{"gene":"SH2D1B","run_date":"2026-06-10T07:46:31","timeline":{"discoveries":[{"year":2001,"finding":"EAT-2 (SH2D1B) encodes a free SH2 domain that binds phosphorylated tyrosine motifs in the cytoplasmic tails of SLAM family receptors CD84, CD150, CD229, and CD244. Crystal structure of EAT-2 in complex with a phosphotyrosine peptide from CD150 (Tyr281) is very similar to SAP/SH2D1A bound to the same peptide, explaining high affinity for pTyr motifs. Unlike SAP, EAT-2 does not bind non-phosphorylated CD150. EAT-2 acts as a natural inhibitor by interfering with recruitment of the tyrosine phosphatase SHP-2 to these receptors.","method":"X-ray crystallography (EAT-2–phosphopeptide complex), binding assays, competition/inhibition assays with SHP-2 recruitment","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with functional binding assays and SHP-2 inhibition experiment, single rigorous study with multiple orthogonal methods","pmids":["11689425"],"is_preprint":false},{"year":2005,"finding":"EAT-2 associates with the SLAM-related receptor 2B4 in NK cells and inhibits natural cytotoxicity and IFN-γ secretion. This inhibitory mechanism requires tyrosine phosphorylation of the C-terminal tail of EAT-2. The related adaptor ERT shares this inhibitory function in mouse NK cells. EAT-2 and SAP have distinct and opposing functions: SAP activates while EAT-2 inhibits NK cell function.","method":"Co-immunoprecipitation, EAT-2 knockout and overexpression mouse models, functional NK cell assays (cytotoxicity, cytokine secretion), phosphorylation-site mutagenesis","journal":"Nature immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, genetic KO and OE mouse models, multiple functional readouts, replicated with ERT adaptor","pmids":["16127454"],"is_preprint":false},{"year":2005,"finding":"Upon activation, CRACC (CS-1) associates with EAT-2 in human NK cells. EAT-2 association induces phosphorylation of CRACC (partially reduced by Src kinase inhibitor). PLCγ1, PLCγ2, and PI3K are the major downstream signaling mediators of the CRACC/EAT-2 complex in NK cell cytotoxicity. EAT-2 also associates with 2B4 predominantly in resting NK cells, whereas SAP preferentially binds 2B4 upon activation.","method":"Co-immunoprecipitation, pharmacological Src kinase inhibition, signaling pathway analysis (PI3K, PLCγ) in human NK cells","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and downstream signaling assays, single lab, two orthogonal methods","pmids":["16339536"],"is_preprint":false},{"year":2006,"finding":"NTB-A is tyrosine-phosphorylated in resting human NK cells by Src family kinases and associates with both SAP and EAT-2. EAT-2 (but not SAP) is recruited specifically to the second tyrosine of NTB-A's cytoplasmic tail, and this tyrosine is sufficient and essential for NTB-A-mediated cytotoxicity. NTB-A can mediate cytotoxicity in the absence of SAP, likely via EAT-2, whereas NTB-A-mediated IFN-γ production depends on SAP.","method":"Co-immunoprecipitation, NTB-A-negative NK cell line reconstitution with tyrosine mutants, SAP siRNA knockdown, functional cytotoxicity and cytokine assays","journal":"Journal of immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — receptor reconstitution in null line with site-directed mutants, SAP knockdown, multiple functional readouts, single rigorous study with multiple orthogonal methods","pmids":["16920955"],"is_preprint":false},{"year":2009,"finding":"CRACC positively regulates NK cell function by a mechanism dependent on EAT-2 (but not SAP). In the absence of EAT-2, CRACC potently inhibits NK cell function. In T cells, which lack EAT-2, CRACC is inhibitory. Thus EAT-2 switches CRACC from an inhibitory to an activating receptor.","method":"CRACC-deficient mouse, EAT-2-deficient mouse, functional NK and T cell assays, genetic epistasis","journal":"Nature immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO of CRACC and EAT-2, epistasis experiment, multiple functional readouts, replicated across cell types","pmids":["19151721"],"is_preprint":false},{"year":2002,"finding":"CD84 undergoes rapid tyrosine phosphorylation upon ligation and recruits the SH2 domain-containing adaptors SAP and EAT-2, identifying CD84 as a SLAM family receptor that engages EAT-2 signaling in B cells.","method":"Co-immunoprecipitation, anti-CD84 ligation, tyrosine phosphorylation assay","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP and phosphorylation assay, single lab, two methods (ligation + Co-IP)","pmids":["12115647"],"is_preprint":false},{"year":2014,"finding":"EAT-2 mediates NK cell activation by coupling SLAM family receptors to PLCγ, calcium fluxes, and Erk kinase. This signaling is triggered by one or two tyrosines in the C-terminal tail of EAT-2 (absent in SAP). Unlike SAP, EAT-2 does not enhance NK–target conjugate formation; instead it accelerates polarization and exocytosis of cytotoxic granules toward hematopoietic target cells.","method":"Genetic (EAT-2 KO and tyrosine mutant knock-in), biochemical (PLCγ, Ca2+, Erk assays), live-cell imaging of granule polarization","journal":"The Journal of experimental medicine","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with site-directed C-terminal tyrosine mutants, multiple orthogonal biochemical and imaging methods, clearly distinguishes mechanism from SAP","pmids":["24687958"],"is_preprint":false},{"year":2015,"finding":"EAT-2 negatively regulates cytokine (IL-12) production in dendritic cells downstream of SLAM engagement. A promoter polymorphism in the NZB mouse reduces EAT-2 expression ~70% in DCs. SLAM co-engagement blocks p38 MAPK and JNK signaling in DCs, an effect reversed in DCs with low EAT-2 (NZB allele). EAT-2 knockdown in normal DCs increases IL-12 production and enhances Th1 differentiation.","method":"EAT-2 gene silencing in DCs, CD40/SLAM cross-linking, downstream signaling assays (p38 MAPK, JNK), T cell co-culture cytokine assays, subcongenic mouse mapping","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown and signaling pathway assays, single lab, multiple orthogonal methods (signaling + cytokine + T cell assays)","pmids":["26432891"],"is_preprint":false},{"year":2016,"finding":"X-ray crystallographic structure of human EAT-2 (SH2D1B) was determined in an unliganded form. Conformational differences were observed in ligand-binding loops compared to mouse EAT-2–peptide complex. EAT-2 shows similar binding energies to unphosphorylated ligands as SAP, which is inconsistent with prior biochemical data showing EAT-2 has lower affinity for unphosphorylated peptides than SAP, suggesting additional factors beyond the SH2 domain contribute to this difference.","method":"X-ray crystallography, computational binding energy comparison","journal":"Protein and peptide letters","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — crystal structure determined but single lab, limited functional validation, contradicts prior biochemical data","pmids":["27586300"],"is_preprint":false},{"year":2013,"finding":"EAT-2-mediated immune activation requires an intact SH2 domain: an R31Q SH2 domain mutant form of EAT-2 failed to enhance NK cell anti-tumor activity, DC maturation, monocyte phagocytosis, or pro-inflammatory cytokine kinetics in human cells, indicating that EAT-2 interaction with SLAM receptors via its SH2 domain is required for these functions.","method":"EAT-2 overexpression vs. R31Q SH2 mutant in human PBMCs; functional assays (NK cytotoxicity, DC maturation, cytokine measurement)","journal":"International immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — active-site SH2 mutant (R31Q) compared to wild-type, multiple functional readouts, single lab","pmids":["24374770"],"is_preprint":false},{"year":1996,"finding":"EAT-2 (SH2D1B) was identified as a novel gene containing a unique but biochemically functional SH2 domain, upregulated by the EWS/FLI1 fusion oncogene in Ewing's sarcoma. Expression correlated with NIH3T3 transformation by EWS/FLI1-related chimeric proteins. Human EAT-2 was mapped to chromosome 1q22.","method":"Representational difference analysis (RDA) cloning, SH2 domain functional assay, chromosomal mapping","journal":"Oncogene","confidence":"Low","confidence_rationale":"Tier 3 / Weak — initial identification with SH2 biochemical functionality assay, single lab, limited mechanistic follow-up","pmids":["9000139"],"is_preprint":false}],"current_model":"SH2D1B/EAT-2 is a free SH2 domain-containing intracellular adaptor expressed in innate immune cells (NK cells, macrophages, dendritic cells, B cells) that binds phosphotyrosine motifs in the cytoplasmic tails of SLAM family receptors (CD84, CD150/SLAM, CD229, CD244/2B4, CRACC, NTB-A); in NK cells, EAT-2 couples these receptors via C-terminal tyrosines to PLCγ, calcium, and Erk signaling to accelerate cytotoxic granule polarization and exocytosis, while in the absence of EAT-2 the same receptors become inhibitory; in dendritic cells, EAT-2 negatively regulates SLAM-triggered IL-12 production by suppressing p38 MAPK and JNK signaling downstream of CD40/SLAM co-engagement, and its activity in all contexts requires an intact SH2 domain."},"narrative":{"mechanistic_narrative":"SH2D1B (EAT-2) is a free SH2 domain-containing intracellular adaptor that couples SLAM family immune receptors to downstream signaling, governing the activation threshold of innate immune effector cells [PMID:11689425, PMID:24687958]. Its SH2 domain binds phosphotyrosine motifs in the cytoplasmic tails of SLAM family receptors including CD150, CD84, CD229, CD244/2B4, CRACC, and NTB-A, with a binding mode crystallographically similar to the related adaptor SAP but specific for the phosphorylated receptor; in doing so EAT-2 can compete with the recruitment of the phosphatase SHP-2 [PMID:11689425, PMID:16920955, PMID:12115647]. In NK cells, EAT-2 acts through one or two tyrosines in its C-terminal tail — features absent from SAP — to link these receptors to PLCγ, calcium flux, and Erk signaling, accelerating polarization and exocytosis of cytotoxic granules toward target cells rather than enhancing conjugate formation [PMID:24687958, PMID:16339536]. EAT-2 is a decisive switch in receptor outcome: it converts CRACC from an inhibitory to an activating receptor, and in its absence the same SLAM receptors signal inhibition [PMID:19151721]. All of these activating functions require an intact SH2 domain, as the R31Q mutant abolishes EAT-2-dependent NK, DC, and monocyte responses [PMID:24374770]. In dendritic cells EAT-2 instead acts as a negative regulator, suppressing SLAM-triggered IL-12 production by blocking p38 MAPK and JNK signaling and thereby limiting Th1 differentiation [PMID:26432891].","teleology":[{"year":1996,"claim":"Established EAT-2 as a distinct gene encoding a biochemically functional SH2 domain, placing it in the SH2 adaptor landscape before any immune function was known.","evidence":"RDA cloning, SH2 domain functional assay, and chromosomal mapping in the context of EWS/FLI1-driven transformation","pmids":["9000139"],"confidence":"Low","gaps":["Limited mechanistic follow-up; immune role not yet defined","Functional relationship of EWS/FLI1 upregulation to physiological EAT-2 function unclear"]},{"year":2001,"claim":"Defined the structural basis for EAT-2 recognition of SLAM family receptors and showed it binds phosphorylated, not unphosphorylated, receptor tails — answering how EAT-2 engages its receptors and how it differs from SAP.","evidence":"X-ray crystallography of the EAT-2–CD150 phosphopeptide complex with binding and SHP-2 competition assays","pmids":["11689425"],"confidence":"High","gaps":["Functional consequence in living immune cells not directly tested","Whether SHP-2 displacement is the dominant in vivo mechanism not resolved"]},{"year":2002,"claim":"Identified CD84 as a SLAM family receptor that recruits both SAP and EAT-2 upon ligation, extending the EAT-2 receptor repertoire into B cells.","evidence":"Co-immunoprecipitation and tyrosine phosphorylation assay following CD84 ligation","pmids":["12115647"],"confidence":"Medium","gaps":["Downstream signaling consequences in B cells not defined","No functional readout beyond receptor association"]},{"year":2005,"claim":"Demonstrated that EAT-2 associates with 2B4 and CRACC and identified PLCγ and PI3K as downstream mediators, while revealing that EAT-2 and SAP have opposing functions on NK cells.","evidence":"Reciprocal Co-IP, EAT-2 KO and overexpression mouse models, Src kinase inhibition, and functional NK cytotoxicity/cytokine assays","pmids":["16127454","16339536"],"confidence":"High","gaps":["Apparent contradiction between inhibitory (2B4) and activating signaling readouts not reconciled","Role of EAT-2 C-terminal tyrosines not yet mapped"]},{"year":2006,"claim":"Showed EAT-2 is recruited to a specific tyrosine of NTB-A required for cytotoxicity, establishing that EAT-2 can mediate receptor function independently of SAP.","evidence":"Co-IP, reconstitution of NTB-A-null NK cells with tyrosine mutants, and SAP siRNA knockdown with functional assays","pmids":["16920955"],"confidence":"High","gaps":["Mechanism linking the NTB-A tyrosine to EAT-2 effector signaling not detailed","Division of labor between SAP (cytokine) and EAT-2 (cytotoxicity) mechanistically incomplete"]},{"year":2009,"claim":"Established EAT-2 as a molecular switch that converts CRACC from inhibitory to activating, defining the principle that receptor outcome depends on adaptor availability.","evidence":"CRACC- and EAT-2-deficient mice with genetic epistasis and functional NK and T cell assays","pmids":["19151721"],"confidence":"High","gaps":["Biochemical basis of the inhibitory-to-activating switch not resolved","Whether the switch applies uniformly to all SLAM receptors unknown"]},{"year":2013,"claim":"Confirmed that EAT-2 immune activation strictly requires SH2-domain receptor engagement across multiple cell types.","evidence":"Overexpression of wild-type versus R31Q SH2 mutant EAT-2 in human PBMCs with NK, DC, monocyte, and cytokine readouts","pmids":["24374770"],"confidence":"Medium","gaps":["Single lab; effects shown via overexpression rather than endogenous editing","Which receptors mediate each cell-type effect not dissected"]},{"year":2014,"claim":"Resolved the activating mechanism in NK cells, mapping it to C-terminal tyrosines that couple receptors to PLCγ/Ca2+/Erk and drive granule polarization and exocytosis rather than conjugate formation.","evidence":"EAT-2 KO and tyrosine knock-in mice, biochemical PLCγ/Ca2+/Erk assays, and live-cell imaging of granule polarization","pmids":["24687958"],"confidence":"High","gaps":["Identity of effectors recruited to the C-terminal tyrosines not fully defined","How the same receptors yield inhibition without EAT-2 not biochemically resolved"]},{"year":2015,"claim":"Revealed a contrasting negative-regulatory role in dendritic cells, where EAT-2 suppresses IL-12 by blocking p38/JNK, linking EAT-2 dosage to Th1 outcomes.","evidence":"EAT-2 silencing in DCs, CD40/SLAM cross-linking, p38/JNK signaling assays, T cell co-culture, and subcongenic NZB mouse mapping","pmids":["26432891"],"confidence":"Medium","gaps":["Mechanism by which EAT-2 inhibits p38/JNK not defined","Reconciliation of activating (NK) versus inhibitory (DC) roles not established"]},{"year":2016,"claim":"Provided an unliganded human EAT-2 structure, exposing conformational flexibility in ligand-binding loops and a discrepancy with prior binding affinity data.","evidence":"X-ray crystallography of unliganded human EAT-2 with computational binding energy comparison","pmids":["27586300"],"confidence":"Medium","gaps":["Contradicts prior biochemical affinity data; additional factors beyond SH2 domain inferred but not identified","Functional relevance of unliganded conformation untested"]},{"year":null,"claim":"How EAT-2 mediates opposite signaling outcomes — activating in NK cells versus inhibitory in dendritic cells — through the same SLAM receptor engagements remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Effectors bound by the C-terminal tyrosines not identified","Cell-type-specific signaling determinants unknown","Quantitative role of EAT-2 dosage versus SAP competition not defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,3,6]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,7]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,6]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1,4,6,7]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,6]}],"complexes":[],"partners":["CD244","CRACC","NTB-A","CD84","CD150","CD229","SHP-2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O14796","full_name":"SH2 domain-containing protein 1B","aliases":["EWS/FLI1-activated transcript 2","EAT-2"],"length_aa":132,"mass_kda":15.3,"function":"Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9 and CD244 (PubMed:11689425). In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4 without effecting its tyrosine phosphorylation; downstream signaling involves PLCG1 and ERK activation (PubMed:24687958). Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (By similarity). In the context of NK cell-mediated cytotoxicity does not enhance conjugate formation with target cells but stimulates polarization of the microtubule-organizing center and cytotoxic granules toward the NK cell synapse (PubMed:24687958). Negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (By similarity)","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/O14796/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SH2D1B","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/SH2D1B","total_profiled":1310},"omim":[{"mim_id":"608510","title":"SH2 DOMAIN-CONTAINING 1B; SH2D1B","url":"https://www.omim.org/entry/608510"},{"mim_id":"606625","title":"SLAM FAMILY, MEMBER 7; SLAMF7","url":"https://www.omim.org/entry/606625"},{"mim_id":"600684","title":"T-LYMPHOCYTE SURFACE ANTIGEN LY-9; LY9","url":"https://www.omim.org/entry/600684"},{"mim_id":"152700","title":"SYSTEMIC LUPUS ERYTHEMATOSUS; SLE","url":"https://www.omim.org/entry/152700"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":7.1},{"tissue":"skeletal muscle","ntpm":11.4},{"tissue":"tongue","ntpm":6.1}],"url":"https://www.proteinatlas.org/search/SH2D1B"},"hgnc":{"alias_symbol":["EAT2"],"prev_symbol":[]},"alphafold":{"accession":"O14796","domains":[{"cath_id":"3.30.505.10","chopping":"13-101","consensus_level":"high","plddt":92.1838,"start":13,"end":101}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O14796","model_url":"https://alphafold.ebi.ac.uk/files/AF-O14796-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O14796-F1-predicted_aligned_error_v6.png","plddt_mean":80.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SH2D1B","jax_strain_url":"https://www.jax.org/strain/search?query=SH2D1B"},"sequence":{"accession":"O14796","fasta_url":"https://rest.uniprot.org/uniprotkb/O14796.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O14796/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O14796"}},"corpus_meta":[{"pmid":"19151721","id":"PMC_19151721","title":"Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2, on natural killer cell function.","date":"2009","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/19151721","citation_count":148,"is_preprint":false},{"pmid":"15020415","id":"PMC_15020415","title":"eat-2 and eat-18 are required for nicotinic neurotransmission in the Caenorhabditis elegans pharynx.","date":"2004","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/15020415","citation_count":139,"is_preprint":false},{"pmid":"16127454","id":"PMC_16127454","title":"Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptor.","date":"2005","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/16127454","citation_count":117,"is_preprint":false},{"pmid":"11689425","id":"PMC_11689425","title":"Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells.","date":"2001","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/11689425","citation_count":116,"is_preprint":false},{"pmid":"16339536","id":"PMC_16339536","title":"The cytotoxicity receptor CRACC (CS-1) recruits EAT-2 and activates the PI3K and phospholipase Cgamma signaling pathways in human NK cells.","date":"2005","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/16339536","citation_count":106,"is_preprint":false},{"pmid":"9000139","id":"PMC_9000139","title":"EAT-2 is a novel SH2 domain containing protein that is up regulated by Ewing's sarcoma EWS/FLI1 fusion gene.","date":"1996","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/9000139","citation_count":88,"is_preprint":false},{"pmid":"24687958","id":"PMC_24687958","title":"EAT-2, a SAP-like adaptor, controls NK cell activation through phospholipase Cγ, Ca++, and Erk, leading to granule polarization.","date":"2014","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/24687958","citation_count":79,"is_preprint":false},{"pmid":"12115647","id":"PMC_12115647","title":"CD84 is up-regulated on a major population of human memory B cells and recruits the SH2 domain containing proteins SAP and EAT-2.","date":"2002","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/12115647","citation_count":73,"is_preprint":false},{"pmid":"16920955","id":"PMC_16920955","title":"Molecular analysis of NTB-A signaling: a role for EAT-2 in NTB-A-mediated activation of human NK cells.","date":"2006","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/16920955","citation_count":43,"is_preprint":false},{"pmid":"32566245","id":"PMC_32566245","title":"Lifespan and healthspan benefits of exogenous H2S in C. elegans are independent from effects downstream of eat-2 mutation.","date":"2020","source":"NPJ aging and mechanisms of disease","url":"https://pubmed.ncbi.nlm.nih.gov/32566245","citation_count":34,"is_preprint":false},{"pmid":"21149608","id":"PMC_21149608","title":"Expression of the SLAM family of receptors adapter EAT-2 as a novel strategy for enhancing beneficial immune responses to vaccine antigens.","date":"2010","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/21149608","citation_count":31,"is_preprint":false},{"pmid":"32243475","id":"PMC_32243475","title":"EAT-18 is an essential auxiliary protein interacting with the non-alpha nAChR subunit EAT-2 to form a functional receptor.","date":"2020","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/32243475","citation_count":14,"is_preprint":false},{"pmid":"22745373","id":"PMC_22745373","title":"Vaccines expressing the innate immune modulator EAT-2 elicit potent effector memory T lymphocyte responses despite pre-existing vaccine immunity.","date":"2012","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/22745373","citation_count":14,"is_preprint":false},{"pmid":"21912619","id":"PMC_21912619","title":"Vaccine platforms combining circumsporozoite protein and potent immune modulators, rEA or EAT-2, paradoxically result in opposing immune responses.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21912619","citation_count":13,"is_preprint":false},{"pmid":"24374770","id":"PMC_24374770","title":"Manipulation of EAT-2 expression promotes induction of multiple beneficial regulatory and effector functions of the human innate immune system as a novel immunomodulatory strategy.","date":"2013","source":"International immunology","url":"https://pubmed.ncbi.nlm.nih.gov/24374770","citation_count":13,"is_preprint":false},{"pmid":"23949283","id":"PMC_23949283","title":"Improved cytotoxic T-lymphocyte immune responses to a tumor antigen by vaccines co-expressing the SLAM-associated adaptor EAT-2.","date":"2013","source":"Cancer gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/23949283","citation_count":12,"is_preprint":false},{"pmid":"30898771","id":"PMC_30898771","title":"Cross Talk with the GAR-3 Receptor Contributes to Feeding Defects in Caenorhabditis elegans eat-2 Mutants.","date":"2019","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30898771","citation_count":9,"is_preprint":false},{"pmid":"26432891","id":"PMC_26432891","title":"Identification of the SLAM Adapter Molecule EAT-2 as a Lupus-Susceptibility Gene That Acts through Impaired Negative Regulation of Dendritic Cell Signaling.","date":"2015","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/26432891","citation_count":5,"is_preprint":false},{"pmid":"37450052","id":"PMC_37450052","title":"EAT-2 attenuates C. elegans development via metabolic remodeling in a chemically defined food environment.","date":"2023","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/37450052","citation_count":4,"is_preprint":false},{"pmid":"27586300","id":"PMC_27586300","title":"The X-ray Crystallographic Structure of Human EAT2 (SH2D1B).","date":"2016","source":"Protein and peptide letters","url":"https://pubmed.ncbi.nlm.nih.gov/27586300","citation_count":1,"is_preprint":false},{"pmid":"41142196","id":"PMC_41142196","title":"Optimizing a C. elegans whole organism screen biased for chemicals that target the nematode clade specific receptor EAT-2.","date":"2025","source":"microPublication biology","url":"https://pubmed.ncbi.nlm.nih.gov/41142196","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11957,"output_tokens":3198,"usd":0.04192,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10601,"output_tokens":3410,"usd":0.069127,"stage2_stop_reason":"end_turn"},"total_usd":0.111047,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"EAT-2 (SH2D1B) encodes a free SH2 domain that binds phosphorylated tyrosine motifs in the cytoplasmic tails of SLAM family receptors CD84, CD150, CD229, and CD244. Crystal structure of EAT-2 in complex with a phosphotyrosine peptide from CD150 (Tyr281) is very similar to SAP/SH2D1A bound to the same peptide, explaining high affinity for pTyr motifs. Unlike SAP, EAT-2 does not bind non-phosphorylated CD150. EAT-2 acts as a natural inhibitor by interfering with recruitment of the tyrosine phosphatase SHP-2 to these receptors.\",\n      \"method\": \"X-ray crystallography (EAT-2–phosphopeptide complex), binding assays, competition/inhibition assays with SHP-2 recruitment\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with functional binding assays and SHP-2 inhibition experiment, single rigorous study with multiple orthogonal methods\",\n      \"pmids\": [\"11689425\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"EAT-2 associates with the SLAM-related receptor 2B4 in NK cells and inhibits natural cytotoxicity and IFN-γ secretion. This inhibitory mechanism requires tyrosine phosphorylation of the C-terminal tail of EAT-2. The related adaptor ERT shares this inhibitory function in mouse NK cells. EAT-2 and SAP have distinct and opposing functions: SAP activates while EAT-2 inhibits NK cell function.\",\n      \"method\": \"Co-immunoprecipitation, EAT-2 knockout and overexpression mouse models, functional NK cell assays (cytotoxicity, cytokine secretion), phosphorylation-site mutagenesis\",\n      \"journal\": \"Nature immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, genetic KO and OE mouse models, multiple functional readouts, replicated with ERT adaptor\",\n      \"pmids\": [\"16127454\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Upon activation, CRACC (CS-1) associates with EAT-2 in human NK cells. EAT-2 association induces phosphorylation of CRACC (partially reduced by Src kinase inhibitor). PLCγ1, PLCγ2, and PI3K are the major downstream signaling mediators of the CRACC/EAT-2 complex in NK cell cytotoxicity. EAT-2 also associates with 2B4 predominantly in resting NK cells, whereas SAP preferentially binds 2B4 upon activation.\",\n      \"method\": \"Co-immunoprecipitation, pharmacological Src kinase inhibition, signaling pathway analysis (PI3K, PLCγ) in human NK cells\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and downstream signaling assays, single lab, two orthogonal methods\",\n      \"pmids\": [\"16339536\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"NTB-A is tyrosine-phosphorylated in resting human NK cells by Src family kinases and associates with both SAP and EAT-2. EAT-2 (but not SAP) is recruited specifically to the second tyrosine of NTB-A's cytoplasmic tail, and this tyrosine is sufficient and essential for NTB-A-mediated cytotoxicity. NTB-A can mediate cytotoxicity in the absence of SAP, likely via EAT-2, whereas NTB-A-mediated IFN-γ production depends on SAP.\",\n      \"method\": \"Co-immunoprecipitation, NTB-A-negative NK cell line reconstitution with tyrosine mutants, SAP siRNA knockdown, functional cytotoxicity and cytokine assays\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — receptor reconstitution in null line with site-directed mutants, SAP knockdown, multiple functional readouts, single rigorous study with multiple orthogonal methods\",\n      \"pmids\": [\"16920955\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"CRACC positively regulates NK cell function by a mechanism dependent on EAT-2 (but not SAP). In the absence of EAT-2, CRACC potently inhibits NK cell function. In T cells, which lack EAT-2, CRACC is inhibitory. Thus EAT-2 switches CRACC from an inhibitory to an activating receptor.\",\n      \"method\": \"CRACC-deficient mouse, EAT-2-deficient mouse, functional NK and T cell assays, genetic epistasis\",\n      \"journal\": \"Nature immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO of CRACC and EAT-2, epistasis experiment, multiple functional readouts, replicated across cell types\",\n      \"pmids\": [\"19151721\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"CD84 undergoes rapid tyrosine phosphorylation upon ligation and recruits the SH2 domain-containing adaptors SAP and EAT-2, identifying CD84 as a SLAM family receptor that engages EAT-2 signaling in B cells.\",\n      \"method\": \"Co-immunoprecipitation, anti-CD84 ligation, tyrosine phosphorylation assay\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP and phosphorylation assay, single lab, two methods (ligation + Co-IP)\",\n      \"pmids\": [\"12115647\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"EAT-2 mediates NK cell activation by coupling SLAM family receptors to PLCγ, calcium fluxes, and Erk kinase. This signaling is triggered by one or two tyrosines in the C-terminal tail of EAT-2 (absent in SAP). Unlike SAP, EAT-2 does not enhance NK–target conjugate formation; instead it accelerates polarization and exocytosis of cytotoxic granules toward hematopoietic target cells.\",\n      \"method\": \"Genetic (EAT-2 KO and tyrosine mutant knock-in), biochemical (PLCγ, Ca2+, Erk assays), live-cell imaging of granule polarization\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with site-directed C-terminal tyrosine mutants, multiple orthogonal biochemical and imaging methods, clearly distinguishes mechanism from SAP\",\n      \"pmids\": [\"24687958\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"EAT-2 negatively regulates cytokine (IL-12) production in dendritic cells downstream of SLAM engagement. A promoter polymorphism in the NZB mouse reduces EAT-2 expression ~70% in DCs. SLAM co-engagement blocks p38 MAPK and JNK signaling in DCs, an effect reversed in DCs with low EAT-2 (NZB allele). EAT-2 knockdown in normal DCs increases IL-12 production and enhances Th1 differentiation.\",\n      \"method\": \"EAT-2 gene silencing in DCs, CD40/SLAM cross-linking, downstream signaling assays (p38 MAPK, JNK), T cell co-culture cytokine assays, subcongenic mouse mapping\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown and signaling pathway assays, single lab, multiple orthogonal methods (signaling + cytokine + T cell assays)\",\n      \"pmids\": [\"26432891\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"X-ray crystallographic structure of human EAT-2 (SH2D1B) was determined in an unliganded form. Conformational differences were observed in ligand-binding loops compared to mouse EAT-2–peptide complex. EAT-2 shows similar binding energies to unphosphorylated ligands as SAP, which is inconsistent with prior biochemical data showing EAT-2 has lower affinity for unphosphorylated peptides than SAP, suggesting additional factors beyond the SH2 domain contribute to this difference.\",\n      \"method\": \"X-ray crystallography, computational binding energy comparison\",\n      \"journal\": \"Protein and peptide letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — crystal structure determined but single lab, limited functional validation, contradicts prior biochemical data\",\n      \"pmids\": [\"27586300\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"EAT-2-mediated immune activation requires an intact SH2 domain: an R31Q SH2 domain mutant form of EAT-2 failed to enhance NK cell anti-tumor activity, DC maturation, monocyte phagocytosis, or pro-inflammatory cytokine kinetics in human cells, indicating that EAT-2 interaction with SLAM receptors via its SH2 domain is required for these functions.\",\n      \"method\": \"EAT-2 overexpression vs. R31Q SH2 mutant in human PBMCs; functional assays (NK cytotoxicity, DC maturation, cytokine measurement)\",\n      \"journal\": \"International immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — active-site SH2 mutant (R31Q) compared to wild-type, multiple functional readouts, single lab\",\n      \"pmids\": [\"24374770\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"EAT-2 (SH2D1B) was identified as a novel gene containing a unique but biochemically functional SH2 domain, upregulated by the EWS/FLI1 fusion oncogene in Ewing's sarcoma. Expression correlated with NIH3T3 transformation by EWS/FLI1-related chimeric proteins. Human EAT-2 was mapped to chromosome 1q22.\",\n      \"method\": \"Representational difference analysis (RDA) cloning, SH2 domain functional assay, chromosomal mapping\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — initial identification with SH2 biochemical functionality assay, single lab, limited mechanistic follow-up\",\n      \"pmids\": [\"9000139\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SH2D1B/EAT-2 is a free SH2 domain-containing intracellular adaptor expressed in innate immune cells (NK cells, macrophages, dendritic cells, B cells) that binds phosphotyrosine motifs in the cytoplasmic tails of SLAM family receptors (CD84, CD150/SLAM, CD229, CD244/2B4, CRACC, NTB-A); in NK cells, EAT-2 couples these receptors via C-terminal tyrosines to PLCγ, calcium, and Erk signaling to accelerate cytotoxic granule polarization and exocytosis, while in the absence of EAT-2 the same receptors become inhibitory; in dendritic cells, EAT-2 negatively regulates SLAM-triggered IL-12 production by suppressing p38 MAPK and JNK signaling downstream of CD40/SLAM co-engagement, and its activity in all contexts requires an intact SH2 domain.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SH2D1B (EAT-2) is a free SH2 domain-containing intracellular adaptor that couples SLAM family immune receptors to downstream signaling, governing the activation threshold of innate immune effector cells [#0, #6]. Its SH2 domain binds phosphotyrosine motifs in the cytoplasmic tails of SLAM family receptors including CD150, CD84, CD229, CD244/2B4, CRACC, and NTB-A, with a binding mode crystallographically similar to the related adaptor SAP but specific for the phosphorylated receptor; in doing so EAT-2 can compete with the recruitment of the phosphatase SHP-2 [#0, #3, #5]. In NK cells, EAT-2 acts through one or two tyrosines in its C-terminal tail — features absent from SAP — to link these receptors to PLCγ, calcium flux, and Erk signaling, accelerating polarization and exocytosis of cytotoxic granules toward target cells rather than enhancing conjugate formation [#6, #2]. EAT-2 is a decisive switch in receptor outcome: it converts CRACC from an inhibitory to an activating receptor, and in its absence the same SLAM receptors signal inhibition [#4]. All of these activating functions require an intact SH2 domain, as the R31Q mutant abolishes EAT-2-dependent NK, DC, and monocyte responses [#9]. In dendritic cells EAT-2 instead acts as a negative regulator, suppressing SLAM-triggered IL-12 production by blocking p38 MAPK and JNK signaling and thereby limiting Th1 differentiation [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Established EAT-2 as a distinct gene encoding a biochemically functional SH2 domain, placing it in the SH2 adaptor landscape before any immune function was known.\",\n      \"evidence\": \"RDA cloning, SH2 domain functional assay, and chromosomal mapping in the context of EWS/FLI1-driven transformation\",\n      \"pmids\": [\"9000139\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Limited mechanistic follow-up; immune role not yet defined\", \"Functional relationship of EWS/FLI1 upregulation to physiological EAT-2 function unclear\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Defined the structural basis for EAT-2 recognition of SLAM family receptors and showed it binds phosphorylated, not unphosphorylated, receptor tails — answering how EAT-2 engages its receptors and how it differs from SAP.\",\n      \"evidence\": \"X-ray crystallography of the EAT-2–CD150 phosphopeptide complex with binding and SHP-2 competition assays\",\n      \"pmids\": [\"11689425\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence in living immune cells not directly tested\", \"Whether SHP-2 displacement is the dominant in vivo mechanism not resolved\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Identified CD84 as a SLAM family receptor that recruits both SAP and EAT-2 upon ligation, extending the EAT-2 receptor repertoire into B cells.\",\n      \"evidence\": \"Co-immunoprecipitation and tyrosine phosphorylation assay following CD84 ligation\",\n      \"pmids\": [\"12115647\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream signaling consequences in B cells not defined\", \"No functional readout beyond receptor association\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Demonstrated that EAT-2 associates with 2B4 and CRACC and identified PLCγ and PI3K as downstream mediators, while revealing that EAT-2 and SAP have opposing functions on NK cells.\",\n      \"evidence\": \"Reciprocal Co-IP, EAT-2 KO and overexpression mouse models, Src kinase inhibition, and functional NK cytotoxicity/cytokine assays\",\n      \"pmids\": [\"16127454\", \"16339536\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Apparent contradiction between inhibitory (2B4) and activating signaling readouts not reconciled\", \"Role of EAT-2 C-terminal tyrosines not yet mapped\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Showed EAT-2 is recruited to a specific tyrosine of NTB-A required for cytotoxicity, establishing that EAT-2 can mediate receptor function independently of SAP.\",\n      \"evidence\": \"Co-IP, reconstitution of NTB-A-null NK cells with tyrosine mutants, and SAP siRNA knockdown with functional assays\",\n      \"pmids\": [\"16920955\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking the NTB-A tyrosine to EAT-2 effector signaling not detailed\", \"Division of labor between SAP (cytokine) and EAT-2 (cytotoxicity) mechanistically incomplete\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Established EAT-2 as a molecular switch that converts CRACC from inhibitory to activating, defining the principle that receptor outcome depends on adaptor availability.\",\n      \"evidence\": \"CRACC- and EAT-2-deficient mice with genetic epistasis and functional NK and T cell assays\",\n      \"pmids\": [\"19151721\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Biochemical basis of the inhibitory-to-activating switch not resolved\", \"Whether the switch applies uniformly to all SLAM receptors unknown\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Confirmed that EAT-2 immune activation strictly requires SH2-domain receptor engagement across multiple cell types.\",\n      \"evidence\": \"Overexpression of wild-type versus R31Q SH2 mutant EAT-2 in human PBMCs with NK, DC, monocyte, and cytokine readouts\",\n      \"pmids\": [\"24374770\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; effects shown via overexpression rather than endogenous editing\", \"Which receptors mediate each cell-type effect not dissected\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Resolved the activating mechanism in NK cells, mapping it to C-terminal tyrosines that couple receptors to PLCγ/Ca2+/Erk and drive granule polarization and exocytosis rather than conjugate formation.\",\n      \"evidence\": \"EAT-2 KO and tyrosine knock-in mice, biochemical PLCγ/Ca2+/Erk assays, and live-cell imaging of granule polarization\",\n      \"pmids\": [\"24687958\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of effectors recruited to the C-terminal tyrosines not fully defined\", \"How the same receptors yield inhibition without EAT-2 not biochemically resolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Revealed a contrasting negative-regulatory role in dendritic cells, where EAT-2 suppresses IL-12 by blocking p38/JNK, linking EAT-2 dosage to Th1 outcomes.\",\n      \"evidence\": \"EAT-2 silencing in DCs, CD40/SLAM cross-linking, p38/JNK signaling assays, T cell co-culture, and subcongenic NZB mouse mapping\",\n      \"pmids\": [\"26432891\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which EAT-2 inhibits p38/JNK not defined\", \"Reconciliation of activating (NK) versus inhibitory (DC) roles not established\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Provided an unliganded human EAT-2 structure, exposing conformational flexibility in ligand-binding loops and a discrepancy with prior binding affinity data.\",\n      \"evidence\": \"X-ray crystallography of unliganded human EAT-2 with computational binding energy comparison\",\n      \"pmids\": [\"27586300\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Contradicts prior biochemical affinity data; additional factors beyond SH2 domain inferred but not identified\", \"Functional relevance of unliganded conformation untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How EAT-2 mediates opposite signaling outcomes — activating in NK cells versus inhibitory in dendritic cells — through the same SLAM receptor engagements remains unresolved.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Effectors bound by the C-terminal tyrosines not identified\", \"Cell-type-specific signaling determinants unknown\", \"Quantitative role of EAT-2 dosage versus SAP competition not defined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 3, 6]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1, 4, 6, 7]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 6]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CD244\", \"CRACC\", \"NTB-A\", \"CD84\", \"CD150\", \"CD229\", \"SHP-2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}