{"gene":"SH2D3C","run_date":"2026-06-10T07:46:31","timeline":{"discoveries":[{"year":2013,"finding":"Computational modeling predicted that human SH2D3C (NSP3) interacts with p130Cas to form a multi-domain signaling platform; mutations NSP3(L469R), NSP3(L623E), and NSP3(R627E) were predicted to reduce binding affinity to p130Cas, with NSP3(L469R) showing the most significant structural deviation and increased conformational flexibility by molecular dynamics simulation.","method":"Computational molecular docking and molecular dynamics simulation (in silico only; no wet-lab validation reported)","journal":"Cell biochemistry and biophysics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — purely computational study, no experimental biochemical or cellular validation of the predicted NSP3-p130Cas interaction","pmids":["23494262"],"is_preprint":false}],"current_model":"No experimentally validated mechanistic findings are available for the human SH2D3C (NSP3) protein in the retrieved literature; the only paper addressing this protein used purely computational methods to predict its interaction with p130Cas as part of a cell signaling complex."},"narrative":{"mechanistic_narrative":"Mechanistic understanding of human SH2D3C (NSP3) rests on a single computational study, which used molecular docking and molecular dynamics simulation to predict that NSP3 interacts with p130Cas to form a multi-domain signaling platform, and that the substitutions L469R, L623E, and R627E would reduce p130Cas binding affinity, with L469R causing the largest structural deviation and increased conformational flexibility [PMID:23494262]. Beyond this in silico prediction, no wet-lab biochemical, cellular, or structural characterization of SH2D3C has been established in the available corpus.","teleology":[{"year":2013,"claim":"To address whether NSP3 could physically engage p130Cas in a signaling complex, an in silico study modeled the interaction and the effect of point mutations, establishing a candidate binding interface and residues predicted to be critical for affinity.","evidence":"Computational molecular docking and molecular dynamics simulation, no wet-lab validation","pmids":["23494262"],"confidence":"Low","gaps":["Purely computational; the predicted NSP3-p130Cas interaction has not been confirmed by any biochemical or cellular assay","No experimental validation of the L469R, L623E, or R627E mutational effects on binding","No determination of the cellular context, localization, or downstream signaling role of the predicted complex"]},{"year":null,"claim":"Whether SH2D3C physically binds p130Cas in cells and what signaling or cellular function this complex serves remains entirely uncharacterized experimentally.","evidence":"No direct experimental evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No reconstitution or co-immunoprecipitation confirming the interaction","No defined molecular activity, localization, or pathway assignment","No loss-of-function phenotype reported"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8N5H7","full_name":"SH2 domain-containing protein 3C","aliases":["Cas/HEF1-associated signal transducer","Chat-H","Novel SH2-containing protein 3","SH2 domain-containing Eph receptor-binding protein 1","SHEP1"],"length_aa":860,"mass_kda":94.4,"function":"Acts as an adapter protein that mediates cell signaling pathways involved in cellular functions such as cell adhesion and migration, tissue organization, and the regulation of the immune response (PubMed:12432078, PubMed:20881139). Plays a role in integrin-mediated cell adhesion through BCAR1-CRK-RAPGEF1 signaling and activation of the small GTPase RAP1 (PubMed:12432078). Promotes cell migration and invasion through the extracellular matrix (PubMed:20881139). Required for marginal zone B-cell development and thymus-independent type 2 immune responses (By similarity). Mediates migration and adhesion of B cells in the splenic marginal zone via promoting hyperphosphorylation of NEDD9/CASL (By similarity). Plays a role in CXCL13-induced chemotaxis of B-cells (By similarity). Plays a role in the migration of olfactory sensory neurons (OSNs) into the forebrain and the innervation of the olfactory bulb by the OSN axons during development (By similarity). Required for the efficient tyrosine phosphorylation of BCAR1 in OSN axons (By similarity) Important regulator of chemokine-induced, integrin-mediated T lymphocyte adhesion and migration, acting upstream of RAP1 (By similarity). Required for tissue-specific adhesion of T lymphocytes to peripheral tissues (By similarity). Required for basal and CXCL2 stimulated serine-threonine phosphorylation of NEDD9 (By similarity). May be involved in the regulation of T-cell receptor-mediated IL2 production through the activation of the JNK pathway in T-cells (By similarity) May be involved in the BCAR1/CAS-mediated JNK activation pathway","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q8N5H7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SH2D3C","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SH2D3C","total_profiled":1310},"omim":[{"mim_id":"604722","title":"SH2 DOMAIN-CONTAINING PROTEIN 3C; SH2D3C","url":"https://www.omim.org/entry/604722"},{"mim_id":"602265","title":"NEURAL PRECURSOR CELL EXPRESSED, DEVELOPMENTALLY DOWNREGULATED 9; NEDD9","url":"https://www.omim.org/entry/602265"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SH2D3C"},"hgnc":{"alias_symbol":["NSP3"],"prev_symbol":[]},"alphafold":{"accession":"Q8N5H7","domains":[{"cath_id":"3.30.505.10","chopping":"194-334","consensus_level":"high","plddt":91.2151,"start":194,"end":334},{"cath_id":"1.10.840.10","chopping":"573-852","consensus_level":"high","plddt":93.286,"start":573,"end":852}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N5H7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N5H7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N5H7-F1-predicted_aligned_error_v6.png","plddt_mean":66.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SH2D3C","jax_strain_url":"https://www.jax.org/strain/search?query=SH2D3C"},"sequence":{"accession":"Q8N5H7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N5H7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N5H7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N5H7"}},"corpus_meta":[{"pmid":"29128390","id":"PMC_29128390","title":"Nsp3 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Replication.","date":"2017","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/29162711","citation_count":206,"is_preprint":false},{"pmid":"19386706","id":"PMC_19386706","title":"The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket.","date":"2009","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/19386706","citation_count":194,"is_preprint":false},{"pmid":"33853786","id":"PMC_33853786","title":"Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking.","date":"2021","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/33853786","citation_count":166,"is_preprint":false},{"pmid":"16271890","id":"PMC_16271890","title":"Structural basis of severe acute respiratory syndrome coronavirus ADP-ribose-1''-phosphate dephosphorylation by a conserved domain of nsP3.","date":"2005","source":"Structure 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microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/32749662","citation_count":39,"is_preprint":false},{"pmid":"29702546","id":"PMC_29702546","title":"Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus.","date":"2018","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/29702546","citation_count":38,"is_preprint":false},{"pmid":"11462002","id":"PMC_11462002","title":"A human rotavirus with rearranged genes 7 and 11 encodes a modified NSP3 protein and suggests an additional mechanism for gene rearrangement.","date":"2001","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/11462002","citation_count":37,"is_preprint":false},{"pmid":"20015978","id":"PMC_20015978","title":"Novel functions of the alphavirus nonstructural protein nsP3 C-terminal region.","date":"2009","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/20015978","citation_count":36,"is_preprint":false},{"pmid":"8623548","id":"PMC_8623548","title":"Complete sequence of Venezuelan equine encephalitis virus subtype IE reveals conserved and hypervariable domains within the C terminus of nsP3.","date":"1996","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/8623548","citation_count":36,"is_preprint":false},{"pmid":"26063427","id":"PMC_26063427","title":"Rotavirus NSP3 Is a Translational Surrogate of the Poly(A) Binding Protein-Poly(A) Complex.","date":"2015","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/26063427","citation_count":35,"is_preprint":false},{"pmid":"7871749","id":"PMC_7871749","title":"Comparative nucleotide and amino acid sequence analysis of the sequence-specific RNA-binding rotavirus nonstructural protein NSP3.","date":"1995","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/7871749","citation_count":35,"is_preprint":false},{"pmid":"27901124","id":"PMC_27901124","title":"Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27901124","citation_count":35,"is_preprint":false},{"pmid":"10867195","id":"PMC_10867195","title":"Rearrangement generated in double genes, NSP1 and NSP3, of viable progenies from a human rotavirus strain.","date":"2000","source":"Virus research","url":"https://pubmed.ncbi.nlm.nih.gov/10867195","citation_count":35,"is_preprint":false},{"pmid":"12093167","id":"PMC_12093167","title":"Rotavirus protein NSP3 shuts off host cell protein synthesis.","date":"2002","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/12093167","citation_count":34,"is_preprint":false},{"pmid":"15047801","id":"PMC_15047801","title":"RoXaN, a novel cellular protein containing TPR, LD, and zinc finger motifs, forms a ternary complex with eukaryotic initiation factor 4G and rotavirus NSP3.","date":"2004","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/15047801","citation_count":33,"is_preprint":false},{"pmid":"27268056","id":"PMC_27268056","title":"Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2.","date":"2016","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27268056","citation_count":33,"is_preprint":false},{"pmid":"27105836","id":"PMC_27105836","title":"Venezuelan equine encephalitis virus non-structural protein 3 (nsP3) interacts with RNA helicases DDX1 and DDX3 in infected cells.","date":"2016","source":"Antiviral research","url":"https://pubmed.ncbi.nlm.nih.gov/27105836","citation_count":32,"is_preprint":false},{"pmid":"16528043","id":"PMC_16528043","title":"Deletions in the hypervariable domain of the nsP3 gene attenuate Semliki Forest virus virulence.","date":"2006","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/16528043","citation_count":31,"is_preprint":false},{"pmid":"29375517","id":"PMC_29375517","title":"Interactions of Alphavirus nsP3 Protein with Host Proteins.","date":"2018","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/29375517","citation_count":30,"is_preprint":false},{"pmid":"24756552","id":"PMC_24756552","title":"Discovery of in silico hits targeting the nsP3 macro domain of chikungunya virus.","date":"2014","source":"Journal of molecular modeling","url":"https://pubmed.ncbi.nlm.nih.gov/24756552","citation_count":30,"is_preprint":false},{"pmid":"37651466","id":"PMC_37651466","title":"A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/37651466","citation_count":29,"is_preprint":false},{"pmid":"31815237","id":"PMC_31815237","title":"Evaluation of the Antiviral Potential of Halogenated Dihydrorugosaflavonoids and Molecular Modeling with nsP3 Protein of Chikungunya Virus (CHIKV).","date":"2019","source":"ACS omega","url":"https://pubmed.ncbi.nlm.nih.gov/31815237","citation_count":28,"is_preprint":false},{"pmid":"30691473","id":"PMC_30691473","title":"Involvement of PRRSV NSP3 and NSP5 in the autophagy process.","date":"2019","source":"Virology journal","url":"https://pubmed.ncbi.nlm.nih.gov/30691473","citation_count":27,"is_preprint":false},{"pmid":"35597097","id":"PMC_35597097","title":"Design, synthesis and evaluation of inhibitors of the SARS-CoV-2 nsp3 macrodomain.","date":"2022","source":"Bioorganic & medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35597097","citation_count":27,"is_preprint":false},{"pmid":"37487098","id":"PMC_37487098","title":"Nsp3-N interactions are critical for SARS-CoV-2 fitness and virulence.","date":"2023","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/37487098","citation_count":26,"is_preprint":false},{"pmid":"32611753","id":"PMC_32611753","title":"Expression of Separate Heterologous Proteins from the Rotavirus NSP3 Genome Segment Using a Translational 2A Stop-Restart Element.","date":"2020","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/32611753","citation_count":26,"is_preprint":false},{"pmid":"26296883","id":"PMC_26296883","title":"X-ray Structural and Functional Studies of the Three Tandemly Linked Domains of Non-structural Protein 3 (nsp3) from Murine Hepatitis Virus Reveal Conserved Functions.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26296883","citation_count":26,"is_preprint":false},{"pmid":"39285216","id":"PMC_39285216","title":"Alphavirus nsP3 organizes into tubular scaffolds essential for infection and the cytoplasmic granule architecture.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39285216","citation_count":25,"is_preprint":false},{"pmid":"21489987","id":"PMC_21489987","title":"Active participation of cellular chaperone Hsp90 in regulating the function of rotavirus nonstructural protein 3 (NSP3).","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21489987","citation_count":24,"is_preprint":false},{"pmid":"22442114","id":"PMC_22442114","title":"Rotavirus variant replicates efficiently although encoding an aberrant NSP3 that fails to induce nuclear localization of poly(A)-binding protein.","date":"2012","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/22442114","citation_count":24,"is_preprint":false},{"pmid":"33568506","id":"PMC_33568506","title":"Phosphorylation Sites in the Hypervariable Domain in Chikungunya Virus nsP3 Are Crucial for Viral Replication.","date":"2021","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/33568506","citation_count":23,"is_preprint":false},{"pmid":"23494262","id":"PMC_23494262","title":"Investigation of binding phenomenon of NSP3 and p130Cas mutants and their effect on cell signalling.","date":"2013","source":"Cell biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/23494262","citation_count":23,"is_preprint":false},{"pmid":"32333884","id":"PMC_32333884","title":"Is the ADP ribose site of the Chikungunya virus NSP3 Macro domain a target for antiviral approaches?","date":"2020","source":"Acta tropica","url":"https://pubmed.ncbi.nlm.nih.gov/32333884","citation_count":21,"is_preprint":false},{"pmid":"26280524","id":"PMC_26280524","title":"Development of novel antibodies against non-structural proteins nsP1, nsP3 and nsP4 of chikungunya virus: potential use in basic research.","date":"2015","source":"Archives of virology","url":"https://pubmed.ncbi.nlm.nih.gov/26280524","citation_count":21,"is_preprint":false},{"pmid":"31406937","id":"PMC_31406937","title":"A model to study the inhibition of nsP2B-nsP3 protease of dengue virus with imidazole, oxazole, triazole thiadiazole, and thiazolidine based scaffolds.","date":"2019","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/31406937","citation_count":21,"is_preprint":false},{"pmid":"36839595","id":"PMC_36839595","title":"Discovery and Development Strategies for SARS-CoV-2 NSP3 Macrodomain Inhibitors.","date":"2023","source":"Pathogens (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/36839595","citation_count":20,"is_preprint":false},{"pmid":"35037841","id":"PMC_35037841","title":"Molecular modelling and structure-activity relationship of a natural derivative of o-hydroxybenzoate as a potent inhibitor of dual NSP3 and NSP12 of SARS-CoV-2: in silico study.","date":"2022","source":"Journal of biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/35037841","citation_count":20,"is_preprint":false},{"pmid":"34076483","id":"PMC_34076483","title":"NAP1L1 and NAP1L4 Binding to Hypervariable Domain of Chikungunya Virus nsP3 Protein Is Bivalent and Requires Phosphorylation.","date":"2021","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/34076483","citation_count":19,"is_preprint":false},{"pmid":"32933112","id":"PMC_32933112","title":"Venezuelan Equine Encephalitis Virus nsP3 Phosphorylation Can Be Mediated by IKKβ Kinase Activity and Abrogation of Phosphorylation Inhibits Negative-Strand Synthesis.","date":"2020","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/32933112","citation_count":19,"is_preprint":false},{"pmid":"32581106","id":"PMC_32581106","title":"Hypervariable Domain of nsP3 of Eastern Equine Encephalitis Virus Is a Critical Determinant of Viral Virulence.","date":"2020","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/32581106","citation_count":19,"is_preprint":false},{"pmid":"21185049","id":"PMC_21185049","title":"Lineage replacement accompanying duplication and rapid fixation of an RNA element in the nsP3 gene in a species of alphavirus.","date":"2010","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/21185049","citation_count":19,"is_preprint":false},{"pmid":"31493651","id":"PMC_31493651","title":"Structural characterization and biological function of bivalent binding of CD2AP to intrinsically disordered domain of chikungunya virus nsP3 protein.","date":"2019","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/31493651","citation_count":19,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":52151,"output_tokens":693,"usd":0.083424,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6547,"output_tokens":777,"usd":0.02608,"stage2_stop_reason":"end_turn"},"total_usd":0.109504,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify which papers are about the canonical human gene SH2D3C (also known as NSP3, a human signaling protein) versus viral proteins that share the \"NSP3\" or \"nsP3\" name.\n\nSH2D3C/NSP3 is a human SH2-domain containing protein (Novel SH2-containing Protein 3) involved in cell signaling, distinct from:\n- Rotavirus NSP3 (non-structural protein 3)\n- Alphavirus nsP3 (non-structural protein 3)\n- Coronavirus Nsp3 (non-structural protein 3)\n\nThese are all viral proteins that share the \"NSP3\" abbreviation but are entirely different proteins from the human SH2D3C gene.\n\nThe only paper that appears to be about the actual human SH2D3C protein is paper [90] (PMID:23494262), which discusses \"NSP3\" in the context of novel SH2-containing protein and p130Cas binding in cell signaling. This appears to be about the human SH2D3C/NSP3 protein.\n\nLet me evaluate paper [90]: It discusses NSP3 and p130Cas as \"multi-domain signalling platforms\" and performs molecular dynamics and docking analysis of mutations. However, this is purely computational (in silico) — molecular docking and MD simulation only, no wet-lab experiments. This is Tier 4 evidence.\n\nAll other papers are about viral NSP3 proteins (rotavirus, alphavirus, coronavirus) which are symbol collisions, not the human SH2D3C gene.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"Computational modeling predicted that human SH2D3C (NSP3) interacts with p130Cas to form a multi-domain signaling platform; mutations NSP3(L469R), NSP3(L623E), and NSP3(R627E) were predicted to reduce binding affinity to p130Cas, with NSP3(L469R) showing the most significant structural deviation and increased conformational flexibility by molecular dynamics simulation.\",\n      \"method\": \"Computational molecular docking and molecular dynamics simulation (in silico only; no wet-lab validation reported)\",\n      \"journal\": \"Cell biochemistry and biophysics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — purely computational study, no experimental biochemical or cellular validation of the predicted NSP3-p130Cas interaction\",\n      \"pmids\": [\"23494262\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"No experimentally validated mechanistic findings are available for the human SH2D3C (NSP3) protein in the retrieved literature; the only paper addressing this protein used purely computational methods to predict its interaction with p130Cas as part of a cell signaling complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Mechanistic understanding of human SH2D3C (NSP3) rests on a single computational study, which used molecular docking and molecular dynamics simulation to predict that NSP3 interacts with p130Cas to form a multi-domain signaling platform, and that the substitutions L469R, L623E, and R627E would reduce p130Cas binding affinity, with L469R causing the largest structural deviation and increased conformational flexibility [#0]. Beyond this in silico prediction, no wet-lab biochemical, cellular, or structural characterization of SH2D3C has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"To address whether NSP3 could physically engage p130Cas in a signaling complex, an in silico study modeled the interaction and the effect of point mutations, establishing a candidate binding interface and residues predicted to be critical for affinity.\",\n      \"evidence\": \"Computational molecular docking and molecular dynamics simulation, no wet-lab validation\",\n      \"pmids\": [\"23494262\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Purely computational; the predicted NSP3-p130Cas interaction has not been confirmed by any biochemical or cellular assay\",\n        \"No experimental validation of the L469R, L623E, or R627E mutational effects on binding\",\n        \"No determination of the cellular context, localization, or downstream signaling role of the predicted complex\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether SH2D3C physically binds p130Cas in cells and what signaling or cellular function this complex serves remains entirely uncharacterized experimentally.\",\n      \"evidence\": \"No direct experimental evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No reconstitution or co-immunoprecipitation confirming the interaction\",\n        \"No defined molecular activity, localization, or pathway assignment\",\n        \"No loss-of-function phenotype reported\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"loss","faith_supported":1,"faith_total":1,"faith_pct":100.0}}