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FLASH GENE
Symbol DNM2 contributors: mct/shn - updated : 28-11-2018
HGNC name dynamin 2
HGNC id 2974
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
21 splicing 3684 98 870 - 1995 7590285
21 splicing 3684 - 870 - 1995 7590285
20 splicing 3672 - 866 - 1995 7590285
20 splicing 3672 - 866 - 1995 7590285
21 - 3681 - 869 - -
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   predominantly
Visualeyeretina    Mus musculus
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
cells
SystemCellPubmedSpeciesStageRna symbol
Visualcone photoreceptor Mus musculus
cell lineage
cell lines
fluid/secretion
at STAGE
cell cycle     cell cycle, checkpoint, G2M
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)
  • addition of NME1 or NME2 to DNM2 facilitates DNM2 oligomerization and increases GTPase activity, both required for vesicle scission
  • 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