{"gene":"RCN1","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2017,"finding":"RCN1 (reticulocalbin 1) is transactivated by NF-κB during ER stress. The first two EF-hand calcium-binding motifs of RCN1 specifically interact with IP3R1 on loop 3 of its ER luminal domain, inhibiting ER calcium release and suppressing PERK-CHOP signaling, thereby inhibiting ER stress-induced apoptosis.","method":"Co-immunoprecipitation (Co-IP) identifying RCN1-IP3R1 interaction; EF-hand domain mutagenesis; depletion/overexpression assays measuring UPR activation, calcium release, and apoptosis","journal":"Oncogenesis","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP identifying binding domain, domain-specific mutagenesis, multiple orthogonal functional assays (calcium release, PERK-CHOP signaling, apoptosis) in a single study","pmids":["28319095"],"is_preprint":false},{"year":2021,"finding":"RCN1 promotes dissociation of GRP78 from IRE1α in sorafenib-resistant HCC cells by interacting with GRP78 through its EFh1/2 domain, leading to sustained activation of the IRE1α-XBP1s pathway and downstream c-MYC signaling.","method":"Co-immunoprecipitation identifying RCN1-GRP78 interaction via EFh1/2 domain; overexpression/knockdown in sorafenib-resistant HCC cells with pathway activity readouts","journal":"Cell death discovery","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP interaction identified and domain implicated, functional readouts in cellular model; single lab","pmids":["34663798"],"is_preprint":false},{"year":2025,"finding":"RCN1 uses its EF-hand (EFh1/2) domains to sense ER calcium concentration and modulates its binding to IP3R1 accordingly, suppressing IP3R1-GRP75 interaction and ER-to-mitochondria calcium transfer. Downregulation of RCN1 strengthens ER-mitochondria coupling. TRIM11-mediated ubiquitination regulates RCN1 protein stability.","method":"Co-IP; overexpression/knockdown in HCC xenograft and spontaneous models; proteomic analysis; functional assays for ER-mitochondria calcium transfer","journal":"Drug resistance updates","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple interaction partners identified by Co-IP, domain attribution, in vivo model; single lab","pmids":["41385809"],"is_preprint":false},{"year":2014,"finding":"RCN1 functions as a negative modulator of B-RAF activity in cardiomyocytes, inhibiting phenylephrine-induced hypertrophy and reducing MEK1/2 phosphorylation. Conversely, adenoviral knockdown of RCN1 induced cardiomyocyte hypertrophy and increased MEK1/2 phosphorylation.","method":"Eukaryotic cDNA expression screen with dual-luciferase B-RAF reporter assay; adenovirus-mediated overexpression and miRNA-mediated knockdown of RCN1; measurement of MEK1/2 phosphorylation and hypertrophic markers in neonatal rat cardiomyocytes","journal":"Cardiovascular research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional screen identified RCN1, gain-of-function and loss-of-function in cardiomyocytes with specific pathway readout; single lab","pmids":["24492844"],"is_preprint":false},{"year":2025,"finding":"RCN1 binds KIF14 (identified by immunoprecipitation-mass spectrometry), and this interaction promotes activation of the PI3K-AKT-mTOR pathway, facilitating proliferation, migration, and invasion of cervical cancer cells.","method":"Immunoprecipitation tandem mass spectrometry (IP-MS) identifying KIF14 as RCN1 binding partner; knockdown and overexpression assays; Western blotting for PI3K-AKT-mTOR pathway; mouse xenograft model","journal":"International journal of general medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — IP-MS identified binding partner, supported by functional knockdown/overexpression with pathway readouts; single lab","pmids":["40927771"],"is_preprint":false},{"year":2025,"finding":"ALKBH5 demethylase upregulates RCN1 expression by reducing m6A-YTHDF2-mediated degradation of RCN1 mRNA. Overexpression of RCN1 upregulates XBP1, GRP78, and IRE1α protein levels and promotes ER stress in keloid fibroblasts; RCN1 interacts with XBP1 as shown by Co-IP. Knockdown of RCN1 inhibited keloid formation in a mouse model.","method":"Methylated RNA immunoprecipitation (MeRIP) assessing m6A modification of RCN1 mRNA; co-immunoprecipitation confirming RCN1-XBP1 interaction; overexpression/knockdown with Western blot for ER stress markers; TEM for ER structure; in vivo mouse keloid model","journal":"Journal of cosmetic dermatology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (MeRIP, Co-IP, in vivo model); single lab","pmids":["40214031"],"is_preprint":false},{"year":2025,"finding":"RCN1 knockdown in DLBCL cells suppresses activation of the PI3K/AKT signaling pathway, and reactivation of PI3K/AKT with agonist 740Y-P offsets the anti-tumor effect of RCN1 knockdown, placing RCN1 upstream of PI3K/AKT in DLBCL malignancy and macrophage M2 polarization.","method":"Genetic knockdown with pathway rescue by PI3K/AKT agonist; Western blotting for PI3K/AKT markers; flow cytometry for macrophage polarization markers","journal":"Molecular and cellular probes","confidence":"Low","confidence_rationale":"Tier 3 / Weak — epistasis by pharmacological rescue, single lab, single paper, no direct binding data","pmids":["40659094"],"is_preprint":false},{"year":2025,"finding":"TRIM11-mediated ubiquitination regulates RCN1 protein stability in endothelial cells under glycolipotoxicity conditions; RCN1 overexpression alleviates ER stress (reducing PERK phosphorylation and CHOP expression) and promotes angiogenesis, while RCN1 silencing intensifies PERK-CHOP signaling and impairs endothelial function.","method":"Proteomic analysis; overexpression and siRNA-mediated silencing; Western blotting for PERK phosphorylation and CHOP; RNA sequencing; in vivo diabetic mouse ulcer healing model","journal":"Cellular and molecular life sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — TRIM11-RCN1 ubiquitination pathway identified with functional consequences in vitro and in vivo; single lab","pmids":["40853392"],"is_preprint":false},{"year":2023,"finding":"RCN1 knockdown in AML cells upregulates type I interferon (IFN-1) expression and promotes pyroptosis through caspase-1 and gasdermin D (GSDMD) signaling. RCN1 suppression also inhibited tumor growth in NSG mouse xenograft models.","method":"shRNA-mediated RCN1 knockdown; flow cytometry and Western blotting for caspase-1 and GSDMD; IFN-1 measurement; NSG mouse xenograft model; Rcn1 gene deletion in mouse AML cell lines","journal":"Molecular oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined molecular pathway (caspase-1/GSDMD) and in vivo validation; single lab","pmids":["37746742"],"is_preprint":false},{"year":2025,"finding":"miR-26b directly binds to the 3'-UTR of RCN1 mRNA and suppresses RCN1 expression, placing RCN1 downstream of miR-26b in NSCLC cell proliferation, invasion, and migration. miR-26b expression is downregulated by DNA hypermethylation in NSCLC.","method":"Luciferase reporter assay confirming direct miR-26b binding to RCN1 3'-UTR; methylation-specific PCR; Western blotting; functional cell assays (MTT, transwell)","journal":"Journal of thoracic disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase reporter with direct 3'-UTR binding confirmed, functional rescue assays; single lab","pmids":["40688319"],"is_preprint":false}],"current_model":"RCN1 (reticulocalbin 1) is an ER-resident calcium-binding protein whose EF-hand domains sense ER calcium and bind IP3R1 to suppress ER calcium release; it is regulated post-translationally by TRIM11-mediated ubiquitination and at the mRNA level by ALKBH5/YTHDF2-dependent m6A modification and by miR-26b targeting its 3'-UTR; it acts as a negative modulator of B-RAF/MEK and PI3K/AKT signaling and inhibits ER stress-induced apoptosis via the PERK-CHOP pathway, while its interaction with GRP78 through the EFh1/2 domain activates the IRE1α-XBP1s-c-MYC axis in drug-resistant cancer contexts."},"narrative":{"mechanistic_narrative":"RCN1 (reticulocalbin 1) is an ER-resident EF-hand calcium-binding protein that acts as a negative regulator of ER stress signaling and ER-mitochondria calcium coupling [PMID:28319095, PMID:41385809]. Its first two EF-hand motifs bind the luminal domain of IP3R1 to inhibit ER calcium release, and this calcium-sensing interaction also suppresses IP3R1-GRP75 association and ER-to-mitochondria calcium transfer; loss of RCN1 strengthens ER-mitochondria coupling [PMID:28319095, PMID:41385809]. Through dampening of the UPR, RCN1 limits PERK-CHOP signaling and thereby inhibits ER stress-induced apoptosis, a protective role demonstrated in cancer and in endothelial cells under glycolipotoxic stress [PMID:28319095, PMID:40853392]. In drug-resistant and tumor contexts RCN1 engages additional UPR machinery: its EFh1/2 domain binds GRP78 to promote GRP78 dissociation from IRE1α and sustain IRE1α-XBP1s-c-MYC signaling, and it interacts with XBP1 to drive ER stress in keloid fibroblasts [PMID:34663798, PMID:40214031]. RCN1 functions as a negative modulator of B-RAF/MEK signaling in cardiomyocytes and, conversely, supports PI3K-AKT(-mTOR) signaling to promote tumor cell proliferation, migration, and invasion, in part through binding KIF14 [PMID:24492844, PMID:40927771]. RCN1 protein abundance is controlled by TRIM11-mediated ubiquitination, while its mRNA is regulated by ALKBH5/m6A-YTHDF2-dependent decay and by miR-26b targeting of its 3'-UTR [PMID:41385809, PMID:40214031, PMID:40688319].","teleology":[{"year":2014,"claim":"Established RCN1 as a signaling modulator rather than a purely structural ER protein by placing it as a negative regulator of the B-RAF/MEK cascade.","evidence":"cDNA expression screen with B-RAF luciferase reporter plus gain- and loss-of-function in neonatal rat cardiomyocytes measuring MEK1/2 phosphorylation and hypertrophy","pmids":["24492844"],"confidence":"Medium","gaps":["No direct binding partner in the B-RAF pathway identified","Mechanism linking ER calcium binding to MEK regulation not resolved"]},{"year":2017,"claim":"Defined the core molecular mechanism: RCN1 binds IP3R1 via its first two EF-hands to suppress ER calcium release and the PERK-CHOP arm of the UPR, protecting against ER stress-induced apoptosis.","evidence":"Reciprocal Co-IP with EF-hand mutagenesis mapping the IP3R1 luminal loop 3 interaction, plus calcium-release, UPR, and apoptosis assays under NF-κB-driven ER stress","pmids":["28319095"],"confidence":"High","gaps":["Structural basis of EF-hand/IP3R1 recognition not solved","Whether calcium occupancy of the EF-hands gates the interaction not directly tested in this study"]},{"year":2021,"claim":"Extended RCN1's UPR role to the IRE1α arm, showing it can promote pro-survival IRE1α-XBP1s-c-MYC signaling in a drug-resistance context.","evidence":"Co-IP mapping RCN1-GRP78 interaction to the EFh1/2 domain plus overexpression/knockdown with pathway readouts in sorafenib-resistant HCC cells","pmids":["34663798"],"confidence":"Medium","gaps":["Single lab, no reciprocal validation of GRP78 dissociation in vitro","How RCN1 reconciles UPR suppression (PERK-CHOP) with UPR activation (IRE1α) is unresolved"]},{"year":2023,"claim":"Linked RCN1 to control of innate immune/cell-death programs, showing its loss triggers IFN-1 and caspase-1/GSDMD pyroptosis.","evidence":"shRNA knockdown and Rcn1 deletion in AML cells with caspase-1/GSDMD and IFN-1 readouts plus NSG xenografts","pmids":["37746742"],"confidence":"Medium","gaps":["Molecular connection from ER calcium/UPR role to pyroptosis not defined","No direct partner mediating IFN-1 induction identified"]},{"year":2025,"claim":"Connected RCN1 abundance to upstream regulation by TRIM11 ubiquitination and to ER-mitochondria calcium crosstalk via the IP3R1-GRP75 axis.","evidence":"Co-IP, proteomics, and calcium-transfer assays in HCC xenograft and spontaneous models","pmids":["41385809"],"confidence":"Medium","gaps":["TRIM11 ubiquitination site on RCN1 not mapped","Quantitative contribution of ER-mito coupling to drug resistance not isolated"]},{"year":2025,"claim":"Defined mRNA-level control of RCN1 by m6A (ALKBH5/YTHDF2) and miR-26b, and added downstream effectors KIF14/PI3K-AKT and XBP1 across multiple tumor and fibrosis contexts.","evidence":"MeRIP and Co-IP in keloid fibroblasts (XBP1), IP-MS plus xenografts in cervical cancer (KIF14/PI3K-AKT-mTOR), luciferase 3'-UTR reporter in NSCLC (miR-26b), and PI3K/AKT rescue in DLBCL","pmids":["40214031","40927771","40688319","40659094"],"confidence":"Medium","gaps":["DLBCL epistasis rests on pharmacological rescue without direct binding data","Whether KIF14 binding and PI3K-AKT activation are mechanistically coupled not established","Tissue specificity of m6A vs miR-26b control not compared"]},{"year":null,"claim":"It remains unresolved how RCN1's single calcium-sensing/EF-hand activity is mechanistically partitioned between opposing outputs (PERK-CHOP suppression versus IRE1α-XBP1s activation; B-RAF/MEK inhibition versus PI3K-AKT promotion) across cell types.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of RCN1 in any complex","No unified framework reconciling pro-survival and pro-death roles","Calcium-dependence of partner switching not directly measured"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140097","term_label":"catalytic activity, acting on DNA","supporting_discovery_ids":[0,2]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0140299","term_label":"molecular sensor activity","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0,2,7]}],"pathway":[{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[0,7]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3,4,6]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[0,8]}],"complexes":[],"partners":["IP3R1","GRP78","GRP75","XBP1","KIF14","TRIM11"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15293","full_name":"Reticulocalbin-1","aliases":[],"length_aa":331,"mass_kda":38.9,"function":"May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment","subcellular_location":"Endoplasmic reticulum lumen","url":"https://www.uniprot.org/uniprotkb/Q15293/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RCN1","classification":"Not Classified","n_dependent_lines":40,"n_total_lines":1208,"dependency_fraction":0.033112582781456956},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"COPA","stoichiometry":0.2},{"gene":"COPB2","stoichiometry":0.2},{"gene":"COPE","stoichiometry":0.2},{"gene":"HMGCS1","stoichiometry":0.2},{"gene":"SAR1B","stoichiometry":0.2},{"gene":"TMED2","stoichiometry":0.2},{"gene":"YIPF5","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/RCN1","total_profiled":1310},"omim":[{"mim_id":"614282","title":"STROMAL CELL-DERIVED FACTOR 4; SDF4","url":"https://www.omim.org/entry/614282"},{"mim_id":"606278","title":"F-BOX AND WD40 DOMAIN PROTEIN 7; FBXW7","url":"https://www.omim.org/entry/606278"},{"mim_id":"603420","title":"CALUMENIN; CALU","url":"https://www.omim.org/entry/603420"},{"mim_id":"602735","title":"RETICULOCALBIN 1; RCN1","url":"https://www.omim.org/entry/602735"},{"mim_id":"114105","title":"PROTEIN PHOSPHATASE 3, CATALYTIC SUBUNIT, ALPHA ISOFORM; PPP3CA","url":"https://www.omim.org/entry/114105"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Endoplasmic reticulum","reliability":"Supported"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"epididymis","ntpm":623.3}],"url":"https://www.proteinatlas.org/search/RCN1"},"hgnc":{"alias_symbol":["Rcal","PIG20","FLJ37041"],"prev_symbol":["RCN"]},"alphafold":{"accession":"Q15293","domains":[{"cath_id":"-","chopping":"75-222_265-323","consensus_level":"medium","plddt":89.1699,"start":75,"end":323}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15293","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15293-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15293-F1-predicted_aligned_error_v6.png","plddt_mean":76.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RCN1","jax_strain_url":"https://www.jax.org/strain/search?query=RCN1"},"sequence":{"accession":"Q15293","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15293.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15293/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15293"}},"corpus_meta":[{"pmid":"12148532","id":"PMC_12148532","title":"Overexpression of RCN1 and RCN2, rice TERMINAL FLOWER 1/CENTRORADIALIS homologs, confers delay of phase transition and altered panicle morphology in rice.","date":"2002","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12148532","citation_count":219,"is_preprint":false},{"pmid":"10607292","id":"PMC_10607292","title":"The RCN1-encoded A subunit of protein phosphatase 2A increases phosphatase activity in vivo.","date":"1999","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10607292","citation_count":79,"is_preprint":false},{"pmid":"18162590","id":"PMC_18162590","title":"Specificity of RCN1-mediated protein phosphatase 2A regulation in meristem organization and stress response in roots.","date":"2007","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/18162590","citation_count":73,"is_preprint":false},{"pmid":"18650210","id":"PMC_18650210","title":"Roles of RCN1, regulatory A subunit of protein phosphatase 2A, in methyl jasmonate signaling and signal crosstalk between methyl jasmonate and abscisic acid.","date":"2008","source":"Plant & cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/18650210","citation_count":66,"is_preprint":false},{"pmid":"28319095","id":"PMC_28319095","title":"RCN1 suppresses ER stress-induced apoptosis via calcium homeostasis and PERK-CHOP signaling.","date":"2017","source":"Oncogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/28319095","citation_count":59,"is_preprint":false},{"pmid":"17954914","id":"PMC_17954914","title":"The SCFCdc4 ubiquitin ligase regulates calcineurin signaling through degradation of phosphorylated Rcn1, an inhibitor of calcineurin.","date":"2007","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/17954914","citation_count":49,"is_preprint":false},{"pmid":"12684004","id":"PMC_12684004","title":"The Caenorhabditis elegans homologue of Down syndrome critical region 1, RCN-1, inhibits multiple functions of the phosphatase calcineurin.","date":"2003","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12684004","citation_count":40,"is_preprint":false},{"pmid":"26708605","id":"PMC_26708605","title":"Rice Stomatal Closure Requires Guard Cell Plasma Membrane ATP-Binding Cassette Transporter RCN1/OsABCG5.","date":"2015","source":"Molecular plant","url":"https://pubmed.ncbi.nlm.nih.gov/26708605","citation_count":39,"is_preprint":false},{"pmid":"16798939","id":"PMC_16798939","title":"RCN1-regulated phosphatase activity and EIN2 modulate hypocotyl gravitropism by a mechanism that does not require ethylene signaling.","date":"2006","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/16798939","citation_count":38,"is_preprint":false},{"pmid":"22759596","id":"PMC_22759596","title":"Exposure to benzo[a]pyrene of Hepatic Cytochrome P450 Reductase Null (HRN) and P450 Reductase Conditional Null (RCN) mice: Detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and 32P-postlabelling.","date":"2012","source":"Toxicology letters","url":"https://pubmed.ncbi.nlm.nih.gov/22759596","citation_count":33,"is_preprint":false},{"pmid":"34663798","id":"PMC_34663798","title":"RCN1 induces sorafenib resistance and malignancy in hepatocellular carcinoma by activating c-MYC signaling via the IRE1α-XBP1s pathway.","date":"2021","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/34663798","citation_count":32,"is_preprint":false},{"pmid":"32871760","id":"PMC_32871760","title":"Salivary NUS1 and RCN1 Levels as Biomarkers for Oral Squamous Cell Carcinoma Diagnosis.","date":"2020","source":"In vivo (Athens, Greece)","url":"https://pubmed.ncbi.nlm.nih.gov/32871760","citation_count":22,"is_preprint":false},{"pmid":"22093065","id":"PMC_22093065","title":"Identification of RCN1 and RSA3 as ethanol-tolerant genes in Saccharomyces cerevisiae using a high copy barcoded library.","date":"2011","source":"FEMS yeast research","url":"https://pubmed.ncbi.nlm.nih.gov/22093065","citation_count":20,"is_preprint":false},{"pmid":"25214702","id":"PMC_25214702","title":"Mechanistic Evaluation of the Ni(IPr)2-Catalyzed Cycloaddition of Alkynes and Nitriles to Afford Pyridines: Evidence for the Formation of a Key η1-Ni(IPr)2(RCN) Intermediate.","date":"2013","source":"Organometallics","url":"https://pubmed.ncbi.nlm.nih.gov/25214702","citation_count":20,"is_preprint":false},{"pmid":"24492844","id":"PMC_24492844","title":"B-RAF and its novel negative regulator reticulocalbin 1 (RCN1) modulates cardiomyocyte hypertrophy.","date":"2014","source":"Cardiovascular research","url":"https://pubmed.ncbi.nlm.nih.gov/24492844","citation_count":18,"is_preprint":false},{"pmid":"17237471","id":"PMC_17237471","title":"Genetic interaction between 2 tillering genes, reduced culm number 1 (rcn1) and tillering dwarf gene d3, in rice.","date":"2007","source":"The Journal of heredity","url":"https://pubmed.ncbi.nlm.nih.gov/17237471","citation_count":14,"is_preprint":false},{"pmid":"38057406","id":"PMC_38057406","title":"RCN1 deficiency inhibits oral squamous cell carcinoma progression and THP-1 macrophage M2 polarization.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38057406","citation_count":13,"is_preprint":false},{"pmid":"1259412","id":"PMC_1259412","title":"Enhancement of rIn:rCn-induced interferon production by amphotericin B.","date":"1976","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/1259412","citation_count":11,"is_preprint":false},{"pmid":"24908511","id":"PMC_24908511","title":"Rice RCN1/OsABCG5 mutation alters accumulation of essential and nonessential minerals and causes a high Na/K ratio, resulting in a salt-sensitive phenotype.","date":"2014","source":"Plant science : an international journal of experimental plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/24908511","citation_count":9,"is_preprint":false},{"pmid":"36602183","id":"PMC_36602183","title":"An Experimental and Master Equation Investigation of Kinetics of the CH2OO + RCN Reactions (R = H, CH3, C2H5) and Their Atmospheric Relevance.","date":"2023","source":"The journal of physical chemistry. A","url":"https://pubmed.ncbi.nlm.nih.gov/36602183","citation_count":9,"is_preprint":false},{"pmid":"37746742","id":"PMC_37746742","title":"Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells.","date":"2023","source":"Molecular oncology","url":"https://pubmed.ncbi.nlm.nih.gov/37746742","citation_count":7,"is_preprint":false},{"pmid":"38713738","id":"PMC_38713738","title":"Downregulation of RCN1 inhibits esophageal squamous cell carcinoma progression and M2 macrophage polarization.","date":"2024","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/38713738","citation_count":6,"is_preprint":false},{"pmid":"22941310","id":"PMC_22941310","title":"Immunomodulatory response of mice splenocytes induced by RcaL, a lectin isolated from cobia fish (Rachycentron canadum) serum.","date":"2012","source":"Applied biochemistry and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/22941310","citation_count":4,"is_preprint":false},{"pmid":"40650067","id":"PMC_40650067","title":"GPX1 and RCN1 as New Endoplasmic Reticulum Stress-Related Biomarkers in Multiple Sclerosis Brain Tissue and Their Involvement in the APP-CD74 Pathway: An Integrated Study Combining Machine Learning and Multi-Omics.","date":"2025","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/40650067","citation_count":2,"is_preprint":false},{"pmid":"40214031","id":"PMC_40214031","title":"ALKBH5 Inhibits YTHDF2-m6A-Mediated Degradation of RCN1 mRNA to Promote Keloid Formation by Activating IRE1α-XBP1-Mediated ER Stress.","date":"2025","source":"Journal of cosmetic dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/40214031","citation_count":2,"is_preprint":false},{"pmid":"23987813","id":"PMC_23987813","title":"The rice REDUCED CULM NUMBER11 gene controls vegetative growth under low-temperature conditions in paddy fields independent of RCN1/OsABCG5.","date":"2013","source":"Plant science : an international journal of experimental plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/23987813","citation_count":2,"is_preprint":false},{"pmid":"41385809","id":"PMC_41385809","title":"Hyperbaric oxygen targets RCN1 to modulate ER-mitochondria crosstalk and ameliorate sorafenib resistance in hepatocellular carcinoma.","date":"2025","source":"Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/41385809","citation_count":1,"is_preprint":false},{"pmid":"40659094","id":"PMC_40659094","title":"RCN1 affects malignant progression and macrophage M2 polarization in diffuse large B-cell lymphoma.","date":"2025","source":"Molecular and cellular probes","url":"https://pubmed.ncbi.nlm.nih.gov/40659094","citation_count":1,"is_preprint":false},{"pmid":"39241105","id":"PMC_39241105","title":"Biochemical analyses reveal new insights into RCAN1/Rcn1 inhibition of calcineurin.","date":"2024","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/39241105","citation_count":1,"is_preprint":false},{"pmid":"40927771","id":"PMC_40927771","title":"RCN1 Binds KIF14 and Promotes the Malignant Growth of Cervical Cancer Through the PI3K-AKT Pathway.","date":"2025","source":"International journal of general medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40927771","citation_count":1,"is_preprint":false},{"pmid":"8902504","id":"PMC_8902504","title":"Replication of rat coronaviruses in intestinal cell line, RCN-9, derived from F344 rats.","date":"1996","source":"Experimental animals","url":"https://pubmed.ncbi.nlm.nih.gov/8902504","citation_count":1,"is_preprint":false},{"pmid":"40853392","id":"PMC_40853392","title":"RCN1 downregulation-driven endoplasmic reticulum stress impairs endothelial function and diabetic foot ulcer healing.","date":"2025","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/40853392","citation_count":0,"is_preprint":false},{"pmid":"38715219","id":"PMC_38715219","title":"Rcn1, the fission yeast homolog of human DSCR1, regulates arsenite tolerance independently from calcineurin.","date":"2024","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/38715219","citation_count":0,"is_preprint":false},{"pmid":"40688319","id":"PMC_40688319","title":"Role of miR-26b in regulating non-small cell lung cancer progression via targeting RCN1.","date":"2025","source":"Journal of thoracic disease","url":"https://pubmed.ncbi.nlm.nih.gov/40688319","citation_count":0,"is_preprint":false},{"pmid":"41968321","id":"PMC_41968321","title":"RCN1 helps to alleviate the damage of drought stress to rice young spike differentiation.","date":"2026","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/41968321","citation_count":0,"is_preprint":false},{"pmid":"37823257","id":"PMC_37823257","title":"Expression of concern: A cascade process for directly converting nitriles (RCN) to cyanamides (RNHCN) via SO2F2-activated Tiemann rearrangement.","date":"2023","source":"Organic & biomolecular chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/37823257","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":19796,"output_tokens":2824,"usd":0.050874,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10059,"output_tokens":2948,"usd":0.061997,"stage2_stop_reason":"end_turn"},"total_usd":0.112871,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"RCN1 (reticulocalbin 1) is transactivated by NF-κB during ER stress. The first two EF-hand calcium-binding motifs of RCN1 specifically interact with IP3R1 on loop 3 of its ER luminal domain, inhibiting ER calcium release and suppressing PERK-CHOP signaling, thereby inhibiting ER stress-induced apoptosis.\",\n      \"method\": \"Co-immunoprecipitation (Co-IP) identifying RCN1-IP3R1 interaction; EF-hand domain mutagenesis; depletion/overexpression assays measuring UPR activation, calcium release, and apoptosis\",\n      \"journal\": \"Oncogenesis\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP identifying binding domain, domain-specific mutagenesis, multiple orthogonal functional assays (calcium release, PERK-CHOP signaling, apoptosis) in a single study\",\n      \"pmids\": [\"28319095\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RCN1 promotes dissociation of GRP78 from IRE1α in sorafenib-resistant HCC cells by interacting with GRP78 through its EFh1/2 domain, leading to sustained activation of the IRE1α-XBP1s pathway and downstream c-MYC signaling.\",\n      \"method\": \"Co-immunoprecipitation identifying RCN1-GRP78 interaction via EFh1/2 domain; overexpression/knockdown in sorafenib-resistant HCC cells with pathway activity readouts\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP interaction identified and domain implicated, functional readouts in cellular model; single lab\",\n      \"pmids\": [\"34663798\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RCN1 uses its EF-hand (EFh1/2) domains to sense ER calcium concentration and modulates its binding to IP3R1 accordingly, suppressing IP3R1-GRP75 interaction and ER-to-mitochondria calcium transfer. Downregulation of RCN1 strengthens ER-mitochondria coupling. TRIM11-mediated ubiquitination regulates RCN1 protein stability.\",\n      \"method\": \"Co-IP; overexpression/knockdown in HCC xenograft and spontaneous models; proteomic analysis; functional assays for ER-mitochondria calcium transfer\",\n      \"journal\": \"Drug resistance updates\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple interaction partners identified by Co-IP, domain attribution, in vivo model; single lab\",\n      \"pmids\": [\"41385809\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"RCN1 functions as a negative modulator of B-RAF activity in cardiomyocytes, inhibiting phenylephrine-induced hypertrophy and reducing MEK1/2 phosphorylation. Conversely, adenoviral knockdown of RCN1 induced cardiomyocyte hypertrophy and increased MEK1/2 phosphorylation.\",\n      \"method\": \"Eukaryotic cDNA expression screen with dual-luciferase B-RAF reporter assay; adenovirus-mediated overexpression and miRNA-mediated knockdown of RCN1; measurement of MEK1/2 phosphorylation and hypertrophic markers in neonatal rat cardiomyocytes\",\n      \"journal\": \"Cardiovascular research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional screen identified RCN1, gain-of-function and loss-of-function in cardiomyocytes with specific pathway readout; single lab\",\n      \"pmids\": [\"24492844\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RCN1 binds KIF14 (identified by immunoprecipitation-mass spectrometry), and this interaction promotes activation of the PI3K-AKT-mTOR pathway, facilitating proliferation, migration, and invasion of cervical cancer cells.\",\n      \"method\": \"Immunoprecipitation tandem mass spectrometry (IP-MS) identifying KIF14 as RCN1 binding partner; knockdown and overexpression assays; Western blotting for PI3K-AKT-mTOR pathway; mouse xenograft model\",\n      \"journal\": \"International journal of general medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — IP-MS identified binding partner, supported by functional knockdown/overexpression with pathway readouts; single lab\",\n      \"pmids\": [\"40927771\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ALKBH5 demethylase upregulates RCN1 expression by reducing m6A-YTHDF2-mediated degradation of RCN1 mRNA. Overexpression of RCN1 upregulates XBP1, GRP78, and IRE1α protein levels and promotes ER stress in keloid fibroblasts; RCN1 interacts with XBP1 as shown by Co-IP. Knockdown of RCN1 inhibited keloid formation in a mouse model.\",\n      \"method\": \"Methylated RNA immunoprecipitation (MeRIP) assessing m6A modification of RCN1 mRNA; co-immunoprecipitation confirming RCN1-XBP1 interaction; overexpression/knockdown with Western blot for ER stress markers; TEM for ER structure; in vivo mouse keloid model\",\n      \"journal\": \"Journal of cosmetic dermatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (MeRIP, Co-IP, in vivo model); single lab\",\n      \"pmids\": [\"40214031\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"RCN1 knockdown in DLBCL cells suppresses activation of the PI3K/AKT signaling pathway, and reactivation of PI3K/AKT with agonist 740Y-P offsets the anti-tumor effect of RCN1 knockdown, placing RCN1 upstream of PI3K/AKT in DLBCL malignancy and macrophage M2 polarization.\",\n      \"method\": \"Genetic knockdown with pathway rescue by PI3K/AKT agonist; Western blotting for PI3K/AKT markers; flow cytometry for macrophage polarization markers\",\n      \"journal\": \"Molecular and cellular probes\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — epistasis by pharmacological rescue, single lab, single paper, no direct binding data\",\n      \"pmids\": [\"40659094\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TRIM11-mediated ubiquitination regulates RCN1 protein stability in endothelial cells under glycolipotoxicity conditions; RCN1 overexpression alleviates ER stress (reducing PERK phosphorylation and CHOP expression) and promotes angiogenesis, while RCN1 silencing intensifies PERK-CHOP signaling and impairs endothelial function.\",\n      \"method\": \"Proteomic analysis; overexpression and siRNA-mediated silencing; Western blotting for PERK phosphorylation and CHOP; RNA sequencing; in vivo diabetic mouse ulcer healing model\",\n      \"journal\": \"Cellular and molecular life sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — TRIM11-RCN1 ubiquitination pathway identified with functional consequences in vitro and in vivo; single lab\",\n      \"pmids\": [\"40853392\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RCN1 knockdown in AML cells upregulates type I interferon (IFN-1) expression and promotes pyroptosis through caspase-1 and gasdermin D (GSDMD) signaling. RCN1 suppression also inhibited tumor growth in NSG mouse xenograft models.\",\n      \"method\": \"shRNA-mediated RCN1 knockdown; flow cytometry and Western blotting for caspase-1 and GSDMD; IFN-1 measurement; NSG mouse xenograft model; Rcn1 gene deletion in mouse AML cell lines\",\n      \"journal\": \"Molecular oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined molecular pathway (caspase-1/GSDMD) and in vivo validation; single lab\",\n      \"pmids\": [\"37746742\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"miR-26b directly binds to the 3'-UTR of RCN1 mRNA and suppresses RCN1 expression, placing RCN1 downstream of miR-26b in NSCLC cell proliferation, invasion, and migration. miR-26b expression is downregulated by DNA hypermethylation in NSCLC.\",\n      \"method\": \"Luciferase reporter assay confirming direct miR-26b binding to RCN1 3'-UTR; methylation-specific PCR; Western blotting; functional cell assays (MTT, transwell)\",\n      \"journal\": \"Journal of thoracic disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase reporter with direct 3'-UTR binding confirmed, functional rescue assays; single lab\",\n      \"pmids\": [\"40688319\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RCN1 (reticulocalbin 1) is an ER-resident calcium-binding protein whose EF-hand domains sense ER calcium and bind IP3R1 to suppress ER calcium release; it is regulated post-translationally by TRIM11-mediated ubiquitination and at the mRNA level by ALKBH5/YTHDF2-dependent m6A modification and by miR-26b targeting its 3'-UTR; it acts as a negative modulator of B-RAF/MEK and PI3K/AKT signaling and inhibits ER stress-induced apoptosis via the PERK-CHOP pathway, while its interaction with GRP78 through the EFh1/2 domain activates the IRE1α-XBP1s-c-MYC axis in drug-resistant cancer contexts.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RCN1 (reticulocalbin 1) is an ER-resident EF-hand calcium-binding protein that acts as a negative regulator of ER stress signaling and ER-mitochondria calcium coupling [#0, #2]. Its first two EF-hand motifs bind the luminal domain of IP3R1 to inhibit ER calcium release, and this calcium-sensing interaction also suppresses IP3R1-GRP75 association and ER-to-mitochondria calcium transfer; loss of RCN1 strengthens ER-mitochondria coupling [#0, #2]. Through dampening of the UPR, RCN1 limits PERK-CHOP signaling and thereby inhibits ER stress-induced apoptosis, a protective role demonstrated in cancer and in endothelial cells under glycolipotoxic stress [#0, #7]. In drug-resistant and tumor contexts RCN1 engages additional UPR machinery: its EFh1/2 domain binds GRP78 to promote GRP78 dissociation from IRE1\\u03b1 and sustain IRE1\\u03b1-XBP1s-c-MYC signaling, and it interacts with XBP1 to drive ER stress in keloid fibroblasts [#1, #5]. RCN1 functions as a negative modulator of B-RAF/MEK signaling in cardiomyocytes and, conversely, supports PI3K-AKT(-mTOR) signaling to promote tumor cell proliferation, migration, and invasion, in part through binding KIF14 [#3, #4]. RCN1 protein abundance is controlled by TRIM11-mediated ubiquitination, while its mRNA is regulated by ALKBH5/m6A-YTHDF2-dependent decay and by miR-26b targeting of its 3'-UTR [#2, #5, #9].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Established RCN1 as a signaling modulator rather than a purely structural ER protein by placing it as a negative regulator of the B-RAF/MEK cascade.\",\n      \"evidence\": \"cDNA expression screen with B-RAF luciferase reporter plus gain- and loss-of-function in neonatal rat cardiomyocytes measuring MEK1/2 phosphorylation and hypertrophy\",\n      \"pmids\": [\"24492844\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No direct binding partner in the B-RAF pathway identified\", \"Mechanism linking ER calcium binding to MEK regulation not resolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined the core molecular mechanism: RCN1 binds IP3R1 via its first two EF-hands to suppress ER calcium release and the PERK-CHOP arm of the UPR, protecting against ER stress-induced apoptosis.\",\n      \"evidence\": \"Reciprocal Co-IP with EF-hand mutagenesis mapping the IP3R1 luminal loop 3 interaction, plus calcium-release, UPR, and apoptosis assays under NF-\\u03baB-driven ER stress\",\n      \"pmids\": [\"28319095\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Structural basis of EF-hand/IP3R1 recognition not solved\", \"Whether calcium occupancy of the EF-hands gates the interaction not directly tested in this study\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extended RCN1's UPR role to the IRE1\\u03b1 arm, showing it can promote pro-survival IRE1\\u03b1-XBP1s-c-MYC signaling in a drug-resistance context.\",\n      \"evidence\": \"Co-IP mapping RCN1-GRP78 interaction to the EFh1/2 domain plus overexpression/knockdown with pathway readouts in sorafenib-resistant HCC cells\",\n      \"pmids\": [\"34663798\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single lab, no reciprocal validation of GRP78 dissociation in vitro\", \"How RCN1 reconciles UPR suppression (PERK-CHOP) with UPR activation (IRE1\\u03b1) is unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Linked RCN1 to control of innate immune/cell-death programs, showing its loss triggers IFN-1 and caspase-1/GSDMD pyroptosis.\",\n      \"evidence\": \"shRNA knockdown and Rcn1 deletion in AML cells with caspase-1/GSDMD and IFN-1 readouts plus NSG xenografts\",\n      \"pmids\": [\"37746742\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Molecular connection from ER calcium/UPR role to pyroptosis not defined\", \"No direct partner mediating IFN-1 induction identified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Connected RCN1 abundance to upstream regulation by TRIM11 ubiquitination and to ER-mitochondria calcium crosstalk via the IP3R1-GRP75 axis.\",\n      \"evidence\": \"Co-IP, proteomics, and calcium-transfer assays in HCC xenograft and spontaneous models\",\n      \"pmids\": [\"41385809\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"TRIM11 ubiquitination site on RCN1 not mapped\", \"Quantitative contribution of ER-mito coupling to drug resistance not isolated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined mRNA-level control of RCN1 by m6A (ALKBH5/YTHDF2) and miR-26b, and added downstream effectors KIF14/PI3K-AKT and XBP1 across multiple tumor and fibrosis contexts.\",\n      \"evidence\": \"MeRIP and Co-IP in keloid fibroblasts (XBP1), IP-MS plus xenografts in cervical cancer (KIF14/PI3K-AKT-mTOR), luciferase 3'-UTR reporter in NSCLC (miR-26b), and PI3K/AKT rescue in DLBCL\",\n      \"pmids\": [\"40214031\", \"40927771\", \"40688319\", \"40659094\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"DLBCL epistasis rests on pharmacological rescue without direct binding data\", \"Whether KIF14 binding and PI3K-AKT activation are mechanistically coupled not established\", \"Tissue specificity of m6A vs miR-26b control not compared\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how RCN1's single calcium-sensing/EF-hand activity is mechanistically partitioned between opposing outputs (PERK-CHOP suppression versus IRE1\\u03b1-XBP1s activation; B-RAF/MEK inhibition versus PI3K-AKT promotion) across cell types.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of RCN1 in any complex\", \"No unified framework reconciling pro-survival and pro-death roles\", \"Calcium-dependence of partner switching not directly measured\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140097\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0140299\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 2, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [0, 7]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 4, 6]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [0, 8]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"IP3R1\", \"GRP78\", \"GRP75\", \"XBP1\", \"KIF14\", \"TRIM11\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}