Affinage

STMN2

Stathmin-2 · UniProt Q93045

Length
179 aa
Mass
20.8 kDa
Annotated
2026-04-28
97 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STMN2 (SCG10) is a neuron-enriched, palmitoylated microtubule-regulatory protein that controls axonal outgrowth, growth cone dynamics, cortical neuron migration, and neuromuscular junction maintenance by modulating microtubule dynamic instability (PMID:9012855, PMID:16838365, PMID:21297631, PMID:35294901). It is anchored to trans-Golgi membranes and growth cone vesicles via palmitoylation of Cys-22/Cys-24 in its N-terminal domain, and its microtubule-destabilizing activity is negatively regulated by phosphorylation at Ser-50/62/73/97 by JNK1/3, PKA, MAPK, CDK, and PAK4; JNK-mediated phosphorylation additionally targets STMN2 for rapid ubiquitin-proteasome-dependent degradation, a mechanism that controls axonal degeneration after injury (PMID:9525956, PMID:11718727, PMID:23188802, PMID:41171096). Nuclear TDP-43 maintains STMN2 expression by sterically blocking a cryptic 3′ splice site in STMN2 pre-mRNA; loss of TDP-43 function—as occurs in ALS and FTD—causes cryptic exon inclusion and STMN2 depletion, leading to impaired axonal regeneration that can be rescued by antisense oligonucleotides targeting the cryptic splice site (PMID:30643292, PMID:36927019). Loss of Stmn2 in mice produces neuromuscular junction denervation, muscle atrophy, and motor deficits that are rescued by a human STMN2 transgene, establishing STMN2 as essential for motor neuron integrity (PMID:35294901).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1988 High

    Initial characterization established that STMN2/SCG10 is a membrane-associated, neuron-enriched protein concentrated in growth cones and axons, setting the stage for functional investigation of its role in neuronal morphogenesis.

    Evidence Immunocytochemistry and cell fractionation in cultured neurons and embryonic CNS

    PMID:3272176

    Open questions at the time
    • No function or molecular activity established at this stage
    • Mechanism of membrane association unknown
  2. 1992 High

    Discovery that a neural-restrictive silencer element (NRSE) in the SCG10 gene represses transcription in non-neuronal cells explained its neuron-specific expression pattern.

    Evidence Promoter deletion analysis, in vitro binding assays, point mutagenesis, and reporter assays in neuronal vs. non-neuronal cells

    PMID:1321646

    Open questions at the time
    • Identity of the silencing factor (later identified as REST/NRSF) not established in this study
    • Whether NRSE is the sole determinant of neuron restriction not resolved
  3. 1997 High

    The core molecular activity of STMN2 was established: it binds microtubules, inhibits their assembly, induces disassembly, and its overexpression enhances neurite outgrowth, linking microtubule destabilization to neuronal morphogenesis.

    Evidence In vitro microtubule assembly/disassembly assays and overexpression in neuronal cell lines

    PMID:9012855

    Open questions at the time
    • Whether STMN2 acts via tubulin sequestration, lattice binding, or both was unresolved
    • Regulation of this activity not yet addressed
  4. 1997 High

    Palmitoylation at cysteines in the N-terminal 34-residue domain was shown to be necessary and sufficient for Golgi membrane targeting, explaining how a soluble-domain protein achieves membrane association.

    Evidence Deletion/fusion constructs in PC12/COS-7 cells, immunofluorescence, [³H]palmitate labeling

    PMID:9030585

    Open questions at the time
    • The palmitoltransferase responsible was not identified
    • Whether palmitoylation is dynamically regulated was unknown
  5. 1998 High

    Mapping of phosphorylation sites (Ser-50/62/73/97 by PKA, MAPK, CDK) and demonstration that phosphorylation negatively regulates microtubule-destabilizing activity established the principal regulatory mechanism for STMN2 function.

    Evidence In vitro kinase assays, 2D gels, phospho-site mutagenesis, COS-7 microtubule disruption assay

    PMID:9525956

    Open questions at the time
    • Which kinases are physiologically dominant in neurons not yet resolved
    • Whether phosphorylation also affects protein stability was unknown
  6. 2000 High

    Immuno-EM localized STMN2 specifically to the trans-Golgi and growth cone vesicles, and mutagenesis confirmed palmitoylation at Cys-22/24 is required for this sorting, defining its subcellular niche of action.

    Evidence Immunoelectron microscopy, subcellular fractionation, mutant constructs in PC12 and primary neurons

    PMID:10947801

    Open questions at the time
    • Vesicular trafficking machinery delivering SCG10 to growth cones not identified
  7. 2002 High

    RGS proteins were found to physically interact with STMN2 and modulate its microtubule-destabilizing activity: RGSZ1 inhibits and RGS6 potentiates it, revealing unexpected regulation by G-protein signaling modulators.

    Evidence Yeast two-hybrid, direct binding assays, turbidimetric microtubule assays, co-IP, PC12 differentiation assays

    PMID:11882662 PMID:12140291

    Open questions at the time
    • Physiological contexts for RGS-SCG10 regulation in vivo not established
    • Whether RGS modulation involves G-protein coupling is unclear
  8. 2005 High

    SPR-based dissection showed that phosphorylation at Ser-97 fully abolishes microtubule-depolymerizing activity by reducing tubulin heterodimer binding, while Ser-50 phosphorylation only partially reduces activity, establishing site-specific hierarchical regulation.

    Evidence Surface plasmon resonance, in vitro microtubule depolymerization assays with phospho-site mutant proteins

    PMID:15825189

    Open questions at the time
    • Whether these sites are phosphorylated independently or sequentially in vivo was unknown
  9. 2006 High

    Multiple studies converged to show that JNK1 is the physiologically dominant kinase for STMN2 in cortical neurons, phosphorylating Ser-62/73 to control microtubule dynamics, axodendritic length, and tubulin turnover measured by FRAP; simultaneously, bidirectional manipulation (siRNA and protein transduction) in hippocampal neurons confirmed STMN2 is required for neurite outgrowth and growth cone microtubule dynamicity.

    Evidence JNK1 affinity purification from brain, Jnk1−/− cortex analysis, FRAP, siRNA knockdown and polyarginine protein transduction in primary neurons

    PMID:16618812 PMID:16838365

    Open questions at the time
    • Whether JNK1 regulates STMN2 turnover in addition to activity was not yet known
  10. 2007 High

    In vitro single-microtubule dynamics analysis revealed that STMN2 has polarity-dependent effects: it stabilizes plus ends (increased growth rate) while destabilizing minus ends (increased catastrophe), and also binds along microtubule lengths, distinguishing it from pure tubulin-sequestering stathmin family members.

    Evidence In vitro reconstitution with individual microtubule dynamics measurement

    PMID:17311410

    Open questions at the time
    • Structural basis for polarity-specific effects unresolved
    • Whether lateral binding contributes to activity in cells not demonstrated
  11. 2008 Medium

    STMN2 was found to interact with chromogranin A at the trans-Golgi and to be required for regulated secretion from chromaffin cells, broadening its function beyond microtubule regulation to secretory granule biogenesis.

    Evidence Phage display, co-IP, siRNA knockdown, CHGA secretion assay, granule fractionation

    PMID:18549247

    Open questions at the time
    • Mechanism by which STMN2 affects granule density/secretion not fully resolved
    • Not independently replicated
  12. 2011 High

    JNK1-mediated phosphorylation of STMN2 was shown to govern multipolar-stage exit and radial migration in developing cortex; a phosphomimetic STMN2 mutant rescued migration defects in Jnk1−/− embryos, establishing STMN2 as a critical JNK1 effector in cortical development.

    Evidence Jnk1−/− mouse, in utero electroporation of phospho-mutant STMN2, cortical migration assays

    PMID:21297631

    Open questions at the time
    • Whether other JNK substrates contribute to migration alongside STMN2 not excluded
    • Downstream mechanism linking phospho-STMN2 to migration machinery unclear
  13. 2012 High

    After axonal injury, STMN2 is rapidly degraded distal to the injury site via JNK-dependent phosphorylation targeting it for destruction; maintaining STMN2 levels post-injury preserves mitochondrial motility and delays Wallerian degeneration, establishing STMN2 as a sentinel of axonal integrity.

    Evidence Mouse DRG axotomy, JNK inhibitors, phospho-site mutants, STMN2 knockdown and overexpression with degeneration and mitochondrial motility readouts

    PMID:23188802

    Open questions at the time
    • E3 ubiquitin ligase mediating injury-induced degradation not identified
    • Whether proteasomal vs. calpain pathways contribute under injury conditions was unclear
  14. 2014 Medium

    CB1 cannabinoid receptor activation was shown to recruit JNK to phosphorylate and degrade STMN2, stabilizing axonal microtubules and inducing ectopic filopodia, linking exogenous cannabinoid signaling to STMN2 turnover.

    Evidence Proteomics of THC-sensitive proteins, mass spectrometry, CB1 activation assays, phosphorylation/degradation assays in vivo

    PMID:24469251

    Open questions at the time
    • Whether endocannabinoid signaling regulates STMN2 physiologically not established
    • Single lab finding
  15. 2019 High

    A pivotal discovery showed that TDP-43 depletion or cytoplasmic mislocalization causes STMN2 loss through aberrant splicing, and that STMN2 is required for axonal outgrowth and regeneration in human motor neurons, directly linking TDP-43 pathology in ALS/FTD to a specific functional deficit.

    Evidence TDP-43 knockdown in iPSC-derived motor neurons, patient motor neurons, postmortem spinal cord analysis, regeneration assays, post-translational stabilization rescue

    PMID:30643292

    Open questions at the time
    • Exact binding site of TDP-43 on STMN2 pre-mRNA not yet mapped
    • Whether STMN2 loss is sufficient for motor neuron death vs. dysfunction not resolved
  16. 2022 High

    Genetic loss of Stmn2 in mice was shown to cause neuromuscular junction denervation, muscle atrophy, and motor deficits—phenotypes rescued by a human STMN2 BAC transgene—establishing STMN2 as essential for motor neuron maintenance in vivo.

    Evidence Gene-edited Stmn2 loss-of-function mice, BAC transgene rescue, NMJ analysis, motor behavior assays

    PMID:35294901

    Open questions at the time
    • Whether STMN2 loss causes motor neuron death or only dysfunction/denervation not fully distinguished
    • Age-dependent progression of phenotype not characterized long-term
  17. 2023 High

    The molecular mechanism of TDP-43-dependent STMN2 regulation was elucidated: TDP-43 binds a GU-rich region to sterically block a cryptic 3′ splice site; ASOs or dCasRx targeting this region restore STMN2 expression and axonal regeneration even without TDP-43, providing a therapeutic strategy for ALS.

    Evidence GU-rich sequence analysis, dCasRx and ASO treatment in iPSC motor neurons, humanized mouse with CSF ASO injection

    PMID:36927019

    Open questions at the time
    • Long-term efficacy and safety of ASO approach in humans not established
    • Whether restoring STMN2 alone is sufficient to halt ALS progression unknown
  18. 2024 Medium

    Stress-induced nuclear TDP-43 condensation was shown to transiently inactivate TDP-43, causing rapid STMN2 protein depletion and splicing loss-of-function, suggesting that even reversible TDP-43 phase transitions compromise STMN2 expression.

    Evidence Confocal nanoscanning, co-IP in stressed cells, STMN2 splicing and protein analysis

    PMID:38941189

    Open questions at the time
    • Whether transient STMN2 loss during stress contributes to cumulative neurodegeneration not established
    • Single lab finding
  19. 2025 High

    The degradation pathway and domain logic of STMN2 turnover were clarified: the ubiquitin-proteasome system is the primary degradation route; the N-terminal membrane-targeting domain promotes fast turnover while the stathmin-like domain stabilizes the protein through tubulin binding, which also competes with trans-Golgi membrane association.

    Evidence Proteasome inhibitor assays in U2OS and iPSC neurons, proximity labeling, pull-down with soluble vs. membrane-bound STMN2, domain deletions

    PMID:41171096

    Open questions at the time
    • E3 ligase(s) targeting STMN2 for ubiquitination not identified
    • How tubulin-binding vs. membrane-targeting equilibrium is regulated in vivo unclear
  20. 2025 Medium

    SRSF7 was identified as a second RNA-processing regulator of STMN2 abundance; its depletion reduces STMN2 and impairs axonal regeneration, and C9ORF72 poly-PR dipeptide repeats perturb SRSF7 phosphorylation, linking a second ALS genetic mechanism to STMN2 loss.

    Evidence Global phospho-proteomics, SRSF7 siRNA in iPSC-derived neurons, STMN2 rescue, axonal regeneration assay

    PMID:40140908

    Open questions at the time
    • Whether SRSF7 acts on STMN2 splicing, stability, or both not resolved
    • Single lab, not independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the E3 ubiquitin ligase(s) mediating STMN2 proteasomal degradation, the structural basis for its polarity-dependent effects on microtubule dynamics, whether STMN2 restoration alone is sufficient to prevent motor neuron death in ALS, and the palmitoyl transferase responsible for its membrane targeting.
  • E3 ligase identity unknown
  • No structural model of STMN2-tubulin or STMN2-microtubule complex
  • Whether STMN2 restoration is disease-modifying in human ALS remains untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005794 Golgi apparatus 3 GO:0005856 cytoskeleton 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 2
Partners
ADKCAMICHGAMAPK10MAPK8RGS17RGS6TARDBP

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 SCG10/STMN2 binds to microtubules, inhibits their assembly, and can induce microtubule disassembly; overexpression enhances neurite outgrowth in a stably transfected neuronal cell line, identifying SCG10 as a regulator of neurite extension through microtubule instability. In vitro microtubule assembly/disassembly assay, overexpression in neuronal cell line Proceedings of the National Academy of Sciences of the United States of America High 9012855
1997 SCG10/STMN2 is targeted to the Golgi complex via its N-terminal 34-amino-acid domain; this domain is necessary and sufficient for membrane targeting and Golgi localization, and the two cysteine residues within this domain are palmitoylated. Deletion/fusion constructs in PC12 and COS-7 cells, immunofluorescence, [3H]palmitic acid biosynthetic labeling The Journal of biological chemistry High 9030585
1998 SCG10/STMN2 phosphorylation sites were mapped in vitro: Ser-50 and Ser-97 are targeted by PKA, Ser-62 and Ser-73 by MAPK, and Ser-73 by CDK. Non-phosphorylatable mutants have increased microtubule-destabilizing activity, whereas phosphomimetic (Ser→Asp) mutants have decreased activity, demonstrating that phosphorylation negatively regulates SCG10 microtubule-destabilizing activity. In vitro phosphorylation assays, 2D gel electrophoresis, phosphorylation-site mutagenesis, COS-7 overexpression with microtubule disruption assay The Journal of biological chemistry High 9525956
2000 SCG10/STMN2 is specifically localized to the trans-Golgi complex and growth cone vesicles; palmitoylation at Cys-22 and Cys-24 in the N-terminal domain is required for Golgi sorting and growth cone targeting, and fusion of the N-terminal domain to cytosolic proteins is sufficient for growth cone targeting in neurons. Immunoelectron microscopy, subcellular fractionation, mutant/fusion cDNA constructs in PC12 cells and primary neurons The European journal of neuroscience High 10947801
2001 JNK3/SAPKβ binds tightly and specifically to SCG10/STMN2 and phosphorylates it at Ser-62 and Ser-73, reducing its microtubule-destabilizing activity; endogenous SCG10 undergoes increased phosphorylation in sympathetic neurons upon JNK3 activation following NGF deprivation. In vitro kinase binding and phosphorylation assays, primary sympathetic neuron experiments FEBS letters High 11718727
2002 RGSZ1 directly interacts with SCG10/STMN2 and binding of RGSZ1 blocks SCG10's ability to induce microtubule disassembly; both proteins co-translocate to the Golgi in NGF-treated PC12 cells. Yeast two-hybrid, direct binding assays, turbidimetric and microscopy-based microtubule polymerization assays, GFP-tagged RGSZ1 in PC12 cells The Journal of biological chemistry High 11882662
2002 RGS6 interacts with SCG10/STMN2 via the GGL domain of RGS6 and the stathmin domain of SCG10; co-expression potentiates SCG10-mediated microtubule disruption and synergistically enhances NGF-induced PC12 differentiation. Yeast two-hybrid mapping, GST pull-down in COS-7 cells, co-immunoprecipitation, co-localization, microtubule disruption assay, PC12 differentiation assay The Journal of biological chemistry High 12140291
2006 JNK1 phosphorylates SCG10/STMN2 in vivo at Ser-62 and Ser-73, regulating its microtubule-depolymerizing activity; JNK phosphorylation of SCG10 determines axodendritic length in cerebrocortical cultures, and inhibition of cytoplasmic JNK or expression of SCG10-62A/73A inhibits tubulin fluorescence recovery after photobleaching. Affinity purification of JNK-interacting proteins from brain, in vivo phosphorylation assays, JNK1-/- cortex analysis, cerebrocortical culture loss-of-function, FRAP The Journal of cell biology High 16618812
2006 SCG10/STMN2 knockdown by siRNA suppresses neurite outgrowth in hippocampal neurons and converts growth cone microtubules to a more stable state; protein transduction of SCG10 stimulates neurite outgrowth and increases microtubule dynamicity in growth cones. siRNA knockdown, immunodepletion, polyarginine-tag protein transduction, immunofluorescence of growth cone microtubules in primary neurons Journal of neurobiology High 16838365
2007 SCG10/STMN2 differentially regulates microtubule plus and minus ends in vitro: it stabilizes plus ends by increasing growth rate and extent, while destabilizing minus ends by increasing shortening rate and catastrophe frequency; SCG10 also binds along microtubule lengths. In vitro dynamic instability analysis of individual microtubules, tubulin polymerization assays, microtubule binding assays Biochemistry High 17311410
2011 JNK1 phosphorylation of SCG10/STMN2 governs multipolar-stage exit and radial migration rate in developing cortex; expression of a phosphomimetic SCG10 mutant restored normal migration in Jnk1-/- mouse embryos. Jnk1-/- mouse analysis, in utero electroporation of phosphomimetic SCG10, cortical neuron migration assays Nature neuroscience High 21297631
2012 SCG10/STMN2 is an axonal JNK substrate that is rapidly degraded after axotomy in a JNK-dependent manner; JNK phosphorylation sites on SCG10 are required for its rapid degradation. In healthy axons, SCG10 undergoes fast axonal transport and JNK-dependent turnover; injury blocks delivery, causing selective loss distal to injury. SCG10 knockdown accelerates axon fragmentation, while maintaining SCG10 after injury promotes mitochondrial movement and delays degeneration. Mouse DRG axotomy model, JNK inhibitor treatment, phospho-site mutants, SCG10 knockdown and overexpression with axon degeneration/mitochondrial motility readouts Proceedings of the National Academy of Sciences of the United States of America High 23188802
2013 PAK4 phosphorylates SCG10/STMN2 on Ser-50, and this phosphorylation regulates microtubule dynamics to promote gastric cancer cell migration and invasion. Co-immunoprecipitation, in vitro kinase assay, PAK4 siRNA and pharmacological inhibition, xenograft mouse models, invasion assays Oncogene Medium 23893240
2013 SCG10/STMN2 directly interacts with the KFFEQ motif of the APP intracellular domain and promotes non-amyloidogenic APP processing by facilitating APP trafficking to the cell surface via the secretory pathway; this depends on SCG10's palmitoylation-mediated membrane anchoring. Co-immunoprecipitation, knockdown and overexpression of SCG10, measurement of sAPPα, CTFα, Aβ1-40, Aβ1-42; palmitoylation mutant analysis; APP accumulation in post-Golgi vesicles; in vivo amyloid plaque assay in APPswe/PS1dE9 mice Human molecular genetics Medium 23863461
2014 CB1 cannabinoid receptor activation recruits JNK to phosphorylate SCG10/STMN2, promoting its rapid degradation in axons and microtubule stabilization; THC triggers this pathway to alter axon morphology and enable ectopic filopodia formation. Proteomic analysis of THC-sensitive proteins, mass spectrometry, in vivo mouse experiments, CB1 receptor activation assays, phosphorylation and degradation assays The EMBO journal Medium 24469251
2019 TDP-43 depletion or mislocalization causes loss of STMN2 expression due to altered splicing; STMN2 is necessary for normal axonal outgrowth and regeneration in human motor neurons; post-translational stabilization of STMN2 rescues neurite outgrowth and axon regeneration deficits induced by TDP-43 depletion. TDP-43 knockdown in iPSC-derived motor neurons, patient-specific motor neurons, postmortem spinal cord analysis, axonal outgrowth and regeneration assays, post-translational stabilization rescue experiments Nature neuroscience High 30643292
2022 Loss of Stmn2 in mice causes neuromuscular junction denervation and fragmentation, muscle atrophy, impaired motor behavior, and imbalance in neuronal microtubule dynamics in the spinal cord; human STMN2 BAC transgene rescues motor phenotypes in Stmn2 mutant mice. Gene-edited Stmn2 loss-of-function mice, BAC transgene rescue, neuromuscular junction analysis, motor behavior assays, microtubule dynamics analysis Neuron High 35294901
2023 TDP-43 binding to a GU-rich region sterically blocks recognition of the cryptic 3' splice site in STMN2 pre-mRNA; dCasRx or antisense oligonucleotides (ASOs) targeting this region suppress cryptic splicing and restore axonal regeneration and stathmin-2-dependent lysosome trafficking in TDP-43-deficient human motor neurons; ASO injection into CSF of humanized mice restored STMN2 expression independently of TDP-43. Molecular mechanism of TDP-43 binding by GU-rich sequence analysis, dCasRx targeting, ASO treatment in iPSC motor neurons, gene-edited humanized mouse model with CSF ASO injection Science (New York, N.Y.) High 36927019
2008 SCG10/STMN2 interacts with chromogranin A (CHGA) at the trans-Golgi; knockdown of SCG10 by siRNA nearly abolishes regulated secretion of CHGA and CHGB from chromaffin cells; a dominant-negative palmitoylation-deficient SCG10 mutant blocks regulated secretion, and SCG10 siRNA alters chromaffin granule buoyant density. Phage display, co-immunoprecipitation, siRNA knockdown, CHGA-EAP secretion assay, granule fractionation Biochemistry Medium 18549247
2010 KBP interacts with SCG10/STMN2 (confirmed by yeast two-hybrid and validated binding), and epistasis in zebrafish demonstrates an in vivo interaction between KBP and SCG10 in neuronal differentiation relevant to Goldberg-Shprintzen syndrome. Yeast two-hybrid screen, binding assay validation, zebrafish epistasis experiments, PC12 KBP depletion neurite outgrowth assay Human molecular genetics Medium 20621975
2011 Calmyrin1 (CaMy1) directly interacts with SCG10/STMN2 in a Ca2+-dependent manner requiring the C-terminal domain of CaMy1 and the N-terminal domain of SCG10; CaMy1 interferes with SCG10 microtubule-inhibitory activity and overexpression of CaMy1 inhibits SCG10-mediated neurite outgrowth in NGF-stimulated PC12 cells. Yeast two-hybrid, pull-down, co-immunoprecipitation, proximity ligation assay, microtubule polymerization assay, PC12 neurite outgrowth assay with domain mutants Biochimica et biophysica acta Medium 21215777
2015 Spy1 binds to SCG10/STMN2, mediates its JNK-dependent phosphorylation and degradation after sciatic nerve injury; Spy1 inhibition attenuates SCG10 phosphorylation and delays injury-induced axonal degeneration. Co-immunoprecipitation, Spy1 overexpression/inhibition, sciatic nerve injury model, axonal degeneration assays The Journal of biological chemistry Medium 25869138
2005 Phosphorylation of SCG10/STMN2 at Ser-97 (but not Ser-50 alone) abolishes microtubule-depolymerizing activity by reducing tubulin heterodimer binding affinity; Ser-50 phosphorylation maintains partial MT-depolymerizing activity and modulates the T2S complex formation differently from Ser-97. Surface plasmon resonance, in vitro microtubule depolymerization assays, phosphorylation-site mutant proteins Journal of neuroscience research High 15825189
2006 MAP1B and SCG10/STMN2 have antagonistic effects on microtubule stability; in double-transfected cells SCG10 is more potent at destabilizing microtubules than MAP1B can rescue; in addition to binding tubulin dimers, SCG10 also binds to intact microtubules in growth cones of DRG neurons. Recombinant protein microtubule assembly assays, COS-7 co-transfection, immunofluorescence of DRG growth cones Cell motility and the cytoskeleton Medium 17009328
2006 Taxol treatment and tau overexpression both induce degradation of SCG10/STMN2 protein via a calpain-dependent mechanism (blocked by MDL-28170 but not caspase inhibitors) in PC12 and neuroblastoma cells. Taxol treatment, tau overexpression in neuroblastoma cells, calpain and caspase inhibitor treatment, Western blot Experimental neurology Medium 16822511
1992 A neural-restrictive silencer element (NRSE) in the SCG10 gene selectively represses expression in non-neuronal cells; a specific protein (NRSBF) binds the NRSE in non-neuronal but not neuronal nuclear extracts; a point mutation abolishing NRSBF binding in vitro also eliminates silencing in vivo. Deletion analysis, in vitro transcription factor binding assays, point mutation, reporter assays in neuronal and non-neuronal cells Neuron High 1321646
1988 SCG10/STMN2 protein is tightly membrane-associated (not an integral membrane protein), localizes to perinuclear cytoplasm, axons, and growth cones of cultured neurons, and is highly expressed in embryonic CNS. Immunocytochemistry with affinity-purified antibody, cell fractionation Neuron High 3272176
2006 STMN2 is a direct transcriptional target of β-catenin/TCF signaling; the TCF binding site at -1713 of the STMN2 promoter is critical for β-catenin/TCF-dependent expression; STMN2 is required for anchorage-independent growth of β-catenin/TCF-activated hepatoma cells. Promoter deletion mapping, chromatin immunoprecipitation, β-catenin transient transfection, LiCl treatment, siRNA knockdown, colony formation assay Biochemical and biophysical research communications Medium 16712787
2021 STMN2 promotes EMT in hepatocellular carcinoma by destabilizing microtubules to disrupt the MT-Smad complex, facilitating Smad2/3 phosphorylation and nuclear translocation, thereby enhancing TGF-β signaling even in the absence of TGF-β stimulation. STMN2 overexpression/knockdown in HCC cells, co-immunoprecipitation of MT-Smad complex, Smad2/3 phosphorylation and nuclear translocation assays, in vitro invasion assays, xenograft in vivo models Cancer letters Medium 33705863
2025 STMN2 is primarily degraded by the ubiquitin-proteasome system; its N-terminal membrane-targeting domain promotes fast turnover while its tubulin-binding stathmin-like domain promotes stabilization; tubulin binds preferentially to soluble over membrane-bound STMN2, and tubulin binding reduces STMN2 targeting to trans-Golgi network membranes. Proteasome inhibitor assays in U2OS cells and iPSC-derived neurons, proximity labeling, imaging, pull-down assays with soluble vs. membrane-bound STMN2, domain deletion analysis The Journal of cell biology High 41171096
2025 SRSF7 depletion decreases STMN2 abundance and impairs axonal regeneration; this phenotype can be rescued by exogenous STMN2; poly-PR (C9ORF72 dipeptide repeat) perturbs SRSF7 phosphorylation, linking C9ORF72 gain-of-function to STMN2 loss-of-function. Global phospho-proteomics, SRSF7 siRNA in iPSC-derived neurons, STMN2 rescue assay, axonal regeneration assay Acta neuropathologica communications Medium 40140908
2024 Stress-induced nuclear TDP-43 condensation transiently inactivates TDP-43, leading to loss of interaction with protein binding partners and STMN2 splicing loss of function; STMN2 protein is rapidly depleted early during stress, and ALS-linked mutations alter this condensation. Confocal nanoscanning assay, co-immunoprecipitation in stressed cells, STMN2 splicing analysis, Western blot for STMN2 protein Cell reports Medium 38941189
2024 SCG10/STMN2 interacts with adenosine kinase (ADK); ADK suppresses injured neurite regrowth while SCG10 enhances it; ADK acts upstream of SCG10 in a regulatory axis governing neuronal recovery after spinal cord injury. Mass spectrometry, co-immunoprecipitation, GST pull-down, excitotoxicity neural injury model, overexpression/inhibition experiments, in vivo SCI mouse motor function assay Neuroscience Medium 38423163

Source papers

Stage 0 corpus · 97 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair. Nature neuroscience 478 30643292
1992 A common silencer element in the SCG10 and type II Na+ channel genes binds a factor present in nonneuronal cells but not in neuronal cells. Neuron 363 1321646
1988 The NGF-inducible SCG10 mRNA encodes a novel membrane-bound protein present in growth cones and abundant in developing neurons. Neuron 224 3272176
1990 A cell type-preferred silencer element that controls the neural-specific expression of the SCG10 gene. Neuron 187 2322462
2014 Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. The EMBO journal 180 24469251
1997 Regulation of microtubule dynamics by the neuronal growth-associated protein SCG10. Proceedings of the National Academy of Sciences of the United States of America 178 9012855
2023 Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies. Science (New York, N.Y.) 159 36927019
2006 JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length. The Journal of cell biology 154 16618812
2013 Dynamic regulation of SCG10 in regenerating axons after injury. Experimental neurology 153 24246279
2012 SCG10 is a JNK target in the axonal degeneration pathway. Proceedings of the National Academy of Sciences of the United States of America 153 23188802
2004 Role of the microtubule destabilizing proteins SCG10 and stathmin in neuronal growth. Journal of neurobiology 139 14598370
1988 The induction of a neural-specific gene, SCG10, by nerve growth factor in PC12 cells is transcriptional, protein synthesis dependent, and glucocorticoid inhibitable. Developmental biology 134 2837417
2002 Transcriptional upregulation of SCG10 and CAP-23 is correlated with regeneration of the axons of peripheral and central neurons in vivo. Molecular and cellular neurosciences 98 12213442
2002 SCG10-related neuronal growth-associated proteins in neural development, plasticity, degeneration, and aging. Journal of neuroscience research 98 12391585
2011 Phosphorylation of SCG10/stathmin-2 determines multipolar stage exit and neuronal migration rate. Nature neuroscience 97 21297631
1997 Targeting of SCG10 to the area of the Golgi complex is mediated by its NH2-terminal region. The Journal of biological chemistry 91 9030585
1989 Homology between the cDNAs encoding phosphoprotein p19 and SCG10 reveals a novel mammalian gene family preferentially expressed in developing brain. DNA (Mary Ann Liebert, Inc.) 87 2776625
1998 Identification of in vitro phosphorylation sites in the growth cone protein SCG10. Effect Of phosphorylation site mutants on microtubule-destabilizing activity. The Journal of biological chemistry 85 9525956
2006 SCG10, a microtubule destabilizing factor, stimulates the neurite outgrowth by modulating microtubule dynamics in rat hippocampal primary cultured neurons. Journal of neurobiology 80 16838365
1998 SCLIP: a novel SCG10-like protein of the stathmin family expressed in the nervous system. Journal of neurochemistry 77 9603203
2000 Localization and targeting of SCG10 to the trans-Golgi apparatus and growth cone vesicles. The European journal of neuroscience 72 10947801
1994 Differential localization of SCG10 and p19/stathmin messenger RNAs in adult rat brain indicates distinct roles for these growth-associated proteins. Neuroscience 71 7936211
2022 Loss of mouse Stmn2 function causes motor neuropathy. Neuron 59 35294901
1997 Differential distribution of stathmin and SCG10 in developing neurons in culture. Journal of neuroscience research 59 9452014
1995 SCG10 expresses growth-associated manner in developing rat brain, but shows a different pattern to p19/stathmin or GAP-43. Brain research. Developmental brain research 57 8719331
2013 PAK4 kinase-mediated SCG10 phosphorylation involved in gastric cancer metastasis. Oncogene 55 23893240
2004 L1/Laminin modulation of growth cone response to EphB triggers growth pauses and regulates the microtubule destabilizing protein SCG10. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 14985440
2002 RGS6 interacts with SCG10 and promotes neuronal differentiation. Role of the G gamma subunit-like (GGL) domain of RGS6. The Journal of biological chemistry 55 12140291
1993 Molecular diversity of the SCG10/stathmin gene family in the mouse. Genomics 55 8288240
2005 Clusterin interacts with SCLIP (SCG10-like protein) and promotes neurite outgrowth of PC12 cells. Experimental cell research 51 16038898
1990 Effect of nerve growth factor and fibroblast growth factor on SCG10 and c-fos expression and neurite outgrowth in protein kinase C-depleted PC12 cells. The Journal of biological chemistry 50 2105318
2006 The "SCG10-LIke Protein" SCLIP is a novel regulator of axonal branching in hippocampal neurons, unlike SCG10. Molecular and cellular neurosciences 49 17145186
2001 Expression of SCG10 and stathmin proteins in the rat olfactory system during development and axonal regeneration. The Journal of comparative neurology 48 11283962
2007 Stathmin family protein SCG10 differentially regulates the plus and minus end dynamics of microtubules at steady state in vitro: implications for its role in neurite outgrowth. Biochemistry 39 17311410
1999 Differential regulation of the growth-associated proteins, GAP-43 and SCG-10, in response to unilateral cortical ablation in adult rats. Neuroscience 39 10338302
2010 KBP interacts with SCG10, linking Goldberg-Shprintzen syndrome to microtubule dynamics and neuronal differentiation. Human molecular genetics 37 20621975
1995 SCG10, a neuron-specific growth-associated protein in Alzheimer's disease. Neurobiology of aging 36 8622778
2024 RNA aptamer reveals nuclear TDP-43 pathology is an early aggregation event that coincides with STMN-2 cryptic splicing and precedes clinical manifestation in ALS. Acta neuropathologica 35 38443601
2000 The SCG10-related gene family in the developing rat retina: persistent expression of SCLIP and stathmin in mature ganglion cell layer. Brain research 33 10760501
2021 Novel Variant Linked to Amyotrophic Lateral Sclerosis Risk and Clinical Phenotype. Frontiers in aging neuroscience 32 33841129
2002 The interaction of RGSZ1 with SCG10 attenuates the ability of SCG10 to promote microtubule disassembly. The Journal of biological chemistry 32 11882662
1999 Quantitative non-radioactive in situ hybridization study of GAP-43 and SCG10 mRNAs in the cerebral cortex of adult and infant macaque monkeys. Cerebral cortex (New York, N.Y. : 1991) 32 10426411
2000 Expression of GAP-43 and SCG10 mRNAs in lateral geniculate nucleus of normal and monocularly deprived macaque monkeys. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 10934252
1997 Purification, characterization, and in vitro phosphorylation of the neuron-specific membrane-associated protein SCG10. Protein expression and purification 31 9126608
2001 c-Jun N-terminal kinase-3 (JNK3)/stress-activated protein kinase-beta (SAPKbeta) binds and phosphorylates the neuronal microtubule regulator SCG10. FEBS letters 29 11718727
2024 Stress-induced TDP-43 nuclear condensation causes splicing loss of function and STMN2 depletion. Cell reports 27 38941189
2006 The control of microtubule stability in vitro and in transfected cells by MAP1B and SCG10. Cell motility and the cytoskeleton 27 17009328
2005 Improved sciatic nerve regeneration by local thyroid hormone treatment in adult rat is accompanied by increased expression of SCG10. Experimental neurology 24 16289052
2013 SCG10 promotes non-amyloidogenic processing of amyloid precursor protein by facilitating its trafficking to the cell surface. Human molecular genetics 23 23863461
2001 Expression of stathmin and SCG10 proteins in the olfactory neurogenesis during development and after lesion in the adulthood. Brain research bulletin 23 11226711
1996 Differential induction and intracellular localization of SCG10 messenger RNA is associated with neuronal differentiation. Neuroscience 23 8735217
2006 STMN2 is a novel target of beta-catenin/TCF-mediated transcription in human hepatoma cells. Biochemical and biophysical research communications 22 16712787
1994 SCG10 mRNA localization in the hippocampus: comparison with other mRNAs encoding neuronal growth-associated proteins (nGAPs). Brain research 21 7812771
1992 Differential mRNA expression of the phosphoprotein p19/SCG10 gene family in mouse preimplantation embryos, uterus, and placenta. Reproduction, fertility, and development 21 1438949
2008 The trans-Golgi proteins SCLIP and SCG10 interact with chromogranin A to regulate neuroendocrine secretion. Biochemistry 20 18549247
2021 STMN2 mediates nuclear translocation of Smad2/3 and enhances TGFβ signaling by destabilizing microtubules to promote epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer letters 16 33705863
2010 SCG10 expression on activation of hepatic stellate cells promotes cell motility through interference with microtubules. The American journal of pathology 14 20802173
2005 Site-specific phosphorylation of SCG10 in neuronal plasticity: role of Ser73 phosphorylation by N-methyl D-aspartic acid receptor activation in rat hippocampus. Neuroscience letters 14 16368189
2001 Perforant path lesion induces up-regulation of stathmin messenger RNA, but not SCG10 messenger RNA, in the adult rat hippocampus. Neuroscience 14 11226690
1997 Expression, purification, and characterization of a highly soluble N-terminal-truncated form of the neuron-specific membrane-associated phosphoprotein SCG10. Protein expression and purification 14 9056495
2004 Modulation of the stathmin-like microtubule destabilizing activity of RB3, a neuron-specific member of the SCG10 family, by its N-terminal domain. The Journal of biological chemistry 13 15039434
2004 The b1 isoform of protocadherin-gamma (Pcdhgamma) interacts with the microtubule-destabilizing protein SCG10. FEBS letters 13 15581637
2022 STMN2 overexpression promotes cell proliferation and EMT in pancreatic cancer mediated by WNT/β-catenin signaling. Cancer gene therapy 12 36460804
2003 Identification of upregulated SCG10 mRNA expression associated with late-phase long-term potentiation in the rat hippocampal Schaffer-CA1 pathway in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 12 12878703
1998 A novel SCG10-related gene uniquely expressed in the nervous system. Gene 12 9714847
2005 Role of Ser50 phosphorylation in SCG10 regulation of microtubule depolymerization. Journal of neuroscience research 11 15825189
2015 Proximity of SCG10 and prion protein in membrane rafts. Journal of neurochemistry 10 26663033
2009 Characterization of spatial and temporal expression pattern of SCG10 during zebrafish development. Gene expression patterns : GEP 10 19272335
2006 A newly modified SCG10 promoter and Cre/loxP-mediated gene amplification system achieve highly specific neuronal expression in animal brains. Gene therapy 10 16625241
2004 Olf/EBF proteins are expressed in neuroblastoma cells: potential regulators of the Chromogranin A and SCG10 promoters. International journal of cancer 10 15054865
2009 SCG10-like protein (SCLIP) is a STAT3-interacting protein involved in maintaining epithelial morphology in MCF-7 breast cancer cells. The Biochemical journal 9 19824884
2015 Spy1 Protein Mediates Phosphorylation and Degradation of SCG10 Protein in Axonal Degeneration. The Journal of biological chemistry 8 25869138
2008 BRI3 associates with SCG10 and attenuates NGF-induced neurite outgrowth in PC12 cells. BMB reports 8 18452648
2004 Analysis of the regulation of microtubule dynamics by interaction of RGSZ1 (RGS20) with the neuronal stathmin, SCG10. Methods in enzymology 8 15488170
2006 Taxol and tau overexpression induced calpain-dependent degradation of the microtubule-destabilizing protein SCG10. Experimental neurology 7 16822511
2004 Time-course study of SCG10 mRNA levels associated with LTP induction and maintenance in the rat Schaffer-CA1 pathway in vivo. Brain research. Molecular brain research 7 14741408
2011 Calmyrin1 binds to SCG10 protein (stathmin2) to modulate neurite outgrowth. Biochimica et biophysica acta 6 21215777
2000 Preliminary crystallographic study of a complex formed between the alpha/beta-tubulin heterodimer and the neuronal growth-associated protein SCG10. Journal of structural biology 6 11042086
2025 C9ORF72 poly-PR disrupts expression of ALS/FTD-implicated STMN2 through SRSF7. Acta neuropathologica communications 5 40140908
2024 Targeting STMN2 for neuroprotection and neuromuscular recovery in Spinal Muscular Atrophy: evidence from in vitro and in vivo SMA models. Cellular and molecular life sciences : CMLS 5 39725771
2021 Investigation into the role of Stmn2 in vascular smooth muscle phenotype transformation during vascular injury via RNA sequencing and experimental validation. Environmental science and pollution research international 5 34389950
2010 Mutations in SCG10 are not involved in Hirschsprung disease. PloS one 5 21187955
2002 Expression of super cervical ganglion-10 (SCG-10) mRNA in the monkey cerebral cortex during postnatal development. Neuroscience letters 5 11959419
2022 Questioning the Association of the STMN2 Dinucleotide Repeat With Amyotrophic Lateral Sclerosis. Neurology. Genetics 4 35923349
2024 HOXC10 promotes hypertrophic scar fibroblast fibrosis through the regulation of STMN2 and the TGF-β/Smad signaling pathway. Histochemistry and cell biology 3 39152325
2014 RARB and STMN2 polymorphisms are not associated with sporadic Creutzfeldt-Jakob disease (CJD) in the Korean population. Molecular biology reports 3 24414001
2011 Position-dependent effect of a neural-restrictive silencer-like element present in the promoter downstream of the SCG10-like protein gene. Journal of biochemistry 3 21705344
2025 Tubulin Regulates the Stability and Localization of STMN2 by Binding Preferentially to Its Soluble Form. bioRxiv : the preprint server for biology 1 40060442
2025 Machine learning-based proteomics profiling of ALS identifies downregulation of RPS29 that maintains protein homeostasis and STMN2 level. Communications biology 1 40775435
2025 Tubulin regulates stability and localization of STMN2 by binding preferentially to its soluble form. The Journal of cell biology 1 41171096
2024 The Interaction between ADK and SCG10 Regulate the Repair of Nerve Damage. Neuroscience 1 38423163
2021 Genome Sequence of Linnemannia hyalina Strain SCG-10, a Cold-Adapted and Nitrate-Reducing Fungus Isolated from Cornfield Soil in Minnesota, USA. Microbiology resource announcements 1 34528820
2026 Regulation of neuronal invasion of small cell lung cancer by STMN2/β-alanine-controlled metabolic reprogramming. Cell reports 0 41904954
2025 Vitreous STMN2 levels reflect TDP-43-associated neurodegeneration in postmortem eyes and brains. Journal of Alzheimer's disease reports 0 41180957
2025 U7 small nuclear RNA splice-switching therapeutics for STMN2 and UNC13A in Amyotrophic Lateral Sclerosis. bioRxiv : the preprint server for biology 0 41394711
2025 Dual-targeting snRNA gene therapy rescues STMN2 and UNC13A splicing in TDP-43 proteinopathies. bioRxiv : the preprint server for biology 0 41573891
2022 Analysis of STMN2 CA repeats in italian ALS patients shows no association. Amyotrophic lateral sclerosis & frontotemporal degeneration 0 35876065