, PMID:22807679, PMID:31953913, PMID:28100610]. Loss-of-function mutations in SAP (SH2D1A), which uncouples SLAMF1 signaling and shifts the pathway toward inhibitory SHP-1/SHP-2 recruitment, cause X-linked lymphoproliferative disease [PMID:9774102, PMID:22683123]."},"prefetch_data":{"uniprot":{"accession":"Q13291","full_name":"Signaling lymphocytic activation molecule","aliases":["CDw150","IPO-3","SLAM family member 1"],"length_aa":335,"mass_kda":37.2,"function":"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. SLAMF1-induced signal-transduction events in T-lymphocytes are different from those in B-cells. Two modes of SLAMF1 signaling seem to exist: one depending on SH2D1A (and perhaps SH2D1B) and another in which protein-tyrosine phosphatase 2C (PTPN11)-dependent signal transduction operates. Initially it has been proposed that association with SH2D1A prevents binding to inhibitory effectors including INPP5D/SHIP1 and PTPN11/SHP-2 (PubMed:11806999). However, signaling is also regulated by SH2D1A which can simultaneously interact with and recruit FYN which subsequently phosphorylates and activates SLAMF1 (PubMed:12458214). Mediates IL-2-independent proliferation of activated T-cells during immune responses and induces IFN-gamma production (By similarity). Downstreaming signaling involves INPP5D, DOK1 and DOK2 leading to inhibited IFN-gamma production in T-cells, and PRKCQ, BCL10 and NFKB1 leading to increased T-cell activation and Th2 cytokine production (By similarity). Promotes T-cell receptor-induced IL-4 secretion by CD4(+) cells (By similarity). Inhibits antigen receptor-mediated production of IFN-gamma, but not IL-2, in CD4(-)/CD8(-) T-cells (By similarity). Required for IL-4 production by germinal centers T follicular helper (T(Fh))cells (By similarity). May inhibit CD40-induced signal transduction in monocyte-derived dendritic cells (PubMed:16317102). May play a role in allergic responses and may regulate allergen-induced Th2 cytokine and Th1 cytokine secretion (By similarity). In conjunction with SLAMF6 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage. Involved in the peripheral differentiation of indifferent natural killer T (iNKT) cells toward a regulatory NKT2 type (By similarity). In macrophages involved in down-regulation of IL-12, TNF and nitric oxide in response to lipopolysaccharide (LPS) (By similarity). In B-cells activates the ERK signaling pathway independently of SH2D1A but implicating both, SYK and INPP5D, and activates Akt signaling dependent on SYK and SH2D1A (By similarity). In B-cells also activates p38 MAPK and JNK1 and JNK2 (PubMed:20231852). In conjunction with CD84/SLAMF5 and SLAMF6 may be a negative regulator of the humoral immune response (By similarity). Involved in innate immune response against Gram-negative bacteria in macrophages; probably recognizes OmpC and/or OmpF on the bacterial surface, regulates phagosome maturation and recruitment of the PI3K complex II (PI3KC3-C2) leading to accumulation of PdtIns(3)P and NOX2 activity in the phagosomes (PubMed:20818396) (Microbial infection) Acts as a receptor for Measles virus; also including isoform 4","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q13291/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SLAMF1","classification":"Not Classified","n_dependent_lines":5,"n_total_lines":1208,"dependency_fraction":0.0041390728476821195},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SLAMF1","total_profiled":1310},"omim":[{"mim_id":"609607","title":"NECTIN CELL ADHESION MOLECULE 4; NECTIN4","url":"https://www.omim.org/entry/609607"},{"mim_id":"608849","title":"U2AF HOMOLOGY MOTIF KINASE 1; UHMK1","url":"https://www.omim.org/entry/608849"},{"mim_id":"608510","title":"SH2 DOMAIN-CONTAINING 1B; SH2D1B","url":"https://www.omim.org/entry/608510"},{"mim_id":"603492","title":"SLAM FAMILY, MEMBER 1; SLAMF1","url":"https://www.omim.org/entry/603492"},{"mim_id":"602410","title":"BROMODOMAIN- AND PHD FINGER-CONTAINING PROTEIN; BRPF1","url":"https://www.omim.org/entry/602410"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":59.1}],"url":"https://www.proteinatlas.org/search/SLAMF1"},"hgnc":{"alias_symbol":["CD150","IPO-3","IPO3"],"prev_symbol":["SLAM"]},"alphafold":{"accession":"Q13291","domains":[{"cath_id":"2.60.40.10","chopping":"31-139","consensus_level":"high","plddt":84.7803,"start":31,"end":139},{"cath_id":"2.60.40.10","chopping":"145-229","consensus_level":"high","plddt":89.6195,"start":145,"end":229}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13291","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q13291-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q13291-F1-predicted_aligned_error_v6.png","plddt_mean":74.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SLAMF1","jax_strain_url":"https://www.jax.org/strain/search?query=SLAMF1"},"sequence":{"accession":"Q13291","fasta_url":"https://rest.uniprot.org/uniprotkb/Q13291.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q13291/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13291"}},"corpus_meta":[{"pmid":"15989959","id":"PMC_15989959","title":"SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells.","date":"2005","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/15989959","citation_count":2449,"is_preprint":false},{"pmid":"10972291","id":"PMC_10972291","title":"SLAM (CDw150) is a cellular receptor for measles virus.","date":"2000","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/10972291","citation_count":865,"is_preprint":false},{"pmid":"9774102","id":"PMC_9774102","title":"The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM.","date":"1998","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/9774102","citation_count":705,"is_preprint":false},{"pmid":"21219180","id":"PMC_21219180","title":"SLAM family receptors and SAP adaptors in immunity.","date":"2011","source":"Annual review of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/21219180","citation_count":404,"is_preprint":false},{"pmid":"20525889","id":"PMC_20525889","title":"Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150).","date":"2010","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/20525889","citation_count":353,"is_preprint":false},{"pmid":"18031695","id":"PMC_18031695","title":"Homotypic interactions mediated by Slamf1 and Slamf6 receptors control NKT cell lineage development.","date":"2007","source":"Immunity","url":"https://pubmed.ncbi.nlm.nih.gov/18031695","citation_count":287,"is_preprint":false},{"pmid":"29622725","id":"PMC_29622725","title":"SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis.","date":"2018","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/29622725","citation_count":285,"is_preprint":false},{"pmid":"11390585","id":"PMC_11390585","title":"Morbilliviruses use signaling lymphocyte activation molecules (CD150) as cellular receptors.","date":"2001","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/11390585","citation_count":268,"is_preprint":false},{"pmid":"12545174","id":"PMC_12545174","title":"SAP couples Fyn to SLAM immune receptors.","date":"2003","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/12545174","citation_count":249,"is_preprint":false},{"pmid":"14523387","id":"PMC_14523387","title":"The SAP and SLAM families in immune responses and X-linked lymphoproliferative disease.","date":"2003","source":"Nature reviews. Immunology","url":"https://pubmed.ncbi.nlm.nih.gov/14523387","citation_count":233,"is_preprint":false},{"pmid":"18020706","id":"PMC_18020706","title":"Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques.","date":"2007","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/18020706","citation_count":213,"is_preprint":false},{"pmid":"17201683","id":"PMC_17201683","title":"Regulation of cellular and humoral immune responses by the SLAM and SAP families of molecules.","date":"2007","source":"Annual review of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/17201683","citation_count":210,"is_preprint":false},{"pmid":"11477403","id":"PMC_11477403","title":"Regulation of SLAM-mediated signal transduction by SAP, the X-linked lymphoproliferative gene product.","date":"2001","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/11477403","citation_count":205,"is_preprint":false},{"pmid":"16219798","id":"PMC_16219798","title":"SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity.","date":"2005","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/16219798","citation_count":199,"is_preprint":false},{"pmid":"29456159","id":"PMC_29456159","title":"CD150high Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine.","date":"2018","source":"Cell stem cell","url":"https://pubmed.ncbi.nlm.nih.gov/29456159","citation_count":195,"is_preprint":false},{"pmid":"12941904","id":"PMC_12941904","title":"Efficient isolation of wild strains of canine distemper virus in Vero cells expressing canine SLAM (CD150) and their adaptability to marmoset B95a cells.","date":"2003","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/12941904","citation_count":183,"is_preprint":false},{"pmid":"12050387","id":"PMC_12050387","title":"SLAM (CD150)-independent measles virus entry as revealed by recombinant virus expressing green fluorescent protein.","date":"2002","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/12050387","citation_count":181,"is_preprint":false},{"pmid":"12496974","id":"PMC_12496974","title":"The dual-function CD150 receptor subfamily: the viral attraction.","date":"2003","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/12496974","citation_count":179,"is_preprint":false},{"pmid":"16493427","id":"PMC_16493427","title":"Immune regulation by SLAM family receptors and SAP-related adaptors.","date":"2006","source":"Nature reviews. Immunology","url":"https://pubmed.ncbi.nlm.nih.gov/16493427","citation_count":177,"is_preprint":false},{"pmid":"19079134","id":"PMC_19079134","title":"SLAM receptors and SAP influence lymphocyte interactions, development and function.","date":"2009","source":"Nature reviews. Immunology","url":"https://pubmed.ncbi.nlm.nih.gov/19079134","citation_count":175,"is_preprint":false},{"pmid":"11312320","id":"PMC_11312320","title":"CD150 (SLAM) is a receptor for measles virus but is not involved in viral contact-mediated proliferation inhibition.","date":"2001","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/11312320","citation_count":160,"is_preprint":false},{"pmid":"11145884","id":"PMC_11145884","title":"CDw150(SLAM) is a receptor for a lymphotropic strain of measles virus and may account for the immunosuppressive properties of this virus.","date":"2001","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/11145884","citation_count":150,"is_preprint":false},{"pmid":"9091591","id":"PMC_9091591","title":"Soluble and membrane-bound forms of signaling lymphocytic activation molecule (SLAM) induce proliferation and Ig synthesis by activated human B lymphocytes.","date":"1997","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/9091591","citation_count":137,"is_preprint":false},{"pmid":"26682762","id":"PMC_26682762","title":"SLAM family receptors in normal immunity and immune pathologies.","date":"2015","source":"Current opinion in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/26682762","citation_count":126,"is_preprint":false},{"pmid":"20300214","id":"PMC_20300214","title":"SLAM-family receptors: immune regulators with or without SAP-family adaptors.","date":"2010","source":"Cold Spring Harbor perspectives in biology","url":"https://pubmed.ncbi.nlm.nih.gov/20300214","citation_count":118,"is_preprint":false},{"pmid":"23731618","id":"PMC_23731618","title":"CS1, a SLAM family receptor involved in immune regulation, is a therapeutic target in multiple myeloma.","date":"2013","source":"Critical reviews in oncology/hematology","url":"https://pubmed.ncbi.nlm.nih.gov/23731618","citation_count":100,"is_preprint":false},{"pmid":"18031694","id":"PMC_18031694","title":"Consequence of the SLAM-SAP signaling pathway in innate-like and conventional lymphocytes.","date":"2007","source":"Immunity","url":"https://pubmed.ncbi.nlm.nih.gov/18031694","citation_count":99,"is_preprint":false},{"pmid":"29949974","id":"PMC_29949974","title":"Dissecting newly transcribed and old RNA using GRAND-SLAM.","date":"2018","source":"Bioinformatics (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/29949974","citation_count":93,"is_preprint":false},{"pmid":"22683123","id":"PMC_22683123","title":"Positive and negative signaling through SLAM receptors regulate synapse organization and thresholds of cytolysis.","date":"2012","source":"Immunity","url":"https://pubmed.ncbi.nlm.nih.gov/22683123","citation_count":93,"is_preprint":false},{"pmid":"12787752","id":"PMC_12787752","title":"The SLAM family of immune-cell receptors.","date":"2003","source":"Current opinion in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/12787752","citation_count":90,"is_preprint":false},{"pmid":"12618381","id":"PMC_12618381","title":"SLAM: cross-species gene finding and alignment with a generalized pair hidden Markov model.","date":"2003","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/12618381","citation_count":89,"is_preprint":false},{"pmid":"20042501","id":"PMC_20042501","title":"Measles virus infection of alveolar macrophages and dendritic cells precedes spread to lymphatic organs in transgenic mice expressing human signaling lymphocytic activation molecule (SLAM, CD150).","date":"2009","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/20042501","citation_count":86,"is_preprint":false},{"pmid":"17100873","id":"PMC_17100873","title":"NK cell regulation by SLAM family receptors and SAP-related adapters.","date":"2006","source":"Immunological reviews","url":"https://pubmed.ncbi.nlm.nih.gov/17100873","citation_count":84,"is_preprint":false},{"pmid":"12029158","id":"PMC_12029158","title":"Analysis of receptor (CD46, CD150) usage by measles virus.","date":"2002","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/12029158","citation_count":78,"is_preprint":false},{"pmid":"16365421","id":"PMC_16365421","title":"Ly9 (CD229)-deficient mice exhibit T cell defects yet do not share several phenotypic characteristics associated with SLAM- and SAP-deficient mice.","date":"2006","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/16365421","citation_count":73,"is_preprint":false},{"pmid":"29729453","id":"PMC_29729453","title":"The SLAM family receptors: Potential therapeutic targets for inflammatory and autoimmune diseases.","date":"2018","source":"Autoimmunity reviews","url":"https://pubmed.ncbi.nlm.nih.gov/29729453","citation_count":71,"is_preprint":false},{"pmid":"18421379","id":"PMC_18421379","title":"DC-SIGN and CD150 have distinct roles in transmission of measles virus from dendritic cells to T-lymphocytes.","date":"2008","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/18421379","citation_count":71,"is_preprint":false},{"pmid":"23554862","id":"PMC_23554862","title":"Experimental adaptation of wild-type canine distemper virus (CDV) to the human entry receptor CD150.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23554862","citation_count":70,"is_preprint":false},{"pmid":"20071568","id":"PMC_20071568","title":"Measles virus selectively blind to signaling lymphocytic activation molecule (SLAM; CD150) is attenuated and induces strong adaptive immune responses in rhesus monkeys.","date":"2010","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/20071568","citation_count":67,"is_preprint":false},{"pmid":"11714966","id":"PMC_11714966","title":"Induction of the measles virus receptor SLAM (CD150) on monocytes.","date":"2001","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/11714966","citation_count":64,"is_preprint":false},{"pmid":"17237411","id":"PMC_17237411","title":"Slamf1, the NKT cell control gene Nkt1.","date":"2007","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/17237411","citation_count":64,"is_preprint":false},{"pmid":"18031696","id":"PMC_18031696","title":"The SLAM-associated protein signaling pathway is required for development of CD4+ T cells selected by homotypic thymocyte interaction.","date":"2007","source":"Immunity","url":"https://pubmed.ncbi.nlm.nih.gov/18031696","citation_count":64,"is_preprint":false},{"pmid":"15248250","id":"PMC_15248250","title":"Measles virus receptors: SLAM and CD46.","date":"2004","source":"Reviews in medical virology","url":"https://pubmed.ncbi.nlm.nih.gov/15248250","citation_count":63,"is_preprint":false},{"pmid":"21450813","id":"PMC_21450813","title":"Measles virus glycoprotein-pseudotyped lentiviral vector-mediated gene transfer into quiescent lymphocytes requires binding to both SLAM and CD46 entry receptors.","date":"2011","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/21450813","citation_count":62,"is_preprint":false},{"pmid":"22184727","id":"PMC_22184727","title":"Increased expression of SLAM receptors SLAMF3 and SLAMF6 in systemic lupus erythematosus T lymphocytes promotes Th17 differentiation.","date":"2011","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/22184727","citation_count":59,"is_preprint":false},{"pmid":"19593793","id":"PMC_19593793","title":"Evaluation of the long-term reconstituting subset of hematopoietic stem cells with CD150.","date":"2009","source":"Stem cells (Dayton, Ohio)","url":"https://pubmed.ncbi.nlm.nih.gov/19593793","citation_count":58,"is_preprint":false},{"pmid":"18292085","id":"PMC_18292085","title":"Dynamic interaction of the measles virus hemagglutinin with its receptor signaling lymphocytic activation molecule (SLAM, CD150).","date":"2008","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18292085","citation_count":57,"is_preprint":false},{"pmid":"20345977","id":"PMC_20345977","title":"Altered expression of signalling lymphocyte activation molecule (SLAM) family receptors CS1 (CD319) and 2B4 (CD244) in patients with systemic lupus erythematosus.","date":"2010","source":"Clinical and experimental immunology","url":"https://pubmed.ncbi.nlm.nih.gov/20345977","citation_count":57,"is_preprint":false},{"pmid":"30833791","id":"PMC_30833791","title":"SLAM receptors foster iNKT cell development by reducing TCR signal strength after positive selection.","date":"2019","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30833791","citation_count":56,"is_preprint":false},{"pmid":"12692284","id":"PMC_12692284","title":"CD46- and CD150-independent endothelial cell infection with wild-type measles viruses.","date":"2003","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/12692284","citation_count":55,"is_preprint":false},{"pmid":"12008921","id":"PMC_12008921","title":"The morbillivirus receptor SLAM (CD150).","date":"2002","source":"Microbiology and immunology","url":"https://pubmed.ncbi.nlm.nih.gov/12008921","citation_count":54,"is_preprint":false},{"pmid":"17135325","id":"PMC_17135325","title":"Measles virus infection of SLAM (CD150) knockin mice reproduces tropism and immunosuppression in human infection.","date":"2006","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/17135325","citation_count":52,"is_preprint":false},{"pmid":"16260741","id":"PMC_16260741","title":"Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice.","date":"2005","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/16260741","citation_count":51,"is_preprint":false},{"pmid":"15914854","id":"PMC_15914854","title":"Wild-type Rinderpest virus uses SLAM (CD150) as its receptor.","date":"2005","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/15914854","citation_count":50,"is_preprint":false},{"pmid":"16365433","id":"PMC_16365433","title":"A signal adaptor SLAM-associated protein regulates spontaneous autoimmunity and Fas-dependent lymphoproliferation in MRL-Faslpr lupus mice.","date":"2006","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/16365433","citation_count":48,"is_preprint":false},{"pmid":"26619119","id":"PMC_26619119","title":"SLAMF1 regulation of chemotaxis and autophagy determines CLL patient response.","date":"2015","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/26619119","citation_count":47,"is_preprint":false},{"pmid":"28693884","id":"PMC_28693884","title":"The flavonoid rutin modulates microglial/macrophage activation to a CD150/CD206 M2 phenotype.","date":"2017","source":"Chemico-biological interactions","url":"https://pubmed.ncbi.nlm.nih.gov/28693884","citation_count":43,"is_preprint":false},{"pmid":"27521267","id":"PMC_27521267","title":"The Self-Specific Activation Receptor SLAM Family Is Critical for NK Cell Education.","date":"2016","source":"Immunity","url":"https://pubmed.ncbi.nlm.nih.gov/27521267","citation_count":43,"is_preprint":false},{"pmid":"25799045","id":"PMC_25799045","title":"Migration of myeloid cells during inflammation is differentially regulated by the cell surface receptors Slamf1 and Slamf8.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25799045","citation_count":39,"is_preprint":false},{"pmid":"20631152","id":"PMC_20631152","title":"Identification of key residues in virulent canine distemper virus hemagglutinin that control CD150/SLAM-binding activity.","date":"2010","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/20631152","citation_count":39,"is_preprint":false},{"pmid":"11536173","id":"PMC_11536173","title":"Signaling lymphocytic activation molecule (SLAM) regulates T cellular cytotoxicity.","date":"2001","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/11536173","citation_count":39,"is_preprint":false},{"pmid":"16775330","id":"PMC_16775330","title":"High pathogenicity of wild-type measles virus infection in CD150 (SLAM) transgenic mice.","date":"2006","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/16775330","citation_count":37,"is_preprint":false},{"pmid":"25926831","id":"PMC_25926831","title":"Negative Regulation of Humoral Immunity Due to Interplay between the SLAMF1, SLAMF5, and SLAMF6 Receptors.","date":"2015","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/25926831","citation_count":37,"is_preprint":false},{"pmid":"28100610","id":"PMC_28100610","title":"The Measles Virus Receptor SLAMF1 Can Mediate Particle Endocytosis.","date":"2017","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/28100610","citation_count":35,"is_preprint":false},{"pmid":"21094032","id":"PMC_21094032","title":"The role of SLAM/CD2 polymorphisms in systemic autoimmunity.","date":"2010","source":"Current opinion in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/21094032","citation_count":35,"is_preprint":false},{"pmid":"18606638","id":"PMC_18606638","title":"Impaired SLAM-SLAM homotypic interaction between invariant NKT cells and dendritic cells affects differentiation of IL-4/IL-10-secreting NKT2 cells in nonobese diabetic mice.","date":"2008","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/18606638","citation_count":34,"is_preprint":false},{"pmid":"29945865","id":"PMC_29945865","title":"SLAM-ITseq: sequencing cell type-specific transcriptomes without cell sorting.","date":"2018","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/29945865","citation_count":33,"is_preprint":false},{"pmid":"23225888","id":"PMC_23225888","title":"Cutting edge: Ly9 (CD229), a SLAM family receptor, negatively regulates the development of thymic innate memory-like CD8+ T and invariant NKT cells.","date":"2012","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/23225888","citation_count":33,"is_preprint":false},{"pmid":"15315965","id":"PMC_15315965","title":"The adaptor protein SH2D1A regulates signaling through CD150 (SLAM) in B cells.","date":"2004","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/15315965","citation_count":31,"is_preprint":false},{"pmid":"17011767","id":"PMC_17011767","title":"The role of SAP and the SLAM family in autoimmunity.","date":"2006","source":"Current opinion in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/17011767","citation_count":30,"is_preprint":false},{"pmid":"16584920","id":"PMC_16584920","title":"SLAM family receptors and SAP-related adaptors: matters arising.","date":"2006","source":"Trends in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/16584920","citation_count":29,"is_preprint":false},{"pmid":"32954947","id":"PMC_32954947","title":"Neutrophil autophagy during human active tuberculosis is modulated by SLAMF1.","date":"2020","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/32954947","citation_count":28,"is_preprint":false},{"pmid":"21091715","id":"PMC_21091715","title":"The role of SAP and SLAM family molecules in the humoral immune response.","date":"2010","source":"Annals of the New York Academy of Sciences","url":"https://pubmed.ncbi.nlm.nih.gov/21091715","citation_count":28,"is_preprint":false},{"pmid":"16365151","id":"PMC_16365151","title":"Fine-tuning of immune responses by SLAM-related receptors.","date":"2005","source":"Journal of leukocyte biology","url":"https://pubmed.ncbi.nlm.nih.gov/16365151","citation_count":27,"is_preprint":false},{"pmid":"24642916","id":"PMC_24642916","title":"Fine specificity and molecular competition in SLAM family receptor signalling.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24642916","citation_count":26,"is_preprint":false},{"pmid":"22807679","id":"PMC_22807679","title":"The receptor Slamf1 on the surface of myeloid lineage cells controls susceptibility to infection by Trypanosoma cruzi.","date":"2012","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/22807679","citation_count":26,"is_preprint":false},{"pmid":"27484638","id":"PMC_27484638","title":"Canine distemper virus isolated from a monkey efficiently replicates on Vero cells expressing non-human primate SLAM receptors but not human SLAM receptor.","date":"2016","source":"BMC veterinary research","url":"https://pubmed.ncbi.nlm.nih.gov/27484638","citation_count":26,"is_preprint":false},{"pmid":"11855632","id":"PMC_11855632","title":"The measles virus hemagglutinin downregulates the cellular receptor SLAM (CD150).","date":"2002","source":"Archives of virology","url":"https://pubmed.ncbi.nlm.nih.gov/11855632","citation_count":25,"is_preprint":false},{"pmid":"12242590","id":"PMC_12242590","title":"Mouse novel Ly9: a new member of the expanding CD150 (SLAM) family of leukocyte cell-surface receptors.","date":"2002","source":"Immunogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/12242590","citation_count":25,"is_preprint":false},{"pmid":"24941157","id":"PMC_24941157","title":"Role of SLAM family receptors and specific adapter SAP in innate-like lymphocytes.","date":"2014","source":"Critical reviews in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/24941157","citation_count":24,"is_preprint":false},{"pmid":"26608324","id":"PMC_26608324","title":"Canine Distemper Virus Fusion Activation: Critical Role of Residue E123 of CD150/SLAM.","date":"2015","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/26608324","citation_count":24,"is_preprint":false},{"pmid":"30359773","id":"PMC_30359773","title":"SLAM family receptors in natural killer cells - Mediators of adhesion, activation and inhibition via cis and trans interactions.","date":"2018","source":"Clinical immunology (Orlando, Fla.)","url":"https://pubmed.ncbi.nlm.nih.gov/30359773","citation_count":24,"is_preprint":false},{"pmid":"30616923","id":"PMC_30616923","title":"SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?","date":"2018","source":"Clinical immunology (Orlando, Fla.)","url":"https://pubmed.ncbi.nlm.nih.gov/30616923","citation_count":22,"is_preprint":false},{"pmid":"18039911","id":"PMC_18039911","title":"Immunohistochemical demonstration of the putative canine distemper virus receptor CD150 in dogs with and without distemper.","date":"2007","source":"Veterinary pathology","url":"https://pubmed.ncbi.nlm.nih.gov/18039911","citation_count":22,"is_preprint":false},{"pmid":"15123741","id":"PMC_15123741","title":"SLAM Family Receptors Regulate Immunity with and without SAP-related Adaptors.","date":"2004","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/15123741","citation_count":22,"is_preprint":false},{"pmid":"31953913","id":"PMC_31953913","title":"Omp25-dependent engagement of SLAMF1 by Brucella abortus in dendritic cells limits acute inflammation and favours bacterial persistence in vivo.","date":"2020","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31953913","citation_count":22,"is_preprint":false},{"pmid":"30911116","id":"PMC_30911116","title":"NK cell recognition of hematopoietic cells by SLAM-SAP families.","date":"2019","source":"Cellular & molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30911116","citation_count":21,"is_preprint":false},{"pmid":"21791413","id":"PMC_21791413","title":"Identification of Flt3⁺CD150⁻ myeloid progenitors in adult mouse bone marrow that harbor T lymphoid developmental potential.","date":"2011","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/21791413","citation_count":21,"is_preprint":false},{"pmid":"38366599","id":"PMC_38366599","title":"SLAM-ITseq identifies that Nrf2 induces liver regeneration through the pentose phosphate pathway.","date":"2024","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/38366599","citation_count":20,"is_preprint":false},{"pmid":"12766168","id":"PMC_12766168","title":"SLAM-associated protein deficiency causes imbalanced early signal transduction and blocks downstream activation in T cells from X-linked lymphoproliferative disease patients.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12766168","citation_count":20,"is_preprint":false},{"pmid":"31243395","id":"PMC_31243395","title":"Sequencing cell-type-specific transcriptomes with SLAM-ITseq.","date":"2019","source":"Nature protocols","url":"https://pubmed.ncbi.nlm.nih.gov/31243395","citation_count":19,"is_preprint":false},{"pmid":"26060253","id":"PMC_26060253","title":"IPO3-mediated Nonclassical Nuclear Import of NF-κB Essential Modulator (NEMO) Drives DNA Damage-dependent NF-κB Activation.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26060253","citation_count":19,"is_preprint":false},{"pmid":"22194822","id":"PMC_22194822","title":"A two-gene signature, SKI and SLAMF1, predicts time-to-treatment in previously untreated patients with chronic lymphocytic leukemia.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22194822","citation_count":19,"is_preprint":false},{"pmid":"17919264","id":"PMC_17919264","title":"Characterization of mouse CD229 (Ly9), a leukocyte cell surface molecule of the CD150 (SLAM) family.","date":"2007","source":"Tissue antigens","url":"https://pubmed.ncbi.nlm.nih.gov/17919264","citation_count":19,"is_preprint":false},{"pmid":"17215871","id":"PMC_17215871","title":"The role of SLAM family receptors in immune cell signaling.","date":"2006","source":"Biochemistry and cell biology = Biochimie et biologie cellulaire","url":"https://pubmed.ncbi.nlm.nih.gov/17215871","citation_count":19,"is_preprint":false},{"pmid":"32054954","id":"PMC_32054954","title":"SLAM family member 8 is expressed in and enhances the growth of anaplastic large cell lymphoma.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32054954","citation_count":19,"is_preprint":false},{"pmid":"32983115","id":"PMC_32983115","title":"Increased Plasma Levels of the Co-stimulatory Proteins CDCP1 and SLAMF1 in Patients With Autoimmune Endocrine Diseases.","date":"2020","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/32983115","citation_count":19,"is_preprint":false},{"pmid":"38778223","id":"PMC_38778223","title":"SLAM-Drop-seq reveals mRNA kinetic rates throughout the cell cycle.","date":"2023","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/38778223","citation_count":18,"is_preprint":false},{"pmid":"17692919","id":"PMC_17692919","title":"Enhancement of anti-tumor activity in vitro and in vivo by CD150 and SAP.","date":"2007","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/17692919","citation_count":18,"is_preprint":false},{"pmid":"31430904","id":"PMC_31430904","title":"Specificity of Morbillivirus Hemagglutinins to Recognize SLAM of Different Species.","date":"2019","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/31430904","citation_count":18,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":42651,"output_tokens":5999,"usd":0.108969},"stage2":{"model":"claude-opus-4-6","input_tokens":9600,"output_tokens":4045,"usd":0.223688},"total_usd":0.332657,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"SLAMF1 (CD150/SLAM) functions as a cellular receptor for measles virus; transfection of human SLAMF1 cDNA into non-susceptible cell lines enabled measles virus binding, replication, and cytopathic effects, establishing SLAMF1 as the entry receptor for wild-type measles virus strains.\",\n      \"method\": \"Transfection of SLAMF1 cDNA into resistant cell lines followed by virus binding and infection assays\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted receptor function in heterologous cells, replicated by multiple labs\",\n      \"pmids\": [\"10972291\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"SAP (SLAM-associated protein) binds to the SLAMF1 cytoplasmic region via its SH2 domain, acting as an inhibitor that blocks recruitment of SHP-2 to SLAMF1, thereby regulating SLAM-mediated signaling; SAP gene mutations were found in XLP patients, linking defective SLAMF1 signaling regulation to the disease.\",\n      \"method\": \"Co-immunoprecipitation, SH2 domain binding assays, patient mutational analysis\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct binding demonstrated, replicated and foundational paper with >700 citations\",\n      \"pmids\": [\"9774102\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"SLAMF1 receptor engagement triggers protein tyrosine phosphorylation signaling in T cells strictly dependent on SAP expression; this signal involves SHIP, Dok2, Dok1, Shc, and RasGAP, with SAP facilitating selective recruitment and activation of Src-related kinase FynT to SLAMF1; signaling via this pathway alters cytokine production profile during T cell activation.\",\n      \"method\": \"T cell signaling assays with SAP-deficient and reconstituted cell lines, phosphorylation assays, cytokine production measurement\",\n      \"journal\": \"Nature immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal biochemical methods, specific pathway components identified\",\n      \"pmids\": [\"11477403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"SAP couples FynT to SLAMF1 by binding the SH3 domain of FynT through the SAP SH2 domain via a non-canonical surface-surface interaction; a crystal structure of a ternary SLAM-SAP-Fyn-SH3 complex revealed this interaction mode and showed that SAP binding precludes the auto-inhibited conformation of Fyn, promoting kinase activation after recruitment.\",\n      \"method\": \"Crystal structure determination of ternary complex, in vitro binding assays\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure with functional validation of interaction mechanism\",\n      \"pmids\": [\"12545174\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"SLAMF1 (CD150) is used as a cellular receptor by canine distemper virus and rinderpest virus (acting on their respective host species SLAM orthologs), demonstrating that SLAM usage as a receptor is a common property of morbilliviruses; virus entry via SLAM was confirmed by pseudotype assays.\",\n      \"method\": \"Expression of species-specific SLAM in CHO cells, infection assays, VSV pseudotype entry assays\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted receptor function across multiple morbilliviruses\",\n      \"pmids\": [\"11390585\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Homotypic interactions mediated by Slamf1 (SLAM) and Slamf6 (Ly108) between thymocytes provide 'second signals' during TCR engagement that recruit SAP and Fyn kinase, which are essential for NKT cell lineage expansion and differentiation; this cosignaling pathway is only available when selecting ligands are presented by thymocytes (not epithelial cells) because stromal cells do not express Slamf1/Slamf6.\",\n      \"method\": \"Genetic knockout mice, bone marrow chimeras, flow cytometric analysis of NKT development, epistasis experiments\",\n      \"journal\": \"Immunity\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with multiple knockout combinations and defined phenotypic readout\",\n      \"pmids\": [\"18031695\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"SLAMF1 (CD150) receptor ligation on germinal center T follicular helper (GC TFH) cells is specifically required for IL-4 production by these cells, as demonstrated by SLAM-deficient mice that lacked IL-4 production in GC TFH cells despite only a moderate defect in TFH differentiation.\",\n      \"method\": \"SLAM knockout mouse analysis, flow cytometry, intracellular cytokine staining\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with specific functional readout and mechanistic distinction from TFH differentiation\",\n      \"pmids\": [\"20525889\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The measles virus hemagglutinin (H protein) is responsible for downregulating SLAMF1 from the cell surface after infection; transfection of hemagglutinin expression plasmid alone induced SLAM downregulation in cells expressing or coming in contact with hemagglutinin-expressing cells, while the fusion protein had no such effect.\",\n      \"method\": \"Transfection of individual MV envelope proteins, flow cytometric measurement of surface SLAM expression\",\n      \"journal\": \"Archives of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean dissection of hemagglutinin vs. fusion protein role, single lab\",\n      \"pmids\": [\"11855632\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Measles virus hemagglutinin isoleucine 194 is essential for primary binding to SLAMF1 (measured by surface plasmon resonance); after binding, a quartet of residues on propeller blade 5 mediates receptor-specific conformational changes required for membrane fusion, establishing distinct binding and fusion-triggering sites on the hemagglutinin-SLAMF1 interface.\",\n      \"method\": \"Site-directed mutagenesis, surface plasmon resonance, receptor-specific fusion assays, crystal structure localization of residues\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — mutagenesis combined with biophysical binding measurement and functional fusion assay\",\n      \"pmids\": [\"18292085\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"CD150 (SLAMF1) ligation in DT40 B cells induces ERK signaling requiring SHIP but not SH2D1A, while CD150-mediated Akt phosphorylation requires Syk and SH2D1A and is negatively regulated by Lyn and Btk; Lyn directly phosphorylates Y327 in the SLAMF1 cytoplasmic tail, demonstrating SH2D1A-dependent switching of SLAMF1 downstream signaling pathways.\",\n      \"method\": \"DT40 B cell knockout sublines, phosphorylation assays, kinase-specific inhibitors, direct kinase phosphorylation assay\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple genetic knockouts and biochemical assays in defined cell system\",\n      \"pmids\": [\"15315965\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"SLAMF1 ligation in CLL cells with an agonistic monoclonal antibody induces ROS accumulation, phosphorylation of p38, JNK1/2, and BCL2, and promotes autophagic flux; mechanistically, Beclin1 dissociates from BCL2 upon SLAMF1 ligation, leading to formation of an autophagy macrocomplex containing SLAMF1, Beclin1, and VPS34; SLAMF1-silenced cells showed increased CXCR4, CD38, and CD44 expression and enhanced chemotactic responses to CXCL12.\",\n      \"method\": \"SLAMF1 silencing (RNAi), agonistic antibody ligation, co-immunoprecipitation, immunoblotting, autophagy flux assays, migration assays\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (Co-IP, KD, functional assays) in primary CLL and cell lines\",\n      \"pmids\": [\"26619119\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Slamf1 and Slamf8 differentially regulate NADPH-oxidase (Nox2)-dependent reactive oxygen species (ROS) production by myeloid cells in response to bacteria; Slamf1 is required for optimal ROS production and promotes myeloid cell migration in vivo, while Slamf8 negatively regulates ROS production and its absence accelerates myeloid cell migration; inhibiting ROS in Slamf8-deficient macrophages blocked enhanced in vitro migration.\",\n      \"method\": \"Knockout mice, in vivo migration assays (peritonitis, skin sensitization, intestinal repopulation), in vitro transwell migration assays, ROS production measurement with DPI inhibition\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO phenotypes with in vivo and in vitro mechanistic dissection and pharmacological rescue\",\n      \"pmids\": [\"25799045\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"SLAMF1 (and related family members Ly108 and 2B4) regulate immunological synapse organization between cytotoxic lymphocytes and B cell targets; in the absence of SAP, signaling through Ly108 and 2B4 results in increased SHP-1 phosphatase recruitment, altered SHP-1 localization, and decreased activation of Src kinases at the synapse, leading to impaired actin clearance and defective killing of B cell targets.\",\n      \"method\": \"SAP-deficient mouse CD8+ T cells, cytotoxicity assays against different targets, confocal imaging of immunological synapses, phosphatase recruitment assays\",\n      \"journal\": \"Immunity\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — mechanistic dissection with imaging, biochemistry, and functional readouts\",\n      \"pmids\": [\"22683123\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"SLAMF1 engagement by measles virus induces MeV endocytosis via a macropinocytosis-like pathway; MeV engagement of SLAMF1 triggers membrane blebbing, actin cytoskeleton rearrangement, and the RhoA-ROCK-myosin II signaling axis to mediate viral particle internalization; chemical inhibition of macropinocytosis or actin dynamics blocked MeV entry.\",\n      \"method\": \"Live-cell imaging, chemical inhibitors (RhoA-ROCK-myosin II pathway, macropinocytosis inhibitors), colocalization studies, infection assays in SLAMF1+ vs SLAMF1- cells\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple pharmacological dissections with imaging and functional infection assays\",\n      \"pmids\": [\"28100610\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Slamf1 is required on myeloid cells for efficient intracellular replication of Trypanosoma cruzi; Slamf1-deficient mice were completely protected from lethal parasite challenge, with Slamf1-deficient myeloid cells impaired in parasite replication and showing altered cytokine production; anti-Slamf1 monoclonal antibody treatment also reduced cardiac parasites.\",\n      \"method\": \"Slamf1 knockout mice, in vivo and in vitro infection assays, anti-Slamf1 antibody blockade, cytokine production assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular phenotype, confirmed with antibody blockade\",\n      \"pmids\": [\"22807679\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Brucella abortus outer membrane protein Omp25 specifically binds SLAMF1 on dendritic cells; this Omp25-SLAMF1 engagement limits NF-κB translocation, decreases pro-inflammatory cytokine secretion, and impairs DC activation without affecting Brucella intracellular trafficking; at chronic infection stage, the Omp25-SLAMF1 axis is essential for bacterial persistence in vivo.\",\n      \"method\": \"In vitro binding assays (Omp25-SLAMF1 interaction), NF-κB translocation assays, cytokine measurement, mouse infection models (acute and chronic stages)\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct protein-protein interaction established with in vivo functional validation\",\n      \"pmids\": [\"31953913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SLAMF1 is expressed on human neutrophils upon Mycobacterium tuberculosis stimulation; SLAMF1 colocalizes with LC3B+ vesicles, and SLAMF1 activation increases neutrophil autophagy induced by Mtb; tuberculosis patients' neutrophils display reduced SLAMF1 levels and lower autophagy against Mtb.\",\n      \"method\": \"Flow cytometry, confocal microscopy (SLAMF1-LC3B colocalization), SLAMF1 agonistic antibody stimulation, autophagy assays\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — colocalization and antibody activation with functional readout, single lab, limited mechanistic depth\",\n      \"pmids\": [\"32954947\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"SLAMF1 (CD150) is downregulated from the cell surface after measles virus infection or contact with MV envelope proteins; anti-SLAM antibodies block virus binding but do not interfere with contact-mediated proliferation inhibition, demonstrating that MV-induced proliferation inhibition is independent of SLAMF1 and CD46 receptor engagement.\",\n      \"method\": \"Anti-SLAM antibody blocking assays, flow cytometric measurement of surface SLAM after infection/contact, cell proliferation assays\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional dissection with antibody blocking and receptor downregulation measurement\",\n      \"pmids\": [\"11312320\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"SLAMF1 (CD150) expression is induced on monocytes by phytohaemagglutinin, bacterial lipopolysaccharide, or measles virus itself (which do not constitutively express SLAM); once induced, SLAM serves as the functional MV receptor on activated monocytes, as confirmed by anti-SLAM antibody blocking of infection.\",\n      \"method\": \"Flow cytometry of monocyte SLAM expression under various stimuli, anti-SLAM antibody blocking of MV infection\",\n      \"journal\": \"The Journal of general virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct receptor induction and functional blocking demonstrated\",\n      \"pmids\": [\"11714966\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"SLAMF1 acts as a self-ligand (homophilic interaction) that promotes B cell proliferation and Ig synthesis; soluble SLAMF1 and L cells transfected with membrane SLAMF1 both enhanced proliferation and IgM, IgG, IgA production by activated human B cells, establishing SLAMF1-SLAMF1 homotypic interaction as a costimulatory signal for B cells.\",\n      \"method\": \"Recombinant soluble SLAMF1, SLAMF1-transfected L cells, B cell proliferation assays, Ig production measurement by ELISA\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reconstituted homophilic interaction with functional B cell readout\",\n      \"pmids\": [\"9091591\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"SLAMF1, SLAMF5, and SLAMF6 act as negative regulators of humoral immune responses; combined knockout of all three genes resulted in enhanced T-dependent and T-independent antibody responses, with B-cell-intrinsic effects being more pronounced than T-cell effects as established by adoptive co-transfer experiments.\",\n      \"method\": \"Single and triple knockout mice, adoptive co-transfer of B and T cells, T-dependent and T-independent antibody response assays\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with adoptive transfer dissection, but mechanism downstream not fully defined\",\n      \"pmids\": [\"25926831\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"SLAMF1 engagement promotes T cell-mediated cytotoxicity; in CD4+ and CD8+ T cells SLAM enhanced TCR-mediated killing, and in Herpesvirus saimiri-transformed T cells SLAM engagement alone triggered cytotoxicity requiring release of lytic granules, extracellular Ca2+, cytoskeletal rearrangements, and MEK1/2 signaling in a CD95-independent manner.\",\n      \"method\": \"Cytotoxicity assays, pharmacological inhibition (MEK1/2, Ca2+, cytoskeletal), granule release assays\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — pharmacological dissection of signaling requirements for SLAMF1-mediated cytotoxicity\",\n      \"pmids\": [\"11536173\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SLAM family receptors (SFRs), with SLAMF6 alone being sufficient, promote iNKT cell development by reducing TCR signal strength after positive selection, improving iNKT cell survival; this involves the SAP-Fyn complex and the phosphatase SHP-1; loss of SFRs upregulated PD-1 expression on iNKT cells as a compensatory mechanism.\",\n      \"method\": \"SFR-deficient mice (seven simultaneous SFR knockouts), SLAMF6 single rescue in SFR-deficient background, epistasis with SAP-Fyn and SHP-1, TCR signaling measurement\",\n      \"journal\": \"Nature immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — comprehensive genetic rescue experiments with pathway component dissection\",\n      \"pmids\": [\"30833791\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Impaired SLAMF1 (SLAM) homotypic interaction between iNKT cells and mature dendritic cells from NOD mice results in defective GATA-3 upregulation and reduced IL-4/IL-10 (NKT2) cytokine production; NOD mDC express significantly lower levels of SLAMF1 due to the Slamf1 genetic defect, impairing peripheral NKT2 polarization.\",\n      \"method\": \"Cross-strain iNKT-DC co-culture assays, GATA-3 expression analysis, cytokine production measurement, flow cytometric SLAM expression on NOD vs C57BL/6 DCs\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — cross-strain comparison with functional readout but mechanism not fully biochemically dissected\",\n      \"pmids\": [\"18606638\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"CD150 (SLAMF1) co-localizes with lipid rafts in specific membrane compartments on CD8+ T cells after activation; overexpression of CD150 enhanced cytotoxic activity and IFN-γ secretion in vitro and anti-tumor activity in vivo, while siRNA silencing of CD150 reduced effector functions.\",\n      \"method\": \"Lipid raft fractionation/co-localization, CD150 overexpression and siRNA knockdown, cytotoxicity assays, IFN-γ ELISpot, xenograft tumor model\",\n      \"journal\": \"Molecular immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — functional gain/loss-of-function with lipid raft localization, but mechanistic link not deeply characterized\",\n      \"pmids\": [\"17692919\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SLAMF1 (CD150) is a homophilic cell-surface receptor on immune cells that acts as the primary entry receptor for morbilliviruses (including measles virus) via direct binding of viral hemagglutinin at specific interface residues, and that signals through immunoreceptor tyrosine-based switch motifs (ITSMs) in its cytoplasmic tail; SAP binds these ITSMs and couples SLAMF1 to FynT (via a non-canonical SH2-SH3 interaction), driving downstream phosphorylation cascades involving SHIP, Dok proteins, and RasGAP to regulate T and B cell activation, cytokine production (including IL-4 and IFN-γ), NKT cell development, cytotoxicity, and autophagy, while also functioning as a microbial sensor on myeloid cells to control ROS production, migration, and intracellular pathogen replication.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SLAMF1 (CD150) is a homophilic immunoglobulin-superfamily receptor that orchestrates adaptive and innate immune responses by coupling antigen receptor signaling to cytokine polarization, cytotoxicity, autophagy, and pathogen handling on T cells, B cells, NKT cells, and myeloid cells. Homotypic SLAMF1–SLAMF1 engagement recruits the adaptor SAP, whose SH2 domain binds cytoplasmic immunoreceptor tyrosine-based switch motifs (ITSMs) and simultaneously docks FynT via a non-canonical SH2–SH3 interaction, activating a downstream phosphorylation cascade involving SHIP, Dok1/2, Shc, and RasGAP that drives IL-4 and IFN-γ production, granule-dependent cytotoxicity, and NKT cell lineage development [PMID:9774102, PMID:11477403, PMID:12545174, PMID:18031695, PMID:20525889]. In myeloid cells, SLAMF1 promotes Nox2-dependent ROS production and autophagy through a Beclin-1–VPS34 macrocomplex, regulates intracellular replication of pathogens such as Trypanosoma cruzi and Brucella abortus, and is exploited by morbilliviruses—including measles, canine distemper, and rinderpest viruses—as the primary entry receptor via direct hemagglutinin binding that triggers macropinocytosis-like internalization [PMID:10972291, PMID:11390585, PMID:26619119, PMID:25799045, PMID:22807679, PMID:31953913, PMID:28100610]. Loss-of-function mutations in SAP (SH2D1A), which uncouples SLAMF1 signaling and shifts the pathway toward inhibitory SHP-1/SHP-2 recruitment, cause X-linked lymphoproliferative disease [PMID:9774102, PMID:22683123].\",\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"Establishing that SLAMF1 undergoes homophilic (self-ligand) interaction and that this engagement costimulates B cell proliferation and immunoglobulin production resolved the question of the receptor's natural ligand and placed SLAMF1 as a lymphocyte costimulatory molecule.\",\n      \"evidence\": \"Recombinant soluble SLAMF1 and SLAMF1-transfected L cells in B cell proliferation/Ig secretion assays\",\n      \"pmids\": [\"9091591\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of homophilic interaction not defined\", \"Signaling events downstream of B cell engagement not characterized\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Identification of SAP as an SH2-domain adaptor that binds the SLAMF1 cytoplasmic tail and blocks SHP-2 recruitment—and its mutational loss in XLP patients—established the first signaling mechanism downstream of SLAMF1 and linked it to human immunodeficiency.\",\n      \"evidence\": \"Co-immunoprecipitation, SH2 domain binding assays, and patient mutational analysis\",\n      \"pmids\": [\"9774102\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase effectors downstream of SAP–SLAMF1 unknown\", \"Whether SAP loss rewires rather than merely ablates signaling was unresolved\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Demonstrating that SLAMF1 cDNA transfection confers measles virus susceptibility to resistant cells resolved the identity of the primary wild-type measles virus entry receptor, a long-standing question in morbillivirus biology.\",\n      \"evidence\": \"Heterologous expression of SLAMF1 in non-susceptible cell lines followed by MV binding and infection assays\",\n      \"pmids\": [\"10972291\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular interface between hemagglutinin and SLAMF1 undefined\", \"Whether other morbilliviruses share SLAM usage unknown at this point\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Multiple studies established that SLAMF1 signaling proceeds through a SAP-dependent phosphorylation cascade (FynT, SHIP, Dok1/2, RasGAP) that controls cytokine production and T cell cytotoxicity, and that SLAMF1 serves as a shared morbillivirus receptor across species.\",\n      \"evidence\": \"SAP-deficient/reconstituted T cell signaling assays, pharmacological inhibition of MEK1/2 and calcium, pseudotype entry assays with species-specific SLAM orthologs\",\n      \"pmids\": [\"11477403\", \"11536173\", \"11390585\", \"11312320\", \"11714966\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How SAP couples to FynT mechanistically remained unclear\", \"Contribution of individual downstream effectors (e.g., Dok vs SHIP) not dissected in vivo\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"The crystal structure of the ternary SLAM–SAP–Fyn-SH3 complex revealed a non-canonical SH2–SH3 surface interaction through which SAP recruits and activates FynT, explaining how an adaptor lacking enzymatic activity transduces SLAMF1 signals.\",\n      \"evidence\": \"X-ray crystallography of ternary complex with in vitro binding validation\",\n      \"pmids\": [\"12545174\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Ternary complex formation not demonstrated in intact cells with endogenous proteins at that time\", \"Whether the same mechanism applies at all SLAM-family receptors not tested\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Dissection of SLAMF1 signaling in B cells showed SH2D1A-dependent switching between ERK (via SHIP) and Akt (via Syk) pathways, with Lyn phosphorylating SLAMF1 Y327, demonstrating that SLAMF1 operates as a signaling platform whose output depends on adapter availability.\",\n      \"evidence\": \"DT40 B cell knockout sublines for individual kinases/adaptors with phosphorylation and pathway-specific readouts\",\n      \"pmids\": [\"15315965\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relevance of Y327 phosphorylation in primary B cells not validated\", \"Integration of ERK vs Akt branches in physiological B cell responses unclear\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Genetic epistasis in knockout mice demonstrated that SLAMF1 (with SLAMF6) provides essential thymocyte-derived costimulatory signals for NKT cell lineage development via SAP-Fyn recruitment, and that SLAMF1 lipid-raft localization in CD8+ T cells enhances cytotoxicity and IFN-γ production.\",\n      \"evidence\": \"Multiple knockout/chimeric mice for NKT analysis; lipid raft fractionation, overexpression/siRNA, and xenograft models for CD8+ T cells\",\n      \"pmids\": [\"18031695\", \"17692919\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative contributions of SLAMF1 vs SLAMF6 to NKT development not fully separated\", \"Mechanism linking lipid raft localization to enhanced signaling not biochemically defined\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Identification of hemagglutinin residue I194 as the primary SLAMF1-binding determinant and a distinct fusion-triggering site on blade 5 established a two-step model of MV entry (binding then conformational change), while NOD mouse studies showed that reduced SLAMF1 on dendritic cells impairs NKT2 polarization via defective GATA-3 induction.\",\n      \"evidence\": \"Site-directed mutagenesis with SPR and fusion assays for MV entry; cross-strain DC–NKT co-culture for NOD phenotype\",\n      \"pmids\": [\"18292085\", \"18606638\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full atomic structure of SLAMF1–hemagglutinin complex not yet solved\", \"Whether NOD SLAMF1 defect is solely expression-level or includes functional polymorphism unclear\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"SLAMF1 was shown to regulate immunological synapse organization in cytotoxic lymphocytes: in the absence of SAP, SLAM-family signaling recruits SHP-1 instead of Fyn, impairing actin clearance and B cell killing; separately, SLAMF1 on myeloid cells was found essential for intracellular Trypanosoma cruzi replication, with knockout mice fully protected from lethal challenge.\",\n      \"evidence\": \"SAP-deficient mouse CD8+ T cell synapse imaging and cytotoxicity assays; Slamf1 KO mice and anti-SLAMF1 antibody blockade in T. cruzi infection\",\n      \"pmids\": [\"22683123\", \"22807679\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How SLAMF1 promotes parasite replication at the molecular level unknown\", \"Relative contribution of SHP-1 vs loss of Fyn to cytotoxic defect not separated\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"SLAMF1 was placed as a positive regulator of autophagy (via a Beclin-1–VPS34 macrocomplex and ROS/p38/JNK signaling) and Nox2-dependent ROS production in myeloid cells, while triple SLAM-family knockout studies revealed SLAMF1 as a negative regulator of humoral responses, adding B-cell-intrinsic suppressive function to its portfolio.\",\n      \"evidence\": \"RNAi/agonistic antibody in CLL cells with co-IP of SLAMF1–Beclin-1–VPS34; Slamf1 KO myeloid ROS and migration assays; triple KO adoptive transfer for antibody responses\",\n      \"pmids\": [\"26619119\", \"25799045\", \"25926831\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How Beclin-1 is recruited to SLAMF1 (direct vs indirect) not established\", \"Mechanism by which SLAMF1 restrains antibody responses at the molecular level unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Demonstrating that MV engagement of SLAMF1 triggers a macropinocytosis-like entry pathway via RhoA–ROCK–myosin II defined the cell-biological mechanism of SLAMF1-mediated viral internalization, beyond simple receptor binding.\",\n      \"evidence\": \"Live-cell imaging and pharmacological inhibition of actin dynamics and RhoA–ROCK–myosin II pathway in SLAMF1+ cells during MV infection\",\n      \"pmids\": [\"28100610\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether this entry pathway is shared by all morbilliviruses not tested\", \"SLAMF1 cytoplasmic domain signaling events that trigger macropinocytosis not defined\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Comprehensive SFR-knockout and single-gene rescue experiments showed that SLAMF6, more than SLAMF1, is the critical family member reducing TCR signal strength to permit iNKT survival after positive selection, refining the earlier model of redundant SLAMF1/SLAMF6 roles in NKT development.\",\n      \"evidence\": \"Seven-SFR-deficient mice with SLAMF6 single rescue, epistasis with SAP-Fyn and SHP-1\",\n      \"pmids\": [\"30833791\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether SLAMF1 has any non-redundant role in iNKT development beyond SLAMF6 remains unclear\", \"Cell-type-specific redundancy among SFRs in humans not addressed\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"SLAMF1 was identified as a direct target of bacterial immune evasion (Brucella Omp25 binds SLAMF1 to suppress NF-κB and DC activation) and as a promoter of neutrophil autophagy during M. tuberculosis infection, extending its microbial-sensor role to chronic bacterial pathogens.\",\n      \"evidence\": \"In vitro Omp25–SLAMF1 binding assays and in vivo Brucella persistence models; SLAMF1–LC3B colocalization and agonistic antibody stimulation in Mtb-exposed neutrophils\",\n      \"pmids\": [\"31953913\", \"32954947\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Omp25–SLAMF1 binding interface not structurally defined\", \"Whether SLAMF1-driven autophagy in neutrophils restricts Mtb growth in vivo unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include: the atomic structure of the SLAMF1 homophilic interface, the mechanism by which SLAMF1 cytoplasmic signals trigger macropinocytosis and autophagy complex assembly, and how SLAMF1 restrains humoral immune responses at the molecular level.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No high-resolution structure of SLAMF1 homophilic complex\", \"Mechanism linking SLAMF1 cytoplasmic domain to Beclin-1–VPS34 recruitment unknown\", \"Molecular basis of B-cell-intrinsic antibody suppression undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 4, 8, 19]},\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [19, 5, 12]},\n      {\"term_id\": \"GO:0001618\", \"supporting_discovery_ids\": [0, 4, 13]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 7, 17, 18, 24]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [13, 16]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1, 2, 5, 6, 12, 20, 21, 22]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 3, 9, 10]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [10, 16]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [0, 4, 14, 15]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [\n      \"SLAMF1–SAP–FynT ternary signaling complex\",\n      \"SLAMF1–Beclin-1–VPS34 autophagy macrocomplex\"\n    ],\n    \"partners\": [\n      \"SH2D1A\",\n      \"FYN\",\n      \"SHIP1\",\n      \"DOK1\",\n      \"DOK2\",\n      \"BECN1\",\n      \"PIK3C3\",\n      \"LYN\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}