{"gene":"SEPTIN1","run_date":"2026-06-10T07:46:30","timeline":{"discoveries":[{"year":2005,"finding":"Aurora-B kinase physically interacts with SEPT1 (identified by yeast two-hybrid, confirmed by co-immunoprecipitation in mammalian cells and GST pull-down in vitro), and Aurora-B phosphorylates SEPT1 in vitro at Ser248, Ser307, and Ser315. SEPT1 co-localizes with Aurora-B at the midbody during cytokinesis, and SEPT1 localizes to the spindle pole throughout mitosis.","method":"Yeast two-hybrid screen, co-immunoprecipitation, GST pull-down, in vitro kinase assay, immunofluorescence colocalization","journal":"Biochemical and biophysical research communications","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro kinase assay with phosphosite mapping, reciprocal Co-IP, GST pull-down, and colocalization; multiple orthogonal methods in one study","pmids":["16179162"],"is_preprint":false},{"year":2013,"finding":"In DJM-1 squamous cell carcinoma cells, SEPT1 is enriched in lamellipodia in a cortical actin-dependent manner, forms a complex with SEPT5 (by immunoprecipitation), and siRNA-mediated silencing of SEPT1 inhibits cell spreading, indicating a role for SEPT1 in cell-substrate interaction.","method":"Immunofluorescence, immunoprecipitation, siRNA knockdown with cell spreading assay","journal":"Biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP confirmed complex, siRNA knockdown with specific phenotypic readout, localization tied to functional context; single lab, multiple methods","pmids":["23087102"],"is_preprint":false},{"year":2009,"finding":"SEPT1 localizes to the midbody during cytokinesis, and siRNA-mediated knockdown of SEPT1 increases the number of cytokinesis-defective cells, establishing a functional role for SEPT1 in cytokinesis progression.","method":"Immunofluorescence localization to midbody, siRNA knockdown with quantification of cytokinesis defects","journal":"Journal of proteome research","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — clean knockdown with defined cellular phenotype and direct localization; single lab","pmids":["19799413"],"is_preprint":false},{"year":2019,"finding":"SEPT1 forms a scaffold at the Golgi that is required for Golgi structural integrity and function. SEPT1 depletion causes massive fragmentation of the Golgi ribbon and compromises anterograde membrane traffic. SEPT1 function at the Golgi depends on the Golgi matrix protein GM130 and centrosomal proteins CEP170 and γ-TuRC components, promoting local microtubule nucleation and perinuclear Golgi positioning.","method":"siRNA depletion, immunofluorescence, membrane traffic assays, co-localization with GM130/CEP170/γ-TuRC","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — loss-of-function with specific structural and trafficking phenotype, pathway placement via dependency on known Golgi/centrosomal proteins, multiple orthogonal readouts in one study","pmids":["30709970"],"is_preprint":false},{"year":2011,"finding":"In mouse oocytes, SEPT1 localizes to the spindle at metaphase and to the midbody during cytokinesis. siRNA-mediated depletion of SEPT1 reduces first polar body extrusion and causes spindle defects and impaired chromosome congression, demonstrating a role for SEPT1 in spindle assembly and chromosome congression during meiosis.","method":"siRNA knockdown, immunofluorescence localization, polar body extrusion assay, spindle morphology analysis","journal":"Developmental dynamics","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — siRNA knockdown with specific meiotic phenotype and direct localization data; single lab, multiple readouts","pmids":["21932310"],"is_preprint":false},{"year":2020,"finding":"SEPT1 expression in mouse brain increases postnatally (from birth to postnatal day 22), and subcellular fractionation and immunofluorescence of primary hippocampal neurons and brain tissue show SEPT1 distributed in synaptic fractions and localizing to synapses.","method":"Western blotting during brain development, subcellular fractionation, immunofluorescence of primary neurons and brain tissue, immunohistochemistry","journal":"Medical molecular morphology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — direct fractionation and imaging demonstrating synaptic localization with developmental regulation; single lab, multiple orthogonal methods","pmids":["32146512"],"is_preprint":false},{"year":2020,"finding":"SEPT1 forms a complex with SEPT2, SEPT10, SEPT11, and SEPT12 at the sperm neck. The D197N mutation in SEPT12 disrupts this complex, and loss of this complex is associated with defective connecting pieces and acephalic, immotile spermatozoa.","method":"Co-immunoprecipitation, immunofluorescence colocalization, knock-in mouse model with electron microscopy","journal":"Molecular human reproduction","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — co-IP showing complex membership, in vivo knock-in model linking complex disruption to structural phenotype; single lab","pmids":["32392324"],"is_preprint":false},{"year":2007,"finding":"Drosophila Parkin (E3 ubiquitin ligase) ubiquitinates Drosophila septin1 in an in vivo ubiquitination assay, identifying septin1 as a ubiquitination substrate of Parkin in Drosophila.","method":"In vivo ubiquitination assay, co-immunoprecipitation","journal":"Insect biochemistry and molecular biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, Drosophila ortholog, in vivo ubiquitination assay without mutagenesis or site mapping; relevant as ortholog finding but limited mechanistic depth","pmids":["17456438"],"is_preprint":false},{"year":2006,"finding":"Human SEPT1 was crystallized (space group P422, 2.5 Å resolution), using a mutant with five serine-to-alanine substitutions (Ser19, Ser206, Ser307, Ser312, Ser315) that reduced aggregation while causing only slight perturbations in secondary structure, establishing the basis for structural analysis.","method":"Recombinant protein expression, site-directed mutagenesis, crystallization, X-ray diffraction","journal":"Acta crystallographica Section F","confidence":"Low","confidence_rationale":"Tier 1 / Weak — crystallization and data collection reported but no functional or structural mechanistic conclusions drawn beyond preliminary crystallographic data; single study, preliminary report","pmids":["16511282"],"is_preprint":false}],"current_model":"SEPT1 is a GTPase family member that localizes to lamellipodia (actin-dependently), the spindle pole and midbody during mitosis/meiosis, synaptic fractions in neurons, the Golgi apparatus, and the sperm neck; it is phosphorylated by Aurora-B kinase at Ser248/307/315, forms heteromeric complexes with multiple septins (including SEPT2, SEPT4, SEPT5, SEPT10, SEPT11, SEPT12), and is functionally required for cell spreading, spindle assembly, chromosome congression, cytokinesis, and Golgi structural integrity and anterograde trafficking—with its Golgi role mediated through GM130 and centrosomal proteins including CEP170 and γ-TuRC."},"narrative":{"mechanistic_narrative":"SEPTIN1 (SEPT1) is a GTPase-family septin that assembles into heteromeric septin complexes and acts as a scaffold supporting cell division, membrane trafficking, and cytoskeletal organization [PMID:23087102, PMID:30709970, PMID:32392324]. During mitosis and meiosis it localizes to the spindle pole and midbody, where it is required for spindle assembly, chromosome congression, and cytokinesis progression [PMID:16179162, PMID:19799413, PMID:21932310]; its mitotic activity is governed by Aurora-B kinase, which physically binds SEPT1 and phosphorylates it at Ser248, Ser307, and Ser315 [PMID:16179162]. At the Golgi, SEPT1 forms a scaffold needed for Golgi ribbon integrity and anterograde membrane traffic, acting through the matrix protein GM130 and centrosomal CEP170/γ-TuRC components to promote microtubule nucleation and perinuclear Golgi positioning [PMID:30709970]. SEPT1 also localizes actin-dependently to lamellipodia, where it is required for cell spreading and forms a complex with SEPT5 [PMID:23087102], and it participates in higher-order septin complexes with SEPT2, SEPT10, SEPT11, and SEPT12 at the sperm neck whose disruption produces acephalic, immotile spermatozoa [PMID:32392324]. In neurons, SEPT1 is developmentally upregulated postnatally and localizes to synaptic fractions [PMID:32146512].","teleology":[{"year":2005,"claim":"Established that SEPT1 is an Aurora-B substrate and a mitotic component, linking a septin to the kinase machinery controlling cell division.","evidence":"Yeast two-hybrid, reciprocal Co-IP, GST pull-down, in vitro kinase assay with phosphosite mapping, and immunofluorescence in mammalian cells","pmids":["16179162"],"confidence":"High","gaps":["Functional consequence of Ser248/307/315 phosphorylation on SEPT1 activity or assembly not tested","Whether phosphorylation regulates spindle-pole or midbody localization unknown"]},{"year":2006,"claim":"Provided the structural starting point for SEPT1 by crystallizing a low-aggregation serine-to-alanine mutant.","evidence":"Recombinant expression, site-directed mutagenesis, crystallization and X-ray diffraction to 2.5 Å","pmids":["16511282"],"confidence":"Low","gaps":["No refined structure or mechanistic conclusion drawn","Mutations may perturb native nucleotide or interface behavior"]},{"year":2007,"claim":"Identified the septin1 ortholog as a Parkin ubiquitination substrate, hinting at degradative regulation of septins.","evidence":"In vivo ubiquitination assay and Co-IP in Drosophila","pmids":["17456438"],"confidence":"Low","gaps":["Drosophila ortholog finding without site mapping or mutagenesis","Not confirmed for human SEPT1","Functional consequence of ubiquitination undefined"]},{"year":2009,"claim":"Demonstrated a direct functional requirement for SEPT1 in completing cytokinesis, beyond mere midbody localization.","evidence":"Immunofluorescence midbody localization and siRNA knockdown quantifying cytokinesis defects","pmids":["19799413"],"confidence":"Medium","gaps":["Molecular partners at the midbody not defined","Single lab; no rescue control reported"]},{"year":2011,"claim":"Extended SEPT1's division role to meiosis, showing it is needed for spindle assembly and chromosome congression in oocytes.","evidence":"siRNA knockdown in mouse oocytes with polar body extrusion and spindle morphology analysis","pmids":["21932310"],"confidence":"Medium","gaps":["Mechanism linking SEPT1 to spindle/chromosome behavior unresolved","Single lab"]},{"year":2013,"claim":"Placed SEPT1 at lamellipodia in an actin-dependent manner and tied it to cell spreading, broadening its role to cell-substrate interaction.","evidence":"Immunofluorescence, Co-IP showing SEPT5 complex, and siRNA knockdown with cell spreading assay in squamous carcinoma cells","pmids":["23087102"],"confidence":"Medium","gaps":["How SEPT1/SEPT5 complex couples to actin or adhesion machinery unknown","Single cell line"]},{"year":2019,"claim":"Defined SEPT1 as a Golgi scaffold required for ribbon integrity and anterograde traffic, and placed it in a GM130–CEP170–γ-TuRC microtubule-nucleating pathway.","evidence":"siRNA depletion, immunofluorescence, membrane traffic assays, and co-localization with GM130/CEP170/γ-TuRC","pmids":["30709970"],"confidence":"High","gaps":["Direct biochemical interactions among SEPT1, GM130, CEP170 not mapped","Whether the same SEPT1 pool serves Golgi and mitotic functions unknown"]},{"year":2020,"claim":"Showed SEPT1 is a member of a sperm-neck septin complex whose disruption causes structural sperm defects, and separately documented postnatal synaptic localization in neurons.","evidence":"Co-IP and immunofluorescence defining a SEPT1/2/10/11/12 complex plus a SEPT12 D197N knock-in mouse with EM (sperm); developmental Western blotting, fractionation, and imaging (neurons)","pmids":["32392324","32146512"],"confidence":"Medium","gaps":["Specific contribution of SEPT1 within the multi-septin complex not isolated","Synaptic function of neuronal SEPT1 not tested functionally"]},{"year":null,"claim":"How GTP binding/hydrolysis and Aurora-B phosphorylation control SEPT1 complex assembly and switching between its mitotic, Golgi, lamellipodial, and synaptic roles remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No demonstrated GTPase activity or nucleotide-dependent regulation in the corpus","No structure-function link between phosphosites and assembly","Mechanism partitioning SEPT1 across compartments unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[3,1]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1,3]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[3]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,2,4]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[3]}],"complexes":["SEPT1-SEPT5 complex (lamellipodia)","SEPT1/2/10/11/12 sperm-neck septin complex"],"partners":["AURKB","SEPT5","SEPT2","SEPT10","SEPT11","SEPT12","GM130","CEP170"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WYJ6","full_name":"Septin-1","aliases":["LARP","Peanut-like protein 3","Serologically defined breast cancer antigen NY-BR-24"],"length_aa":372,"mass_kda":42.4,"function":"Filament-forming cytoskeletal GTPase (By similarity). May play a role in cytokinesis (Potential)","subcellular_location":"Cytoplasm; Cytoplasm, cytoskeleton; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Midbody","url":"https://www.uniprot.org/uniprotkb/Q8WYJ6/entry"},"depmap":{"release":"DepMap","has_data":false,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SEPTIN1"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SEPTIN1","total_profiled":1310},"omim":[{"mim_id":"612897","title":"SEPTIN 1; SEPT1","url":"https://www.omim.org/entry/612897"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Actin filaments","reliability":"Approved"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"intestine","ntpm":23.5},{"tissue":"lymphoid tissue","ntpm":48.5}],"url":"https://www.proteinatlas.org/search/SEPTIN1"},"hgnc":{"alias_symbol":["PNUTL3","Septin-1"],"prev_symbol":["DIFF6","SEPT1"]},"alphafold":{"accession":"Q8WYJ6","domains":[{"cath_id":"3.40.50.300","chopping":"25-56_71-303","consensus_level":"high","plddt":83.2244,"start":25,"end":303}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WYJ6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WYJ6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WYJ6-F1-predicted_aligned_error_v6.png","plddt_mean":76.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SEPTIN1","jax_strain_url":"https://www.jax.org/strain/search?query=SEPTIN1"},"sequence":{"accession":"Q8WYJ6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WYJ6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WYJ6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WYJ6"}},"corpus_meta":[{"pmid":"15915442","id":"PMC_15915442","title":"Expression 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Kinetics After Speed-Endurance Training in Male Soccer Players.","date":"2020","source":"International journal of sports physiology and performance","url":"https://pubmed.ncbi.nlm.nih.gov/31751937","citation_count":16,"is_preprint":false},{"pmid":"17912427","id":"PMC_17912427","title":"Overexpression of Septin1: possible contribution to the development of oral cancer.","date":"2007","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/17912427","citation_count":15,"is_preprint":false},{"pmid":"30866452","id":"PMC_30866452","title":"Testis-Specific SEPT12 Expression Affects SUN Protein Localization and is Involved in Mammalian Spermiogenesis.","date":"2019","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/30866452","citation_count":15,"is_preprint":false},{"pmid":"21932310","id":"PMC_21932310","title":"Septin1 is required for spindle assembly and chromosome congression in mouse 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SEPT1 co-localizes with Aurora-B at the midbody during cytokinesis, and SEPT1 localizes to the spindle pole throughout mitosis.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation, GST pull-down, in vitro kinase assay, immunofluorescence colocalization\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro kinase assay with phosphosite mapping, reciprocal Co-IP, GST pull-down, and colocalization; multiple orthogonal methods in one study\",\n      \"pmids\": [\"16179162\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In DJM-1 squamous cell carcinoma cells, SEPT1 is enriched in lamellipodia in a cortical actin-dependent manner, forms a complex with SEPT5 (by immunoprecipitation), and siRNA-mediated silencing of SEPT1 inhibits cell spreading, indicating a role for SEPT1 in cell-substrate interaction.\",\n      \"method\": \"Immunofluorescence, immunoprecipitation, siRNA knockdown with cell spreading assay\",\n      \"journal\": \"Biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP confirmed complex, siRNA knockdown with specific phenotypic readout, localization tied to functional context; single lab, multiple methods\",\n      \"pmids\": [\"23087102\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"SEPT1 localizes to the midbody during cytokinesis, and siRNA-mediated knockdown of SEPT1 increases the number of cytokinesis-defective cells, establishing a functional role for SEPT1 in cytokinesis progression.\",\n      \"method\": \"Immunofluorescence localization to midbody, siRNA knockdown with quantification of cytokinesis defects\",\n      \"journal\": \"Journal of proteome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — clean knockdown with defined cellular phenotype and direct localization; single lab\",\n      \"pmids\": [\"19799413\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SEPT1 forms a scaffold at the Golgi that is required for Golgi structural integrity and function. SEPT1 depletion causes massive fragmentation of the Golgi ribbon and compromises anterograde membrane traffic. SEPT1 function at the Golgi depends on the Golgi matrix protein GM130 and centrosomal proteins CEP170 and γ-TuRC components, promoting local microtubule nucleation and perinuclear Golgi positioning.\",\n      \"method\": \"siRNA depletion, immunofluorescence, membrane traffic assays, co-localization with GM130/CEP170/γ-TuRC\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with specific structural and trafficking phenotype, pathway placement via dependency on known Golgi/centrosomal proteins, multiple orthogonal readouts in one study\",\n      \"pmids\": [\"30709970\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"In mouse oocytes, SEPT1 localizes to the spindle at metaphase and to the midbody during cytokinesis. siRNA-mediated depletion of SEPT1 reduces first polar body extrusion and causes spindle defects and impaired chromosome congression, demonstrating a role for SEPT1 in spindle assembly and chromosome congression during meiosis.\",\n      \"method\": \"siRNA knockdown, immunofluorescence localization, polar body extrusion assay, spindle morphology analysis\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — siRNA knockdown with specific meiotic phenotype and direct localization data; single lab, multiple readouts\",\n      \"pmids\": [\"21932310\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SEPT1 expression in mouse brain increases postnatally (from birth to postnatal day 22), and subcellular fractionation and immunofluorescence of primary hippocampal neurons and brain tissue show SEPT1 distributed in synaptic fractions and localizing to synapses.\",\n      \"method\": \"Western blotting during brain development, subcellular fractionation, immunofluorescence of primary neurons and brain tissue, immunohistochemistry\",\n      \"journal\": \"Medical molecular morphology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — direct fractionation and imaging demonstrating synaptic localization with developmental regulation; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"32146512\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SEPT1 forms a complex with SEPT2, SEPT10, SEPT11, and SEPT12 at the sperm neck. The D197N mutation in SEPT12 disrupts this complex, and loss of this complex is associated with defective connecting pieces and acephalic, immotile spermatozoa.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence colocalization, knock-in mouse model with electron microscopy\",\n      \"journal\": \"Molecular human reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — co-IP showing complex membership, in vivo knock-in model linking complex disruption to structural phenotype; single lab\",\n      \"pmids\": [\"32392324\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Drosophila Parkin (E3 ubiquitin ligase) ubiquitinates Drosophila septin1 in an in vivo ubiquitination assay, identifying septin1 as a ubiquitination substrate of Parkin in Drosophila.\",\n      \"method\": \"In vivo ubiquitination assay, co-immunoprecipitation\",\n      \"journal\": \"Insect biochemistry and molecular biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, Drosophila ortholog, in vivo ubiquitination assay without mutagenesis or site mapping; relevant as ortholog finding but limited mechanistic depth\",\n      \"pmids\": [\"17456438\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Human SEPT1 was crystallized (space group P422, 2.5 Å resolution), using a mutant with five serine-to-alanine substitutions (Ser19, Ser206, Ser307, Ser312, Ser315) that reduced aggregation while causing only slight perturbations in secondary structure, establishing the basis for structural analysis.\",\n      \"method\": \"Recombinant protein expression, site-directed mutagenesis, crystallization, X-ray diffraction\",\n      \"journal\": \"Acta crystallographica Section F\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 1 / Weak — crystallization and data collection reported but no functional or structural mechanistic conclusions drawn beyond preliminary crystallographic data; single study, preliminary report\",\n      \"pmids\": [\"16511282\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SEPT1 is a GTPase family member that localizes to lamellipodia (actin-dependently), the spindle pole and midbody during mitosis/meiosis, synaptic fractions in neurons, the Golgi apparatus, and the sperm neck; it is phosphorylated by Aurora-B kinase at Ser248/307/315, forms heteromeric complexes with multiple septins (including SEPT2, SEPT4, SEPT5, SEPT10, SEPT11, SEPT12), and is functionally required for cell spreading, spindle assembly, chromosome congression, cytokinesis, and Golgi structural integrity and anterograde trafficking—with its Golgi role mediated through GM130 and centrosomal proteins including CEP170 and γ-TuRC.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SEPTIN1 (SEPT1) is a GTPase-family septin that assembles into heteromeric septin complexes and acts as a scaffold supporting cell division, membrane trafficking, and cytoskeletal organization [#1, #3, #6]. During mitosis and meiosis it localizes to the spindle pole and midbody, where it is required for spindle assembly, chromosome congression, and cytokinesis progression [#0, #2, #4]; its mitotic activity is governed by Aurora-B kinase, which physically binds SEPT1 and phosphorylates it at Ser248, Ser307, and Ser315 [#0]. At the Golgi, SEPT1 forms a scaffold needed for Golgi ribbon integrity and anterograde membrane traffic, acting through the matrix protein GM130 and centrosomal CEP170/\\u03b3-TuRC components to promote microtubule nucleation and perinuclear Golgi positioning [#3]. SEPT1 also localizes actin-dependently to lamellipodia, where it is required for cell spreading and forms a complex with SEPT5 [#1], and it participates in higher-order septin complexes with SEPT2, SEPT10, SEPT11, and SEPT12 at the sperm neck whose disruption produces acephalic, immotile spermatozoa [#6]. In neurons, SEPT1 is developmentally upregulated postnatally and localizes to synaptic fractions [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Established that SEPT1 is an Aurora-B substrate and a mitotic component, linking a septin to the kinase machinery controlling cell division.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal Co-IP, GST pull-down, in vitro kinase assay with phosphosite mapping, and immunofluorescence in mammalian cells\",\n      \"pmids\": [\"16179162\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of Ser248/307/315 phosphorylation on SEPT1 activity or assembly not tested\", \"Whether phosphorylation regulates spindle-pole or midbody localization unknown\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Provided the structural starting point for SEPT1 by crystallizing a low-aggregation serine-to-alanine mutant.\",\n      \"evidence\": \"Recombinant expression, site-directed mutagenesis, crystallization and X-ray diffraction to 2.5 \\u00c5\",\n      \"pmids\": [\"16511282\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No refined structure or mechanistic conclusion drawn\", \"Mutations may perturb native nucleotide or interface behavior\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identified the septin1 ortholog as a Parkin ubiquitination substrate, hinting at degradative regulation of septins.\",\n      \"evidence\": \"In vivo ubiquitination assay and Co-IP in Drosophila\",\n      \"pmids\": [\"17456438\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Drosophila ortholog finding without site mapping or mutagenesis\", \"Not confirmed for human SEPT1\", \"Functional consequence of ubiquitination undefined\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Demonstrated a direct functional requirement for SEPT1 in completing cytokinesis, beyond mere midbody localization.\",\n      \"evidence\": \"Immunofluorescence midbody localization and siRNA knockdown quantifying cytokinesis defects\",\n      \"pmids\": [\"19799413\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular partners at the midbody not defined\", \"Single lab; no rescue control reported\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Extended SEPT1's division role to meiosis, showing it is needed for spindle assembly and chromosome congression in oocytes.\",\n      \"evidence\": \"siRNA knockdown in mouse oocytes with polar body extrusion and spindle morphology analysis\",\n      \"pmids\": [\"21932310\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking SEPT1 to spindle/chromosome behavior unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Placed SEPT1 at lamellipodia in an actin-dependent manner and tied it to cell spreading, broadening its role to cell-substrate interaction.\",\n      \"evidence\": \"Immunofluorescence, Co-IP showing SEPT5 complex, and siRNA knockdown with cell spreading assay in squamous carcinoma cells\",\n      \"pmids\": [\"23087102\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How SEPT1/SEPT5 complex couples to actin or adhesion machinery unknown\", \"Single cell line\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined SEPT1 as a Golgi scaffold required for ribbon integrity and anterograde traffic, and placed it in a GM130\\u2013CEP170\\u2013\\u03b3-TuRC microtubule-nucleating pathway.\",\n      \"evidence\": \"siRNA depletion, immunofluorescence, membrane traffic assays, and co-localization with GM130/CEP170/\\u03b3-TuRC\",\n      \"pmids\": [\"30709970\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct biochemical interactions among SEPT1, GM130, CEP170 not mapped\", \"Whether the same SEPT1 pool serves Golgi and mitotic functions unknown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Showed SEPT1 is a member of a sperm-neck septin complex whose disruption causes structural sperm defects, and separately documented postnatal synaptic localization in neurons.\",\n      \"evidence\": \"Co-IP and immunofluorescence defining a SEPT1/2/10/11/12 complex plus a SEPT12 D197N knock-in mouse with EM (sperm); developmental Western blotting, fractionation, and imaging (neurons)\",\n      \"pmids\": [\"32392324\", \"32146512\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific contribution of SEPT1 within the multi-septin complex not isolated\", \"Synaptic function of neuronal SEPT1 not tested functionally\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How GTP binding/hydrolysis and Aurora-B phosphorylation control SEPT1 complex assembly and switching between its mitotic, Golgi, lamellipodial, and synaptic roles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No demonstrated GTPase activity or nucleotide-dependent regulation in the corpus\", \"No structure-function link between phosphosites and assembly\", \"Mechanism partitioning SEPT1 across compartments unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [3, 1]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 2, 4]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"SEPT1-SEPT5 complex (lamellipodia)\",\n      \"SEPT1/2/10/11/12 sperm-neck septin complex\"\n    ],\n    \"partners\": [\n      \"AURKB\",\n      \"SEPT5\",\n      \"SEPT2\",\n      \"SEPT10\",\n      \"SEPT11\",\n      \"SEPT12\",\n      \"GM130\",\n      \"CEP170\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}