Affinage

SEPTIN11

Septin-11 · UniProt Q9NVA2

Length
429 aa
Mass
49.4 kDa
Annotated
2026-06-10
14 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2004 Medium

    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

    PMID:15196925

    Open questions at the time
    • GTP hydrolysis kinetics not measured
    • Stoichiometry within native complexes undefined
    • Mechanism dictating microtubule vs actin association unknown
  2. 2006 Medium

    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

    PMID:16767699

    Open questions at the time
    • Functional consequence of the SEPT5-SEPT11 complex not tested
    • Proposed exocytosis role not demonstrated
  3. 2007 Low

    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

    PMID:17546647

    Open questions at the time
    • Single method (immunofluorescence) without biochemical interaction validation
    • No direct functional effect on SEPT11 shown
  4. 2008 Medium

    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

    PMID:18443421

    Open questions at the time
    • Physiological tissue context of SEPT11-SEPT12 complex not defined
    • Filament architecture not resolved
  5. 2009 Medium

    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

    PMID:19234302

    Open questions at the time
    • Molecular mechanism of invasion restriction unresolved
    • Basis for increased cell size on depletion unexplained
  6. 2009 High

    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

    PMID:19380581

    Open questions at the time
    • Septin partners at the GABAergic PSD not identified
    • Molecular link to synapse formation unknown
  7. 2010 Medium

    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

    PMID:20978712

    Open questions at the time
    • Direct role in vesicle fusion/exocytosis not functionally demonstrated
    • Functional difference between splice variants v1/v2 unresolved
  8. 2011 Medium

    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

    PMID:21824005

    Open questions at the time
    • Tissue and molecular cause of lethality not identified
    • No conditional dissection of essential pathways
  9. 2011 Medium

    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

    PMID:22126117

    Open questions at the time
    • Protease responsible for cleavage unknown
    • Whether SEPT11 aggregation is causal or consequential not established
  10. 2016 High

    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

    PMID:27866222

    Open questions at the time
    • Step in insulin signaling cascade affected not pinpointed
    • Whether GTPase activity is required for lipid droplet targeting untested
  11. 2023 Medium

    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

    PMID:37080972

    Open questions at the time
    • Whether SEPT11 directly binds GEF-H1 vs scaffolds indirectly not resolved
    • Role of septin filament assembly in RhoA activation untested
  12. 2023 Low

    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

    PMID:37349244

    Open questions at the time
    • Single method depth limits mechanistic interpretation
    • Pathway linking IFN-gamma to SEPT11 downregulation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SEPT11's distinct cell-type-specific complexes and localizations (synapse, caveolae, lipid droplet, RhoA scaffold) are selected and regulated remains unresolved.
  • No structural model of SEPT11-containing filaments
  • Determinants of partner and membrane selection unknown
  • Whether GTPase cycling regulates its various functions untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0003924 GTPase activity 1 GO:0008092 cytoskeletal protein binding 1 GO:0060090 molecular adaptor activity 1
Localization
GO:0005811 lipid droplet 1 GO:0005856 cytoskeleton 1 GO:0005886 plasma membrane 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1430728 Metabolism 1 R-HSA-162582 Signal Transduction 1 R-HSA-5653656 Vesicle-mediated transport 1
Partners
CAV1FABP5SEPT12SEPT2SEPT4SEPT5SEPT7SEPT9
Complex memberships
heteromeric septin complex

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 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. Biochemical purification from porcine brain, co-immunoprecipitation with anti-SEPT9/anti-SEPT11 antibodies, GTPase mutant overexpression in COS7 cells, immunofluorescence colocalization FEBS letters Medium 15196925
2006 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. Yeast two-hybrid, co-precipitation from JURKAT lysates, fluorescence resonance energy transfer (FRET), Western blot The Journal of pathology Medium 16767699
2007 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. Transient expression of SEPT9 mutants in NMuMG cells, immunofluorescence colocalization Human mutation Low 17546647
2008 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. Co-expression in cells, co-immunoprecipitation, GTP-binding mutant analysis Molecules and cells Medium 18443421
2009 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. siRNA knockdown in HeLa cells, Listeria invasion assay, InlB-coated bead uptake, FRET-based Met signaling assay, immunofluorescence The Journal of biological chemistry Medium 19234302
2009 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. Mass spectrometry and immunoblot of brain fractions, immunofluorescence in cultured neurons, electron microscopy immunocytochemistry, shRNA knockdown with morphological and synaptic contact quantification The Journal of biological chemistry High 19380581
2010 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. Yeast two-hybrid, co-precipitation, FRET, immunofluorescence co-localization in endothelial cells and platelets, Northern blot Thrombosis and haemostasis Medium 20978712
2011 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. Sept11 knockout mouse model, embryonic staging and phenotyping Biological chemistry Medium 21824005
2011 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. Quantitative proteomics (iTRAQ and targeted MS) of detergent-insoluble brain fractions, immunohistochemistry, immunoblot Molecular neurodegeneration Medium 22126117
2016 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. GST pull-down, co-immunoprecipitation, yeast two-hybrid screening, subcellular fractionation, immunocytochemistry, electron microscopy, siRNA knockdown with insulin signaling and lipid accumulation readouts Diabetologia High 27866222
2023 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. 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 Cell death & disease Medium 37080972
2023 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. siRNA knockdown in Ishikawa cells and primary HEECs, cell adhesion assay, IFN-γ treatment with protein level measurement Reproductive biomedicine online Low 37349244

Source papers

Stage 0 corpus · 14 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Biochemical and cell biological characterization of a mammalian septin, Sept11. FEBS letters 93 15196925
2009 Septin 11 is present in GABAergic synapses and plays a functional role in the cytoarchitecture of neurons and GABAergic synaptic connectivity. The Journal of biological chemistry 54 19380581
2009 Septin 11 restricts InlB-mediated invasion by Listeria. The Journal of biological chemistry 48 19234302
2004 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). Leukemia 42 14999297
2007 SEPT9 sequence alternations causing hereditary neuralgic amyotrophy are associated with altered interactions with SEPT4/SEPT11 and resistance to Rho/Rhotekin-signaling. Human mutation 32 17546647
2016 The cytoskeletal protein septin 11 is associated with human obesity and is involved in adipocyte lipid storage and metabolism. Diabetologia 30 27866222
2023 Septin11 promotes hepatocellular carcinoma cell motility by activating RhoA to regulate cytoskeleton and cell adhesion. Cell death & disease 24 37080972
2011 Lethal phenotype of mice carrying a Sept11 null mutation. Biological chemistry 22 21824005
2006 Human endothelial cell septins: SEPT11 is an interaction partner of SEPT5. The Journal of pathology 22 16767699
2011 Aberrant septin 11 is associated with sporadic frontotemporal lobar degeneration. Molecular neurodegeneration 21 22126117
2010 Human endothelial and platelet septin SEPT11: cloning of novel variants and characterisation of interaction partners. Thrombosis and haemostasis 13 20978712
2008 GTP binding is required for SEPT12 to form filaments and to interact with SEPT11. Molecules and cells 12 18443421
2010 A translocation in acute lymphoblastic leukemia that cytogenetically mimics the recurrent MLL-AFF1 translocation and fuses SEPT11 to MLL. Cancer genetics and cytogenetics 5 20633769
2023 Downregulation of SEPTIN11 inhibits endometrial epithelial cell adhesive function in patients with elevated peripheral blood natural killer cell counts. Reproductive biomedicine online 2 37349244

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