| 1997 |
Nedd5 (SEPTIN2) accumulates near the contractile ring from anaphase through telophase and condenses into the midbody; microinjection of anti-Nedd5 antibody causes cytokinesis failure resulting in binucleated cells, establishing a direct role in cytokinesis. GTP hydrolysis is required for assembly of Nedd5-containing fibers, as shown by GTPγS microinjection and GTP-binding-deficient mutants. Nedd5 fibers physically contact actin bundles and focal adhesion complexes and are disrupted by cytochalasin D, C3 exoenzyme, and serum starvation. |
Microinjection of inhibitory antibody, expression of GTPase-deficient mutants, pharmacological disruption (cytochalasin D, C3 exoenzyme, GTPγS), immunofluorescence co-localization |
Genes & development |
High |
9203580
|
| 2003 |
Nedd5 (SEPTIN2) co-immunoprecipitates with the exocyst complex and tubulin from rat brain lysate. Overexpression of a GTPase-defective Nedd5 mutant promotes aberrant neurite sprouting in PC12 cells, indicating that Nedd5 GTPase activity is required for polarized neurite outgrowth. |
Co-immunoprecipitation from brain lysate, overexpression of GTPase-deficient mutant in PC12 cells, immunofluorescence |
Neuroreport |
Medium |
12544826
|
| 2004 |
Septin 2 (SEPT2) is phosphorylated in vivo at a single site; mass spectrometric analysis of recombinant human SEPT2 identified Ser248 as the phosphorylation site; site-directed mutagenesis (S248A) abolished phosphorylation. Predicted kinase is casein kinase 2. |
MALDI-Q-TOF mass spectrometry on purified recombinant protein; site-directed mutagenesis (S248A) |
Rapid communications in mass spectrometry : RCM |
Medium |
15150837
|
| 2006 |
Recombinant human septin 2 binds guanine nucleotides (Kd 0.28 μM for GTPγS, 1.75 μM for GDP) with slow exchange rates and an apparent kcat of ~2.7×10⁻⁴ s⁻¹, similar to Ras-family GTPases. A single septin 2 protein can form homotypic filaments in vitro bound to either GDP or GTP. Septin 2 is phosphorylated in vivo at Ser218 by casein kinase II, and phosphorylation at Ser218 alters nucleotide binding affinity. |
In vitro GTP/GDP binding and hydrolysis assays with recombinant protein; in vitro filament reconstitution; in vivo phosphorylation analysis |
The FEBS journal |
High |
16857012
|
| 2010 |
Septin 2 is modified by SUMO-1 in mouse oocytes during meiotic maturation. Disruption of septin function (inhibitor or siRNA) causes failure of the metaphase I/anaphase I transition and chromosome misalignment, activating the spindle assembly checkpoint (BubR1 labeling). Septin 2 localizes along the meiotic spindle and at the midbody during cytokinesis. |
siRNA knockdown, pharmacological inhibition, immunofluorescence, SUMO modification assay in mouse oocytes |
Cell cycle (Georgetown, Tex.) |
Medium |
20372094
|
| 2010 |
Increased membrane localization of septin-2 in airway epithelial cells mediates decreases in paracellular permeability by altering cortical actin arrangement, in response to both physiological shear stress and particulate matter exposure. Septin-2 redistribution to the membrane regulates barrier function and segregates EGF receptor to the basolateral side. |
Immunofluorescence, siRNA-mediated depletion, permeability assays, actin staining in human airway epithelial cells |
American journal of respiratory cell and molecular biology |
Medium |
20870893
|
| 2011 |
Human SEPT2 can self-assemble into amyloid-like filaments in vitro. Regions within the GTP-binding domain have propensity to aggregate; temperature-induced unfolding generates a β-sheet-rich intermediate that binds Thioflavin-T and forms micrometer-length fibers visible by electron microscopy. |
In vitro aggregation assay, Thioflavin-T binding, electron microscopy, CD spectroscopy |
Biochimie |
Medium |
21967827
|
| 2013 |
SEPT2 preferentially and strongly adsorbs onto PtdIns(4,5)P2 Langmuir monolayers compared to DPPC monolayers, remaining inserted at high surface pressures, while its native secondary structure is preserved only when interacting with PtdIns(4,5)P2. This suggests a specific lipid interaction that may regulate SEPT2 assembly. |
Langmuir monolayer assay, PM-IRRAS spectroscopy |
Biochimica et biophysica acta |
Medium |
23416254
|
| 2016 |
Septin 2 localizes to a subset of mitochondrial constriction sites and directly binds Drp1, as shown by immunoprecipitation of endogenous proteins and pulldown with recombinant proteins. Depletion of septin 2 reduces Drp1 recruitment to mitochondria and results in hyperfused mitochondria and delayed FCCP-induced fission. |
Co-immunoprecipitation of endogenous proteins, pulldown with recombinant proteins, siRNA knockdown, live-cell imaging, immunofluorescence |
EMBO reports |
High |
27215606
|
| 2016 |
Septin 2 is downstream of RhoA in angiotensin II-stimulated adventitial fibroblast-to-myofibroblast differentiation. Overexpression of septin 2 decreases α-SMA expression and inhibits myofibroblast migration. Septin 2 protects α-tubulin acetylation, and RhoA inhibition decreases myofibroblast motility and septin 2 expression. |
Adenovirus-mediated gene transfer, Western blot, migration assay, RhoA inhibition, acetyl-α-tubulin quantification |
Journal of vascular research |
Medium |
27974709
|
| 2019 |
ZIKV protease NS2B-NS3 cleaves Septin-2 at residue 306. Cleavage is protease-activity-dependent, and forced expression of a non-cleavable Septin-2 (R306A or equivalent) restores cytokinesis in NS2B-NS3-expressing cells, establishing Septin-2 cleavage as a direct mechanism of ZIKV-induced cytokinesis defects in neural progenitors. |
Expression of NS2B-NS3 protease, protease-dead mutant controls, non-cleavable Septin-2 rescue, co-immunoprecipitation, cytokinesis assay |
Neuron |
High |
30713029
|
| 2019 |
SEPT2/6/7 heteromeric complexes directly regulate microtubule plus-end dynamics in a biphasic, concentration-dependent manner: lower concentrations enhance MT plus-end growth while higher concentrations inhibit or pause it. SEPT2/6/7 competes with EB1 for binding to GTPγS-stabilized microtubules and triggers EB1 dissociation from plus-end tips both in cis (by binding the MT lattice) and in trans (when MT plus ends collide with SEPT2/6/7 filaments). SEPT2/6/7 filaments are more potent barriers than actin filaments for pausing MT growth. |
In vitro reconstitution of MT dynamics with purified SEPT2/6/7; competitive binding assays with EB1; live-cell imaging |
Molecular biology of the cell |
High |
31577529
|
| 2019 |
ZIKV NS2B-NS3 protease interacts with Septin-2 (identified among binding partners by co-immunoprecipitation) and cleaves it at residue 306. |
Co-immunoprecipitation, in vitro cleavage assay, mutant rescue |
Neuron |
High |
30713029
|
| 2020 |
Septin2, together with Septin6 and Septin7, is required for maturation of nascent endothelial podosomes into matrix-degrading organelles. Septin2 localizes around the perimeter of podosomes near the basolateral plasma membrane. Phosphoinositide-binding residues of Septin2 are required for podosome function, and Septin2-mediated podosome regulation is critical for endothelial cell invasion associated with angiogenesis. |
siRNA knockdown of Septin2/6/7, live-cell imaging, immunofluorescence, PI-binding mutant expression, matrix degradation assay, in vitro invasion assay |
The Journal of cell biology |
High |
31865373
|
| 2020 |
Junctional localization of Septin 2 is required for the organization of adherens junction proteins (nectin-2, afadin), tight junction protein ZO-1, and PECAM-1 in endothelial monolayers. Loss of junctional Septin 2 (via shRNA, TNF-α treatment, or PI(4,5)P2-binding mutant overexpression) disorganizes these junctional proteins, implicating a plasma membrane-interaction-dependent mechanism. |
shRNA knockdown, PI(4,5)P2-binding mutant overexpression, immunofluorescence confocal imaging, immunoblot, RNA-seq |
Arteriosclerosis, thrombosis, and vascular biology |
Medium |
33147991
|
| 2022 |
SEPTIN2 is required for the formation or stabilization of the septin multimer in peripheral nervous system (Schwann cell) myelin: deletion of Septin2 in Schwann cells markedly reduced abundance of all relevant septin subunits (SEPT7, SEPT8, SEPT9, SEPT11), whereas Septin9 deletion had no effect on other septin subunits. |
Cre/loxP conditional knockout in Schwann cells, Western blot of sciatic nerve, immunofluorescence |
Cytoskeleton (Hoboken, N.J.) |
Medium |
36378242
|
| 2023 |
Cyclophilin A isomerizes Septin 2 at proline 259 and this interaction is required for Septin 2 localization to the midbody and for abscission during cytokinesis. Cyclophilin A depletion or loss of isomerase activity induces Septin 2 defects at the midbody. A Septin 2 P259 mutant (isomerization-deficient) shows defective midbody localization and impaired abscission. |
Co-immunoprecipitation, structural/molecular analysis of P259, EGFP-Septin2 mutant expression, Cyclophilin A depletion, abscission assay |
International journal of molecular sciences |
Medium |
37446263
|
| 2023 |
ER stress induces SEPT2 expression; SEPT2 balances the competition between acetylation and ubiquitination of heat shock protein 5 (BiP/GRP78) at Lysine 327, thereby alleviating ER stress and constraining M1-like macrophage polarization and proinflammatory cytokine release. This constitutes a negative feedback loop suppressing IFN-γ-independent macrophage autoactivation. |
High-content screening, siRNA/shRNA knockdown, co-immunoprecipitation, ubiquitination and acetylation assays, macrophage polarization assays |
Nature communications |
Medium |
37978190
|
| 2024 |
Septin2 is S-nitrosylated at Cys111 (SNO-Septin2) in aortic tissue. Unmodified Septin2 interacts with TIAM1; SNO-Septin2 reduces this interaction, releasing TIAM1 to activate the TIAM1-RAC1 axis and downstream NF-κB signaling, resulting in macrophage-mediated vascular inflammation and extracellular matrix degradation that drives aortic aneurysm and dissection. |
Biotin-switch assay + LC-MS/MS to identify S-nitrosylation site, co-immunoprecipitation to detect TIAM1 interaction, RNA-seq, pharmacological inhibition of RAC1 |
Circulation |
High |
38357802
|
| 2025 |
Septin-2 binds a neuron-specific domain of Ankyrin G, and this interaction is required for maintenance of the axon initial segment (AIS). Mutations in SEPT2 (found in humans with cognitive impairment) predicted to block Septin-2 homodimerization largely ablate Ankyrin G interaction; expression of mutant Septin-2 in neurons causes loss of Ankyrin G from the AIS, aberrant MAP2 localization in the distal axon, axonal shortening, and electrophysiological hypoexcitability. |
Co-immunoprecipitation of SEPT2 with Ankyrin G, expression of disease-associated mutants in neurons, immunofluorescence, electrophysiology |
Brain : a journal of neurology |
Medium |
41408595
|
| 2025 |
Septin2 regulates ARHGAP25 (a Rac GAP) function at lamellipodia: SEPTIN2 interacts with ARHGAP25 and co-localizes at lamellipodia. Overexpression of ARHGAP25 suppresses Rac-dependent lamellipodia formation and cell spreading, and this suppression is restored by Septin2 depletion. Conversely, Septin2 overexpression enhances ARHGAP25-mediated suppression in an ARHGAP25-dependent manner. |
Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, overexpression, lamellipodia and cell spreading assays |
FEBS letters |
Medium |
40205813
|
| 2025 |
Hypoxia suppresses Septin2 (SEPT2) transcription in spermatogonia by interfering with POLR2A binding to the Sept2 promoter. Reduced SEPT2 stabilizes the B56γ regulatory subunit of PP2A, enhancing AKT dephosphorylation and causing G1-S phase arrest that impairs spermatogonial proliferation. PP2A inhibitor (okadaic acid) rescues hypoxia-induced proliferative defects. |
DNA pulldown/mass spectrometry (identifying POLR2A), TMT-based quantitative proteomics, co-immunoprecipitation, dual-luciferase reporter, siRNA knockdown and overexpression, pharmacological PP2A inhibition/activation |
Human reproduction open |
Medium |
40487848
|
| 2018 |
CDK2 interacts with SEPT2 and stabilizes SEPT2 protein in hepatocellular carcinoma cells. Both CDK2 and SEPT2 show peak protein levels at G2/M phase. |
Co-immunoprecipitation, Western blot across cell cycle phases |
Cancer science |
Low |
30444001
|
| 2014 |
FHL2 is an interaction protein of Septin2 in mesangial cells. Septin2 knockdown induces apoptosis through FHL2-mediated signaling involving p-ERK1 and p-AKT pathways; this apoptosis is alleviated by FHL2 overexpression. |
Co-immunoprecipitation, siRNA knockdown, label-free quantitative proteomics, Western blot |
Proteomics |
Low |
25103794
|