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FLASH GENE
Symbol DNM2 contributors: mct/shn - updated : 28-11-2018
HGNC name dynamin 2
HGNC id 2974
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal tripartite GTPase domain
  • a PH (pleckstrin homology) domain, that binds phosphoinositides with a very low affinity and this interaction appears to be crucial for its function
  • a intermediary middle domain
  • a basic proline rich C terminus that contains multiple SRC homology 3 (SH3) domains and nine consensus motifs for p34 Cdc2 kinase
  • HOMOLOGY
    interspecies ortholog to Dnm2, Mus musculus
    ortholog to Dnm2, Rattus norvegicus
    ortholog to dnm2, danio rerio
    ortholog to DNM2, Pan troglodytes
    Homologene
    FAMILY
  • dynamin family
  • CATEGORY enzyme , regulatory , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • microtubule associated (centriolar)
  • localizes predominantly at the I-band and perinuclear regions, two regions of intense membrane trafficking in muscle
  • DNM2 is primarily confined to the inner segment compartment of photoreceptors
  • basic FUNCTION
  • large GTPase multidomain, potentially involved in the G2/mitosis transition and in vesicle trafficking
  • having a role in endocytosis at the plasma membrane, membrane trafficking from the trans-Gogi network, formation of actin-stress fibers, actin-membrane interface assembly and centrosome cohesion
  • involved in endocytosis (
  • can act as a signal transducing GTPase affecting transcriptional regulation (
  • regulates actin assembly and actin filament organization at membranes through an interaction with cortactin (
  • implicated in actin assembly in phagocytosis in Sertoli cells
  • involved in actin dynamics and the formation of dynamin 2-positive ruffles during phagocytosis
  • may play a role during acrosome formation and/or acrosomal exocytosis
  • with cortactin, functions as a dynamic actin filament remodeling complex that influences the global organization of the actomyosin cytoskeleton
  • important function in the downregulation of growth factor receptor tyrosine kinases such as the EGFR
  • involved in endocytosis and intracellular membrane trafficking
  • participates in internalization and degradation of the gap junction plaque but also in recycling of Cx43 to the plasma membrane through respectively Rab5/Rab7 and Rab11 pathways (
  • DNM1, DNM2, DNM3, decode action potential firing for synaptic vesicle recycling
  • potential role in retina outer segment protein transport
  • AMPH functions synergistically with full-length DNM2 to catalyze vesicle release
  • PQBP1 and DNM2 are components of a signaling pathway that orchestrates neuronal ciliary morphogenesis in the brain
  • acts within lamellipodia to organize actin filaments and regulate assembly and flow of lamellar actomyosin
  • cardiac membrane-remodelling GTPase, modulates ion channels membrane trafficking in the cardiomyocytes
  • DNM2-dependent endocytosis plays a major role in megakaryocyte (MK) membrane formation and thrombopoiesis
  • role for DNM2-dependent endocytosis in megakaryopoiesis, thrombopoiesis, and bone marrow homeostasis
  • essential role of DNM2 GTPase in preserving normal biphasic insulin secretion and blood glucose homeostasis
  • regulates insulin secretory capacity and dynamics through a mechanism depending on clathrin-mediated endocytosis (CME) and F-actin remodeling
  • acts potentially as a "break" to prevent excess or potentially toxic NO levels under high-salt conditions
  • dynamin family of proteins play important regulatory roles in membrane remodelling and endocytosis, especially within brain and neuronal tissues
  • DNM1 and DNM2 act as key mediators of sperm acrosome formation and function
  • GTPase essential for intracellular vesicle formation and trafficking, cytokinesis and receptor endocytosis
  • CELLULAR PROCESS cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS endocytosis transport , cellular trafficking transport
    PATHWAY
    metabolism
    signaling
    a component
  • forming a protein complex with FNBP1, SRGAP2 and WAS
  • syndapin-dynamin complexes, crucial and sufficient to promote vesicle formation from the trans-Golgi network
  • complex formation of FNBP1 with WAS, WIPF1, and dynamin-2 at the plasma membrane is critical for the formation of podosomes and phagocytic cups
  • SH3KBP1–DNM2 complex appears to function predominantly at later stages of EGFR trafficking, namely in the transport of receptors from RAB7-positive late endosomes
  • component of the neuromuscular junction post-synaptic compartment
  • DNM2, CLTC and lipid rafts mediate SLC12A1 endocytosis and maintain steady-state apical surface SLC12A1 in native renal thick ascending limb (THAL)
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
    protein
  • GTP binding protein with GTPase activity
  • syndapin II isoform interacting with the proline-rich domain (PRD) of dynamin II through its Src-homology 3 (SH3) domain
  • cortactin, profilin, syndapin, and murine Abp1 (
  • sorting nexin 9, SNX9 (
  • Rho family guanine nucleotide exchange factor Vav1 (
  • amphiphysin (
  • SH3KBP1
  • PQBP1 interacts with DNM2 and thereby inhibits its GTPase activity
  • DNM2 dependent endocytosis of FGFR1 is required for angiogenesis in response to FGF2 and the non-classical FGF ligand, FGF21
  • GJB2-DNM2 interaction involves the C-terminus of GJB2 and the GTPase effector domain of DNM2, which is of particular importance for the regulation of the endocytic pathway, and DNM2 regulates GJB2 endocytosis and ubiquitination
  • ARF6 functions as a downstream molecule of DNM2 in clathrin-mediated endocytosis (CME)
  • novel ARF6 activation mechanism by DNM2 through PSD3 and PSD4 in CME in a manner dependent upon the GTPase activity of DNM2
  • MIB1 promotes the interaction between DNM2 and SNX18 in an ubiquitin ligase activity-dependent manner
  • IKZF1 directly binds the DNM2 promoter and suppresses DNM2 expression
  • SNX18 regulates ATG9A trafficking from recycling endosomes by recruiting DNM2
  • cell & other
    REGULATION
    Other DNM2 activity may be temporally regulated by phosphorylation of DNM2 via the kinase CDK1 in spermatogonia, and dephosphorylation by phosphatase PPP3CA during meiotic and post-meiotic spermatogenesis
    ASSOCIATED DISORDERS
    corresponding disease(s) DICMT1 , CNM2 , LCCS5 , SPG69
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in late-onset Alzheimer disease, results in the accumulation of APP in lipid raft-rich plasma membranes
    tumoral     --over  
    is associated with IKAROS dysregulation and may be important in the development of B- Acute Lymphoblastic Leukemia
    constitutional     --low  
    coupled with severe ventricular arrhythmias
    Susceptibility to late-onset Alzheimer disease (LOAD)
    Variant & Polymorphism other polymorphisms increasing the risk of late-onset Alzheimer disease (LOAD)
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularrythm 
    with its multi-ion channel targeting properties, could be a promising target for novel antiarrhythmic therapies
    ANIMAL & CELL MODELS
  • in isolated muscle fibers from wild-type and HTZ mice, Dnm2 localized in regions of intense membrane trafficking (I-band and perinuclear region), emphasizing the pathophysiological hypothesis in which Dnm2-dependent trafficking would be altered