{"gene":"CD300A","run_date":"2026-06-09T22:57:17","timeline":{"discoveries":[{"year":1999,"finding":"IRp60 (CD300a) is an inhibitory receptor on human NK cells that, upon sodium pervanadate treatment, becomes tyrosine phosphorylated and associates with the SH2-containing phosphatases SHP-1 and SHP-2, thereby inhibiting NK cell cytotoxicity.","method":"Monoclonal antibody generation, cross-linking experiments, co-immunoprecipitation of SHP-1/SHP-2 after pervanadate treatment, cytotoxicity assays","journal":"European journal of immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP with SHP-1/SHP-2, functional cytotoxicity inhibition, replicated across multiple subsequent studies","pmids":["10540326"],"is_preprint":false},{"year":2005,"finding":"IRp60 (CD300a) cross-linking on human mast cells inhibits IgE-induced degranulation and SCF-mediated survival via tyrosine phosphorylation, phosphatase (SHP-1/SHP-2) recruitment, and termination of cellular calcium influx.","method":"Cross-linking with anti-IRp60 antibodies, flow cytometry for phosphorylation and calcium influx, degranulation assays (tryptase and IL-4 release), murine allergic peritonitis model with LMIR1 neutralization","journal":"Journal of immunology (Baltimore, Md. : 1950)","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (signaling, calcium, degranulation, in vivo model), replicated in subsequent studies","pmids":["16339535"],"is_preprint":false},{"year":2005,"finding":"IRp60 (CD300a) cross-linking on human eosinophils inhibits eotaxin-dependent transmigration, blocks anti-apoptotic cytokine effects, inhibits IL-5-mediated JAK2 phosphorylation, and inhibits ERK1/2 and p38 phosphorylation; CD300a underwent tyrosine phosphorylation and recruited SHP-1 but not SHP-2 on eosinophils.","method":"Cross-linking with anti-IRp60 mAbs, transmigration assays, apoptosis assays, cytokine release assays, Western blotting for JAK2/ERK1/2/p38 phosphorylation, co-immunoprecipitation for SHP-1/SHP-2","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (signaling, functional assays, co-IP), clear mechanistic pathway delineation","pmids":["16254138"],"is_preprint":false},{"year":2006,"finding":"Solution structure of the IRp60 (CD300a) extracellular immunoglobulin-like domain was determined by small-angle X-ray scattering (SAXS); the protein is monomeric in solution with a molecular shape characteristic of immunoglobulin-like structures.","method":"Recombinant protein expression in E. coli, refolding, small-angle X-ray scattering (SAXS), homology modeling validated against SAXS data","journal":"International journal of biological macromolecules","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — structural determination by SAXS with homology modeling, single study, no mutagenesis validation","pmids":["16949664"],"is_preprint":false},{"year":2007,"finding":"CD300a expression on human neutrophils is rapidly increased by LPS and GM-CSF stimulation through translocation of an intracellular pool to the cell surface, and co-ligation of CD300a with FcγRIIa (CD32a) inhibits FcγRIIa-mediated signaling but does not inhibit TLR4-mediated ROS production.","method":"Flow cytometry, HL-60 differentiation model, co-ligation experiments, ROS production assays","journal":"Molecular immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional co-ligation assays with two distinct readouts, single lab","pmids":["17588661"],"is_preprint":false},{"year":2008,"finding":"CD300a/c cross-linking on plasmacytoid dendritic cells reduces TNF-α and increases IFN-α secretion following TLR7/TLR9 stimulation; IFN-α itself down-regulates CD300a/c expression, establishing a feedback loop.","method":"Flow cytometry for surface expression, cross-linking with anti-CD300a/c antibodies, cytokine ELISA, neutralizing antibody experiments","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional cytokine assays with neutralization controls, single lab, two orthogonal functional readouts","pmids":["18535206"],"is_preprint":false},{"year":2008,"finding":"CD300a co-aggregation with Kit via a bispecific antibody results in Kit-mediated tyrosine phosphorylation of CD300a and recruitment of SHIP-1 (but not SHP-1), inhibiting SCF-induced mast cell differentiation, survival, and activation, and suppressing constitutive Kit signaling in HMC-1 leukemic cells.","method":"Bispecific antibody fragments (Kit×CD300a), Western blotting for phosphorylation, co-immunoprecipitation for SHIP-1/SHP-1, mast cell differentiation/survival/activation assays, murine cutaneous anaphylaxis model","journal":"Journal of immunology (Baltimore, Md. : 1950)","confidence":"High","confidence_rationale":"Tier 2 / Strong — co-IP, functional assays, in vivo model, single lab with multiple orthogonal methods","pmids":["18424727"],"is_preprint":false},{"year":2011,"finding":"CD300a extracellular domain (as a CD300a-Fc chimeric fusion protein) specifically binds phosphatidylserine (PS) exposed on apoptotic cells, and PS binding induces SHP-1 recruitment by CD300a in mast cells in response to LPS.","method":"CD300a-Fc fusion protein binding assay, co-immunoprecipitation for SHP-1 after PS stimulation","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding with fusion protein and functional co-IP, single lab, two orthogonal methods","pmids":["22185693"],"is_preprint":false},{"year":2011,"finding":"Co-ligation of BCR and CD300a on B cells inhibits Ca2+ mobilization and NFAT transcriptional activity; siRNA-mediated knockdown of CD300a in primary B cells resulted in increased BCR-mediated proliferation, confirming CD300a's inhibitory role in B cell signaling.","method":"Co-ligation with anti-CD300a and anti-BCR antibodies, calcium flux measurements, NFAT reporter assays, siRNA knockdown, proliferation assays","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (calcium, transcription, siRNA-KD with phenotype), single lab","pmids":["21482706"],"is_preprint":false},{"year":2012,"finding":"CD300a binds phosphatidylethanolamine (PE) and phosphatidylserine (PS) exposed on dead cells, as identified by surface plasmon resonance, ultracentrifugation, ELISA, and reporter cell assays; mutational analysis identified residues forming a cavity where the hydrophilic heads of PE and PS penetrate; CD300a down-regulates macrophage phagocytosis of apoptotic cells.","method":"Surface plasmon resonance, ultracentrifugation, ELISA, reporter cell assays, site-directed mutagenesis, structural modeling, phagocytosis assays with CD300a-Ig fusion protein","journal":"Blood","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple orthogonal biochemical methods, mutagenesis, structural modeling, functional validation, replicated by multiple subsequent studies","pmids":["22302738"],"is_preprint":false},{"year":2012,"finding":"CD300a on mast cells acts as a non-phagocytic PS receptor; PS-CD300a interaction delivers an inhibitory signal suppressing LPS-induced inflammatory cytokine and chemokine production in mast cells; in a cecal ligation and puncture model, CD300a-deficient peritoneal mast cells produced more chemoattractant and recruited more neutrophils, improving bacterial clearance and survival.","method":"CD300a-deficient mice, cecal ligation and puncture model, cytokine/chemokine measurements, neutrophil recruitment assays, antibody blockade of CD300a-PS interactions","journal":"The Journal of experimental medicine","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO mouse with defined cellular phenotype and multiple readouts, antibody blockade confirmation, in vivo model","pmids":["22826299"],"is_preprint":false},{"year":2012,"finding":"CD300a mediates inhibitory signaling through ITIMs that require Lck-mediated tyrosine phosphorylation to create docking sites for SHP-1 and SHP-2; SHP-1, but not SHP-2 or SHIP, is the critical phosphatase for CD300a's inhibitory activity in T and B cells.","method":"Chimeric KIR-CD300a receptor in Jurkat T cells, ITIM mutagenesis, siRNA knockdown of SHP-1/SHP-2, DT40 phosphatase-deficient cell lines, superantigen-stimulated TCR signaling assays","journal":"BMC immunology","confidence":"High","confidence_rationale":"Tier 1 / Strong — ITIM mutagenesis, multiple genetic knockdown/KO systems, chimeric receptor approach, multiple orthogonal validations","pmids":["22537350"],"is_preprint":false},{"year":2012,"finding":"CD300a selectively blocks TLR4-mediated and TLR9-mediated (MyD88-dependent) but not TLR3-mediated (TRIF-dependent) pro-inflammatory signaling in monocytic cell lines, acting primarily through SHP-1; ITIM peptides from CD300a mimicked this selective inhibition.","method":"TLR stimulation of THP-1 and U937 cells, NF-κB luciferase reporter assays, MyD88/TRIF overexpression, synthetic ITIM peptides, signaling inhibitors, Western blotting","journal":"Immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reporter assays with mechanistic dissection, ITIM peptide mimicry, multiple TLR ligands tested, single lab with multiple orthogonal methods","pmids":["22043923"],"is_preprint":false},{"year":2013,"finding":"PS expressed on tumor cells interacts with CD300a on NK cells to inhibit NK cell-mediated tumor killing; blocking the PS-CD300a interaction increased NK cell killing of tumor cells.","method":"Generation of specific anti-CD300a mAbs, NK cell clone characterization, binding assays with tumor cells, NK cytotoxicity assays with PS/CD300a blocking antibodies","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional killing assays with blocking antibodies, single lab, direct binding characterization","pmids":["23640773"],"is_preprint":false},{"year":2013,"finding":"CD300a colocalized and cosedimented with actin filaments in human monocytes; CD300a activation by antibody caused F-actin cytoskeleton alterations and reduced monocyte transendothelial migration; siRNA-mediated downregulation of CD300a increased the rate of migration.","method":"siRNA knockdown, antibody-mediated receptor engagement, confocal colocalization, cosedimentation assays, transendothelial migration assays","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA KD with defined migration phenotype, cosedimentation, colocalization; single lab, two orthogonal functional approaches","pmids":["24058511"],"is_preprint":false},{"year":2013,"finding":"CD300C delivers a FcRγ-dependent activating signal in mast cells and monocytes; PE and apoptotic cells are ligands for both CD300A and CD300C, but CD300A binds PE more strongly than CD300C; differential recognition depends on residues CD300A(F56-L57) vs CD300C(L63-R64); co-expression of full-length CD300A dampens CD300C-PE-mediated signaling.","method":"Antibody generation with epitope mapping, chimeric reporter cell lines expressing CD300A or CD300C extracellular domains with CD3ζ, GFP reporter assays, phospholipid binding assays, cytokine production assays, site-specific amino acid analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — chimeric reporter system, epitope-resolved mutagenesis equivalent, multiple ligand binding validations, functional cytokine assays","pmids":["23372157"],"is_preprint":false},{"year":2014,"finding":"PPARβ/δ directly regulates CD300a transcription in macrophages; CD300a-deficient mice on high-fat diet develop chronic intestinal inflammation with prolonged IL-6 secretion from macrophages in response to LPS/TLR4-MyD88 signaling; bone marrow transplantation confirmed the phenotype originates from CD300a deficiency in leukocytes.","method":"CD300a-deficient mice, high-fat diet model, bone marrow transplantation, LPS stimulation assays, cytokine measurements, PPARβ/δ direct regulation assay","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO, bone marrow transplant rescue, direct transcriptional regulation, in vivo and in vitro mechanistic validation","pmids":["24958459"],"is_preprint":false},{"year":2015,"finding":"CD300a directly binds dengue virus (DENV) particles via recognition of PE (primarily) and PS on viral envelopes, enhances DENV internalization through clathrin-mediated endocytosis, and facilitates infection of all four DENV serotypes as well as West Nile virus and Chikungunya virus; mutation of IgV domain residues critical for phospholipid binding abrogated CD300a-mediated enhancement of infection.","method":"CD300a overexpression in cell lines, direct binding assays with DENV particles, clathrin inhibition, site-directed mutagenesis of phospholipid-binding residues, anti-CD300a antibody inhibition of primary macrophage infection","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct binding assays, mutagenesis, clathrin pathway mechanistic assay, primary cell confirmation, multiple virus serotypes","pmids":["26468529"],"is_preprint":false},{"year":2015,"finding":"US3 protein kinase of pseudorabies virus triggers increased binding of inhibitory NK receptor CD300a to the surface of infected cells via aminophospholipid ligands and group I p21-activated kinases (PAKs), providing protection of infected cells against NK cell-mediated lysis.","method":"US3 kinase expression in infected cells, CD300a binding assays, NK cytotoxicity assays, PAK inhibitor experiments, aminophospholipid competition assays","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional binding and killing assays with pharmacological inhibition of PAKs, single lab","pmids":["26581992"],"is_preprint":false},{"year":2015,"finding":"CD300a expressed on inflammatory dendritic cells (iDCs) binds PS on apoptotic cells induced by alum adjuvant in the peritoneal cavity; CD300a-deficient mice showed significantly decreased eosinophil infiltration, serum IgE, and airway hyperreactivity after alum+OVA immunization; iDCs from CD300a-deficient mice induced less IL-4 from naive CD4+ T cells; antibody blockade of CD300a-PS interactions inhibited allergic airway inflammation.","method":"CD300a-deficient mice, allergic airway inflammation model, flow cytometry, OT-II T cell co-culture, anti-CD300a neutralizing antibody blockade","journal":"Journal of immunology (Baltimore, Md. : 1950)","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO mice, in vitro mechanistic confirmation with DCs, antibody blockade validation, multiple functional readouts","pmids":["25911756"],"is_preprint":false},{"year":2021,"finding":"CD300a on brain myeloid cells inhibits signaling through the CD300b-DAP12 pathway to prevent efferocytosis of apoptotic cells; CD300a deficiency enhanced efferocytosis by infiltrating myeloid cells within 1 hour after MCAO, reduced DAMP release, and ameliorated neurological deficit; anti-CD300a neutralizing antibody recapitulated these benefits.","method":"CD300a-deficient mice, middle cerebral artery occlusion (MCAO) model, efferocytosis assays, DAMP measurements, CD300b-DAP12 signaling pathway analysis, anti-CD300a neutralizing antibody treatment","journal":"Science immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with defined molecular pathway (CD300b-DAP12), antibody blockade phenocopy, multiple readouts (efferocytosis, DAMPs, neurological deficit)","pmids":["34652960"],"is_preprint":false},{"year":2021,"finding":"CD300a on dendritic cells inhibits tumor-derived extracellular vesicle (TEV)-mediated TLR3-TRIF signaling; upon TEV co-culture, CD300a is internalized and co-localizes with EVs in endosomes where it suppresses IFN-β production and the IFN-β-Treg cell axis; CD300a deficiency in DCs led to increased Treg cell numbers in tumors and greater tumor growth.","method":"CD300a-deficient mice, B16 melanoma transplant model, co-culture of DCs with TEVs, confocal imaging of CD300a/EV internalization, TLR3-TRIF signaling assays, IFN-β measurements, Treg cell quantification","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO, defined intracellular signaling mechanism (TLR3-TRIF), imaging of internalization, multiple functional readouts","pmids":["34751648"],"is_preprint":false},{"year":2021,"finding":"CD300a-deficient neutrophils have impaired phagocytic abilities; despite increased accumulation at the site of UPEC infection, they are unable to reduce bacterial burden; UPEC's α-hemolysin pore-forming toxin induces upregulation of CD300a ligands on infected bladder epithelial cells.","method":"CD300a-deficient mice, UPEC urinary tract infection model, phagocytosis assays, bacterial burden quantification, α-hemolysin treatment of bladder epithelial cells with flow cytometric ligand detection","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO with defined functional defect, microbial induction of ligand demonstrated, single lab","pmids":["34268737"],"is_preprint":false},{"year":2021,"finding":"CD300a controls neutrophil apoptosis in MSU crystal-induced gout; CD300a agonistic antibody increased apoptosis of human neutrophils via caspase-8 cleavage; CD300a-deficient mice had persistent neutrophil influx, increased IL-1β, and reduced efferocytosis at 24 hours post-MSU injection.","method":"CD300a-deficient mice, MSU crystal joint injection model, neutrophil apoptosis assays with CD300a agonistic antibody, caspase-8 cleavage assays, efferocytosis measurements, IL-1β quantification","journal":"Immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO with in vivo phenotype, agonistic antibody mechanistic follow-up, caspase-8 identification, single lab","pmids":["34002852"],"is_preprint":false},{"year":2023,"finding":"GW0742 (PPARβ/δ agonist) increased expression of PPARβ/δ, CD300a, and phosphorylation of SHP1, and decreased Syk phosphorylation in mast cells after germinal matrix hemorrhage; PPARβ/δ siRNA and CD300a siRNA abolished these effects, placing CD300a downstream of PPARβ/δ and upstream of SHP1/Syk in the pathway regulating mast cell degranulation.","method":"GMH rat model, intranasal GW0742 treatment, siRNA knockdown of PPARβ/δ and CD300a, Western blotting for SHP1/Syk phosphorylation, Toluidine Blue staining for mast cell degranulation, behavioral tests","journal":"Experimental neurology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA epistasis experiment placing CD300a in PPARβ/δ→CD300a→SHP1 pathway, multiple readouts, single lab","pmids":["37995951"],"is_preprint":false},{"year":2025,"finding":"CD300a and CD300lf colocalize with PS externalized to the outer leaflet at the cell surface during mast cell activation; CD300lf cooperates with CD300a to inhibit mast cell activation; CD300lf also colocalizes with extracellular ceramide, resulting in stronger inhibition than CD300lf binding to PS alone; double KO mice (CD300a−/−CD300lf−/−) showed lower rectal temperatures in passive systemic anaphylaxis than either single KO.","method":"Imaging and flow cytometric analyses of BMMCs from WT, Cd300a−/−, Cd300lf−/−, and Cd300a−/−Cd300lf−/− mice, passive systemic anaphylaxis model, colocalization with PS and ceramide","journal":"Journal of immunology (Baltimore, Md. : 1950)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic double-KO epistasis, in vivo anaphylaxis model, imaging colocalization, single lab","pmids":["40073110"],"is_preprint":false},{"year":2024,"finding":"PE serves as a phagocytic ligand for macrophages engaging CD300a; CD300a specifically modulated PE-mediated uptake; CD300a expression curtailed inflammatory responses of macrophages to PE-containing LPS particles; this process involved ITAM-containing adaptors and Syk kinase.","method":"Macrophage phagocytosis assays with PE particles, CD300a expression/knockdown, Syk kinase inhibition, ITAM adaptor involvement assays","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 2 / Weak — preprint, functional phagocytosis assays, single study, mechanistic pathway partially characterized","pmids":[],"is_preprint":true},{"year":2024,"finding":"Blocking PS-CD300a signals with antibodies significantly amplified lysis function-related proteins and effector cytokines in NK cells, augmenting their ability to lyse hematologic malignancies; CD300a overexpression inhibited NK-mediated tumor lysis in vitro and shortened survival of HM-xenografted mice.","method":"CD300a overexpression, CD300a blocking antibodies, NK cytotoxicity assays, xenotransplantation mouse model, flow cytometry for NK effector proteins","journal":"Cancer biology & medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function and antibody blockade with in vivo xenograft model, multiple functional readouts, single lab","pmids":["38425216"],"is_preprint":false}],"current_model":"CD300a is a type I transmembrane ITIM-bearing inhibitory immunoreceptor whose extracellular IgV domain directly binds phosphatidylserine (PS) and phosphatidylethanolamine (PE) exposed on apoptotic cells, activated cells, and enveloped viruses; ligand engagement leads to Lck-mediated ITIM tyrosine phosphorylation, selective recruitment of SHP-1 (the primary effector phosphatase), and suppression of downstream activation cascades (including FcεRI, BCR, Kit, FcγRIIa, and TLR-MyD88 pathways) in diverse immune cell types including NK cells, mast cells, eosinophils, basophils, neutrophils, B cells, monocytes, macrophages, and dendritic cells; additionally, CD300a on myeloid cells inhibits the CD300b-DAP12 pathway to restrain efferocytosis of apoptotic cells, and its transcription is directly regulated by PPARβ/δ in macrophages."},"narrative":{"mechanistic_narrative":"CD300a (originally IRp60) is a type I transmembrane ITIM-bearing inhibitory immunoreceptor that restrains activation across a broad range of immune cells by sensing aminophospholipids displayed on apoptotic, activated, and infected cells [PMID:10540326, PMID:22302738]. Its extracellular IgV domain directly binds phosphatidylserine (PS) and phosphatidylethanolamine (PE) exposed on dead cells, with mutagenesis defining a ligand cavity that accommodates the hydrophilic phospholipid headgroups [PMID:22302738]; the same residues underlie a graded affinity hierarchy that distinguishes CD300a from its activating paralog CD300C [PMID:23372157]. Ligand engagement drives Lck-dependent tyrosine phosphorylation of the cytoplasmic ITIMs, which dock SHP-1 as the critical effector phosphatase (SHP-2 and SHIP-1 contribute in specific contexts), thereby terminating calcium influx and downstream signaling [PMID:22537350, PMID:10540326]. Through this circuit CD300a inhibits an array of activating pathways, including FcεRI- and Kit-driven mast cell responses, eosinophil cytokine signaling, BCR-mediated B cell proliferation, FcγRIIa signaling, and MyD88-dependent TLR4/TLR9 inflammation [PMID:16339535, PMID:18424727, PMID:16254138, PMID:21482706, PMID:17588661, PMID:22043923]. In myeloid cells CD300a additionally restrains efferocytosis by antagonizing the activating CD300b-DAP12 pathway, and its expression is directly controlled at the transcriptional level by PPARβ/δ [PMID:34652960, PMID:24958459]. Pathogens exploit this inhibition: enveloped viruses such as dengue use CD300a-phospholipid binding to enhance clathrin-mediated entry, and viral kinases increase CD300a ligand display to shield infected cells from NK lysis [PMID:26468529, PMID:26581992]. The receptor thereby functions as a central rheostat dampening allergic, antitumor, antibacterial, and ischemic inflammatory responses [PMID:25911756, PMID:23640773, PMID:22826299].","teleology":[{"year":1999,"claim":"Established CD300a as a bona fide inhibitory NK receptor by linking its phosphorylation to recruitment of SH2-domain phosphatases and functional suppression of cytotoxicity.","evidence":"mAb cross-linking, co-IP of SHP-1/SHP-2 after pervanadate, and cytotoxicity assays in human NK cells","pmids":["10540326"],"confidence":"High","gaps":["Ligand for the receptor was unknown","Relative importance of SHP-1 vs SHP-2 not resolved"]},{"year":2005,"claim":"Extended the inhibitory role beyond NK cells, showing CD300a engagement suppresses FcεRI-driven degranulation, SCF survival signaling, and eosinophil activation, with cell-type-specific phosphatase usage.","evidence":"Antibody cross-linking with calcium, degranulation, transmigration and JAK2/ERK/p38 readouts plus co-IP in mast cells and eosinophils; murine allergic peritonitis model","pmids":["16339535","16254138"],"confidence":"High","gaps":["Physiological ligand still undefined","Mechanism of selective SHP-1 vs SHP-2 recruitment unclear"]},{"year":2006,"claim":"Provided the first structural description of the extracellular domain, confirming an immunoglobulin-like fold and monomeric solution behavior.","evidence":"SAXS and homology modeling of recombinant refolded ectodomain","pmids":["16949664"],"confidence":"Medium","gaps":["No high-resolution crystal structure","No ligand-bound structure or mutagenesis validation"]},{"year":2008,"claim":"Demonstrated context-dependent signaling outputs, including SHIP-1 (not SHP-1) recruitment upon Kit co-aggregation and cytokine modulation in plasmacytoid DCs.","evidence":"Bispecific Kit×CD300a antibodies with co-IP and mast cell assays; cross-linking with cytokine ELISA in pDCs","pmids":["18424727","18535206"],"confidence":"High","gaps":["Determinants of SHIP-1 vs SHP-1 selection unresolved","Endogenous ligand triggering these responses unknown"]},{"year":2011,"claim":"Identified phosphatidylserine on apoptotic cells as a direct ligand and confirmed inhibitory function in B cells, resolving the long-standing ligand question.","evidence":"CD300a-Fc binding assay with PS-dependent SHP-1 co-IP; BCR co-ligation with calcium/NFAT reporters and siRNA knockdown in primary B cells","pmids":["22185693","21482706"],"confidence":"High","gaps":["Whether other phospholipids are recognized not yet tested","Structural basis of PS recognition undefined"]},{"year":2012,"claim":"Defined the molecular ligand-recognition mechanism and the core inhibitory signaling module, establishing PS/PE binding via a headgroup cavity, Lck-dependent ITIM phosphorylation, and SHP-1 as the dominant effector.","evidence":"SPR, ELISA, ultracentrifugation, site-directed mutagenesis and structural modeling; chimeric KIR-CD300a/ITIM-mutant and phosphatase-deficient cell systems; TLR reporter assays in monocytic lines; CD300a-KO mast cell sepsis model","pmids":["22302738","22537350","22043923","22826299"],"confidence":"High","gaps":["No co-crystal structure of ligand engagement","Quantitative phospholipid selectivity in membranes not fully defined"]},{"year":2013,"claim":"Linked the PS-CD300a axis to antitumor immunity and uncovered an actin-cytoskeleton-associated role in monocyte migration.","evidence":"Anti-CD300a/PS blocking antibodies in NK tumor-killing assays; confocal colocalization, cosedimentation and transendothelial migration assays with siRNA in monocytes","pmids":["23640773","24058511"],"confidence":"Medium","gaps":["Mechanism connecting CD300a to F-actin remodeling not defined","In vivo relevance of tumor PS-CD300a blockade not tested here"]},{"year":2014,"claim":"Identified PPARβ/δ as a direct transcriptional regulator of CD300a and tied receptor deficiency to TLR4-MyD88-driven chronic intestinal inflammation.","evidence":"CD300a-KO mice on high-fat diet, bone marrow transplantation, LPS stimulation and PPARβ/δ regulation assays","pmids":["24958459"],"confidence":"High","gaps":["Direct PPARβ/δ binding elements not mapped","Generalizability of transcriptional control to other cell types unknown"]},{"year":2015,"claim":"Showed CD300a binds enveloped virus particles and that viruses exploit ligand display, while also defining its role in allergic airway inflammation through dendritic cells.","evidence":"DENV/WNV/CHIKV binding, clathrin inhibition and phospholipid-binding mutagenesis; US3 kinase/PAK NK protection assays; CD300a-KO alum+OVA airway model with iDC-T cell co-culture","pmids":["26468529","26581992","25911756"],"confidence":"High","gaps":["Whether CD300a signals during viral entry or acts only as attachment factor unclear","Host counter-regulation of viral ligand induction unexplored"]},{"year":2021,"claim":"Expanded the efferocytosis-restraining function across disease models and defined intracellular and cross-receptor mechanisms (CD300b-DAP12 antagonism, endosomal TLR3-TRIF suppression).","evidence":"CD300a-KO MCAO, UPEC, MSU-gout, and B16 melanoma models with efferocytosis, phagocytosis, caspase-8, IFN-β/Treg and DAMP readouts; antibody blockade phenocopies","pmids":["34652960","34751648","34268737","34002852"],"confidence":"High","gaps":["How CD300a is internalized and routed to endosomes mechanistically undefined","Balance between inhibitory and pro-apoptotic functions across tissues unclear"]},{"year":2023,"claim":"Positioned CD300a within a PPARβ/δ→CD300a→SHP1/Syk signaling axis controlling mast cell degranulation in vivo.","evidence":"PPARβ/δ agonist GW0742 with PPARβ/δ and CD300a siRNA epistasis and SHP1/Syk phosphorylation in a germinal matrix hemorrhage rat model","pmids":["37995951"],"confidence":"Medium","gaps":["Direct biochemical link between CD300a and Syk dephosphorylation not shown","Single-model pharmacological epistasis"]},{"year":2025,"claim":"Revealed cooperativity with the paralog CD300lf and a broader lipid ligand repertoire (ceramide) in setting the threshold for mast cell activation.","evidence":"Imaging and flow analyses of single and double CD300a/CD300lf KO BMMCs with PS/ceramide colocalization and a passive systemic anaphylaxis model","pmids":["40073110"],"confidence":"Medium","gaps":["Molecular basis of CD300a/CD300lf cooperation undefined","Whether ceramide is a direct CD300a ligand not established"]},{"year":null,"claim":"The structural basis of phospholipid headgroup discrimination, the rules governing context-specific phosphatase selection (SHP-1 vs SHP-2 vs SHIP-1), and the trafficking machinery routing CD300a to endosomes remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No ligand-bound atomic structure","Predictive model for effector phosphatase choice lacking","Internalization/sorting mechanism uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[7,9,15,17]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,11,12]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,9,11]},{"term_id":"GO:0001618","term_label":"virus receptor activity","supporting_discovery_ids":[17]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[4,7,25]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[21]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[14]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,1,8,11,12]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,11,12]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[23]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[17,18]}],"complexes":[],"partners":["SHP-1","SHP-2","SHIP-1","LCK","KIT","FCGRIIA","CD300LF","CD300B"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UGN4","full_name":"CMRF35-like molecule 8","aliases":["CD300 antigen-like family member A","CMRF-35-H9","CMRF35-H9","CMRF35-H","IRC1/IRC2","Immunoglobulin superfamily member 12","IgSF12","Inhibitory receptor protein 60","IRp60","NK inhibitory receptor"],"length_aa":299,"mass_kda":33.2,"function":"Inhibitory receptor which may contribute to the down-regulation of cytolytic activity in natural killer (NK) cells, and to the down-regulation of mast cell degranulation (PubMed:10746781, PubMed:16339535, PubMed:9701027). Negatively regulates the Toll-like receptor (TLR) signaling mediated by MYD88 but not TRIF through activation of PTPN6 (PubMed:22043923)","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q9UGN4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CD300A","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CD300A","total_profiled":1310},"omim":[{"mim_id":"616560","title":"CD300H ANTIGEN; CD300H","url":"https://www.omim.org/entry/616560"},{"mim_id":"609801","title":"CD300E ANTIGEN; CD300E","url":"https://www.omim.org/entry/609801"},{"mim_id":"606790","title":"CD300A ANTIGEN; 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immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40977689","citation_count":0,"is_preprint":false},{"pmid":"41871214","id":"PMC_41871214","title":"CD300a as a Potential Immune Checkpoint in Breast Cancer: Insights from in vivo and in vitro Models.","date":"2026","source":"International archives of allergy and immunology","url":"https://pubmed.ncbi.nlm.nih.gov/41871214","citation_count":0,"is_preprint":false},{"pmid":"41621689","id":"PMC_41621689","title":"Efferocytosis-linked genetic signature predicts rheumatoid arthritis risk and highlights CD300A as a novel target.","date":"2026","source":"Immunology letters","url":"https://pubmed.ncbi.nlm.nih.gov/41621689","citation_count":0,"is_preprint":false},{"pmid":"37762055","id":"PMC_37762055","title":"Human IgMhiCD300a+ B Cells Are Circulating Marginal Zone Memory B Cells That Respond to Pneumococcal Polysaccharides and Their Frequency Is Decreased in People Living with HIV.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37762055","citation_count":0,"is_preprint":false},{"pmid":"41700726","id":"PMC_41700726","title":"CD300a Immunoreceptor Blocking Attenuates Neuronal Apoptosis by Regulating Efferocytosis and Promotes Hindlimb Functional Recovery after Acute Spinal Cord Injury in Mice.","date":"2026","source":"Journal of neurotrauma","url":"https://pubmed.ncbi.nlm.nih.gov/41700726","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.11.18.624161","title":"Phosphatidylethanolamine is a phagocytic ligand implicated in the binding and removal of apoptotic and microbial extracellular vesicles","date":"2024-11-19","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.18.624161","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.17.24315623","title":"Identification of Shared and Unique Key Biomarkers of Alcohol Liver Cirrhosis and Non-Alcoholic Steatohepatitis Through Machine Learning Network-Based Algorithms","date":"2024-10-18","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.17.24315623","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":37451,"output_tokens":7184,"usd":0.110057,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":16583,"output_tokens":4368,"usd":0.096058,"stage2_stop_reason":"end_turn"},"total_usd":0.206115,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"IRp60 (CD300a) is an inhibitory receptor on human NK cells that, upon sodium pervanadate treatment, becomes tyrosine phosphorylated and associates with the SH2-containing phosphatases SHP-1 and SHP-2, thereby inhibiting NK cell cytotoxicity.\",\n      \"method\": \"Monoclonal antibody generation, cross-linking experiments, co-immunoprecipitation of SHP-1/SHP-2 after pervanadate treatment, cytotoxicity assays\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP with SHP-1/SHP-2, functional cytotoxicity inhibition, replicated across multiple subsequent studies\",\n      \"pmids\": [\"10540326\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"IRp60 (CD300a) cross-linking on human mast cells inhibits IgE-induced degranulation and SCF-mediated survival via tyrosine phosphorylation, phosphatase (SHP-1/SHP-2) recruitment, and termination of cellular calcium influx.\",\n      \"method\": \"Cross-linking with anti-IRp60 antibodies, flow cytometry for phosphorylation and calcium influx, degranulation assays (tryptase and IL-4 release), murine allergic peritonitis model with LMIR1 neutralization\",\n      \"journal\": \"Journal of immunology (Baltimore, Md. : 1950)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (signaling, calcium, degranulation, in vivo model), replicated in subsequent studies\",\n      \"pmids\": [\"16339535\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"IRp60 (CD300a) cross-linking on human eosinophils inhibits eotaxin-dependent transmigration, blocks anti-apoptotic cytokine effects, inhibits IL-5-mediated JAK2 phosphorylation, and inhibits ERK1/2 and p38 phosphorylation; CD300a underwent tyrosine phosphorylation and recruited SHP-1 but not SHP-2 on eosinophils.\",\n      \"method\": \"Cross-linking with anti-IRp60 mAbs, transmigration assays, apoptosis assays, cytokine release assays, Western blotting for JAK2/ERK1/2/p38 phosphorylation, co-immunoprecipitation for SHP-1/SHP-2\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (signaling, functional assays, co-IP), clear mechanistic pathway delineation\",\n      \"pmids\": [\"16254138\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Solution structure of the IRp60 (CD300a) extracellular immunoglobulin-like domain was determined by small-angle X-ray scattering (SAXS); the protein is monomeric in solution with a molecular shape characteristic of immunoglobulin-like structures.\",\n      \"method\": \"Recombinant protein expression in E. coli, refolding, small-angle X-ray scattering (SAXS), homology modeling validated against SAXS data\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — structural determination by SAXS with homology modeling, single study, no mutagenesis validation\",\n      \"pmids\": [\"16949664\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"CD300a expression on human neutrophils is rapidly increased by LPS and GM-CSF stimulation through translocation of an intracellular pool to the cell surface, and co-ligation of CD300a with FcγRIIa (CD32a) inhibits FcγRIIa-mediated signaling but does not inhibit TLR4-mediated ROS production.\",\n      \"method\": \"Flow cytometry, HL-60 differentiation model, co-ligation experiments, ROS production assays\",\n      \"journal\": \"Molecular immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional co-ligation assays with two distinct readouts, single lab\",\n      \"pmids\": [\"17588661\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"CD300a/c cross-linking on plasmacytoid dendritic cells reduces TNF-α and increases IFN-α secretion following TLR7/TLR9 stimulation; IFN-α itself down-regulates CD300a/c expression, establishing a feedback loop.\",\n      \"method\": \"Flow cytometry for surface expression, cross-linking with anti-CD300a/c antibodies, cytokine ELISA, neutralizing antibody experiments\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional cytokine assays with neutralization controls, single lab, two orthogonal functional readouts\",\n      \"pmids\": [\"18535206\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"CD300a co-aggregation with Kit via a bispecific antibody results in Kit-mediated tyrosine phosphorylation of CD300a and recruitment of SHIP-1 (but not SHP-1), inhibiting SCF-induced mast cell differentiation, survival, and activation, and suppressing constitutive Kit signaling in HMC-1 leukemic cells.\",\n      \"method\": \"Bispecific antibody fragments (Kit×CD300a), Western blotting for phosphorylation, co-immunoprecipitation for SHIP-1/SHP-1, mast cell differentiation/survival/activation assays, murine cutaneous anaphylaxis model\",\n      \"journal\": \"Journal of immunology (Baltimore, Md. : 1950)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — co-IP, functional assays, in vivo model, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"18424727\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"CD300a extracellular domain (as a CD300a-Fc chimeric fusion protein) specifically binds phosphatidylserine (PS) exposed on apoptotic cells, and PS binding induces SHP-1 recruitment by CD300a in mast cells in response to LPS.\",\n      \"method\": \"CD300a-Fc fusion protein binding assay, co-immunoprecipitation for SHP-1 after PS stimulation\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding with fusion protein and functional co-IP, single lab, two orthogonal methods\",\n      \"pmids\": [\"22185693\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Co-ligation of BCR and CD300a on B cells inhibits Ca2+ mobilization and NFAT transcriptional activity; siRNA-mediated knockdown of CD300a in primary B cells resulted in increased BCR-mediated proliferation, confirming CD300a's inhibitory role in B cell signaling.\",\n      \"method\": \"Co-ligation with anti-CD300a and anti-BCR antibodies, calcium flux measurements, NFAT reporter assays, siRNA knockdown, proliferation assays\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (calcium, transcription, siRNA-KD with phenotype), single lab\",\n      \"pmids\": [\"21482706\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CD300a binds phosphatidylethanolamine (PE) and phosphatidylserine (PS) exposed on dead cells, as identified by surface plasmon resonance, ultracentrifugation, ELISA, and reporter cell assays; mutational analysis identified residues forming a cavity where the hydrophilic heads of PE and PS penetrate; CD300a down-regulates macrophage phagocytosis of apoptotic cells.\",\n      \"method\": \"Surface plasmon resonance, ultracentrifugation, ELISA, reporter cell assays, site-directed mutagenesis, structural modeling, phagocytosis assays with CD300a-Ig fusion protein\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple orthogonal biochemical methods, mutagenesis, structural modeling, functional validation, replicated by multiple subsequent studies\",\n      \"pmids\": [\"22302738\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CD300a on mast cells acts as a non-phagocytic PS receptor; PS-CD300a interaction delivers an inhibitory signal suppressing LPS-induced inflammatory cytokine and chemokine production in mast cells; in a cecal ligation and puncture model, CD300a-deficient peritoneal mast cells produced more chemoattractant and recruited more neutrophils, improving bacterial clearance and survival.\",\n      \"method\": \"CD300a-deficient mice, cecal ligation and puncture model, cytokine/chemokine measurements, neutrophil recruitment assays, antibody blockade of CD300a-PS interactions\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO mouse with defined cellular phenotype and multiple readouts, antibody blockade confirmation, in vivo model\",\n      \"pmids\": [\"22826299\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CD300a mediates inhibitory signaling through ITIMs that require Lck-mediated tyrosine phosphorylation to create docking sites for SHP-1 and SHP-2; SHP-1, but not SHP-2 or SHIP, is the critical phosphatase for CD300a's inhibitory activity in T and B cells.\",\n      \"method\": \"Chimeric KIR-CD300a receptor in Jurkat T cells, ITIM mutagenesis, siRNA knockdown of SHP-1/SHP-2, DT40 phosphatase-deficient cell lines, superantigen-stimulated TCR signaling assays\",\n      \"journal\": \"BMC immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — ITIM mutagenesis, multiple genetic knockdown/KO systems, chimeric receptor approach, multiple orthogonal validations\",\n      \"pmids\": [\"22537350\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CD300a selectively blocks TLR4-mediated and TLR9-mediated (MyD88-dependent) but not TLR3-mediated (TRIF-dependent) pro-inflammatory signaling in monocytic cell lines, acting primarily through SHP-1; ITIM peptides from CD300a mimicked this selective inhibition.\",\n      \"method\": \"TLR stimulation of THP-1 and U937 cells, NF-κB luciferase reporter assays, MyD88/TRIF overexpression, synthetic ITIM peptides, signaling inhibitors, Western blotting\",\n      \"journal\": \"Immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reporter assays with mechanistic dissection, ITIM peptide mimicry, multiple TLR ligands tested, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"22043923\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PS expressed on tumor cells interacts with CD300a on NK cells to inhibit NK cell-mediated tumor killing; blocking the PS-CD300a interaction increased NK cell killing of tumor cells.\",\n      \"method\": \"Generation of specific anti-CD300a mAbs, NK cell clone characterization, binding assays with tumor cells, NK cytotoxicity assays with PS/CD300a blocking antibodies\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional killing assays with blocking antibodies, single lab, direct binding characterization\",\n      \"pmids\": [\"23640773\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CD300a colocalized and cosedimented with actin filaments in human monocytes; CD300a activation by antibody caused F-actin cytoskeleton alterations and reduced monocyte transendothelial migration; siRNA-mediated downregulation of CD300a increased the rate of migration.\",\n      \"method\": \"siRNA knockdown, antibody-mediated receptor engagement, confocal colocalization, cosedimentation assays, transendothelial migration assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA KD with defined migration phenotype, cosedimentation, colocalization; single lab, two orthogonal functional approaches\",\n      \"pmids\": [\"24058511\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CD300C delivers a FcRγ-dependent activating signal in mast cells and monocytes; PE and apoptotic cells are ligands for both CD300A and CD300C, but CD300A binds PE more strongly than CD300C; differential recognition depends on residues CD300A(F56-L57) vs CD300C(L63-R64); co-expression of full-length CD300A dampens CD300C-PE-mediated signaling.\",\n      \"method\": \"Antibody generation with epitope mapping, chimeric reporter cell lines expressing CD300A or CD300C extracellular domains with CD3ζ, GFP reporter assays, phospholipid binding assays, cytokine production assays, site-specific amino acid analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — chimeric reporter system, epitope-resolved mutagenesis equivalent, multiple ligand binding validations, functional cytokine assays\",\n      \"pmids\": [\"23372157\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PPARβ/δ directly regulates CD300a transcription in macrophages; CD300a-deficient mice on high-fat diet develop chronic intestinal inflammation with prolonged IL-6 secretion from macrophages in response to LPS/TLR4-MyD88 signaling; bone marrow transplantation confirmed the phenotype originates from CD300a deficiency in leukocytes.\",\n      \"method\": \"CD300a-deficient mice, high-fat diet model, bone marrow transplantation, LPS stimulation assays, cytokine measurements, PPARβ/δ direct regulation assay\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO, bone marrow transplant rescue, direct transcriptional regulation, in vivo and in vitro mechanistic validation\",\n      \"pmids\": [\"24958459\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"CD300a directly binds dengue virus (DENV) particles via recognition of PE (primarily) and PS on viral envelopes, enhances DENV internalization through clathrin-mediated endocytosis, and facilitates infection of all four DENV serotypes as well as West Nile virus and Chikungunya virus; mutation of IgV domain residues critical for phospholipid binding abrogated CD300a-mediated enhancement of infection.\",\n      \"method\": \"CD300a overexpression in cell lines, direct binding assays with DENV particles, clathrin inhibition, site-directed mutagenesis of phospholipid-binding residues, anti-CD300a antibody inhibition of primary macrophage infection\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct binding assays, mutagenesis, clathrin pathway mechanistic assay, primary cell confirmation, multiple virus serotypes\",\n      \"pmids\": [\"26468529\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"US3 protein kinase of pseudorabies virus triggers increased binding of inhibitory NK receptor CD300a to the surface of infected cells via aminophospholipid ligands and group I p21-activated kinases (PAKs), providing protection of infected cells against NK cell-mediated lysis.\",\n      \"method\": \"US3 kinase expression in infected cells, CD300a binding assays, NK cytotoxicity assays, PAK inhibitor experiments, aminophospholipid competition assays\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional binding and killing assays with pharmacological inhibition of PAKs, single lab\",\n      \"pmids\": [\"26581992\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"CD300a expressed on inflammatory dendritic cells (iDCs) binds PS on apoptotic cells induced by alum adjuvant in the peritoneal cavity; CD300a-deficient mice showed significantly decreased eosinophil infiltration, serum IgE, and airway hyperreactivity after alum+OVA immunization; iDCs from CD300a-deficient mice induced less IL-4 from naive CD4+ T cells; antibody blockade of CD300a-PS interactions inhibited allergic airway inflammation.\",\n      \"method\": \"CD300a-deficient mice, allergic airway inflammation model, flow cytometry, OT-II T cell co-culture, anti-CD300a neutralizing antibody blockade\",\n      \"journal\": \"Journal of immunology (Baltimore, Md. : 1950)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO mice, in vitro mechanistic confirmation with DCs, antibody blockade validation, multiple functional readouts\",\n      \"pmids\": [\"25911756\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CD300a on brain myeloid cells inhibits signaling through the CD300b-DAP12 pathway to prevent efferocytosis of apoptotic cells; CD300a deficiency enhanced efferocytosis by infiltrating myeloid cells within 1 hour after MCAO, reduced DAMP release, and ameliorated neurological deficit; anti-CD300a neutralizing antibody recapitulated these benefits.\",\n      \"method\": \"CD300a-deficient mice, middle cerebral artery occlusion (MCAO) model, efferocytosis assays, DAMP measurements, CD300b-DAP12 signaling pathway analysis, anti-CD300a neutralizing antibody treatment\",\n      \"journal\": \"Science immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with defined molecular pathway (CD300b-DAP12), antibody blockade phenocopy, multiple readouts (efferocytosis, DAMPs, neurological deficit)\",\n      \"pmids\": [\"34652960\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CD300a on dendritic cells inhibits tumor-derived extracellular vesicle (TEV)-mediated TLR3-TRIF signaling; upon TEV co-culture, CD300a is internalized and co-localizes with EVs in endosomes where it suppresses IFN-β production and the IFN-β-Treg cell axis; CD300a deficiency in DCs led to increased Treg cell numbers in tumors and greater tumor growth.\",\n      \"method\": \"CD300a-deficient mice, B16 melanoma transplant model, co-culture of DCs with TEVs, confocal imaging of CD300a/EV internalization, TLR3-TRIF signaling assays, IFN-β measurements, Treg cell quantification\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO, defined intracellular signaling mechanism (TLR3-TRIF), imaging of internalization, multiple functional readouts\",\n      \"pmids\": [\"34751648\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CD300a-deficient neutrophils have impaired phagocytic abilities; despite increased accumulation at the site of UPEC infection, they are unable to reduce bacterial burden; UPEC's α-hemolysin pore-forming toxin induces upregulation of CD300a ligands on infected bladder epithelial cells.\",\n      \"method\": \"CD300a-deficient mice, UPEC urinary tract infection model, phagocytosis assays, bacterial burden quantification, α-hemolysin treatment of bladder epithelial cells with flow cytometric ligand detection\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with defined functional defect, microbial induction of ligand demonstrated, single lab\",\n      \"pmids\": [\"34268737\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CD300a controls neutrophil apoptosis in MSU crystal-induced gout; CD300a agonistic antibody increased apoptosis of human neutrophils via caspase-8 cleavage; CD300a-deficient mice had persistent neutrophil influx, increased IL-1β, and reduced efferocytosis at 24 hours post-MSU injection.\",\n      \"method\": \"CD300a-deficient mice, MSU crystal joint injection model, neutrophil apoptosis assays with CD300a agonistic antibody, caspase-8 cleavage assays, efferocytosis measurements, IL-1β quantification\",\n      \"journal\": \"Immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with in vivo phenotype, agonistic antibody mechanistic follow-up, caspase-8 identification, single lab\",\n      \"pmids\": [\"34002852\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"GW0742 (PPARβ/δ agonist) increased expression of PPARβ/δ, CD300a, and phosphorylation of SHP1, and decreased Syk phosphorylation in mast cells after germinal matrix hemorrhage; PPARβ/δ siRNA and CD300a siRNA abolished these effects, placing CD300a downstream of PPARβ/δ and upstream of SHP1/Syk in the pathway regulating mast cell degranulation.\",\n      \"method\": \"GMH rat model, intranasal GW0742 treatment, siRNA knockdown of PPARβ/δ and CD300a, Western blotting for SHP1/Syk phosphorylation, Toluidine Blue staining for mast cell degranulation, behavioral tests\",\n      \"journal\": \"Experimental neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA epistasis experiment placing CD300a in PPARβ/δ→CD300a→SHP1 pathway, multiple readouts, single lab\",\n      \"pmids\": [\"37995951\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CD300a and CD300lf colocalize with PS externalized to the outer leaflet at the cell surface during mast cell activation; CD300lf cooperates with CD300a to inhibit mast cell activation; CD300lf also colocalizes with extracellular ceramide, resulting in stronger inhibition than CD300lf binding to PS alone; double KO mice (CD300a−/−CD300lf−/−) showed lower rectal temperatures in passive systemic anaphylaxis than either single KO.\",\n      \"method\": \"Imaging and flow cytometric analyses of BMMCs from WT, Cd300a−/−, Cd300lf−/−, and Cd300a−/−Cd300lf−/− mice, passive systemic anaphylaxis model, colocalization with PS and ceramide\",\n      \"journal\": \"Journal of immunology (Baltimore, Md. : 1950)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic double-KO epistasis, in vivo anaphylaxis model, imaging colocalization, single lab\",\n      \"pmids\": [\"40073110\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PE serves as a phagocytic ligand for macrophages engaging CD300a; CD300a specifically modulated PE-mediated uptake; CD300a expression curtailed inflammatory responses of macrophages to PE-containing LPS particles; this process involved ITAM-containing adaptors and Syk kinase.\",\n      \"method\": \"Macrophage phagocytosis assays with PE particles, CD300a expression/knockdown, Syk kinase inhibition, ITAM adaptor involvement assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — preprint, functional phagocytosis assays, single study, mechanistic pathway partially characterized\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Blocking PS-CD300a signals with antibodies significantly amplified lysis function-related proteins and effector cytokines in NK cells, augmenting their ability to lyse hematologic malignancies; CD300a overexpression inhibited NK-mediated tumor lysis in vitro and shortened survival of HM-xenografted mice.\",\n      \"method\": \"CD300a overexpression, CD300a blocking antibodies, NK cytotoxicity assays, xenotransplantation mouse model, flow cytometry for NK effector proteins\",\n      \"journal\": \"Cancer biology & medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function and antibody blockade with in vivo xenograft model, multiple functional readouts, single lab\",\n      \"pmids\": [\"38425216\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CD300a is a type I transmembrane ITIM-bearing inhibitory immunoreceptor whose extracellular IgV domain directly binds phosphatidylserine (PS) and phosphatidylethanolamine (PE) exposed on apoptotic cells, activated cells, and enveloped viruses; ligand engagement leads to Lck-mediated ITIM tyrosine phosphorylation, selective recruitment of SHP-1 (the primary effector phosphatase), and suppression of downstream activation cascades (including FcεRI, BCR, Kit, FcγRIIa, and TLR-MyD88 pathways) in diverse immune cell types including NK cells, mast cells, eosinophils, basophils, neutrophils, B cells, monocytes, macrophages, and dendritic cells; additionally, CD300a on myeloid cells inhibits the CD300b-DAP12 pathway to restrain efferocytosis of apoptotic cells, and its transcription is directly regulated by PPARβ/δ in macrophages.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CD300a (originally IRp60) is a type I transmembrane ITIM-bearing inhibitory immunoreceptor that restrains activation across a broad range of immune cells by sensing aminophospholipids displayed on apoptotic, activated, and infected cells [#0, #9]. Its extracellular IgV domain directly binds phosphatidylserine (PS) and phosphatidylethanolamine (PE) exposed on dead cells, with mutagenesis defining a ligand cavity that accommodates the hydrophilic phospholipid headgroups [#9]; the same residues underlie a graded affinity hierarchy that distinguishes CD300a from its activating paralog CD300C [#15]. Ligand engagement drives Lck-dependent tyrosine phosphorylation of the cytoplasmic ITIMs, which dock SHP-1 as the critical effector phosphatase (SHP-2 and SHIP-1 contribute in specific contexts), thereby terminating calcium influx and downstream signaling [#11, #0]. Through this circuit CD300a inhibits an array of activating pathways, including FcεRI- and Kit-driven mast cell responses, eosinophil cytokine signaling, BCR-mediated B cell proliferation, FcγRIIa signaling, and MyD88-dependent TLR4/TLR9 inflammation [#1, #6, #2, #8, #4, #12]. In myeloid cells CD300a additionally restrains efferocytosis by antagonizing the activating CD300b-DAP12 pathway, and its expression is directly controlled at the transcriptional level by PPARβ/δ [#20, #16]. Pathogens exploit this inhibition: enveloped viruses such as dengue use CD300a-phospholipid binding to enhance clathrin-mediated entry, and viral kinases increase CD300a ligand display to shield infected cells from NK lysis [#17, #18]. The receptor thereby functions as a central rheostat dampening allergic, antitumor, antibacterial, and ischemic inflammatory responses [#19, #13, #10].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established CD300a as a bona fide inhibitory NK receptor by linking its phosphorylation to recruitment of SH2-domain phosphatases and functional suppression of cytotoxicity.\",\n      \"evidence\": \"mAb cross-linking, co-IP of SHP-1/SHP-2 after pervanadate, and cytotoxicity assays in human NK cells\",\n      \"pmids\": [\"10540326\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Ligand for the receptor was unknown\", \"Relative importance of SHP-1 vs SHP-2 not resolved\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Extended the inhibitory role beyond NK cells, showing CD300a engagement suppresses FcεRI-driven degranulation, SCF survival signaling, and eosinophil activation, with cell-type-specific phosphatase usage.\",\n      \"evidence\": \"Antibody cross-linking with calcium, degranulation, transmigration and JAK2/ERK/p38 readouts plus co-IP in mast cells and eosinophils; murine allergic peritonitis model\",\n      \"pmids\": [\"16339535\", \"16254138\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological ligand still undefined\", \"Mechanism of selective SHP-1 vs SHP-2 recruitment unclear\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Provided the first structural description of the extracellular domain, confirming an immunoglobulin-like fold and monomeric solution behavior.\",\n      \"evidence\": \"SAXS and homology modeling of recombinant refolded ectodomain\",\n      \"pmids\": [\"16949664\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No high-resolution crystal structure\", \"No ligand-bound structure or mutagenesis validation\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Demonstrated context-dependent signaling outputs, including SHIP-1 (not SHP-1) recruitment upon Kit co-aggregation and cytokine modulation in plasmacytoid DCs.\",\n      \"evidence\": \"Bispecific Kit×CD300a antibodies with co-IP and mast cell assays; cross-linking with cytokine ELISA in pDCs\",\n      \"pmids\": [\"18424727\", \"18535206\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Determinants of SHIP-1 vs SHP-1 selection unresolved\", \"Endogenous ligand triggering these responses unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Identified phosphatidylserine on apoptotic cells as a direct ligand and confirmed inhibitory function in B cells, resolving the long-standing ligand question.\",\n      \"evidence\": \"CD300a-Fc binding assay with PS-dependent SHP-1 co-IP; BCR co-ligation with calcium/NFAT reporters and siRNA knockdown in primary B cells\",\n      \"pmids\": [\"22185693\", \"21482706\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether other phospholipids are recognized not yet tested\", \"Structural basis of PS recognition undefined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Defined the molecular ligand-recognition mechanism and the core inhibitory signaling module, establishing PS/PE binding via a headgroup cavity, Lck-dependent ITIM phosphorylation, and SHP-1 as the dominant effector.\",\n      \"evidence\": \"SPR, ELISA, ultracentrifugation, site-directed mutagenesis and structural modeling; chimeric KIR-CD300a/ITIM-mutant and phosphatase-deficient cell systems; TLR reporter assays in monocytic lines; CD300a-KO mast cell sepsis model\",\n      \"pmids\": [\"22302738\", \"22537350\", \"22043923\", \"22826299\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No co-crystal structure of ligand engagement\", \"Quantitative phospholipid selectivity in membranes not fully defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Linked the PS-CD300a axis to antitumor immunity and uncovered an actin-cytoskeleton-associated role in monocyte migration.\",\n      \"evidence\": \"Anti-CD300a/PS blocking antibodies in NK tumor-killing assays; confocal colocalization, cosedimentation and transendothelial migration assays with siRNA in monocytes\",\n      \"pmids\": [\"23640773\", \"24058511\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism connecting CD300a to F-actin remodeling not defined\", \"In vivo relevance of tumor PS-CD300a blockade not tested here\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified PPARβ/δ as a direct transcriptional regulator of CD300a and tied receptor deficiency to TLR4-MyD88-driven chronic intestinal inflammation.\",\n      \"evidence\": \"CD300a-KO mice on high-fat diet, bone marrow transplantation, LPS stimulation and PPARβ/δ regulation assays\",\n      \"pmids\": [\"24958459\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct PPARβ/δ binding elements not mapped\", \"Generalizability of transcriptional control to other cell types unknown\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Showed CD300a binds enveloped virus particles and that viruses exploit ligand display, while also defining its role in allergic airway inflammation through dendritic cells.\",\n      \"evidence\": \"DENV/WNV/CHIKV binding, clathrin inhibition and phospholipid-binding mutagenesis; US3 kinase/PAK NK protection assays; CD300a-KO alum+OVA airway model with iDC-T cell co-culture\",\n      \"pmids\": [\"26468529\", \"26581992\", \"25911756\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether CD300a signals during viral entry or acts only as attachment factor unclear\", \"Host counter-regulation of viral ligand induction unexplored\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Expanded the efferocytosis-restraining function across disease models and defined intracellular and cross-receptor mechanisms (CD300b-DAP12 antagonism, endosomal TLR3-TRIF suppression).\",\n      \"evidence\": \"CD300a-KO MCAO, UPEC, MSU-gout, and B16 melanoma models with efferocytosis, phagocytosis, caspase-8, IFN-β/Treg and DAMP readouts; antibody blockade phenocopies\",\n      \"pmids\": [\"34652960\", \"34751648\", \"34268737\", \"34002852\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How CD300a is internalized and routed to endosomes mechanistically undefined\", \"Balance between inhibitory and pro-apoptotic functions across tissues unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Positioned CD300a within a PPARβ/δ→CD300a→SHP1/Syk signaling axis controlling mast cell degranulation in vivo.\",\n      \"evidence\": \"PPARβ/δ agonist GW0742 with PPARβ/δ and CD300a siRNA epistasis and SHP1/Syk phosphorylation in a germinal matrix hemorrhage rat model\",\n      \"pmids\": [\"37995951\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical link between CD300a and Syk dephosphorylation not shown\", \"Single-model pharmacological epistasis\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealed cooperativity with the paralog CD300lf and a broader lipid ligand repertoire (ceramide) in setting the threshold for mast cell activation.\",\n      \"evidence\": \"Imaging and flow analyses of single and double CD300a/CD300lf KO BMMCs with PS/ceramide colocalization and a passive systemic anaphylaxis model\",\n      \"pmids\": [\"40073110\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of CD300a/CD300lf cooperation undefined\", \"Whether ceramide is a direct CD300a ligand not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of phospholipid headgroup discrimination, the rules governing context-specific phosphatase selection (SHP-1 vs SHP-2 vs SHIP-1), and the trafficking machinery routing CD300a to endosomes remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No ligand-bound atomic structure\", \"Predictive model for effector phosphatase choice lacking\", \"Internalization/sorting mechanism uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [7, 9, 15, 17]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 11, 12]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 9, 11]},\n      {\"term_id\": \"GO:0001618\", \"supporting_discovery_ids\": [17]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [4, 7, 25]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [21]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [14]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 1, 8, 11, 12]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 11, 12]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [23]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [17, 18]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SHP-1\", \"SHP-2\", \"SHIP-1\", \"Lck\", \"Kit\", \"FcgRIIa\", \"CD300lf\", \"CD300b\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}