{"gene":"TNKS","run_date":"2026-06-10T10:51:55","timeline":{"discoveries":[{"year":2012,"finding":"TNKS (tankyrase) forms a ternary complex with Axin and the kinesin motor protein KIF3A on the trans-Golgi network; insulin treatment suppresses TNKS ADP-ribosylase activity, leading to reduced ADP-ribosylation and ubiquitination of Axin and TNKS, stabilizing the complex and enabling GLUT4 translocation to the plasma membrane in an Akt-dependent manner.","method":"Co-immunoprecipitation, knockdown of individual complex components, TNKS2 knockout mice with metabolic phenotyping, subcellular co-localization imaging","journal":"Cell research","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, genetic KO mouse model with defined metabolic phenotype, multiple orthogonal methods (KD, KO, imaging, enzymatic activity assay)","pmids":["22473005"],"is_preprint":false},{"year":2024,"finding":"Upon induction of necroptosis, PARP5A (TNKS) is recruited by adaptor protein TAX1BP1 and, together with its binding partner RNF146, forms liquid-like condensates via multivalent interactions; within these condensates PARP5A performs poly-ADP-ribosylation (PARylation) of activated RIPK1, which is then subject to PARylation-dependent ubiquitination (PARdU) predominantly on K376 of mouse RIPK1, promoting proteasomal degradation of kinase-activated RIPK1 and restraining necroptosis.","method":"Phase-separation assays, Co-IP, site-directed mutagenesis (K376 RIPK1), proteasome inhibition, loss-of-function in mouse embryonic fibroblasts","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods including mutagenesis (K376), phase-separation reconstitution, Co-IP, and genetic loss-of-function with defined cell death phenotype in a single rigorous study","pmids":["38272024"],"is_preprint":false},{"year":2024,"finding":"TNKS and TNKS2 bind the peroxisomal membrane protein PEX14 and, together with RNF146, regulate peroxisome protein import efficiency via PARsylation at the peroxisome membrane; loss of peroxisomes increases TNKS/2 and RNF146-dependent degradation of AXIN1, which is sufficient to alter β-catenin transcription.","method":"Genome-wide CRISPRi screen, genetic epistasis (RNF146 dependence on TNKS/2 activity), peroxisome import assays, β-catenin reporter assay","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide screen with genetic epistasis and functional pathway readout, single lab, two orthogonal approaches","pmids":["38967608"],"is_preprint":false},{"year":2003,"finding":"Formin-binding protein FBP17 directly binds tankyrase (TNKS) via a specific TNKS-binding motif, as demonstrated by two-hybrid assay and co-immunoprecipitation of endogenous proteins.","method":"Yeast two-hybrid, co-immunoprecipitation of endogenous proteins in 293T cells","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — two orthogonal binding assays (Y2H + endogenous Co-IP), single lab","pmids":["14596906"],"is_preprint":false},{"year":2019,"finding":"TNKS1 directly interacts with β-catenin (shown by immunoprecipitation with β-catenin antibody) and functions as a positive regulator of the Wnt/β-catenin pathway; TNKS1 knockdown in glioblastoma cells suppresses Wnt/β-catenin signaling and reduces cell growth, invasion, and increases apoptosis.","method":"Co-immunoprecipitation, TNKS1 knockdown/overexpression with Wnt pathway readouts, cell viability and invasion assays","journal":"OncoTargets and therapy","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP plus functional KD/OE experiments, single lab, two orthogonal methods","pmids":["31849489"],"is_preprint":false},{"year":2022,"finding":"USP25 deubiquitinates TNKS1, stabilizing it and promoting Wnt/β-catenin pathway activity; USP25 knockdown increases TNKS1 ubiquitination and decreases TNKS1 protein levels, while USP25 overexpression has the opposite effect.","method":"Co-immunoprecipitation to detect TNKS1 ubiquitination, USP25 knockdown/overexpression with Western blot for Wnt pathway markers","journal":"Disease markers","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP ubiquitination assay combined with KD/OE functional readouts, single lab","pmids":["35450028"],"is_preprint":false},{"year":2023,"finding":"TNKS forms a complex with USP25 that stabilizes TNKS protein levels; disruption of the TNKS–USP25 protein–protein interaction by the small molecule UAT-B leads to decreased TNKS levels, triggers apoptosis, and modulates the Wnt/β-catenin pathway in colorectal cancer cells and xenograft models.","method":"Small-molecule PPI inhibitor (UAT-B), Western blot for TNKS protein levels and Wnt markers, in vitro and in vivo xenograft models","journal":"Acta pharmaceutica Sinica. B","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — chemical disruption of defined PPI with in vivo validation, single lab, multiple model systems","pmids":["38261825"],"is_preprint":false},{"year":2020,"finding":"TNKS-2 (Golgi-associated) poly-ADP-ribosylates VEGF in the secretory pathway; this requires a priming mono-ADP-ribosylation of VEGF by ER-associated PARP-16, indicating an interplay between PARP-16 and TNKS-2 in the sequential ADP-ribosylation of VEGF.","method":"Co-immunoprecipitation, ADP-ribosylation assay in secretory pathway compartments, sequential enzymatic dependency experiments","journal":"Molecular and cellular biochemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single Co-IP and enzymatic assay with limited mechanistic follow-up detail in abstract","pmids":["32472322"],"is_preprint":false},{"year":2025,"finding":"In skeletal muscle cells, insulin upregulates Axin1 and TNKS protein levels in an Akt-dependent manner; Axin1 interacts with TNKS (interaction enhanced by insulin), and this Axin1/TNKS axis acts upstream of Tiam1–Rac1 signaling to mediate insulin-stimulated GLUT4 translocation independently of Akt–AS160 phosphorylation.","method":"Co-immunoprecipitation (Axin1–TNKS interaction), siRNA knockdown, TNKS activity inhibition (XAV939), GLUT4myc translocation assay, PAK phosphorylation as Rac1 readout in C2C12 myotubes","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, chemical inhibition, and genetic KD with defined cellular phenotype, single lab, multiple orthogonal methods","pmids":["41207648"],"is_preprint":false},{"year":2025,"finding":"Catalytic inhibition of TNKS prevents TNKS turnover and drives its accumulation in the β-catenin destruction complex (DC), where the scaffolding function of TNKS induces AXIN puncta formation, rigidifies the DC, and impedes β-catenin turnover — providing a mechanistic explanation for the limited efficacy of TNKS catalytic inhibitors; PROTAC-mediated degradation of TNKS stabilizes AXIN without puncta formation and more deeply suppresses WNT/β-catenin signaling.","method":"PROTAC-mediated targeted protein degradation, imaging of AXIN puncta, β-catenin destruction complex analysis, comparison of catalytic inhibitor vs. degrader effects in APC-mutant colorectal cancer cells","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — PROTAC degrader vs. inhibitor comparison with mechanistic imaging readout, preprint, single lab but multiple orthogonal approaches","pmids":["bio_10.1101_2025.09.22.677768"],"is_preprint":true},{"year":2025,"finding":"TNKS1 interacts directly with SLC7A11 (as shown by Co-IP), and TNKS1 overexpression in human aortic smooth muscle cells increases ferroptosis markers (iron content, ROS, lipid peroxidation), driving phenotypic switching from contractile to synthetic phenotype; ferroptosis inhibition restores the contractile phenotype.","method":"Co-immunoprecipitation (TNKS1–SLC7A11), TNKS1 overexpression, ferroptosis marker assays, in vivo aortic dissection model","journal":"International immunopharmacology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP with limited mechanistic follow-up, single lab","pmids":["40359887"],"is_preprint":false},{"year":2025,"finding":"Loss of chromosome 8p in tumors depletes TNKS1 expression and creates a dependency on the functionally redundant TNKS2; structure-guided drug design yielded a first-in-class TNKS2-selective inhibitor that drives selective WNT inhibition in TNKS1-deficient cancer cell and organoid models.","method":"Structure-guided drug design, cell line and organoid models with TNKS1 depletion, WNT pathway reporter assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — structure-guided inhibitor design with functional genetic epistasis (TNKS1 loss creating TNKS2 dependency), preprint, single lab","pmids":["bio_10.1101_2025.03.04.641305"],"is_preprint":true}],"current_model":"TNKS (tankyrase/PARP5A) is a poly-ADP-ribose polymerase that: (1) regulates the Wnt/β-catenin pathway by PARylating Axin to promote its ubiquitination and degradation, with its scaffolding function in the β-catenin destruction complex also influencing pathway activity independently of catalysis; (2) forms a ternary complex with Axin and KIF3A on the trans-Golgi network that is stabilized by insulin-mediated Akt signaling to drive GLUT4 translocation in an Axin/TNKS–Tiam1–Rac1-dependent manner; (3) is recruited with RNF146 by TAX1BP1 into liquid-like condensates upon necroptosis induction, where it PARylates activated RIPK1 to promote its proteasomal degradation and restrain cell death; (4) binds the peroxisomal membrane protein PEX14 to regulate peroxisome protein import; (5) is stabilized by the deubiquitinase USP25, which protects it from proteasomal degradation; and (6) interacts with additional partners including FBP17, β-catenin, and SLC7A11 to modulate diverse cellular processes including telomere maintenance and ferroptosis."},"narrative":{"mechanistic_narrative":"TNKS (tankyrase/PARP5A) is a poly-ADP-ribose polymerase that regulates the Wnt/β-catenin pathway through both its catalytic PARylation of AXIN — which targets AXIN for RNF146-dependent ubiquitination and degradation — and a scaffolding function within the β-catenin destruction complex [PMID:38967608, PMID:bio_10.1101_2025.09.22.677768]. These two activities are functionally distinct: catalytic inhibition prevents TNKS turnover and drives its accumulation in the destruction complex, where its scaffold rigidifies the complex into AXIN puncta and paradoxically impedes β-catenin turnover, whereas targeted degradation of TNKS stabilizes AXIN without puncta and more deeply suppresses Wnt signaling [PMID:bio_10.1101_2025.09.22.677768]. TNKS directly binds β-catenin and acts as a positive regulator of the pathway, with knockdown suppressing tumor cell growth and invasion [PMID:31849489]; its protein stability is controlled by the deubiquitinase USP25, which protects it from proteasomal degradation, and disruption of the TNKS–USP25 interaction depletes TNKS and triggers apoptosis [PMID:35450028, PMID:38261825]. Beyond Wnt, TNKS scaffolds an AXIN–KIF3A complex on the trans-Golgi network and, with AXIN, acts upstream of Tiam1–Rac1 to drive insulin-stimulated GLUT4 translocation, with insulin/Akt signaling controlling TNKS activity and abundance [PMID:22473005, PMID:41207648]. In a separate role, TNKS is recruited by TAX1BP1 with RNF146 into liquid-like condensates upon necroptosis induction, where it PARylates activated RIPK1 to promote its PARylation-dependent ubiquitination and proteasomal degradation, restraining cell death [PMID:38272024]. TNKS and TNKS2 also bind the peroxisomal membrane protein PEX14 and regulate peroxisome protein import [PMID:38967608]. TNKS1 and TNKS2 are functionally redundant, such that chromosome 8p loss depleting TNKS1 creates a selective dependency on TNKS2 [PMID:bio_10.1101_2025.03.04.641305].","teleology":[{"year":2003,"claim":"Establishing the first direct binding partners of tankyrase began to define how it is recruited to substrates and complexes.","evidence":"Yeast two-hybrid and endogenous co-immunoprecipitation identifying FBP17 binding via a TNKS-binding motif","pmids":["14596906"],"confidence":"Medium","gaps":["Functional consequence of the FBP17–TNKS interaction not established","No PARylation substrate role for FBP17 demonstrated"]},{"year":2012,"claim":"Resolved how tankyrase couples insulin signaling to glucose uptake by scaffolding a Golgi-localized AXIN–KIF3A complex whose stability is gated by its own enzymatic activity.","evidence":"Co-IP, component knockdown, TNKS2 knockout mice with metabolic phenotyping, and co-localization imaging on the trans-Golgi network","pmids":["22473005"],"confidence":"High","gaps":["Mechanism linking Akt to suppression of TNKS ADP-ribosylase activity not fully resolved","Relative contribution of catalysis vs. scaffolding to complex stability unclear"]},{"year":2019,"claim":"Confirmed a direct TNKS1–β-catenin interaction and a pro-tumorigenic role for TNKS1 as a positive Wnt regulator in glioblastoma.","evidence":"Co-IP with β-catenin and TNKS1 knockdown/overexpression with viability and invasion readouts","pmids":["31849489"],"confidence":"Medium","gaps":["Whether the β-catenin interaction is direct or AXIN-bridged not distinguished","Catalytic requirement for the growth phenotype not tested"]},{"year":2020,"claim":"Proposed that secretory-pathway TNKS2 participates in sequential ADP-ribosylation of VEGF downstream of a PARP-16 priming event.","evidence":"Co-IP and ADP-ribosylation assays with sequential enzymatic dependency tests in secretory compartments","pmids":["32472322"],"confidence":"Low","gaps":["Single Co-IP and enzymatic assay with limited mechanistic follow-up","Functional consequence of VEGF PARylation not established"]},{"year":2022,"claim":"Identified USP25 as a deubiquitinase that stabilizes TNKS1 and thereby sustains Wnt/β-catenin activity, defining a post-translational control point over TNKS abundance.","evidence":"Co-IP ubiquitination assays plus USP25 knockdown/overexpression with Wnt marker Western blots","pmids":["35450028"],"confidence":"Medium","gaps":["Site of TNKS1 ubiquitin removal by USP25 not mapped","E3 ligase opposing USP25 on TNKS1 not identified"]},{"year":2023,"claim":"Validated the TNKS–USP25 interaction as a druggable node by showing that chemical PPI disruption depletes TNKS and triggers apoptosis in colorectal cancer models.","evidence":"Small-molecule PPI inhibitor UAT-B with Western blot, in vitro and xenograft models","pmids":["38261825"],"confidence":"Medium","gaps":["Structural basis of the TNKS–USP25 interface not defined","Selectivity of UAT-B not fully characterized"]},{"year":2024,"claim":"Revealed a cell-death restraint function in which TNKS is condensate-recruited to PARylate activated RIPK1 and target it for degradation, distinct from its Wnt and metabolic roles.","evidence":"Phase-separation reconstitution, Co-IP, RIPK1 K376 mutagenesis, proteasome inhibition, and MEF loss-of-function","pmids":["38272024"],"confidence":"High","gaps":["TAX1BP1–TNKS recruitment determinants not fully mapped","In vivo necroptosis relevance not established"]},{"year":2024,"claim":"Connected TNKS/TNKS2 to peroxisome biology by showing PEX14 binding and regulation of peroxisome import, with peroxisome loss feeding back onto AXIN1 degradation and β-catenin transcription.","evidence":"Genome-wide CRISPRi screen, RNF146 genetic epistasis, peroxisome import assays, and β-catenin reporter","pmids":["38967608"],"confidence":"Medium","gaps":["Direct PARylation substrate at the peroxisome membrane not identified","Physiological setting of peroxisome–Wnt crosstalk unclear"]},{"year":2025,"claim":"Distinguished TNKS catalytic from scaffolding functions, explaining why catalytic inhibitors fail — enzyme-dead accumulated TNKS rigidifies the destruction complex — while degraders suppress Wnt more effectively.","evidence":"PROTAC degradation vs. catalytic inhibition with AXIN puncta imaging in APC-mutant colorectal cancer cells (preprint)","pmids":["bio_10.1101_2025.09.22.677768"],"confidence":"Medium","gaps":["Preprint, single lab","Structural basis of scaffold-induced AXIN puncta not resolved"]},{"year":2025,"claim":"Extended the insulin/GLUT4 mechanism by placing the Axin1/TNKS axis upstream of Tiam1–Rac1 and parallel to Akt–AS160 in skeletal muscle.","evidence":"Co-IP, siRNA, XAV939 inhibition, GLUT4myc translocation, and PAK phosphorylation readout in C2C12 myotubes","pmids":["41207648"],"confidence":"Medium","gaps":["Direct Rac1-pathway substrate of TNKS PARylation not identified","In vivo muscle relevance not tested"]},{"year":2025,"claim":"Demonstrated TNKS1/TNKS2 functional redundancy as a therapeutic vulnerability, enabling a TNKS2-selective inhibitor effective in TNKS1-deficient (8p-loss) tumors.","evidence":"Structure-guided drug design with TNKS1-depleted cell line and organoid WNT reporter models (preprint)","pmids":["bio_10.1101_2025.03.04.641305"],"confidence":"Medium","gaps":["Preprint, single lab","Breadth of 8p-loss tumor responsiveness not validated clinically"]},{"year":2025,"claim":"Linked TNKS1 to vascular ferroptosis via SLC7A11 binding, associating TNKS1 with smooth muscle phenotypic switching.","evidence":"Co-IP, TNKS1 overexpression, ferroptosis marker assays, and aortic dissection model","pmids":["40359887"],"confidence":"Low","gaps":["Single Co-IP with limited mechanistic follow-up","Whether SLC7A11 is a PARylation substrate not tested"]},{"year":null,"claim":"How TNKS partitions its catalytic and scaffolding activities across its many contexts — Wnt, GLUT4 trafficking, necroptosis, peroxisome import, ferroptosis — and what determines substrate selection in each remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model for context-specific substrate recruitment","Structural determinants distinguishing scaffold vs. catalytic output not defined","Telomere maintenance role not represented by direct evidence in this corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[1,2]},{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[0,1]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,9]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,7]},{"term_id":"GO:0005777","term_label":"peroxisome","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,4,9]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[1]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[5,6]}],"complexes":["β-catenin destruction complex","AXIN–KIF3A–TNKS trans-Golgi ternary complex","TAX1BP1–TNKS–RNF146 necroptosis condensate"],"partners":["AXIN1","KIF3A","RNF146","TAX1BP1","USP25","FBP17","CTNNB1","PEX14"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O95271","full_name":"Poly [ADP-ribose] polymerase tankyrase-1","aliases":["ADP-ribosyltransferase diphtheria toxin-like 5","ARTD5","Poly [ADP-ribose] polymerase 5A","Protein poly-ADP-ribosyltransferase tankyrase-1","TNKS-1","TRF1-interacting ankyrin-related ADP-ribose polymerase","Tankyrase I","Tankyrase-1","TANK1"],"length_aa":1327,"mass_kda":142.0,"function":"Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking (PubMed:10988299, PubMed:11739745, PubMed:16076287, PubMed:19759537, PubMed:21478859, PubMed:22864114, PubMed:23622245, PubMed:25043379, PubMed:28619731). Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation (PubMed:19759537, PubMed:21478859). Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI (PubMed:22864114). May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles (PubMed:10988299). May be involved in spindle pole assembly through PARsylation of NUMA1 (PubMed:16076287). Stimulates 26S proteasome activity (PubMed:23622245)","subcellular_location":"Cytoplasm; Golgi apparatus membrane; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Nucleus, nuclear pore complex; Chromosome, telomere; Cytoplasm, cytoskeleton, spindle pole","url":"https://www.uniprot.org/uniprotkb/O95271/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TNKS","classification":"Not Classified","n_dependent_lines":18,"n_total_lines":1208,"dependency_fraction":0.014900662251655629},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TNKS","total_profiled":1310},"omim":[{"mim_id":"621422","title":"TELOMERASE RNA COMPONENT-INTERACTING RNase; TRIR","url":"https://www.omim.org/entry/621422"},{"mim_id":"620871","title":"DNA DAMAGE-INDUCIBLE 1 HOMOLOG 2; DDI2","url":"https://www.omim.org/entry/620871"},{"mim_id":"620652","title":"SH3 DOMAIN-BINDING PROTEIN 5-LIKE; SH3BP5L","url":"https://www.omim.org/entry/620652"},{"mim_id":"612137","title":"RING FINGER PROTEIN 146; RNF146","url":"https://www.omim.org/entry/612137"},{"mim_id":"607128","title":"TANKYRASE 2; TNKS2","url":"https://www.omim.org/entry/607128"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Nuclear membrane","reliability":"Additional"},{"location":"Nuclear bodies","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TNKS"},"hgnc":{"alias_symbol":["TIN1","TINF1","TNKS1","PARP-5a","PARP5A","pART5","ARTD5"],"prev_symbol":[]},"alphafold":{"accession":"O95271","domains":[{"cath_id":"1.25.40.20","chopping":"183-332","consensus_level":"high","plddt":94.8545,"start":183,"end":332},{"cath_id":"1.25.40.20","chopping":"335-461","consensus_level":"medium","plddt":95.8862,"start":335,"end":461},{"cath_id":"1.25.40.20","chopping":"648-800","consensus_level":"medium","plddt":93.7561,"start":648,"end":800},{"cath_id":"1.10.150.50","chopping":"1032-1086","consensus_level":"high","plddt":83.8513,"start":1032,"end":1086},{"cath_id":"3.90.228.10","chopping":"1116-1312","consensus_level":"high","plddt":69.4271,"start":1116,"end":1312}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O95271","model_url":"https://alphafold.ebi.ac.uk/files/AF-O95271-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O95271-F1-predicted_aligned_error_v6.png","plddt_mean":75.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TNKS","jax_strain_url":"https://www.jax.org/strain/search?query=TNKS"},"sequence":{"accession":"O95271","fasta_url":"https://rest.uniprot.org/uniprotkb/O95271.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O95271/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O95271"}},"corpus_meta":[{"pmid":"22473005","id":"PMC_22473005","title":"The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation.","date":"2012","source":"Cell research","url":"https://pubmed.ncbi.nlm.nih.gov/22473005","citation_count":70,"is_preprint":false},{"pmid":"32393760","id":"PMC_32393760","title":"circ5615 functions as a ceRNA to promote colorectal cancer progression by upregulating TNKS.","date":"2020","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/32393760","citation_count":60,"is_preprint":false},{"pmid":"31811145","id":"PMC_31811145","title":"The tin1 gene retains the function of promoting tillering in maize.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31811145","citation_count":50,"is_preprint":false},{"pmid":"10753188","id":"PMC_10753188","title":"Upregulation of telomerase activity by X-irradiation in mouse leukaemia cells is independent of Tert, Terc, Tnks and Myc transcription.","date":"2000","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/10753188","citation_count":29,"is_preprint":false},{"pmid":"38272024","id":"PMC_38272024","title":"PARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis.","date":"2024","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/38272024","citation_count":24,"is_preprint":false},{"pmid":"22154485","id":"PMC_22154485","title":"Expression of TNKS1 is correlated with pathologic grade and Wnt/β-catenin pathway in human astrocytomas.","date":"2011","source":"Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia","url":"https://pubmed.ncbi.nlm.nih.gov/22154485","citation_count":18,"is_preprint":false},{"pmid":"36923920","id":"PMC_36923920","title":"Pyridine-Based 1,2,4-Triazolo-Tethered Indole Conjugates Potentially Affecting TNKS and PI3K in Colorectal Cancer.","date":"2023","source":"ACS medicinal chemistry 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an Akt-dependent manner.\",\n      \"method\": \"Co-immunoprecipitation, knockdown of individual complex components, TNKS2 knockout mice with metabolic phenotyping, subcellular co-localization imaging\",\n      \"journal\": \"Cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, genetic KO mouse model with defined metabolic phenotype, multiple orthogonal methods (KD, KO, imaging, enzymatic activity assay)\",\n      \"pmids\": [\"22473005\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Upon induction of necroptosis, PARP5A (TNKS) is recruited by adaptor protein TAX1BP1 and, together with its binding partner RNF146, forms liquid-like condensates via multivalent interactions; within these condensates PARP5A performs poly-ADP-ribosylation (PARylation) of activated RIPK1, which is then subject to PARylation-dependent ubiquitination (PARdU) predominantly on K376 of mouse RIPK1, promoting proteasomal degradation of kinase-activated RIPK1 and restraining necroptosis.\",\n      \"method\": \"Phase-separation assays, Co-IP, site-directed mutagenesis (K376 RIPK1), proteasome inhibition, loss-of-function in mouse embryonic fibroblasts\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods including mutagenesis (K376), phase-separation reconstitution, Co-IP, and genetic loss-of-function with defined cell death phenotype in a single rigorous study\",\n      \"pmids\": [\"38272024\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TNKS and TNKS2 bind the peroxisomal membrane protein PEX14 and, together with RNF146, regulate peroxisome protein import efficiency via PARsylation at the peroxisome membrane; loss of peroxisomes increases TNKS/2 and RNF146-dependent degradation of AXIN1, which is sufficient to alter β-catenin transcription.\",\n      \"method\": \"Genome-wide CRISPRi screen, genetic epistasis (RNF146 dependence on TNKS/2 activity), peroxisome import assays, β-catenin reporter assay\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide screen with genetic epistasis and functional pathway readout, single lab, two orthogonal approaches\",\n      \"pmids\": [\"38967608\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Formin-binding protein FBP17 directly binds tankyrase (TNKS) via a specific TNKS-binding motif, as demonstrated by two-hybrid assay and co-immunoprecipitation of endogenous proteins.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation of endogenous proteins in 293T cells\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — two orthogonal binding assays (Y2H + endogenous Co-IP), single lab\",\n      \"pmids\": [\"14596906\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TNKS1 directly interacts with β-catenin (shown by immunoprecipitation with β-catenin antibody) and functions as a positive regulator of the Wnt/β-catenin pathway; TNKS1 knockdown in glioblastoma cells suppresses Wnt/β-catenin signaling and reduces cell growth, invasion, and increases apoptosis.\",\n      \"method\": \"Co-immunoprecipitation, TNKS1 knockdown/overexpression with Wnt pathway readouts, cell viability and invasion assays\",\n      \"journal\": \"OncoTargets and therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP plus functional KD/OE experiments, single lab, two orthogonal methods\",\n      \"pmids\": [\"31849489\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"USP25 deubiquitinates TNKS1, stabilizing it and promoting Wnt/β-catenin pathway activity; USP25 knockdown increases TNKS1 ubiquitination and decreases TNKS1 protein levels, while USP25 overexpression has the opposite effect.\",\n      \"method\": \"Co-immunoprecipitation to detect TNKS1 ubiquitination, USP25 knockdown/overexpression with Western blot for Wnt pathway markers\",\n      \"journal\": \"Disease markers\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP ubiquitination assay combined with KD/OE functional readouts, single lab\",\n      \"pmids\": [\"35450028\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TNKS forms a complex with USP25 that stabilizes TNKS protein levels; disruption of the TNKS–USP25 protein–protein interaction by the small molecule UAT-B leads to decreased TNKS levels, triggers apoptosis, and modulates the Wnt/β-catenin pathway in colorectal cancer cells and xenograft models.\",\n      \"method\": \"Small-molecule PPI inhibitor (UAT-B), Western blot for TNKS protein levels and Wnt markers, in vitro and in vivo xenograft models\",\n      \"journal\": \"Acta pharmaceutica Sinica. B\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — chemical disruption of defined PPI with in vivo validation, single lab, multiple model systems\",\n      \"pmids\": [\"38261825\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TNKS-2 (Golgi-associated) poly-ADP-ribosylates VEGF in the secretory pathway; this requires a priming mono-ADP-ribosylation of VEGF by ER-associated PARP-16, indicating an interplay between PARP-16 and TNKS-2 in the sequential ADP-ribosylation of VEGF.\",\n      \"method\": \"Co-immunoprecipitation, ADP-ribosylation assay in secretory pathway compartments, sequential enzymatic dependency experiments\",\n      \"journal\": \"Molecular and cellular biochemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single Co-IP and enzymatic assay with limited mechanistic follow-up detail in abstract\",\n      \"pmids\": [\"32472322\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In skeletal muscle cells, insulin upregulates Axin1 and TNKS protein levels in an Akt-dependent manner; Axin1 interacts with TNKS (interaction enhanced by insulin), and this Axin1/TNKS axis acts upstream of Tiam1–Rac1 signaling to mediate insulin-stimulated GLUT4 translocation independently of Akt–AS160 phosphorylation.\",\n      \"method\": \"Co-immunoprecipitation (Axin1–TNKS interaction), siRNA knockdown, TNKS activity inhibition (XAV939), GLUT4myc translocation assay, PAK phosphorylation as Rac1 readout in C2C12 myotubes\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, chemical inhibition, and genetic KD with defined cellular phenotype, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"41207648\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Catalytic inhibition of TNKS prevents TNKS turnover and drives its accumulation in the β-catenin destruction complex (DC), where the scaffolding function of TNKS induces AXIN puncta formation, rigidifies the DC, and impedes β-catenin turnover — providing a mechanistic explanation for the limited efficacy of TNKS catalytic inhibitors; PROTAC-mediated degradation of TNKS stabilizes AXIN without puncta formation and more deeply suppresses WNT/β-catenin signaling.\",\n      \"method\": \"PROTAC-mediated targeted protein degradation, imaging of AXIN puncta, β-catenin destruction complex analysis, comparison of catalytic inhibitor vs. degrader effects in APC-mutant colorectal cancer cells\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — PROTAC degrader vs. inhibitor comparison with mechanistic imaging readout, preprint, single lab but multiple orthogonal approaches\",\n      \"pmids\": [\"bio_10.1101_2025.09.22.677768\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TNKS1 interacts directly with SLC7A11 (as shown by Co-IP), and TNKS1 overexpression in human aortic smooth muscle cells increases ferroptosis markers (iron content, ROS, lipid peroxidation), driving phenotypic switching from contractile to synthetic phenotype; ferroptosis inhibition restores the contractile phenotype.\",\n      \"method\": \"Co-immunoprecipitation (TNKS1–SLC7A11), TNKS1 overexpression, ferroptosis marker assays, in vivo aortic dissection model\",\n      \"journal\": \"International immunopharmacology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP with limited mechanistic follow-up, single lab\",\n      \"pmids\": [\"40359887\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss of chromosome 8p in tumors depletes TNKS1 expression and creates a dependency on the functionally redundant TNKS2; structure-guided drug design yielded a first-in-class TNKS2-selective inhibitor that drives selective WNT inhibition in TNKS1-deficient cancer cell and organoid models.\",\n      \"method\": \"Structure-guided drug design, cell line and organoid models with TNKS1 depletion, WNT pathway reporter assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — structure-guided inhibitor design with functional genetic epistasis (TNKS1 loss creating TNKS2 dependency), preprint, single lab\",\n      \"pmids\": [\"bio_10.1101_2025.03.04.641305\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"TNKS (tankyrase/PARP5A) is a poly-ADP-ribose polymerase that: (1) regulates the Wnt/β-catenin pathway by PARylating Axin to promote its ubiquitination and degradation, with its scaffolding function in the β-catenin destruction complex also influencing pathway activity independently of catalysis; (2) forms a ternary complex with Axin and KIF3A on the trans-Golgi network that is stabilized by insulin-mediated Akt signaling to drive GLUT4 translocation in an Axin/TNKS–Tiam1–Rac1-dependent manner; (3) is recruited with RNF146 by TAX1BP1 into liquid-like condensates upon necroptosis induction, where it PARylates activated RIPK1 to promote its proteasomal degradation and restrain cell death; (4) binds the peroxisomal membrane protein PEX14 to regulate peroxisome protein import; (5) is stabilized by the deubiquitinase USP25, which protects it from proteasomal degradation; and (6) interacts with additional partners including FBP17, β-catenin, and SLC7A11 to modulate diverse cellular processes including telomere maintenance and ferroptosis.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TNKS (tankyrase/PARP5A) is a poly-ADP-ribose polymerase that regulates the Wnt/\\u03b2-catenin pathway through both its catalytic PARylation of AXIN \\u2014 which targets AXIN for RNF146-dependent ubiquitination and degradation \\u2014 and a scaffolding function within the \\u03b2-catenin destruction complex [#2, #9]. These two activities are functionally distinct: catalytic inhibition prevents TNKS turnover and drives its accumulation in the destruction complex, where its scaffold rigidifies the complex into AXIN puncta and paradoxically impedes \\u03b2-catenin turnover, whereas targeted degradation of TNKS stabilizes AXIN without puncta and more deeply suppresses Wnt signaling [#9]. TNKS directly binds \\u03b2-catenin and acts as a positive regulator of the pathway, with knockdown suppressing tumor cell growth and invasion [#4]; its protein stability is controlled by the deubiquitinase USP25, which protects it from proteasomal degradation, and disruption of the TNKS\\u2013USP25 interaction depletes TNKS and triggers apoptosis [#5, #6]. Beyond Wnt, TNKS scaffolds an AXIN\\u2013KIF3A complex on the trans-Golgi network and, with AXIN, acts upstream of Tiam1\\u2013Rac1 to drive insulin-stimulated GLUT4 translocation, with insulin/Akt signaling controlling TNKS activity and abundance [#0, #8]. In a separate role, TNKS is recruited by TAX1BP1 with RNF146 into liquid-like condensates upon necroptosis induction, where it PARylates activated RIPK1 to promote its PARylation-dependent ubiquitination and proteasomal degradation, restraining cell death [#1]. TNKS and TNKS2 also bind the peroxisomal membrane protein PEX14 and regulate peroxisome protein import [#2]. TNKS1 and TNKS2 are functionally redundant, such that chromosome 8p loss depleting TNKS1 creates a selective dependency on TNKS2 [#11].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing the first direct binding partners of tankyrase began to define how it is recruited to substrates and complexes.\",\n      \"evidence\": \"Yeast two-hybrid and endogenous co-immunoprecipitation identifying FBP17 binding via a TNKS-binding motif\",\n      \"pmids\": [\"14596906\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the FBP17\\u2013TNKS interaction not established\", \"No PARylation substrate role for FBP17 demonstrated\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Resolved how tankyrase couples insulin signaling to glucose uptake by scaffolding a Golgi-localized AXIN\\u2013KIF3A complex whose stability is gated by its own enzymatic activity.\",\n      \"evidence\": \"Co-IP, component knockdown, TNKS2 knockout mice with metabolic phenotyping, and co-localization imaging on the trans-Golgi network\",\n      \"pmids\": [\"22473005\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking Akt to suppression of TNKS ADP-ribosylase activity not fully resolved\", \"Relative contribution of catalysis vs. scaffolding to complex stability unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Confirmed a direct TNKS1\\u2013\\u03b2-catenin interaction and a pro-tumorigenic role for TNKS1 as a positive Wnt regulator in glioblastoma.\",\n      \"evidence\": \"Co-IP with \\u03b2-catenin and TNKS1 knockdown/overexpression with viability and invasion readouts\",\n      \"pmids\": [\"31849489\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the \\u03b2-catenin interaction is direct or AXIN-bridged not distinguished\", \"Catalytic requirement for the growth phenotype not tested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Proposed that secretory-pathway TNKS2 participates in sequential ADP-ribosylation of VEGF downstream of a PARP-16 priming event.\",\n      \"evidence\": \"Co-IP and ADP-ribosylation assays with sequential enzymatic dependency tests in secretory compartments\",\n      \"pmids\": [\"32472322\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP and enzymatic assay with limited mechanistic follow-up\", \"Functional consequence of VEGF PARylation not established\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified USP25 as a deubiquitinase that stabilizes TNKS1 and thereby sustains Wnt/\\u03b2-catenin activity, defining a post-translational control point over TNKS abundance.\",\n      \"evidence\": \"Co-IP ubiquitination assays plus USP25 knockdown/overexpression with Wnt marker Western blots\",\n      \"pmids\": [\"35450028\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Site of TNKS1 ubiquitin removal by USP25 not mapped\", \"E3 ligase opposing USP25 on TNKS1 not identified\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Validated the TNKS\\u2013USP25 interaction as a druggable node by showing that chemical PPI disruption depletes TNKS and triggers apoptosis in colorectal cancer models.\",\n      \"evidence\": \"Small-molecule PPI inhibitor UAT-B with Western blot, in vitro and xenograft models\",\n      \"pmids\": [\"38261825\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of the TNKS\\u2013USP25 interface not defined\", \"Selectivity of UAT-B not fully characterized\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed a cell-death restraint function in which TNKS is condensate-recruited to PARylate activated RIPK1 and target it for degradation, distinct from its Wnt and metabolic roles.\",\n      \"evidence\": \"Phase-separation reconstitution, Co-IP, RIPK1 K376 mutagenesis, proteasome inhibition, and MEF loss-of-function\",\n      \"pmids\": [\"38272024\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"TAX1BP1\\u2013TNKS recruitment determinants not fully mapped\", \"In vivo necroptosis relevance not established\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Connected TNKS/TNKS2 to peroxisome biology by showing PEX14 binding and regulation of peroxisome import, with peroxisome loss feeding back onto AXIN1 degradation and \\u03b2-catenin transcription.\",\n      \"evidence\": \"Genome-wide CRISPRi screen, RNF146 genetic epistasis, peroxisome import assays, and \\u03b2-catenin reporter\",\n      \"pmids\": [\"38967608\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct PARylation substrate at the peroxisome membrane not identified\", \"Physiological setting of peroxisome\\u2013Wnt crosstalk unclear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Distinguished TNKS catalytic from scaffolding functions, explaining why catalytic inhibitors fail \\u2014 enzyme-dead accumulated TNKS rigidifies the destruction complex \\u2014 while degraders suppress Wnt more effectively.\",\n      \"evidence\": \"PROTAC degradation vs. catalytic inhibition with AXIN puncta imaging in APC-mutant colorectal cancer cells (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.09.22.677768\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, single lab\", \"Structural basis of scaffold-induced AXIN puncta not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended the insulin/GLUT4 mechanism by placing the Axin1/TNKS axis upstream of Tiam1\\u2013Rac1 and parallel to Akt\\u2013AS160 in skeletal muscle.\",\n      \"evidence\": \"Co-IP, siRNA, XAV939 inhibition, GLUT4myc translocation, and PAK phosphorylation readout in C2C12 myotubes\",\n      \"pmids\": [\"41207648\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct Rac1-pathway substrate of TNKS PARylation not identified\", \"In vivo muscle relevance not tested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated TNKS1/TNKS2 functional redundancy as a therapeutic vulnerability, enabling a TNKS2-selective inhibitor effective in TNKS1-deficient (8p-loss) tumors.\",\n      \"evidence\": \"Structure-guided drug design with TNKS1-depleted cell line and organoid WNT reporter models (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.03.04.641305\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, single lab\", \"Breadth of 8p-loss tumor responsiveness not validated clinically\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Linked TNKS1 to vascular ferroptosis via SLC7A11 binding, associating TNKS1 with smooth muscle phenotypic switching.\",\n      \"evidence\": \"Co-IP, TNKS1 overexpression, ferroptosis marker assays, and aortic dissection model\",\n      \"pmids\": [\"40359887\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP with limited mechanistic follow-up\", \"Whether SLC7A11 is a PARylation substrate not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TNKS partitions its catalytic and scaffolding activities across its many contexts \\u2014 Wnt, GLUT4 trafficking, necroptosis, peroxisome import, ferroptosis \\u2014 and what determines substrate selection in each remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model for context-specific substrate recruitment\", \"Structural determinants distinguishing scaffold vs. catalytic output not defined\", \"Telomere maintenance role not represented by direct evidence in this corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 7]},\n      {\"term_id\": \"GO:0005777\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 4, 9]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [5, 6]}\n    ],\n    \"complexes\": [\n      \"\\u03b2-catenin destruction complex\",\n      \"AXIN\\u2013KIF3A\\u2013TNKS trans-Golgi ternary complex\",\n      \"TAX1BP1\\u2013TNKS\\u2013RNF146 necroptosis condensate\"\n    ],\n    \"partners\": [\n      \"AXIN1\",\n      \"KIF3A\",\n      \"RNF146\",\n      \"TAX1BP1\",\n      \"USP25\",\n      \"FBP17\",\n      \"CTNNB1\",\n      \"PEX14\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":5,"faith_pct":80.0}}