{"gene":"SEPTIN11","run_date":"2026-06-10T07:46:30","timeline":{"discoveries":[{"year":2004,"finding":"SEPT11 was identified as a component of septin complexes purified from porcine brain, co-immunoisolating with SEPT9 (and different SEPT9 isoforms). A GTPase-deficient SEPT11 mutant failed to form filaments in COS7 cells, establishing that GTPase activity is required for filament formation. SEPT11 showed cell-type-dependent colocalization with microtubules (HMEC cells) or actin stress fibers (REF52 cells), with filamentous distribution dependent on the cytoskeletal structure it associates with.","method":"Biochemical purification from porcine brain, co-immunoprecipitation with anti-SEPT9/anti-SEPT11 antibodies, GTPase mutant overexpression in COS7 cells, immunofluorescence colocalization","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal immunoisolation from native tissue plus mutagenesis showing GTPase requirement for filament formation, single lab","pmids":["15196925"],"is_preprint":false},{"year":2006,"finding":"SEPT11 physically interacts with SEPT5 in human cells; this interaction requires the GTP-binding domain and the C-terminal extension of the septins. The interaction was demonstrated by yeast two-hybrid, co-precipitation from JURKAT cell lysates, and FRET. Both proteins are co-expressed in HUVECs, suggesting they form a cell-specific septin complex potentially involved in exocytosis.","method":"Yeast two-hybrid, co-precipitation from JURKAT lysates, fluorescence resonance energy transfer (FRET), Western blot","journal":"The Journal of pathology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — three orthogonal methods (Y2H, co-precipitation, FRET) in a single lab confirming SEPT5–SEPT11 interaction and domain requirements","pmids":["16767699"],"is_preprint":false},{"year":2007,"finding":"HNA-associated SEPT9 missense variants (SEPT9F and SEPT9W), but not wild-type SEPT9, colocalized with SEPT11 at cell-cell junctions in epithelial NMuMG cells, indicating that disease-causing SEPT9 mutations alter the mode of interaction with SEPT11 as a partner molecule.","method":"Transient expression of SEPT9 mutants in NMuMG cells, immunofluorescence colocalization","journal":"Human mutation","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (immunofluorescence), limited mechanistic detail on SEPT11 itself","pmids":["17546647"],"is_preprint":false},{"year":2008,"finding":"GTP binding by SEPT12 is required for its interaction with SEPT11; a GTP-binding–deficient SEPT12 mutant (G56A) failed to interact with SEPT11 in co-expression experiments, whereas wild-type SEPT12 co-immunoprecipitated with SEPT11.","method":"Co-expression in cells, co-immunoprecipitation, GTP-binding mutant analysis","journal":"Molecules and cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis combined with co-IP demonstrating nucleotide-dependent SEPT12–SEPT11 interaction, single lab","pmids":["18443421"],"is_preprint":false},{"year":2009,"finding":"SEPT11 restricts InlB-mediated Listeria invasion: siRNA depletion of SEPT11 in HeLa cells increased entry of Listeria and of InlB-coated beads without affecting Met signaling downstream of InlB, distinguishing its role from SEPT2 (which is essential for entry). SEPT11 depletion increased cell size but did not affect actin filament formation or SEPT9–actin colocalization.","method":"siRNA knockdown in HeLa cells, Listeria invasion assay, InlB-coated bead uptake, FRET-based Met signaling assay, immunofluorescence","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal assays (invasion, bead uptake, FRET signaling, immunofluorescence) with siRNA KD in single lab","pmids":["19234302"],"is_preprint":false},{"year":2009,"finding":"SEPT11 is enriched at GABAergic postsynaptic densities (type-II PSDs) in rat brain. In cultured hippocampal neurons, SEPT11 localizes to the neck of dendritic spines and branch bifurcation points. shRNA-mediated knockdown reduced dendritic arborization, decreased density and increased length of dendritic protrusions, and decreased GABAergic synaptic contacts received by neurons.","method":"Mass spectrometry and immunoblot of brain fractions, immunofluorescence in cultured neurons, electron microscopy immunocytochemistry, shRNA knockdown with morphological and synaptic contact quantification","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (MS, EM, immunofluorescence, shRNA KD with defined morphological and synaptic readouts) in a single rigorous study","pmids":["19380581"],"is_preprint":false},{"year":2010,"finding":"SEPT11 interacts with SEPT2, SEPT4, and SEPT7 in platelets and endothelial cells. The SEPT11–SEPT7 interaction was confirmed by FRET. SEPT11 variants (v1, v2) differ in interaction partners: SEPT11_v2 interacts with SEPT4 and SEPT7. SEPT11 co-localizes with tubulin and transferrin receptor, and SEPT4/SEPT11 co-localize with the vesicle protein VAMP1/synaptobrevin 1, linking SEPT11 to vesicle trafficking.","method":"Yeast two-hybrid, co-precipitation, FRET, immunofluorescence co-localization in endothelial cells and platelets, Northern blot","journal":"Thrombosis and haemostasis","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — three orthogonal methods (Y2H, precipitation, FRET) for interaction, single lab, with co-localization data linking to vesicle trafficking","pmids":["20978712"],"is_preprint":false},{"year":2011,"finding":"Homozygous Sept11 null mice die in utero; embryos appear retarded from embryonic day 11.5 and are dead by day 13.5, establishing that SEPT11 is essential for embryonic development.","method":"Sept11 knockout mouse model, embryonic staging and phenotyping","journal":"Biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean genetic KO with defined lethal phenotype, but no molecular mechanism downstream identified; single lab","pmids":["21824005"],"is_preprint":false},{"year":2011,"finding":"SEPT11 is proteolytically cleaved into N-terminal fragments in frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U) brain tissue, and accumulates in detergent-insoluble fractions and thread-like pathological inclusions in affected cortex, indicating aberrant processing and aggregation of SEPT11 in this neurodegenerative disease.","method":"Quantitative proteomics (iTRAQ and targeted MS) of detergent-insoluble brain fractions, immunohistochemistry, immunoblot","journal":"Molecular neurodegeneration","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — orthogonal proteomics strategies plus immunohistochemistry confirming SEPT11 cleavage and accumulation, single lab","pmids":["22126117"],"is_preprint":false},{"year":2016,"finding":"SEPT11 associates with caveolae in mature adipocytes and interacts with caveolin-1 and FABP5 (fatty acid binding protein 5). Lipid loading causes all three proteins to redistribute to the surface of lipid droplets. SEPT11 silencing impaired insulin signaling and insulin-induced lipid accumulation in adipocytes, establishing a role for SEPT11 in lipid traffic and metabolism.","method":"GST pull-down, co-immunoprecipitation, yeast two-hybrid screening, subcellular fractionation, immunocytochemistry, electron microscopy, siRNA knockdown with insulin signaling and lipid accumulation readouts","journal":"Diabetologia","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal interaction methods (GST pull-down, Co-IP, Y2H) plus localization (EM, fractionation) plus functional KD with metabolic readouts in single rigorous study","pmids":["27866222"],"is_preprint":false},{"year":2023,"finding":"SEPT11 promotes HCC cell migration and invasion by activating RhoA: SEPT11 facilitates binding of GEF-H1 to RhoA, enhancing RhoA GTPase activity, which drives cytoskeleton rearrangement and abnormal cell adhesion via ROCK1/cofilin and FAK/paxillin signaling pathways. SEPT11 knockout inhibits migration/invasion in vitro and metastasis in vivo, while overexpression has the opposite effect.","method":"SEPT11 overexpression, shRNA knockdown, CRISPR/Cas9 knockout in HCC cells, in vivo xenograft metastasis model, RhoA activity assay, co-immunoprecipitation (GEF-H1/RhoA), RNA-seq, ATAC-seq","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple genetic perturbations (OE, KD, KO) plus in vivo model plus RhoA activity assay and Co-IP for GEF-H1/RhoA interaction, single lab","pmids":["37080972"],"is_preprint":false},{"year":2023,"finding":"SEPT11 knockdown in endometrial epithelial cells (Ishikawa and primary HEECs) inhibited cell adhesion. Elevated IFN-γ decreased SEPT11 protein levels in these cells, linking IFN-γ signaling to reduced SEPT11-dependent adhesive function.","method":"siRNA knockdown in Ishikawa cells and primary HEECs, cell adhesion assay, IFN-γ treatment with protein level measurement","journal":"Reproductive biomedicine online","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, siRNA KD with functional adhesion readout but limited mechanistic depth on pathway","pmids":["37349244"],"is_preprint":false}],"current_model":"SEPT11 is a GTPase-dependent filament-forming septin that assembles into heteropolymeric complexes with SEPT2, SEPT4, SEPT5, SEPT7, SEPT9, and SEPT12 (requiring intact GTP-binding domains), localizes to actin stress fibers, microtubules, caveolae, lipid droplets, and neuronal dendritic spine necks depending on cell type, and performs context-specific functions including: restricting bacterial invasion via InlB/Met signaling in non-phagocytic cells; supporting dendritic arborization and GABAergic synaptic connectivity in neurons; regulating lipid storage and insulin signaling in adipocytes through interactions with caveolin-1 and FABP5; and promoting hepatocellular carcinoma cell motility by facilitating GEF-H1–mediated RhoA activation to drive ROCK1/cofilin and FAK/paxillin cytoskeletal remodeling."},"narrative":{"mechanistic_narrative":"SEPTIN11 (SEPT11) is a GTPase-dependent filament-forming septin that assembles into cell-type-specific heteromeric septin complexes and contributes to cytoskeletal organization, membrane trafficking, and cell adhesion [PMID:15196925, PMID:20978712]. It was first isolated from brain septin complexes co-purifying with SEPT9, and its assembly into filaments requires an intact GTPase domain, with filaments aligning along either microtubules or actin stress fibers depending on the cellular context [PMID:15196925]. SEPT11 engages multiple septin partners — SEPT5, SEPT12, SEPT2, SEPT4, and SEPT7 — through interactions that depend on the GTP-binding domain and C-terminal extension, and these partnerships couple it to vesicle-trafficking machinery, co-localizing with tubulin, transferrin receptor, and the SNARE protein VAMP1 [PMID:16767699, PMID:18443421, PMID:20978712]. In neurons, SEPT11 concentrates at GABAergic postsynaptic densities and at dendritic spine necks and branch points, where it supports dendritic arborization and the formation of GABAergic synaptic contacts [PMID:19380581]. In adipocytes it associates with caveolae and lipid droplets through interactions with caveolin-1 and FABP5, and is required for insulin signaling and insulin-induced lipid accumulation [PMID:27866222]. SEPT11 also restricts InlB-mediated Listeria invasion of non-phagocytic cells independently of Met signaling, distinguishing it from the entry-promoting SEPT2 [PMID:19234302], and promotes hepatocellular carcinoma migration and metastasis by facilitating GEF-H1 binding to RhoA, thereby activating RhoA and downstream ROCK1/cofilin and FAK/paxillin cytoskeletal remodeling [PMID:37080972]. Loss of Sept11 causes mid-gestation embryonic lethality in mice, establishing it as essential for development [PMID:21824005].","teleology":[{"year":2004,"claim":"Established SEPT11 as a bona fide septin subunit whose filament assembly is GTPase-dependent and cytoskeleton-templated, defining its core biochemical identity.","evidence":"Biochemical purification from porcine brain, co-immunoprecipitation with SEPT9, GTPase-deficient mutant expression in COS7, immunofluorescence colocalization","pmids":["15196925"],"confidence":"Medium","gaps":["GTP hydrolysis kinetics not measured","Stoichiometry within native complexes undefined","Mechanism dictating microtubule vs actin association unknown"]},{"year":2006,"claim":"Defined the domain requirements for SEPT11 heteromer formation by mapping the SEPT5 interaction to the GTP-binding domain and C-terminal extension, supporting cell-specific complex assembly.","evidence":"Yeast two-hybrid, co-precipitation from JURKAT lysates, and FRET in human cells","pmids":["16767699"],"confidence":"Medium","gaps":["Functional consequence of the SEPT5-SEPT11 complex not tested","Proposed exocytosis role not demonstrated"]},{"year":2007,"claim":"Linked SEPT11 to disease by showing that hereditary neuralgic amyotrophy SEPT9 variants altered their colocalization with SEPT11, implicating partner-interaction changes in pathology.","evidence":"Transient expression of SEPT9 mutants in NMuMG epithelial cells with immunofluorescence colocalization","pmids":["17546647"],"confidence":"Low","gaps":["Single method (immunofluorescence) without biochemical interaction validation","No direct functional effect on SEPT11 shown"]},{"year":2008,"claim":"Generalized the nucleotide dependence of SEPT11 partnerships by showing SEPT12 requires GTP binding to associate with SEPT11.","evidence":"Co-expression and co-immunoprecipitation with a GTP-binding-deficient SEPT12 (G56A) mutant","pmids":["18443421"],"confidence":"Medium","gaps":["Physiological tissue context of SEPT11-SEPT12 complex not defined","Filament architecture not resolved"]},{"year":2009,"claim":"Distinguished SEPT11 function from other septins by showing it restricts InlB-mediated bacterial invasion without affecting Met signaling, revealing a non-redundant role at the cell-pathogen interface.","evidence":"siRNA knockdown in HeLa cells with Listeria/InlB-bead invasion assays, FRET-based Met signaling assay, immunofluorescence","pmids":["19234302"],"confidence":"Medium","gaps":["Molecular mechanism of invasion restriction unresolved","Basis for increased cell size on depletion unexplained"]},{"year":2009,"claim":"Identified a neuronal function for SEPT11 at GABAergic synapses and dendritic spine necks, connecting septin filaments to dendritic morphology and inhibitory connectivity.","evidence":"Mass spectrometry/immunoblot of brain fractions, EM immunocytochemistry, and shRNA knockdown in hippocampal neurons with morphological and synaptic quantification","pmids":["19380581"],"confidence":"High","gaps":["Septin partners at the GABAergic PSD not identified","Molecular link to synapse formation unknown"]},{"year":2010,"claim":"Expanded the SEPT11 interactome to SEPT2/SEPT4/SEPT7 and linked it to vesicle trafficking via VAMP1 colocalization, with splice variants differing in partner selection.","evidence":"Yeast two-hybrid, co-precipitation, FRET, and immunofluorescence colocalization in endothelial cells and platelets","pmids":["20978712"],"confidence":"Medium","gaps":["Direct role in vesicle fusion/exocytosis not functionally demonstrated","Functional difference between splice variants v1/v2 unresolved"]},{"year":2011,"claim":"Established that SEPT11 is essential for embryonic development through a genetic knockout causing mid-gestation lethality.","evidence":"Sept11 null mouse with embryonic staging and phenotyping","pmids":["21824005"],"confidence":"Medium","gaps":["Tissue and molecular cause of lethality not identified","No conditional dissection of essential pathways"]},{"year":2011,"claim":"Implicated SEPT11 in neurodegeneration by showing aberrant proteolytic cleavage and aggregation into detergent-insoluble pathological inclusions in FTLD-U brain.","evidence":"iTRAQ/targeted MS of insoluble brain fractions, immunohistochemistry, immunoblot","pmids":["22126117"],"confidence":"Medium","gaps":["Protease responsible for cleavage unknown","Whether SEPT11 aggregation is causal or consequential not established"]},{"year":2016,"claim":"Defined a metabolic role for SEPT11 in adipocytes, linking it via caveolin-1 and FABP5 to lipid droplet biology and insulin signaling.","evidence":"GST pull-down, Co-IP, Y2H, subcellular fractionation, EM, and siRNA knockdown with insulin signaling and lipid accumulation readouts","pmids":["27866222"],"confidence":"High","gaps":["Step in insulin signaling cascade affected not pinpointed","Whether GTPase activity is required for lipid droplet targeting untested"]},{"year":2023,"claim":"Provided a mechanistic route from SEPT11 to cytoskeletal remodeling in cancer, showing it scaffolds GEF-H1/RhoA to activate ROCK1/cofilin and FAK/paxillin signaling and drive HCC metastasis.","evidence":"Overexpression, shRNA, CRISPR knockout in HCC cells, in vivo xenograft metastasis, RhoA activity assay, GEF-H1/RhoA Co-IP, RNA-seq/ATAC-seq","pmids":["37080972"],"confidence":"Medium","gaps":["Whether SEPT11 directly binds GEF-H1 vs scaffolds indirectly not resolved","Role of septin filament assembly in RhoA activation untested"]},{"year":2023,"claim":"Connected SEPT11 to endometrial epithelial adhesion and its suppression by IFN-gamma, suggesting cytokine-regulated control of SEPT11-dependent adhesion.","evidence":"siRNA knockdown in Ishikawa and primary HEEC cells with adhesion assays and IFN-gamma treatment","pmids":["37349244"],"confidence":"Low","gaps":["Single method depth limits mechanistic interpretation","Pathway linking IFN-gamma to SEPT11 downregulation undefined"]},{"year":null,"claim":"How SEPT11's distinct cell-type-specific complexes and localizations (synapse, caveolae, lipid droplet, RhoA scaffold) are selected and regulated remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of SEPT11-containing filaments","Determinants of partner and membrane selection unknown","Whether GTPase cycling regulates its various functions untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003924","term_label":"GTPase activity","supporting_discovery_ids":[0]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,6]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[10]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[9]},{"term_id":"GO:0005811","term_label":"lipid droplet","supporting_discovery_ids":[9]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[6]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[10]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[6]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[9]}],"complexes":["heteromeric septin complex"],"partners":["SEPT9","SEPT5","SEPT12","SEPT2","SEPT4","SEPT7","CAV1","FABP5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NVA2","full_name":"Septin-11","aliases":[],"length_aa":429,"mass_kda":49.4,"function":"Filament-forming cytoskeletal GTPase. May play a role in cytokinesis (Potential). May play a role in the cytoarchitecture of neurons, including dendritic arborization and dendritic spines, and in GABAergic synaptic connectivity (By similarity). During Listeria monocytogenes infection, not required for the bacterial entry process, but restricts its efficacy","subcellular_location":"Cytoplasm, cytoskeleton; Synapse; Cell projection, dendritic spine; Cell projection, axon","url":"https://www.uniprot.org/uniprotkb/Q9NVA2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SEPTIN11","classification":"Not Classified","n_dependent_lines":14,"n_total_lines":1090,"dependency_fraction":0.012844036697247707},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000138758","cell_line_id":"CID000731","localizations":[{"compartment":"cytoskeleton","grade":3},{"compartment":"cytoplasmic","grade":2},{"compartment":"membrane","grade":2}],"interactors":[{"gene":"SEPT6","stoichiometry":10.0},{"gene":"SEPT8","stoichiometry":10.0},{"gene":"SEPT7","stoichiometry":10.0},{"gene":"SEPT9","stoichiometry":10.0},{"gene":"SEPT2","stoichiometry":10.0},{"gene":"COPB2","stoichiometry":0.2},{"gene":"SEPT3","stoichiometry":0.2},{"gene":"SEPT5","stoichiometry":0.2},{"gene":"SEPT10","stoichiometry":0.2},{"gene":"CPVL","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000731","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"},{"location":"Primary cilium","reliability":"Additional"},{"location":"Mid piece","reliability":"Additional"},{"location":"Principal piece","reliability":"Additional"},{"location":"Annulus","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SEPTIN11"},"hgnc":{"alias_symbol":["FLJ10849","Septin-11"],"prev_symbol":["SEPT11"]},"alphafold":{"accession":"Q9NVA2","domains":[{"cath_id":"3.40.50.300","chopping":"36-307","consensus_level":"high","plddt":88.4426,"start":36,"end":307},{"cath_id":"1.20.5","chopping":"344-399","consensus_level":"medium","plddt":87.8511,"start":344,"end":399}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NVA2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NVA2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NVA2-F1-predicted_aligned_error_v6.png","plddt_mean":81.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SEPTIN11","jax_strain_url":"https://www.jax.org/strain/search?query=SEPTIN11"},"sequence":{"accession":"Q9NVA2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NVA2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NVA2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NVA2"}},"corpus_meta":[{"pmid":"15196925","id":"PMC_15196925","title":"Biochemical and cell biological characterization of a mammalian septin, Sept11.","date":"2004","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/15196925","citation_count":93,"is_preprint":false},{"pmid":"19380581","id":"PMC_19380581","title":"Septin 11 is present in GABAergic synapses and plays a functional role in the cytoarchitecture of neurons and GABAergic synaptic connectivity.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19380581","citation_count":54,"is_preprint":false},{"pmid":"19234302","id":"PMC_19234302","title":"Septin 11 restricts InlB-mediated invasion by Listeria.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19234302","citation_count":48,"is_preprint":false},{"pmid":"14999297","id":"PMC_14999297","title":"FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23).","date":"2004","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/14999297","citation_count":42,"is_preprint":false},{"pmid":"17546647","id":"PMC_17546647","title":"SEPT9 sequence alternations causing hereditary neuralgic amyotrophy are associated with altered interactions with SEPT4/SEPT11 and resistance to Rho/Rhotekin-signaling.","date":"2007","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/17546647","citation_count":32,"is_preprint":false},{"pmid":"27866222","id":"PMC_27866222","title":"The cytoskeletal protein septin 11 is associated with human obesity and is involved in adipocyte lipid storage and metabolism.","date":"2016","source":"Diabetologia","url":"https://pubmed.ncbi.nlm.nih.gov/27866222","citation_count":30,"is_preprint":false},{"pmid":"37080972","id":"PMC_37080972","title":"Septin11 promotes hepatocellular carcinoma cell motility by activating RhoA to regulate cytoskeleton and cell adhesion.","date":"2023","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/37080972","citation_count":24,"is_preprint":false},{"pmid":"16767699","id":"PMC_16767699","title":"Human endothelial cell septins: SEPT11 is an interaction partner of SEPT5.","date":"2006","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/16767699","citation_count":22,"is_preprint":false},{"pmid":"21824005","id":"PMC_21824005","title":"Lethal phenotype of mice carrying a Sept11 null mutation.","date":"2011","source":"Biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21824005","citation_count":22,"is_preprint":false},{"pmid":"22126117","id":"PMC_22126117","title":"Aberrant septin 11 is associated with sporadic frontotemporal lobar degeneration.","date":"2011","source":"Molecular neurodegeneration","url":"https://pubmed.ncbi.nlm.nih.gov/22126117","citation_count":21,"is_preprint":false},{"pmid":"20978712","id":"PMC_20978712","title":"Human endothelial and platelet septin SEPT11: cloning of novel variants and characterisation of interaction partners.","date":"2010","source":"Thrombosis and haemostasis","url":"https://pubmed.ncbi.nlm.nih.gov/20978712","citation_count":13,"is_preprint":false},{"pmid":"18443421","id":"PMC_18443421","title":"GTP binding is required for SEPT12 to form filaments and to interact with SEPT11.","date":"2008","source":"Molecules and cells","url":"https://pubmed.ncbi.nlm.nih.gov/18443421","citation_count":12,"is_preprint":false},{"pmid":"20633769","id":"PMC_20633769","title":"A translocation in acute lymphoblastic leukemia that cytogenetically mimics the recurrent MLL-AFF1 translocation and fuses SEPT11 to MLL.","date":"2010","source":"Cancer genetics and cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/20633769","citation_count":5,"is_preprint":false},{"pmid":"37349244","id":"PMC_37349244","title":"Downregulation of SEPTIN11 inhibits endometrial epithelial cell adhesive function in patients with elevated peripheral blood natural killer cell counts.","date":"2023","source":"Reproductive biomedicine online","url":"https://pubmed.ncbi.nlm.nih.gov/37349244","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9020,"output_tokens":3305,"usd":0.038317,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10875,"output_tokens":4047,"usd":0.077775,"stage2_stop_reason":"end_turn"},"total_usd":0.116092,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"SEPT11 was identified as a component of septin complexes purified from porcine brain, co-immunoisolating with SEPT9 (and different SEPT9 isoforms). A GTPase-deficient SEPT11 mutant failed to form filaments in COS7 cells, establishing that GTPase activity is required for filament formation. SEPT11 showed cell-type-dependent colocalization with microtubules (HMEC cells) or actin stress fibers (REF52 cells), with filamentous distribution dependent on the cytoskeletal structure it associates with.\",\n      \"method\": \"Biochemical purification from porcine brain, co-immunoprecipitation with anti-SEPT9/anti-SEPT11 antibodies, GTPase mutant overexpression in COS7 cells, immunofluorescence colocalization\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal immunoisolation from native tissue plus mutagenesis showing GTPase requirement for filament formation, single lab\",\n      \"pmids\": [\"15196925\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"SEPT11 physically interacts with SEPT5 in human cells; this interaction requires the GTP-binding domain and the C-terminal extension of the septins. The interaction was demonstrated by yeast two-hybrid, co-precipitation from JURKAT cell lysates, and FRET. Both proteins are co-expressed in HUVECs, suggesting they form a cell-specific septin complex potentially involved in exocytosis.\",\n      \"method\": \"Yeast two-hybrid, co-precipitation from JURKAT lysates, fluorescence resonance energy transfer (FRET), Western blot\",\n      \"journal\": \"The Journal of pathology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — three orthogonal methods (Y2H, co-precipitation, FRET) in a single lab confirming SEPT5–SEPT11 interaction and domain requirements\",\n      \"pmids\": [\"16767699\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"HNA-associated SEPT9 missense variants (SEPT9F and SEPT9W), but not wild-type SEPT9, colocalized with SEPT11 at cell-cell junctions in epithelial NMuMG cells, indicating that disease-causing SEPT9 mutations alter the mode of interaction with SEPT11 as a partner molecule.\",\n      \"method\": \"Transient expression of SEPT9 mutants in NMuMG cells, immunofluorescence colocalization\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (immunofluorescence), limited mechanistic detail on SEPT11 itself\",\n      \"pmids\": [\"17546647\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"GTP binding by SEPT12 is required for its interaction with SEPT11; a GTP-binding–deficient SEPT12 mutant (G56A) failed to interact with SEPT11 in co-expression experiments, whereas wild-type SEPT12 co-immunoprecipitated with SEPT11.\",\n      \"method\": \"Co-expression in cells, co-immunoprecipitation, GTP-binding mutant analysis\",\n      \"journal\": \"Molecules and cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis combined with co-IP demonstrating nucleotide-dependent SEPT12–SEPT11 interaction, single lab\",\n      \"pmids\": [\"18443421\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"SEPT11 restricts InlB-mediated Listeria invasion: siRNA depletion of SEPT11 in HeLa cells increased entry of Listeria and of InlB-coated beads without affecting Met signaling downstream of InlB, distinguishing its role from SEPT2 (which is essential for entry). SEPT11 depletion increased cell size but did not affect actin filament formation or SEPT9–actin colocalization.\",\n      \"method\": \"siRNA knockdown in HeLa cells, Listeria invasion assay, InlB-coated bead uptake, FRET-based Met signaling assay, immunofluorescence\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal assays (invasion, bead uptake, FRET signaling, immunofluorescence) with siRNA KD in single lab\",\n      \"pmids\": [\"19234302\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"SEPT11 is enriched at GABAergic postsynaptic densities (type-II PSDs) in rat brain. In cultured hippocampal neurons, SEPT11 localizes to the neck of dendritic spines and branch bifurcation points. shRNA-mediated knockdown reduced dendritic arborization, decreased density and increased length of dendritic protrusions, and decreased GABAergic synaptic contacts received by neurons.\",\n      \"method\": \"Mass spectrometry and immunoblot of brain fractions, immunofluorescence in cultured neurons, electron microscopy immunocytochemistry, shRNA knockdown with morphological and synaptic contact quantification\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (MS, EM, immunofluorescence, shRNA KD with defined morphological and synaptic readouts) in a single rigorous study\",\n      \"pmids\": [\"19380581\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"SEPT11 interacts with SEPT2, SEPT4, and SEPT7 in platelets and endothelial cells. The SEPT11–SEPT7 interaction was confirmed by FRET. SEPT11 variants (v1, v2) differ in interaction partners: SEPT11_v2 interacts with SEPT4 and SEPT7. SEPT11 co-localizes with tubulin and transferrin receptor, and SEPT4/SEPT11 co-localize with the vesicle protein VAMP1/synaptobrevin 1, linking SEPT11 to vesicle trafficking.\",\n      \"method\": \"Yeast two-hybrid, co-precipitation, FRET, immunofluorescence co-localization in endothelial cells and platelets, Northern blot\",\n      \"journal\": \"Thrombosis and haemostasis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — three orthogonal methods (Y2H, precipitation, FRET) for interaction, single lab, with co-localization data linking to vesicle trafficking\",\n      \"pmids\": [\"20978712\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Homozygous Sept11 null mice die in utero; embryos appear retarded from embryonic day 11.5 and are dead by day 13.5, establishing that SEPT11 is essential for embryonic development.\",\n      \"method\": \"Sept11 knockout mouse model, embryonic staging and phenotyping\",\n      \"journal\": \"Biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean genetic KO with defined lethal phenotype, but no molecular mechanism downstream identified; single lab\",\n      \"pmids\": [\"21824005\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"SEPT11 is proteolytically cleaved into N-terminal fragments in frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U) brain tissue, and accumulates in detergent-insoluble fractions and thread-like pathological inclusions in affected cortex, indicating aberrant processing and aggregation of SEPT11 in this neurodegenerative disease.\",\n      \"method\": \"Quantitative proteomics (iTRAQ and targeted MS) of detergent-insoluble brain fractions, immunohistochemistry, immunoblot\",\n      \"journal\": \"Molecular neurodegeneration\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — orthogonal proteomics strategies plus immunohistochemistry confirming SEPT11 cleavage and accumulation, single lab\",\n      \"pmids\": [\"22126117\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"SEPT11 associates with caveolae in mature adipocytes and interacts with caveolin-1 and FABP5 (fatty acid binding protein 5). Lipid loading causes all three proteins to redistribute to the surface of lipid droplets. SEPT11 silencing impaired insulin signaling and insulin-induced lipid accumulation in adipocytes, establishing a role for SEPT11 in lipid traffic and metabolism.\",\n      \"method\": \"GST pull-down, co-immunoprecipitation, yeast two-hybrid screening, subcellular fractionation, immunocytochemistry, electron microscopy, siRNA knockdown with insulin signaling and lipid accumulation readouts\",\n      \"journal\": \"Diabetologia\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal interaction methods (GST pull-down, Co-IP, Y2H) plus localization (EM, fractionation) plus functional KD with metabolic readouts in single rigorous study\",\n      \"pmids\": [\"27866222\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SEPT11 promotes HCC cell migration and invasion by activating RhoA: SEPT11 facilitates binding of GEF-H1 to RhoA, enhancing RhoA GTPase activity, which drives cytoskeleton rearrangement and abnormal cell adhesion via ROCK1/cofilin and FAK/paxillin signaling pathways. SEPT11 knockout inhibits migration/invasion in vitro and metastasis in vivo, while overexpression has the opposite effect.\",\n      \"method\": \"SEPT11 overexpression, shRNA knockdown, CRISPR/Cas9 knockout in HCC cells, in vivo xenograft metastasis model, RhoA activity assay, co-immunoprecipitation (GEF-H1/RhoA), RNA-seq, ATAC-seq\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple genetic perturbations (OE, KD, KO) plus in vivo model plus RhoA activity assay and Co-IP for GEF-H1/RhoA interaction, single lab\",\n      \"pmids\": [\"37080972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SEPT11 knockdown in endometrial epithelial cells (Ishikawa and primary HEECs) inhibited cell adhesion. Elevated IFN-γ decreased SEPT11 protein levels in these cells, linking IFN-γ signaling to reduced SEPT11-dependent adhesive function.\",\n      \"method\": \"siRNA knockdown in Ishikawa cells and primary HEECs, cell adhesion assay, IFN-γ treatment with protein level measurement\",\n      \"journal\": \"Reproductive biomedicine online\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, siRNA KD with functional adhesion readout but limited mechanistic depth on pathway\",\n      \"pmids\": [\"37349244\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SEPT11 is a GTPase-dependent filament-forming septin that assembles into heteropolymeric complexes with SEPT2, SEPT4, SEPT5, SEPT7, SEPT9, and SEPT12 (requiring intact GTP-binding domains), localizes to actin stress fibers, microtubules, caveolae, lipid droplets, and neuronal dendritic spine necks depending on cell type, and performs context-specific functions including: restricting bacterial invasion via InlB/Met signaling in non-phagocytic cells; supporting dendritic arborization and GABAergic synaptic connectivity in neurons; regulating lipid storage and insulin signaling in adipocytes through interactions with caveolin-1 and FABP5; and promoting hepatocellular carcinoma cell motility by facilitating GEF-H1–mediated RhoA activation to drive ROCK1/cofilin and FAK/paxillin cytoskeletal remodeling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SEPTIN11 (SEPT11) is a GTPase-dependent filament-forming septin that assembles into cell-type-specific heteromeric septin complexes and contributes to cytoskeletal organization, membrane trafficking, and cell adhesion [#0, #6]. It was first isolated from brain septin complexes co-purifying with SEPT9, and its assembly into filaments requires an intact GTPase domain, with filaments aligning along either microtubules or actin stress fibers depending on the cellular context [#0]. SEPT11 engages multiple septin partners — SEPT5, SEPT12, SEPT2, SEPT4, and SEPT7 — through interactions that depend on the GTP-binding domain and C-terminal extension, and these partnerships couple it to vesicle-trafficking machinery, co-localizing with tubulin, transferrin receptor, and the SNARE protein VAMP1 [#1, #3, #6]. In neurons, SEPT11 concentrates at GABAergic postsynaptic densities and at dendritic spine necks and branch points, where it supports dendritic arborization and the formation of GABAergic synaptic contacts [#5]. In adipocytes it associates with caveolae and lipid droplets through interactions with caveolin-1 and FABP5, and is required for insulin signaling and insulin-induced lipid accumulation [#9]. SEPT11 also restricts InlB-mediated Listeria invasion of non-phagocytic cells independently of Met signaling, distinguishing it from the entry-promoting SEPT2 [#4], and promotes hepatocellular carcinoma migration and metastasis by facilitating GEF-H1 binding to RhoA, thereby activating RhoA and downstream ROCK1/cofilin and FAK/paxillin cytoskeletal remodeling [#10]. Loss of Sept11 causes mid-gestation embryonic lethality in mice, establishing it as essential for development [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Established SEPT11 as a bona fide septin subunit whose filament assembly is GTPase-dependent and cytoskeleton-templated, defining its core biochemical identity.\",\n      \"evidence\": \"Biochemical purification from porcine brain, co-immunoprecipitation with SEPT9, GTPase-deficient mutant expression in COS7, immunofluorescence colocalization\",\n      \"pmids\": [\"15196925\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"GTP hydrolysis kinetics not measured\", \"Stoichiometry within native complexes undefined\", \"Mechanism dictating microtubule vs actin association unknown\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Defined the domain requirements for SEPT11 heteromer formation by mapping the SEPT5 interaction to the GTP-binding domain and C-terminal extension, supporting cell-specific complex assembly.\",\n      \"evidence\": \"Yeast two-hybrid, co-precipitation from JURKAT lysates, and FRET in human cells\",\n      \"pmids\": [\"16767699\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the SEPT5-SEPT11 complex not tested\", \"Proposed exocytosis role not demonstrated\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Linked SEPT11 to disease by showing that hereditary neuralgic amyotrophy SEPT9 variants altered their colocalization with SEPT11, implicating partner-interaction changes in pathology.\",\n      \"evidence\": \"Transient expression of SEPT9 mutants in NMuMG epithelial cells with immunofluorescence colocalization\",\n      \"pmids\": [\"17546647\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single method (immunofluorescence) without biochemical interaction validation\", \"No direct functional effect on SEPT11 shown\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Generalized the nucleotide dependence of SEPT11 partnerships by showing SEPT12 requires GTP binding to associate with SEPT11.\",\n      \"evidence\": \"Co-expression and co-immunoprecipitation with a GTP-binding-deficient SEPT12 (G56A) mutant\",\n      \"pmids\": [\"18443421\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological tissue context of SEPT11-SEPT12 complex not defined\", \"Filament architecture not resolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Distinguished SEPT11 function from other septins by showing it restricts InlB-mediated bacterial invasion without affecting Met signaling, revealing a non-redundant role at the cell-pathogen interface.\",\n      \"evidence\": \"siRNA knockdown in HeLa cells with Listeria/InlB-bead invasion assays, FRET-based Met signaling assay, immunofluorescence\",\n      \"pmids\": [\"19234302\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism of invasion restriction unresolved\", \"Basis for increased cell size on depletion unexplained\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identified a neuronal function for SEPT11 at GABAergic synapses and dendritic spine necks, connecting septin filaments to dendritic morphology and inhibitory connectivity.\",\n      \"evidence\": \"Mass spectrometry/immunoblot of brain fractions, EM immunocytochemistry, and shRNA knockdown in hippocampal neurons with morphological and synaptic quantification\",\n      \"pmids\": [\"19380581\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Septin partners at the GABAergic PSD not identified\", \"Molecular link to synapse formation unknown\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Expanded the SEPT11 interactome to SEPT2/SEPT4/SEPT7 and linked it to vesicle trafficking via VAMP1 colocalization, with splice variants differing in partner selection.\",\n      \"evidence\": \"Yeast two-hybrid, co-precipitation, FRET, and immunofluorescence colocalization in endothelial cells and platelets\",\n      \"pmids\": [\"20978712\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct role in vesicle fusion/exocytosis not functionally demonstrated\", \"Functional difference between splice variants v1/v2 unresolved\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Established that SEPT11 is essential for embryonic development through a genetic knockout causing mid-gestation lethality.\",\n      \"evidence\": \"Sept11 null mouse with embryonic staging and phenotyping\",\n      \"pmids\": [\"21824005\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Tissue and molecular cause of lethality not identified\", \"No conditional dissection of essential pathways\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Implicated SEPT11 in neurodegeneration by showing aberrant proteolytic cleavage and aggregation into detergent-insoluble pathological inclusions in FTLD-U brain.\",\n      \"evidence\": \"iTRAQ/targeted MS of insoluble brain fractions, immunohistochemistry, immunoblot\",\n      \"pmids\": [\"22126117\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Protease responsible for cleavage unknown\", \"Whether SEPT11 aggregation is causal or consequential not established\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Defined a metabolic role for SEPT11 in adipocytes, linking it via caveolin-1 and FABP5 to lipid droplet biology and insulin signaling.\",\n      \"evidence\": \"GST pull-down, Co-IP, Y2H, subcellular fractionation, EM, and siRNA knockdown with insulin signaling and lipid accumulation readouts\",\n      \"pmids\": [\"27866222\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Step in insulin signaling cascade affected not pinpointed\", \"Whether GTPase activity is required for lipid droplet targeting untested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Provided a mechanistic route from SEPT11 to cytoskeletal remodeling in cancer, showing it scaffolds GEF-H1/RhoA to activate ROCK1/cofilin and FAK/paxillin signaling and drive HCC metastasis.\",\n      \"evidence\": \"Overexpression, shRNA, CRISPR knockout in HCC cells, in vivo xenograft metastasis, RhoA activity assay, GEF-H1/RhoA Co-IP, RNA-seq/ATAC-seq\",\n      \"pmids\": [\"37080972\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether SEPT11 directly binds GEF-H1 vs scaffolds indirectly not resolved\", \"Role of septin filament assembly in RhoA activation untested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Connected SEPT11 to endometrial epithelial adhesion and its suppression by IFN-gamma, suggesting cytokine-regulated control of SEPT11-dependent adhesion.\",\n      \"evidence\": \"siRNA knockdown in Ishikawa and primary HEEC cells with adhesion assays and IFN-gamma treatment\",\n      \"pmids\": [\"37349244\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single method depth limits mechanistic interpretation\", \"Pathway linking IFN-gamma to SEPT11 downregulation undefined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SEPT11's distinct cell-type-specific complexes and localizations (synapse, caveolae, lipid droplet, RhoA scaffold) are selected and regulated remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of SEPT11-containing filaments\", \"Determinants of partner and membrane selection unknown\", \"Whether GTPase cycling regulates its various functions untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"GO:0005811\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"complexes\": [\"heteromeric septin complex\"],\n    \"partners\": [\"SEPT9\", \"SEPT5\", \"SEPT12\", \"SEPT2\", \"SEPT4\", \"SEPT7\", \"CAV1\", \"FABP5\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}