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FLASH GENE
Symbol STMN2 contributors: mct/shn - updated : 06-12-2022
HGNC name stathmin-like 2
HGNC id 10577
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal domain
  • a coiled-coil region
  • a C terminus with the stathmin domain
    • conjugated PhosphoP , Other
    HOMOLOGY
    interspecies ortholog to stmn2b, Danio rerio
    ortholog to STMN2, Pan troglodytes
    ortholog to Stmn2, Rattus Norvegicus
    ortholog to Stmn2, Mus musculus
    Homologene
    FAMILY
  • stathmin family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,nuclear envelope
    text
  • in the perinuclear cytoplasm, axons and growth cones
  • localized in both Golgi and cytosolic compartments
  • colocalized to the Golgi apparatus of chromaffin cells and shared localization with CHGA as it transited the Golgi
    • basic FUNCTION
  • playing a role in neuronal differentiation and in modulating membrane interaction with the cytoskeleton during neurite outgrowth
  • able to depolymerize interphase microtubules when overexpressed
  • acts as microtubule destabilizers
  • implicated in axogenesis in several of the same neuronal types
  • promoted growth cone expansion
  • neuron specific that like stathmin can bind to soluble tubulin and depolymerize microtubules
  • having a dual activity at opposite microtubule ends which may be important for its role in regulating growth cone microtubule dynamics
  • implicated in the microtubule regulatory network as a crucial element of cytoskeletal regulation
  • could play a role in the regulation of the adipocyte/osteoblast balance
  • STMN2 and STMN3, interact with CHGA, share partial colocalization in the Golgi apparatus, and may be necessary for typical transmitter storage and release from chromaffin cells
  • promotes axon growth, and its increased activity in the presence of RND1 leads to rapid neurite elongation characteristic for the growth of axons
  • enriched in growth cones and playing a role in neurite outgrowth
  • microtubule destabilizing protein
  • membrane-associated neuronal protein that is largely expressed during development and whose expression correlates with neurite outgrowth
  • neuronal growth-associated protein and also known to be a microtubules destabilizing protein
  • regulates the cytoskeleton by destabilizing the microtubules, through altering dendrites as well as cell shape, size and polarity
  • palmitoylation of stathmins 2 likely occurs at the Golgi and is crucial for its specific subcellular localization and trafficking (
  • SCG10 is likely an axonal-maintenance factor whose loss is permissive for execution of the injury-induced axonal degeneration program
  • microtubule (MT) destabilizer, that maintains MT homeostasis and has a critical role in neuronal development
  • novel function in promoting invasive potential of gastric cancer cells
  • having a novel role as an alpha cell secretory granule protein that modulates glucagon secretion via trafficking through the endosomal-lysosomal system
    • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    text
  • neurogenesis
  • cell migration
    • PATHWAY
    metabolism
    signaling signal transduction
    intracellular signaling cascade
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • REST -dependent gene
  • c-Jun N-terminal kinase-3 (JNK3)/stress-activated protein kinase-beta, SAPKbeta (
  • regulator of G-protein signaling Z1, RGSZ1 (
  • regulator of G-protein signaling 6, RGS6 (
  • transient receptor potential cation channel, subfamily C, member 5, TRPC5 (
  • brain protein I3, BRI3 (
  • RND1
  • CHGA and STMN3 (
  • RND1 interacts with the microtubule regulator STMN2
  • IKBKAP
  • CIB1 via STMN2 couples Ca(2+) signals with the dynamics of microtubules during neuronal outgrowth in the developing brain
  • DHHC3, DHHC7, DHHC15, and DHHC17 (
  • is a physiological substrate of PAK4, which is phosphorylated on serine 50 (Ser50) in a PAK4-dependent manner
  • STMN2 is an interacting partner of WDR47
    • cell & other
    REGULATION
    Phosphorylated by MAP kinase, cAMP-dependent protein kinase, cGMP-dependent protein kinase, p34cdc2 kinase, DNA-dependent protein kinase, Ca2+/calmodulin kinase II, and casein kinase II (
    c-Jun N-terminal kinase-3 (JNK3)/stress-activated protein kinase-beta, SAPKbeta (
    Other regulated by the NRSE/NRSF system
    sumoylated
    modulated by nerve growth factor, dexamethasone or RhoA kinase inhibitor Y-27632, the expression increased at both mRNA and protein levels during osteogenesis of human mesenchymal stem cells derived from adipose tissue (hMADS cells) and bone marrow (hBMS cells)
    regulated by the neuron-restrictive silencer factor REST
    phosphorylated by MAPK8, which was shown earlier to be activated by IKBKAP
    palmitoylated by DHHC3 and DHHC7 (
    TARDBP regulates expression of the neuronal growth-associated factor STMN2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    is found in neurons trans-differentiated from patient fibroblasts expressing an ALS-causing TARDBP mutation, in motor cortex and spinal motor neurons from patients with sporadic ALS
    Susceptibility
  • to Alzheimer disease
  • to sporadic ALS (sALS)
    • Variant & Polymorphism other
  • non-coding CA repeat in Stathmin-2 which is associated with sporadic ALS (sALS) disease risk and has disease modifying effects
  • truncated STMN2 is a marker for TARDBP dysfunction in frontotemporal dementia (FTD)
    • Candidate gene
    Marker
  • utility of STMN2 as an efficient and selective marker of sensory axon regeneration
    • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivestomach
    blocking PAK4-mediated STMN2 phosphorylation might be a potential therapeutic strategy for metastasis of gastric cancer
    neurologyneurodegenerative 
    restoring STMN2 expression warrants examination as a therapeutic strategy for amyotrophic lateral sclerosis (ALS)
    ANIMAL & CELL MODELS
  • Both mosaic founders and homozygous loss-of-function Stmn2 mice exhibited neuromuscular junction denervation and fragmentation, resulting in muscle atrophy and impaired motor behavior, accompanied by an imbalance in neuronal microtubule dynamics in the spinal cord
  • STMN2 knockout heterozygous mice, which better model the partial loss of STMN2 protein found in patients with ALS, display a slowly progressive, motor-selective neuropathy with functional deficits and neuromuscular junction (NMJ) denervation