{"gene":"MAT2B","run_date":"2026-04-28T18:30:28","timeline":{"discoveries":[{"year":2001,"finding":"MAT2B encodes the regulatory beta subunit of the MAT II isozyme; its promoter is regulated by Sp1/Sp3 transcription factors binding a GC-rich region, with an Sp3-bound site at +9 and a TATA element at -32 being key determinants of promoter activity. Down-regulation of MAT2B causes a 6–10-fold increase in intracellular AdoMet levels.","method":"Promoter deletion analysis, luciferase reporter assays, EMSA supershift assays with anti-Sp1/Sp3 antibodies, chromatin immunoprecipitation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods (deletion mapping, EMSA, ChIP) in a single rigorous study","pmids":["11337507"],"is_preprint":false},{"year":2008,"finding":"Knockdown of MAT2B in hepatocellular carcinoma cells induces growth inhibition and apoptosis, associated with down-regulation of cyclin D1 and Bcl-xL and up-regulation of Bcl-xS; SAMe levels are altered upon MAT2B silencing.","method":"Lentivirus-mediated shRNA knockdown, MTT/[3H]thymidine proliferation assays, flow cytometry apoptosis analysis, western blot for cyclin D1, Bcl-xL, Bcl-xS","journal":"World journal of gastroenterology","confidence":"Medium","confidence_rationale":"Tier 2 — clean KD with defined cellular phenotype and downstream marker analysis, single lab","pmids":["18698677"],"is_preprint":false},{"year":2013,"finding":"MAT2B variants V1 and V2 form a scaffold complex with GIT1 that recruits and activates MEK1/ERK, raising cyclin D1 and promoting cell growth. MAT2B directly interacts with MEK1, GIT1, and ERK2; MAT2B promotes binding of GIT1 and ERK2 to MEK1.","method":"In-solution proteomics, co-immunoprecipitation, in vitro translation and recombinant protein pull-down assays, transient knockdown/overexpression, western blot, immunohistochemistry, orthotopic liver cancer model","journal":"Hepatology (Baltimore, Md.)","confidence":"High","confidence_rationale":"Tier 1–2 — reciprocal Co-IP plus in vitro pull-down with recombinant proteins, multiple orthogonal methods, functional validation in vivo","pmids":["23325601"],"is_preprint":false},{"year":2016,"finding":"In porcine intramuscular preadipocytes, MAT2B promotes adipogenesis by modulating intracellular SAMe levels and activating AKT/ERK1/2 signaling; MAT2B directly interacts with AKT, and PI3K inhibition is partially rescued by MAT2B overexpression.","method":"Overexpression and knockdown, flow cytometry, EdU labeling, Co-IP (MAT2B–AKT interaction), western blot for p-AKT and p-ERK1/2, PI3K inhibitor rescue experiments","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2–3 — Co-IP interaction plus epistasis rescue experiment, single lab","pmids":["26940012"],"is_preprint":false},{"year":2018,"finding":"miR-21-3p directly targets MAT2B mRNA in brain microvascular endothelial cells; elevated miR-21-3p after TBI suppresses MAT2B expression, leading to increased apoptosis and NF-κB-mediated inflammation and blood-brain barrier damage.","method":"Luciferase reporter assay (3′UTR targeting), MAT2B-silenced shRNA vector, miR-21-3p antagomir transfection, in vivo intracerebroventricular infusion, Evans Blue extravasation assay","journal":"Journal of neurotrauma","confidence":"Medium","confidence_rationale":"Tier 2 — luciferase validation of direct targeting plus in vivo functional rescue, single lab","pmids":["29695199"],"is_preprint":false},{"year":2019,"finding":"CircMAT2B (a circular RNA derived from the MAT2B locus) promotes glycolysis and HCC malignancy under hypoxia by sponging miR-338-3p, thereby de-repressing PKM2 expression.","method":"Biotin-coupled RNA probe pull-down, biotin-coupled miRNA capture, luciferase reporter assay, FISH, RNA immunoprecipitation, in vitro and in vivo functional assays under hypoxia","journal":"Hepatology (Baltimore, Md.)","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal RNA interaction methods; finding is about the circular RNA, not the MAT2B protein itself","pmids":["31004447"],"is_preprint":false},{"year":2019,"finding":"MAT2B silencing suppresses HCC cell migration and invasion through inhibition of EGFR signaling pathway, including reduced phosphorylation of AKT, EGFR, Src family, FAK, STAT3, and ERK.","method":"Human phospho-kinase array, immunoblotting, zebrafish xenograft model, nude mouse lung metastasis model, shRNA silencing","journal":"Clinical and experimental medicine","confidence":"Medium","confidence_rationale":"Tier 2 — phospho-kinase array plus immunoblot confirmation with in vivo validation, single lab","pmids":["31493275"],"is_preprint":false},{"year":2019,"finding":"miR-21-3p directly inhibits MAT2B expression in neural cells; suppression of miR-21-3p (by ADMSC-derived exosomes or inhibitor) up-regulates MAT2B and attenuates hypoxia/reoxygenation-induced neuronal impairment.","method":"Dual luciferase assay (MAT2B 3′UTR), in vivo MCAO rat model, in vitro hypoxia/reoxygenation neural cell model, miR-21-3p inhibitor and ADMSC exosome treatment","journal":"Croatian medical journal","confidence":"Medium","confidence_rationale":"Tier 2 — luciferase validation of direct targeting corroborated in vivo and in vitro, single lab","pmids":["31686458"],"is_preprint":false},{"year":2022,"finding":"MAT2B protein directly interacts with BAG3 protein in renal cell carcinoma cells, and this interaction affects proliferation, invasion, and apoptosis downstream of the CYTOR/miR-136-5p axis.","method":"Co-IP (MAT2B–BAG3 interaction), dual luciferase reporter assay, RNA pull-down, MTT, Transwell, flow cytometry, in vivo xenograft","journal":"Toxicology and applied pharmacology","confidence":"Medium","confidence_rationale":"Tier 3 — single Co-IP for the MAT2B–BAG3 interaction, supported by functional assays","pmids":["35597301"],"is_preprint":false},{"year":2024,"finding":"MAT2B binds and stabilizes MAT2A in an NADP+-dependent manner; disruption of cellular NADP+ (e.g., by ketogenic diet or pentose phosphate pathway modulation) remodels MAT2A protein levels. The MAT2B–MAT2A interaction is required for SAM synthesis, which in turn regulates mRNA m6A modification and stability in liver tumors.","method":"Co-IP (MAT2B–MAT2A interaction), NADP+ modulation experiments, m6A profiling, mRNA stability assays, in vivo liver tumor model with keto diet intervention, gene editing","journal":"Cell death & disease","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods (Co-IP, metabolic perturbation, m6A profiling, in vivo rescue) establishing a mechanistic regulatory axis","pmids":["39353892"],"is_preprint":false},{"year":2024,"finding":"JX24120 (a chlorpromazine derivative) directly binds MAT2B (Kd = 4.724 μM) and inhibits SAMe synthesis, leading to suppressed mTORC1 signaling, abnormal energy metabolism/protein synthesis, and apoptosis in endometrial cancer; tumor suppression is MAT2B-dependent in vivo.","method":"Direct binding assay (Kd measurement), PDO drug screening, gene editing (MAT2B KO rescue), in vivo xenograft, mTORC1 pathway analysis","journal":"Pharmacological research","confidence":"Medium","confidence_rationale":"Tier 1–2 — direct binding measurement plus gene-editing-based target validation, single lab","pmids":["39293586"],"is_preprint":false},{"year":2025,"finding":"FMO4 facilitates the interaction between MAT2A and MAT2B, thereby promoting SAM synthesis from methionine, increasing glutathione production, and protecting lung adenocarcinoma cells from ferroptosis.","method":"Proteomic analysis, FMO4 loss-of-function (in vitro and in vivo KRAS-driven mouse model), co-IP/interaction assay for MAT2A–MAT2B, ferroptosis assays, metabolic measurements","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — mechanistic link established in vivo and in vitro with protein interaction and metabolic data; preprint, not yet peer-reviewed","pmids":["bio_10.1101_2025.03.31.646284"],"is_preprint":true},{"year":2024,"finding":"IGF2BP3 directly regulates the translation of MAT2B mRNA in leukemia cells, increasing MAT2B protein levels, which boosts SAM production and consequently increases m6A modifications on RNA in a positive feedback loop.","method":"Ribosome/translation profiling, metabolic flux (glycolysis, one-carbon metabolism), m6A quantification, IGF2BP3 loss-of-function","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 — mechanistic claim supported by correlation of IGF2BP3 KD with MAT2B translation, but direct interaction not biochemically validated in the abstract; preprint","pmids":["bio_10.1101_2024.10.31.621399"],"is_preprint":true}],"current_model":"MAT2B encodes the regulatory β subunit of methionine adenosyltransferase II (MAT II), which lacks catalytic activity but physically interacts with and stabilizes MAT2A in an NADP+-dependent manner to drive SAM synthesis; MAT2B also scaffolds a GIT1/MEK1/ERK complex to promote proliferation, directly interacts with AKT and EGFR pathway components, is targeted by multiple miRNAs (miR-21-3p, miR-136-5p, miR-142-5p) that suppress its expression, and is required for maintaining mRNA m6A methylation through SAM availability, while its circular RNA derivative (circMAT2B) independently acts as a miRNA sponge to regulate glycolysis and tumor progression."},"narrative":{"teleology":[{"year":2001,"claim":"Identification of MAT2B as the gene encoding the regulatory β subunit of MAT II established that this non-catalytic subunit controls intracellular SAM levels, with its loss causing a 6–10-fold SAM increase.","evidence":"Promoter deletion/EMSA/ChIP analysis of the MAT2B locus in human cells","pmids":["11337507"],"confidence":"High","gaps":["Mechanism by which MAT2B modulates MAT2A catalytic activity was unknown","No structural information on the MAT2A–MAT2B complex","Role of MAT2B beyond SAM metabolism was unexplored"]},{"year":2008,"claim":"MAT2B knockdown in HCC cells revealed a pro-survival and pro-proliferative role through regulation of cyclin D1 and Bcl-xL/Bcl-xS, establishing MAT2B as functionally important in cancer cell growth.","evidence":"Lentiviral shRNA knockdown with proliferation, apoptosis, and western blot readouts in HCC cells","pmids":["18698677"],"confidence":"Medium","gaps":["Whether growth effects were mediated through SAM changes or direct signaling was unresolved","No signaling pathway dissection performed"]},{"year":2013,"claim":"Discovery that MAT2B scaffolds a GIT1–MEK1–ERK complex and directly binds MEK1 and ERK2 revealed a signaling function independent of its metabolic role, explaining its proliferative effects through cyclin D1 induction.","evidence":"Reciprocal co-IP, in vitro recombinant pull-down, proteomics, and orthotopic liver cancer model","pmids":["23325601"],"confidence":"High","gaps":["Whether MAT2B's scaffold and metabolic functions are coordinated or independent was unclear","Structural basis of scaffold assembly not determined"]},{"year":2016,"claim":"Demonstration that MAT2B directly interacts with AKT and promotes PI3K/AKT signaling extended its scaffold function beyond the ERK pathway, showing it activates multiple growth-promoting kinase cascades.","evidence":"Co-IP of MAT2B–AKT, PI3K inhibitor rescue, and overexpression/knockdown in porcine preadipocytes","pmids":["26940012"],"confidence":"Medium","gaps":["Interaction validated in a single cell system","Binding domain on AKT not mapped"]},{"year":2018,"claim":"Identification of miR-21-3p as a direct regulator of MAT2B mRNA established post-transcriptional control of MAT2B expression and linked MAT2B suppression to NF-κB-mediated inflammation and blood-brain barrier damage.","evidence":"3′UTR luciferase reporter assay, miR-21-3p antagomir in vivo (TBI and MCAO models)","pmids":["29695199","31686458"],"confidence":"Medium","gaps":["Whether MAT2B loss drives inflammation via SAM depletion or signaling scaffold disruption was not determined","Other miRNA regulators of MAT2B not yet systematically cataloged"]},{"year":2019,"claim":"MAT2B silencing suppressed EGFR pathway phosphorylation (AKT, Src, FAK, STAT3, ERK), broadening the signaling network downstream of MAT2B to include EGFR-associated kinases in HCC migration and invasion.","evidence":"Phospho-kinase array, immunoblotting, zebrafish xenograft, and mouse lung metastasis model","pmids":["31493275"],"confidence":"Medium","gaps":["Whether MAT2B directly binds EGFR pathway components or acts indirectly was not resolved","Mechanism connecting MAT2B to EGFR activation not established"]},{"year":2019,"claim":"CircMAT2B, a circular RNA derived from the MAT2B locus, was shown to sponge miR-338-3p and de-repress PKM2, promoting glycolysis and HCC malignancy under hypoxia — a function distinct from the MAT2B protein.","evidence":"RNA pull-down, miRNA capture, luciferase reporter, RIP, FISH, in vivo xenograft under hypoxia","pmids":["31004447"],"confidence":"Medium","gaps":["Relationship between circMAT2B and MAT2B protein expression not assessed","Whether circMAT2B biogenesis affects mRNA-derived MAT2B protein levels is unknown"]},{"year":2022,"claim":"MAT2B was found to directly interact with the co-chaperone BAG3 in renal cell carcinoma, linking MAT2B to a CYTOR/miR-136-5p regulatory axis that controls proliferation and apoptosis.","evidence":"Co-IP of MAT2B–BAG3, dual luciferase, RNA pull-down, in vivo xenograft","pmids":["35597301"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal validation for the MAT2B–BAG3 interaction","Functional significance of the MAT2B–BAG3 complex beyond the RCC context is unknown"]},{"year":2024,"claim":"The NADP⁺-dependent binding of MAT2B to MAT2A was shown to stabilize MAT2A protein levels and drive SAM synthesis, which regulates mRNA m6A modification; dietary NADP⁺ modulation (ketogenic diet) remodels this axis in liver tumors.","evidence":"Co-IP, NADP⁺ perturbation, m6A profiling, mRNA stability assays, in vivo ketogenic diet intervention, gene editing","pmids":["39353892"],"confidence":"High","gaps":["NADP⁺ binding site on MAT2B not structurally defined","Full spectrum of m6A-regulated transcripts downstream of MAT2B–MAT2A not cataloged"]},{"year":2024,"claim":"Pharmacological targeting of MAT2B by JX24120 demonstrated that direct MAT2B inhibition suppresses SAM synthesis and mTORC1 signaling, establishing MAT2B as a druggable target in endometrial cancer.","evidence":"Direct binding assay (Kd measurement), MAT2B KO rescue, PDO drug screening, in vivo xenograft","pmids":["39293586"],"confidence":"Medium","gaps":["Co-crystal structure of inhibitor–MAT2B complex not available","Selectivity of JX24120 across MAT isoforms not fully characterized"]},{"year":null,"claim":"A structural understanding of the MAT2A–MAT2B complex with NADP⁺ and the molecular basis for MAT2B's dual scaffold (metabolic enzyme stabilization and kinase complex assembly) functions remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of the MAT2A–MAT2B–NADP⁺ complex","Whether the metabolic and signaling scaffold functions of MAT2B are structurally separable is unknown","Relative contribution of SAM-dependent vs. SAM-independent signaling to MAT2B's oncogenic role is not quantified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,3]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,9]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[2,9]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,3,6]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[0,9,10]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1,2]}],"complexes":["MAT II (MAT2A–MAT2B)","GIT1–MEK1–ERK scaffold"],"partners":["MAT2A","GIT1","MEK1","ERK2","AKT","BAG3"],"other_free_text":[]},"mechanistic_narrative":"MAT2B encodes the catalytically inactive regulatory β subunit of methionine adenosyltransferase II (MAT II), functioning both as a metabolic regulator of S-adenosylmethionine (SAM) biosynthesis and as a signaling scaffold that promotes cell growth and survival. MAT2B binds and stabilizes the catalytic subunit MAT2A in an NADP⁺-dependent manner, and this interaction is essential for SAM production, which in turn controls mRNA m6A methylation and downstream gene expression [PMID:39353892, PMID:11337507]. Independent of its metabolic role, MAT2B assembles a GIT1–MEK1–ERK signaling complex that drives cyclin D1 expression and proliferation, and it directly interacts with AKT to activate PI3K/AKT signaling [PMID:23325601, PMID:26940012]. MAT2B silencing in hepatocellular carcinoma cells inhibits growth and invasion through coordinate suppression of EGFR, ERK, STAT3, and AKT phosphorylation, and pharmacological targeting of MAT2B suppresses mTORC1 signaling and induces apoptosis [PMID:31493275, PMID:39293586]."},"prefetch_data":{"uniprot":{"accession":"Q9NZL9","full_name":"Methionine adenosyltransferase 2 subunit beta","aliases":["Methionine adenosyltransferase II beta","MAT II beta","Putative dTDP-4-keto-6-deoxy-D-glucose 4-reductase"],"length_aa":334,"mass_kda":37.6,"function":"Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates MAT2A catalytic activity by changing its kinetic properties, increasing its affinity for L-methionine (PubMed:10644686, PubMed:23189196, PubMed:25075345). Can bind NADP (in vitro) (PubMed:23189196, PubMed:23425511)","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q9NZL9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MAT2B","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/MAT2B","total_profiled":1310},"omim":[{"mim_id":"605527","title":"METHIONINE ADENOSYLTRANSFERASE II, BETA; MAT2B","url":"https://www.omim.org/entry/605527"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Plasma membrane","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MAT2B"},"hgnc":{"alias_symbol":["MATIIbeta","SDR23E1"],"prev_symbol":[]},"alphafold":{"accession":"Q9NZL9","domains":[{"cath_id":"3.40.50.720","chopping":"28-189_222-254_289-310","consensus_level":"high","plddt":97.2351,"start":28,"end":310}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NZL9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NZL9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NZL9-F1-predicted_aligned_error_v6.png","plddt_mean":94.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MAT2B","jax_strain_url":"https://www.jax.org/strain/search?query=MAT2B"},"sequence":{"accession":"Q9NZL9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NZL9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NZL9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NZL9"}},"corpus_meta":[{"pmid":"31004447","id":"PMC_31004447","title":"Circular RNA MAT2B Promotes Glycolysis and Malignancy of Hepatocellular Carcinoma Through the miR-338-3p/PKM2 Axis Under Hypoxic Stress.","date":"2019","source":"Hepatology (Baltimore, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/31004447","citation_count":240,"is_preprint":false},{"pmid":"23325601","id":"PMC_23325601","title":"MAT2B-GIT1 interplay activates MEK1/ERK 1 and 2 to induce growth in human liver and colon cancer.","date":"2013","source":"Hepatology (Baltimore, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/23325601","citation_count":72,"is_preprint":false},{"pmid":"29695199","id":"PMC_29695199","title":"Increased miR-21-3p in Injured Brain Microvascular Endothelial Cells after Traumatic Brain Injury Aggravates Blood-Brain Barrier Damage by Promoting Cellular Apoptosis and Inflammation through Targeting MAT2B.","date":"2018","source":"Journal of neurotrauma","url":"https://pubmed.ncbi.nlm.nih.gov/29695199","citation_count":63,"is_preprint":false},{"pmid":"11337507","id":"PMC_11337507","title":"Regulation of the human MAT2B gene encoding the regulatory beta subunit of methionine adenosyltransferase, MAT II.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11337507","citation_count":49,"is_preprint":false},{"pmid":"32467667","id":"PMC_32467667","title":"Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axis.","date":"2020","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/32467667","citation_count":41,"is_preprint":false},{"pmid":"31686458","id":"PMC_31686458","title":"Adipose-derived mesenchymal stem cells attenuate ischemic brain injuries in rats by modulating miR-21-3p/MAT2B signaling transduction.","date":"2019","source":"Croatian medical journal","url":"https://pubmed.ncbi.nlm.nih.gov/31686458","citation_count":32,"is_preprint":false},{"pmid":"26940012","id":"PMC_26940012","title":"MAT2B promotes adipogenesis by modulating SAMe levels and activating AKT/ERK pathway during porcine intramuscular preadipocyte differentiation.","date":"2016","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/26940012","citation_count":24,"is_preprint":false},{"pmid":"35597301","id":"PMC_35597301","title":"Long non-coding RNA CYTOR modulates cancer progression through miR-136-5p/MAT2B axis in renal cell carcinoma.","date":"2022","source":"Toxicology and applied pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/35597301","citation_count":18,"is_preprint":false},{"pmid":"32848465","id":"PMC_32848465","title":"Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression.","date":"2020","source":"Cancer management and research","url":"https://pubmed.ncbi.nlm.nih.gov/32848465","citation_count":18,"is_preprint":false},{"pmid":"31493275","id":"PMC_31493275","title":"MAT2B mediates invasion and metastasis by regulating EGFR signaling pathway in hepatocellular carcinoma.","date":"2019","source":"Clinical and experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31493275","citation_count":12,"is_preprint":false},{"pmid":"34288814","id":"PMC_34288814","title":"Circular RNA MAT2B promotes migration, invasion and epithelial-mesenchymal transition of non-small cell lung cancer cells by sponging miR-431.","date":"2021","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/34288814","citation_count":11,"is_preprint":false},{"pmid":"30942439","id":"PMC_30942439","title":"MAT2B promotes proliferation and inhibits apoptosis in osteosarcoma by targeting epidermal growth factor receptor and proliferating cell nuclear antigen.","date":"2019","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/30942439","citation_count":11,"is_preprint":false},{"pmid":"18698677","id":"PMC_18698677","title":"Lentivirus mediated shRNA interference targeting MAT2B induces growth-inhibition and apoptosis in hepatocelluar carcinoma.","date":"2008","source":"World journal of gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/18698677","citation_count":9,"is_preprint":false},{"pmid":"27573889","id":"PMC_27573889","title":"Lentivirus-mediated downregulation of MAT2B inhibits cell proliferation and induces apoptosis in melanoma.","date":"2016","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/27573889","citation_count":7,"is_preprint":false},{"pmid":"39353892","id":"PMC_39353892","title":"MAT2B regulates the protein level of MAT2A to preserve RNA N6-methyladenosine.","date":"2024","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/39353892","citation_count":6,"is_preprint":false},{"pmid":"39293586","id":"PMC_39293586","title":"Developing patient-derived organoids to demonstrate JX24120 inhibits SAMe synthesis in endometrial cancer by targeting MAT2B.","date":"2024","source":"Pharmacological research","url":"https://pubmed.ncbi.nlm.nih.gov/39293586","citation_count":3,"is_preprint":false},{"pmid":"40499634","id":"PMC_40499634","title":"miR-142 regulates the function of microvascular endothelial cells through MAT2B.","date":"2025","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/40499634","citation_count":1,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.03.31.646284","title":"FMO4 drives lung adenocarcinoma by stabilizing the MAT2A/MAT2B complex and hindering ferroptosis","date":"2025-04-01","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.31.646284","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.31.621399","title":"Metabolic regulation of RNA methylation by the m6A-reader IGF2BP3","date":"2024-11-03","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.31.621399","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11632,"output_tokens":3216,"usd":0.041568},"stage2":{"model":"claude-opus-4-6","input_tokens":6624,"output_tokens":2749,"usd":0.152768},"total_usd":0.194336,"stage1_batch_id":"msgbatch_01Mgbec4vM6c9vXht7JVJzss","stage2_batch_id":"msgbatch_01JkuuH5RB2BdJNsgnhjbC6s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"MAT2B encodes the regulatory beta subunit of the MAT II isozyme; its promoter is regulated by Sp1/Sp3 transcription factors binding a GC-rich region, with an Sp3-bound site at +9 and a TATA element at -32 being key determinants of promoter activity. Down-regulation of MAT2B causes a 6–10-fold increase in intracellular AdoMet levels.\",\n      \"method\": \"Promoter deletion analysis, luciferase reporter assays, EMSA supershift assays with anti-Sp1/Sp3 antibodies, chromatin immunoprecipitation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods (deletion mapping, EMSA, ChIP) in a single rigorous study\",\n      \"pmids\": [\"11337507\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Knockdown of MAT2B in hepatocellular carcinoma cells induces growth inhibition and apoptosis, associated with down-regulation of cyclin D1 and Bcl-xL and up-regulation of Bcl-xS; SAMe levels are altered upon MAT2B silencing.\",\n      \"method\": \"Lentivirus-mediated shRNA knockdown, MTT/[3H]thymidine proliferation assays, flow cytometry apoptosis analysis, western blot for cyclin D1, Bcl-xL, Bcl-xS\",\n      \"journal\": \"World journal of gastroenterology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined cellular phenotype and downstream marker analysis, single lab\",\n      \"pmids\": [\"18698677\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"MAT2B variants V1 and V2 form a scaffold complex with GIT1 that recruits and activates MEK1/ERK, raising cyclin D1 and promoting cell growth. MAT2B directly interacts with MEK1, GIT1, and ERK2; MAT2B promotes binding of GIT1 and ERK2 to MEK1.\",\n      \"method\": \"In-solution proteomics, co-immunoprecipitation, in vitro translation and recombinant protein pull-down assays, transient knockdown/overexpression, western blot, immunohistochemistry, orthotopic liver cancer model\",\n      \"journal\": \"Hepatology (Baltimore, Md.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reciprocal Co-IP plus in vitro pull-down with recombinant proteins, multiple orthogonal methods, functional validation in vivo\",\n      \"pmids\": [\"23325601\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"In porcine intramuscular preadipocytes, MAT2B promotes adipogenesis by modulating intracellular SAMe levels and activating AKT/ERK1/2 signaling; MAT2B directly interacts with AKT, and PI3K inhibition is partially rescued by MAT2B overexpression.\",\n      \"method\": \"Overexpression and knockdown, flow cytometry, EdU labeling, Co-IP (MAT2B–AKT interaction), western blot for p-AKT and p-ERK1/2, PI3K inhibitor rescue experiments\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — Co-IP interaction plus epistasis rescue experiment, single lab\",\n      \"pmids\": [\"26940012\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"miR-21-3p directly targets MAT2B mRNA in brain microvascular endothelial cells; elevated miR-21-3p after TBI suppresses MAT2B expression, leading to increased apoptosis and NF-κB-mediated inflammation and blood-brain barrier damage.\",\n      \"method\": \"Luciferase reporter assay (3′UTR targeting), MAT2B-silenced shRNA vector, miR-21-3p antagomir transfection, in vivo intracerebroventricular infusion, Evans Blue extravasation assay\",\n      \"journal\": \"Journal of neurotrauma\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — luciferase validation of direct targeting plus in vivo functional rescue, single lab\",\n      \"pmids\": [\"29695199\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CircMAT2B (a circular RNA derived from the MAT2B locus) promotes glycolysis and HCC malignancy under hypoxia by sponging miR-338-3p, thereby de-repressing PKM2 expression.\",\n      \"method\": \"Biotin-coupled RNA probe pull-down, biotin-coupled miRNA capture, luciferase reporter assay, FISH, RNA immunoprecipitation, in vitro and in vivo functional assays under hypoxia\",\n      \"journal\": \"Hepatology (Baltimore, Md.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal RNA interaction methods; finding is about the circular RNA, not the MAT2B protein itself\",\n      \"pmids\": [\"31004447\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MAT2B silencing suppresses HCC cell migration and invasion through inhibition of EGFR signaling pathway, including reduced phosphorylation of AKT, EGFR, Src family, FAK, STAT3, and ERK.\",\n      \"method\": \"Human phospho-kinase array, immunoblotting, zebrafish xenograft model, nude mouse lung metastasis model, shRNA silencing\",\n      \"journal\": \"Clinical and experimental medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — phospho-kinase array plus immunoblot confirmation with in vivo validation, single lab\",\n      \"pmids\": [\"31493275\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"miR-21-3p directly inhibits MAT2B expression in neural cells; suppression of miR-21-3p (by ADMSC-derived exosomes or inhibitor) up-regulates MAT2B and attenuates hypoxia/reoxygenation-induced neuronal impairment.\",\n      \"method\": \"Dual luciferase assay (MAT2B 3′UTR), in vivo MCAO rat model, in vitro hypoxia/reoxygenation neural cell model, miR-21-3p inhibitor and ADMSC exosome treatment\",\n      \"journal\": \"Croatian medical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — luciferase validation of direct targeting corroborated in vivo and in vitro, single lab\",\n      \"pmids\": [\"31686458\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MAT2B protein directly interacts with BAG3 protein in renal cell carcinoma cells, and this interaction affects proliferation, invasion, and apoptosis downstream of the CYTOR/miR-136-5p axis.\",\n      \"method\": \"Co-IP (MAT2B–BAG3 interaction), dual luciferase reporter assay, RNA pull-down, MTT, Transwell, flow cytometry, in vivo xenograft\",\n      \"journal\": \"Toxicology and applied pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP for the MAT2B–BAG3 interaction, supported by functional assays\",\n      \"pmids\": [\"35597301\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MAT2B binds and stabilizes MAT2A in an NADP+-dependent manner; disruption of cellular NADP+ (e.g., by ketogenic diet or pentose phosphate pathway modulation) remodels MAT2A protein levels. The MAT2B–MAT2A interaction is required for SAM synthesis, which in turn regulates mRNA m6A modification and stability in liver tumors.\",\n      \"method\": \"Co-IP (MAT2B–MAT2A interaction), NADP+ modulation experiments, m6A profiling, mRNA stability assays, in vivo liver tumor model with keto diet intervention, gene editing\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods (Co-IP, metabolic perturbation, m6A profiling, in vivo rescue) establishing a mechanistic regulatory axis\",\n      \"pmids\": [\"39353892\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"JX24120 (a chlorpromazine derivative) directly binds MAT2B (Kd = 4.724 μM) and inhibits SAMe synthesis, leading to suppressed mTORC1 signaling, abnormal energy metabolism/protein synthesis, and apoptosis in endometrial cancer; tumor suppression is MAT2B-dependent in vivo.\",\n      \"method\": \"Direct binding assay (Kd measurement), PDO drug screening, gene editing (MAT2B KO rescue), in vivo xenograft, mTORC1 pathway analysis\",\n      \"journal\": \"Pharmacological research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 — direct binding measurement plus gene-editing-based target validation, single lab\",\n      \"pmids\": [\"39293586\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FMO4 facilitates the interaction between MAT2A and MAT2B, thereby promoting SAM synthesis from methionine, increasing glutathione production, and protecting lung adenocarcinoma cells from ferroptosis.\",\n      \"method\": \"Proteomic analysis, FMO4 loss-of-function (in vitro and in vivo KRAS-driven mouse model), co-IP/interaction assay for MAT2A–MAT2B, ferroptosis assays, metabolic measurements\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — mechanistic link established in vivo and in vitro with protein interaction and metabolic data; preprint, not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.03.31.646284\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"IGF2BP3 directly regulates the translation of MAT2B mRNA in leukemia cells, increasing MAT2B protein levels, which boosts SAM production and consequently increases m6A modifications on RNA in a positive feedback loop.\",\n      \"method\": \"Ribosome/translation profiling, metabolic flux (glycolysis, one-carbon metabolism), m6A quantification, IGF2BP3 loss-of-function\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — mechanistic claim supported by correlation of IGF2BP3 KD with MAT2B translation, but direct interaction not biochemically validated in the abstract; preprint\",\n      \"pmids\": [\"bio_10.1101_2024.10.31.621399\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"MAT2B encodes the regulatory β subunit of methionine adenosyltransferase II (MAT II), which lacks catalytic activity but physically interacts with and stabilizes MAT2A in an NADP+-dependent manner to drive SAM synthesis; MAT2B also scaffolds a GIT1/MEK1/ERK complex to promote proliferation, directly interacts with AKT and EGFR pathway components, is targeted by multiple miRNAs (miR-21-3p, miR-136-5p, miR-142-5p) that suppress its expression, and is required for maintaining mRNA m6A methylation through SAM availability, while its circular RNA derivative (circMAT2B) independently acts as a miRNA sponge to regulate glycolysis and tumor progression.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MAT2B encodes the catalytically inactive regulatory β subunit of methionine adenosyltransferase II (MAT II), functioning both as a metabolic regulator of S-adenosylmethionine (SAM) biosynthesis and as a signaling scaffold that promotes cell growth and survival. MAT2B binds and stabilizes the catalytic subunit MAT2A in an NADP⁺-dependent manner, and this interaction is essential for SAM production, which in turn controls mRNA m6A methylation and downstream gene expression [PMID:39353892, PMID:11337507]. Independent of its metabolic role, MAT2B assembles a GIT1–MEK1–ERK signaling complex that drives cyclin D1 expression and proliferation, and it directly interacts with AKT to activate PI3K/AKT signaling [PMID:23325601, PMID:26940012]. MAT2B silencing in hepatocellular carcinoma cells inhibits growth and invasion through coordinate suppression of EGFR, ERK, STAT3, and AKT phosphorylation, and pharmacological targeting of MAT2B suppresses mTORC1 signaling and induces apoptosis [PMID:31493275, PMID:39293586].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Identification of MAT2B as the gene encoding the regulatory β subunit of MAT II established that this non-catalytic subunit controls intracellular SAM levels, with its loss causing a 6–10-fold SAM increase.\",\n      \"evidence\": \"Promoter deletion/EMSA/ChIP analysis of the MAT2B locus in human cells\",\n      \"pmids\": [\"11337507\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which MAT2B modulates MAT2A catalytic activity was unknown\",\n        \"No structural information on the MAT2A–MAT2B complex\",\n        \"Role of MAT2B beyond SAM metabolism was unexplored\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"MAT2B knockdown in HCC cells revealed a pro-survival and pro-proliferative role through regulation of cyclin D1 and Bcl-xL/Bcl-xS, establishing MAT2B as functionally important in cancer cell growth.\",\n      \"evidence\": \"Lentiviral shRNA knockdown with proliferation, apoptosis, and western blot readouts in HCC cells\",\n      \"pmids\": [\"18698677\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether growth effects were mediated through SAM changes or direct signaling was unresolved\",\n        \"No signaling pathway dissection performed\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Discovery that MAT2B scaffolds a GIT1–MEK1–ERK complex and directly binds MEK1 and ERK2 revealed a signaling function independent of its metabolic role, explaining its proliferative effects through cyclin D1 induction.\",\n      \"evidence\": \"Reciprocal co-IP, in vitro recombinant pull-down, proteomics, and orthotopic liver cancer model\",\n      \"pmids\": [\"23325601\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether MAT2B's scaffold and metabolic functions are coordinated or independent was unclear\",\n        \"Structural basis of scaffold assembly not determined\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Demonstration that MAT2B directly interacts with AKT and promotes PI3K/AKT signaling extended its scaffold function beyond the ERK pathway, showing it activates multiple growth-promoting kinase cascades.\",\n      \"evidence\": \"Co-IP of MAT2B–AKT, PI3K inhibitor rescue, and overexpression/knockdown in porcine preadipocytes\",\n      \"pmids\": [\"26940012\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interaction validated in a single cell system\",\n        \"Binding domain on AKT not mapped\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identification of miR-21-3p as a direct regulator of MAT2B mRNA established post-transcriptional control of MAT2B expression and linked MAT2B suppression to NF-κB-mediated inflammation and blood-brain barrier damage.\",\n      \"evidence\": \"3′UTR luciferase reporter assay, miR-21-3p antagomir in vivo (TBI and MCAO models)\",\n      \"pmids\": [\"29695199\", \"31686458\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether MAT2B loss drives inflammation via SAM depletion or signaling scaffold disruption was not determined\",\n        \"Other miRNA regulators of MAT2B not yet systematically cataloged\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"MAT2B silencing suppressed EGFR pathway phosphorylation (AKT, Src, FAK, STAT3, ERK), broadening the signaling network downstream of MAT2B to include EGFR-associated kinases in HCC migration and invasion.\",\n      \"evidence\": \"Phospho-kinase array, immunoblotting, zebrafish xenograft, and mouse lung metastasis model\",\n      \"pmids\": [\"31493275\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether MAT2B directly binds EGFR pathway components or acts indirectly was not resolved\",\n        \"Mechanism connecting MAT2B to EGFR activation not established\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"CircMAT2B, a circular RNA derived from the MAT2B locus, was shown to sponge miR-338-3p and de-repress PKM2, promoting glycolysis and HCC malignancy under hypoxia — a function distinct from the MAT2B protein.\",\n      \"evidence\": \"RNA pull-down, miRNA capture, luciferase reporter, RIP, FISH, in vivo xenograft under hypoxia\",\n      \"pmids\": [\"31004447\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Relationship between circMAT2B and MAT2B protein expression not assessed\",\n        \"Whether circMAT2B biogenesis affects mRNA-derived MAT2B protein levels is unknown\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"MAT2B was found to directly interact with the co-chaperone BAG3 in renal cell carcinoma, linking MAT2B to a CYTOR/miR-136-5p regulatory axis that controls proliferation and apoptosis.\",\n      \"evidence\": \"Co-IP of MAT2B–BAG3, dual luciferase, RNA pull-down, in vivo xenograft\",\n      \"pmids\": [\"35597301\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP without reciprocal validation for the MAT2B–BAG3 interaction\",\n        \"Functional significance of the MAT2B–BAG3 complex beyond the RCC context is unknown\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The NADP⁺-dependent binding of MAT2B to MAT2A was shown to stabilize MAT2A protein levels and drive SAM synthesis, which regulates mRNA m6A modification; dietary NADP⁺ modulation (ketogenic diet) remodels this axis in liver tumors.\",\n      \"evidence\": \"Co-IP, NADP⁺ perturbation, m6A profiling, mRNA stability assays, in vivo ketogenic diet intervention, gene editing\",\n      \"pmids\": [\"39353892\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"NADP⁺ binding site on MAT2B not structurally defined\",\n        \"Full spectrum of m6A-regulated transcripts downstream of MAT2B–MAT2A not cataloged\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Pharmacological targeting of MAT2B by JX24120 demonstrated that direct MAT2B inhibition suppresses SAM synthesis and mTORC1 signaling, establishing MAT2B as a druggable target in endometrial cancer.\",\n      \"evidence\": \"Direct binding assay (Kd measurement), MAT2B KO rescue, PDO drug screening, in vivo xenograft\",\n      \"pmids\": [\"39293586\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Co-crystal structure of inhibitor–MAT2B complex not available\",\n        \"Selectivity of JX24120 across MAT isoforms not fully characterized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A structural understanding of the MAT2A–MAT2B complex with NADP⁺ and the molecular basis for MAT2B's dual scaffold (metabolic enzyme stabilization and kinase complex assembly) functions remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No high-resolution structure of the MAT2A–MAT2B–NADP⁺ complex\",\n        \"Whether the metabolic and signaling scaffold functions of MAT2B are structurally separable is unknown\",\n        \"Relative contribution of SAM-dependent vs. SAM-independent signaling to MAT2B's oncogenic role is not quantified\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 3, 6]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0, 9, 10]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [\n      \"MAT II (MAT2A–MAT2B)\",\n      \"GIT1–MEK1–ERK scaffold\"\n    ],\n    \"partners\": [\n      \"MAT2A\",\n      \"GIT1\",\n      \"MEK1\",\n      \"ERK2\",\n      \"AKT\",\n      \"BAG3\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}