{"gene":"SVIL","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":1998,"finding":"Human supervillin (SVIL) is a 205-kDa F-actin binding protein that is tightly associated with both actin filaments and plasma membranes, forming a high-affinity link between the actin cytoskeleton and the membrane. The protein has a bipartite structure: the NH2-terminus contains nuclear localization signals, and the COOH-terminus contains actin-binding sequences homologous to villin segments 2-6 plus the headpiece.","method":"cDNA cloning, sequence analysis, domain characterization, fractionation","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — original cloning and biochemical characterization with domain analysis, single lab but multiple methods (sequence, fractionation, localization signals)","pmids":["9867483"],"is_preprint":false},{"year":2013,"finding":"PLK1 phosphorylates SVIL at Ser238, which promotes SVIL localization to the central spindle and association with PRC1. Phosphorylated SVIL acts as a molecular link between the central spindle and the contractile ring to coordinate myosin II activation at the equatorial cortex during cytokinetic furrowing. SVIL's myosin-II-binding region (N-terminus) is required for myosin II activation; deletion of this region (ΔMyo-SVIL), but not the actin-binding region (ΔAct-SVIL), reduced myosin II activation and caused furrowing defects. Expression of a non-phosphorylatable S238A-SVIL mutant inhibited myosin II activation and induced aberrant furrowing.","method":"In vitro kinase assay (PLK1 phosphorylation of SVIL Ser238), phosphorylation-site mutagenesis (S238A), deletion mutants (ΔMyo-SVIL, ΔAct-SVIL), live-cell imaging of localization, co-immunoprecipitation with PRC1","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro kinase assay with mutagenesis, deletion analysis, Co-IP, and functional furrowing readout; multiple orthogonal methods in single study","pmids":["23750008"],"is_preprint":false},{"year":2022,"finding":"SVIL knockdown in vascular smooth muscle cells (vSMCs) via CRISPR/Cas9 induced phenotypic modulation to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor signaling, and affected vSMC migration via the RhoA/ROCK pathway.","method":"CRISPR/Cas9 knockdown of SVIL in vSMCs, gene expression profiling (RNA-seq), protein kinase phosphorylation analysis","journal":"Neurology. Genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — CRISPR/Cas9 KO with defined cellular phenotype and pathway identification (RhoA/ROCK, KLF4/PDGF), single lab, single study","pmids":["36475054"],"is_preprint":false},{"year":2024,"finding":"SVIL knockdown inhibited activation of the TGFβ1/Smad2/3 pathway in ovarian cancer cells under hypoxic conditions, attenuating cell proliferation, migration, invasion, EMT, and increasing cisplatin-induced apoptosis. In nude mouse in situ tumor models, SVIL knockdown significantly inhibited tumor growth and metastasis.","method":"siRNA knockdown, Western blot (TGFβ1/Smad2/3 pathway components), CCK8 assay, wound-healing assay, Transwell assay, apoptosis assay, nude mouse in situ tumor model","journal":"Gynecologic oncology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Weak — KD with multiple functional readouts and pathway placement (TGFβ1/Smad2/3), in vivo validation, single lab","pmids":["39197416"],"is_preprint":false}],"current_model":"SVIL (supervillin) is a membrane- and F-actin-associated scaffolding protein with a bipartite structure (N-terminal nuclear localization signals; C-terminal villin-like actin-binding domains) that, during cytokinesis, is phosphorylated by PLK1 at Ser238 to localize to the central spindle, associate with PRC1, and—through its N-terminal myosin-II-binding region—coordinate myosin II activation at the equatorial cortex for cleavage furrow ingression; in vascular smooth muscle cells it modulates cell phenotype and migration via RhoA/ROCK and KLF4/PDGF signaling, and in cancer cells it can activate the TGFβ1/Smad2/3 pathway to promote EMT and drug resistance."},"narrative":{"mechanistic_narrative":"SVIL (supervillin) is a membrane- and F-actin-associated scaffolding protein that physically couples the actin cytoskeleton to the plasma membrane and coordinates actomyosin-dependent processes [PMID:9867483]. It has a bipartite architecture: an N-terminus carrying nuclear localization signals and a C-terminus bearing villin-homologous actin-binding sequences plus a headpiece [PMID:9867483]. During cytokinesis, PLK1 phosphorylates SVIL at Ser238, driving its localization to the central spindle and association with PRC1; in this position SVIL bridges the central spindle and the contractile ring, and its N-terminal myosin-II-binding region is required to activate myosin II at the equatorial cortex for cleavage furrow ingression [PMID:23750008]. Beyond cytokinesis, SVIL influences cellular phenotype and motility through actomyosin-linked signaling: its loss in vascular smooth muscle cells shifts cells toward a synthetic phenotype via KLF4/PDGF signaling and alters migration through the RhoA/ROCK pathway [PMID:36475054], and in ovarian cancer cells SVIL supports TGFβ1/Smad2/3 activation to promote proliferation, EMT, and cisplatin resistance under hypoxia [PMID:39197416].","teleology":[{"year":1998,"claim":"Established that SVIL is a high-affinity bridge between F-actin and the plasma membrane, defining the molecular basis for its cytoskeletal scaffolding role and predicting both nuclear and actin-binding functions from its bipartite domain layout.","evidence":"cDNA cloning, sequence/domain analysis, and subcellular fractionation of human supervillin","pmids":["9867483"],"confidence":"Medium","gaps":["Functional roles of the N-terminal NLS versus C-terminal villin-like domains not tested","No direct binding partners beyond F-actin and membrane identified","No cellular phenotype assayed"]},{"year":2013,"claim":"Resolved how SVIL is regulated and deployed during cell division, showing that PLK1 phosphorylation at Ser238 recruits SVIL to the central spindle/PRC1 and that its myosin-II-binding region drives equatorial myosin II activation for furrowing.","evidence":"In vitro PLK1 kinase assay, S238A and domain-deletion mutants (ΔMyo, ΔAct), live-cell imaging, and Co-IP with PRC1","pmids":["23750008"],"confidence":"High","gaps":["Structural basis of SVIL–PRC1 and SVIL–myosin II interactions not defined","How phosphorylation directs spindle targeting mechanistically unresolved","Whether actin-binding domain contributes to furrowing not separated from myosin role"]},{"year":2022,"claim":"Extended SVIL function to vascular smooth muscle cell identity and motility, linking SVIL loss to phenotypic switching and migration through defined signaling axes.","evidence":"CRISPR/Cas9 knockdown in vSMCs with RNA-seq and phospho-kinase profiling implicating KLF4/PDGF and RhoA/ROCK","pmids":["36475054"],"confidence":"Medium","gaps":["Direct molecular link between SVIL and KLF4/PDGF or RhoA/ROCK not established","Single lab, single cell system","Whether effects depend on SVIL's actomyosin scaffolding function untested"]},{"year":2024,"claim":"Placed SVIL in an oncogenic signaling context, showing it supports TGFβ1/Smad2/3-driven EMT, invasion, and chemoresistance in ovarian cancer.","evidence":"siRNA knockdown with functional assays (proliferation, migration, invasion, apoptosis) under hypoxia and a nude mouse in situ tumor model","pmids":["39197416"],"confidence":"Medium","gaps":["Mechanism by which SVIL activates TGFβ1/Smad2/3 not defined","Whether the cytoskeletal scaffolding function mediates the cancer phenotype unknown","Single lab, single tumor type"]},{"year":null,"claim":"How SVIL's actin/membrane scaffolding activity mechanistically connects to the diverse signaling pathways (RhoA/ROCK, KLF4/PDGF, TGFβ1/Smad2/3) it influences remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct biochemical link between SVIL and these signaling nodes","Role of the NLS-bearing N-terminus outside cytokinesis uncharacterized","No structural model integrating membrane/actin binding with signaling"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,3]}],"complexes":[],"partners":["PRC1","PLK1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O95425","full_name":"Supervillin","aliases":["Archvillin","p205/p250"],"length_aa":2214,"mass_kda":247.7,"function":"Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation (PubMed:12711699). Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function (PubMed:19109420). In addition to its cytoskeletal activities, acts as a cofactor or scaffold for KDM1A, facilitating H3K9me2 demethylation and promoting gene activation, especially in neuronal contexts (PubMed:25684206) May be involved in modulation of focal adhesions. Supervillin-mediated down-regulation of focal adhesions involves binding to TRIP6. Plays a role in cytokinesis through KIF14 interaction (By similarity)","subcellular_location":"Cell membrane; Cytoplasm, cytoskeleton; Cell projection, invadopodium; Cell projection, podosome; Midbody; Cleavage furrow","url":"https://www.uniprot.org/uniprotkb/O95425/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SVIL","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000197321","cell_line_id":"CID001935","localizations":[{"compartment":"membrane","grade":3},{"compartment":"vesicles","grade":2}],"interactors":[{"gene":"CALD1","stoichiometry":0.2},{"gene":"CALM3","stoichiometry":0.2},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"SPAST","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001935","total_profiled":1310},"omim":[{"mim_id":"619040","title":"MYOFIBRILLAR MYOPATHY 10; MFM10","url":"https://www.omim.org/entry/619040"},{"mim_id":"604126","title":"SUPERVILLIN; SVIL","url":"https://www.omim.org/entry/604126"},{"mim_id":"601419","title":"MYOPATHY, MYOFIBRILLAR, 1; MFM1","url":"https://www.omim.org/entry/601419"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Plasma membrane","reliability":"Supported"},{"location":"Actin filaments","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"skeletal muscle","ntpm":750.5},{"tissue":"tongue","ntpm":518.7}],"url":"https://www.proteinatlas.org/search/SVIL"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"O95425","domains":[{"cath_id":"3.40.20.10","chopping":"1436-1678","consensus_level":"medium","plddt":90.5858,"start":1436,"end":1678},{"cath_id":"3.40.20.10","chopping":"1861-1994","consensus_level":"medium","plddt":93.1962,"start":1861,"end":1994},{"cath_id":"3.40.20.10","chopping":"2000-2148","consensus_level":"medium","plddt":87.0789,"start":2000,"end":2148},{"cath_id":"1.10.950.10","chopping":"2155-2214","consensus_level":"medium","plddt":86.2138,"start":2155,"end":2214}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O95425","model_url":"https://alphafold.ebi.ac.uk/files/AF-O95425-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O95425-F1-predicted_aligned_error_v6.png","plddt_mean":53.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SVIL","jax_strain_url":"https://www.jax.org/strain/search?query=SVIL"},"sequence":{"accession":"O95425","fasta_url":"https://rest.uniprot.org/uniprotkb/O95425.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O95425/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O95425"}},"corpus_meta":[{"pmid":"9867483","id":"PMC_9867483","title":"Cloning, characterization, and chromosomal localization of human superillin (SVIL).","date":"1998","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/9867483","citation_count":43,"is_preprint":false},{"pmid":"23750008","id":"PMC_23750008","title":"The role of PLK1-phosphorylated SVIL in myosin II activation and cytokinetic furrowing.","date":"2013","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/23750008","citation_count":28,"is_preprint":false},{"pmid":"35068325","id":"PMC_35068325","title":"N6-methyladenosine-induced SVIL antisense RNA 1 restrains lung adenocarcinoma cell proliferation by destabilizing E2F1.","date":"2022","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/35068325","citation_count":15,"is_preprint":false},{"pmid":"39197416","id":"PMC_39197416","title":"SVIL promotes ovarian cancer progression and epithelial-mesenchymal transition under hypoxic conditions through the TGF-β/Smad pathway.","date":"2024","source":"Gynecologic oncology","url":"https://pubmed.ncbi.nlm.nih.gov/39197416","citation_count":8,"is_preprint":false},{"pmid":"40135844","id":"PMC_40135844","title":"AKT1E17K-Interacting lncRNA SVIL-AS1 Promotes AKT1 Oncogenic Functions by Preferentially Blocking AKT1E17K Dephosphorylation.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/40135844","citation_count":4,"is_preprint":false},{"pmid":"39113865","id":"PMC_39113865","title":"Engineered exosomes transporting the lncRNA, SVIL-AS1, inhibit the progression of lung cancer via targeting miR-21-5p.","date":"2024","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/39113865","citation_count":4,"is_preprint":false},{"pmid":"32582973","id":"PMC_32582973","title":"A twin‑pair analysis indicates congenital scoliosis is associated with allele‑specific methylation in the SVIL gene.","date":"2020","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/32582973","citation_count":4,"is_preprint":false},{"pmid":"36475054","id":"PMC_36475054","title":"Somatic Variants in SVIL in Cerebral Aneurysms.","date":"2022","source":"Neurology. Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36475054","citation_count":3,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.10.669560","title":"Gene co-expression network reveals key hub genes associated with endometriosis using bulk RNA-seq","date":"2025-08-12","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.10.669560","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.05.05.652238","title":"Multiomic profiling of hypoxic glioblastoma stem cells reveals expansion of subpopulations with distinct epigenetic and CNV profiles","date":"2025-05-09","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.05.652238","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.06.24.600323","title":"Genomic evolution reshapes cell type diversification in the amniote brain","date":"2024-06-27","source":"bioRxiv","url":"https://doi.org/10.1101/2024.06.24.600323","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7730,"output_tokens":1359,"usd":0.021788,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7992,"output_tokens":2164,"usd":0.04703,"stage2_stop_reason":"end_turn"},"total_usd":0.068818,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"Human supervillin (SVIL) is a 205-kDa F-actin binding protein that is tightly associated with both actin filaments and plasma membranes, forming a high-affinity link between the actin cytoskeleton and the membrane. The protein has a bipartite structure: the NH2-terminus contains nuclear localization signals, and the COOH-terminus contains actin-binding sequences homologous to villin segments 2-6 plus the headpiece.\",\n      \"method\": \"cDNA cloning, sequence analysis, domain characterization, fractionation\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — original cloning and biochemical characterization with domain analysis, single lab but multiple methods (sequence, fractionation, localization signals)\",\n      \"pmids\": [\"9867483\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PLK1 phosphorylates SVIL at Ser238, which promotes SVIL localization to the central spindle and association with PRC1. Phosphorylated SVIL acts as a molecular link between the central spindle and the contractile ring to coordinate myosin II activation at the equatorial cortex during cytokinetic furrowing. SVIL's myosin-II-binding region (N-terminus) is required for myosin II activation; deletion of this region (ΔMyo-SVIL), but not the actin-binding region (ΔAct-SVIL), reduced myosin II activation and caused furrowing defects. Expression of a non-phosphorylatable S238A-SVIL mutant inhibited myosin II activation and induced aberrant furrowing.\",\n      \"method\": \"In vitro kinase assay (PLK1 phosphorylation of SVIL Ser238), phosphorylation-site mutagenesis (S238A), deletion mutants (ΔMyo-SVIL, ΔAct-SVIL), live-cell imaging of localization, co-immunoprecipitation with PRC1\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro kinase assay with mutagenesis, deletion analysis, Co-IP, and functional furrowing readout; multiple orthogonal methods in single study\",\n      \"pmids\": [\"23750008\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SVIL knockdown in vascular smooth muscle cells (vSMCs) via CRISPR/Cas9 induced phenotypic modulation to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor signaling, and affected vSMC migration via the RhoA/ROCK pathway.\",\n      \"method\": \"CRISPR/Cas9 knockdown of SVIL in vSMCs, gene expression profiling (RNA-seq), protein kinase phosphorylation analysis\",\n      \"journal\": \"Neurology. Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — CRISPR/Cas9 KO with defined cellular phenotype and pathway identification (RhoA/ROCK, KLF4/PDGF), single lab, single study\",\n      \"pmids\": [\"36475054\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SVIL knockdown inhibited activation of the TGFβ1/Smad2/3 pathway in ovarian cancer cells under hypoxic conditions, attenuating cell proliferation, migration, invasion, EMT, and increasing cisplatin-induced apoptosis. In nude mouse in situ tumor models, SVIL knockdown significantly inhibited tumor growth and metastasis.\",\n      \"method\": \"siRNA knockdown, Western blot (TGFβ1/Smad2/3 pathway components), CCK8 assay, wound-healing assay, Transwell assay, apoptosis assay, nude mouse in situ tumor model\",\n      \"journal\": \"Gynecologic oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Weak — KD with multiple functional readouts and pathway placement (TGFβ1/Smad2/3), in vivo validation, single lab\",\n      \"pmids\": [\"39197416\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SVIL (supervillin) is a membrane- and F-actin-associated scaffolding protein with a bipartite structure (N-terminal nuclear localization signals; C-terminal villin-like actin-binding domains) that, during cytokinesis, is phosphorylated by PLK1 at Ser238 to localize to the central spindle, associate with PRC1, and—through its N-terminal myosin-II-binding region—coordinate myosin II activation at the equatorial cortex for cleavage furrow ingression; in vascular smooth muscle cells it modulates cell phenotype and migration via RhoA/ROCK and KLF4/PDGF signaling, and in cancer cells it can activate the TGFβ1/Smad2/3 pathway to promote EMT and drug resistance.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SVIL (supervillin) is a membrane- and F-actin-associated scaffolding protein that physically couples the actin cytoskeleton to the plasma membrane and coordinates actomyosin-dependent processes [#0]. It has a bipartite architecture: an N-terminus carrying nuclear localization signals and a C-terminus bearing villin-homologous actin-binding sequences plus a headpiece [#0]. During cytokinesis, PLK1 phosphorylates SVIL at Ser238, driving its localization to the central spindle and association with PRC1; in this position SVIL bridges the central spindle and the contractile ring, and its N-terminal myosin-II-binding region is required to activate myosin II at the equatorial cortex for cleavage furrow ingression [#1]. Beyond cytokinesis, SVIL influences cellular phenotype and motility through actomyosin-linked signaling: its loss in vascular smooth muscle cells shifts cells toward a synthetic phenotype via KLF4/PDGF signaling and alters migration through the RhoA/ROCK pathway [#2], and in ovarian cancer cells SVIL supports TGFβ1/Smad2/3 activation to promote proliferation, EMT, and cisplatin resistance under hypoxia [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established that SVIL is a high-affinity bridge between F-actin and the plasma membrane, defining the molecular basis for its cytoskeletal scaffolding role and predicting both nuclear and actin-binding functions from its bipartite domain layout.\",\n      \"evidence\": \"cDNA cloning, sequence/domain analysis, and subcellular fractionation of human supervillin\",\n      \"pmids\": [\"9867483\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional roles of the N-terminal NLS versus C-terminal villin-like domains not tested\",\n        \"No direct binding partners beyond F-actin and membrane identified\",\n        \"No cellular phenotype assayed\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Resolved how SVIL is regulated and deployed during cell division, showing that PLK1 phosphorylation at Ser238 recruits SVIL to the central spindle/PRC1 and that its myosin-II-binding region drives equatorial myosin II activation for furrowing.\",\n      \"evidence\": \"In vitro PLK1 kinase assay, S238A and domain-deletion mutants (ΔMyo, ΔAct), live-cell imaging, and Co-IP with PRC1\",\n      \"pmids\": [\"23750008\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of SVIL–PRC1 and SVIL–myosin II interactions not defined\",\n        \"How phosphorylation directs spindle targeting mechanistically unresolved\",\n        \"Whether actin-binding domain contributes to furrowing not separated from myosin role\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended SVIL function to vascular smooth muscle cell identity and motility, linking SVIL loss to phenotypic switching and migration through defined signaling axes.\",\n      \"evidence\": \"CRISPR/Cas9 knockdown in vSMCs with RNA-seq and phospho-kinase profiling implicating KLF4/PDGF and RhoA/ROCK\",\n      \"pmids\": [\"36475054\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct molecular link between SVIL and KLF4/PDGF or RhoA/ROCK not established\",\n        \"Single lab, single cell system\",\n        \"Whether effects depend on SVIL's actomyosin scaffolding function untested\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Placed SVIL in an oncogenic signaling context, showing it supports TGFβ1/Smad2/3-driven EMT, invasion, and chemoresistance in ovarian cancer.\",\n      \"evidence\": \"siRNA knockdown with functional assays (proliferation, migration, invasion, apoptosis) under hypoxia and a nude mouse in situ tumor model\",\n      \"pmids\": [\"39197416\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which SVIL activates TGFβ1/Smad2/3 not defined\",\n        \"Whether the cytoskeletal scaffolding function mediates the cancer phenotype unknown\",\n        \"Single lab, single tumor type\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SVIL's actin/membrane scaffolding activity mechanistically connects to the diverse signaling pathways (RhoA/ROCK, KLF4/PDGF, TGFβ1/Smad2/3) it influences remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct biochemical link between SVIL and these signaling nodes\",\n        \"Role of the NLS-bearing N-terminus outside cytokinesis uncharacterized\",\n        \"No structural model integrating membrane/actin binding with signaling\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003779\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PRC1\",\n      \"PLK1\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}