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FLASH GENE
Symbol DNM1L contributors: mct - updated : 16-12-2018
HGNC name dynamin 1-like
HGNC id 2973
Corresponding disease
EMPF encephalopahty, lethal, due to defective mitochondrial peroxisomal fission
Location 12p11.21      Physical location : 32.832.136 - 32.898.584
Synonym name
  • dynamin-related protein 1
  • dynamin family member proline-rich carboxyl-terminal domain less
  • Dnm1p/Vps1p-like protein
  • dynamin-like protein IV
  • Synonym symbol(s) DRP1, DVLP, VPS1, DVLP, DYMPLE, HDYNIV, DRP-1, FLJ41912, DLP1, EMPF
    EC.number 3.6.5.5
    DNA
    TYPE functioning gene
    STRUCTURE 66.45 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    Binding site
    text structure 5' flanking sequence containing three GC boxes that concatenate Ap2- and Sp1-binding motifs, but that does not contain either the TATA or CAAT consensus sequence
    MAPPING cloned Y linked   status provisional
    Map pter - D12S345 - [cen - D12S331 - PFKM - VDR - D12S339 - D12S347 - D12S325 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 polyA site 4612 - 736 - 2004 14741701
    23 polyA site 4534 79.4 710 - 2004 14741701
    18 polyA site 4501 78.1 699 - 2004 14741701
    21 - 4655 - 749 - 2004 14741701
    20 - 4621 - 738 - 2004 14741701
    17 - 4211 - 533 - 2004 14741701
    19 - 4582 - 725 - 2004 14741701
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Endocrineneuroendocrinepituitary  highly
    Hearing/Equilibriumear   highly
    Lymphoid/Immunelymph node    
    Reproductivefemale systemuteruscervix highly
     male systemtestis  highly
    Respiratoryrespiratory tracttrachea  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal tripartite GTPase domain pleckstrin homology (PH)
  • lacking a C terminal proline rich region with a C terminal deletion
  • three consecutive C-terminal domains (MID-UC-CC) contain information necessary for DNM1L-specific function and removing any one of these domains results in a loss of DNM1L function
  • the coiled-coil (CC) domain alone targets specifically and exclusively to mitochondria, implicating its involvement in localizing DNM1L to this organelle
  • HOMOLOGY
    interspecies homolog to yeast dynamin-like highly
    homolog to yeast S.cerevisiae Vps1p GTPase
    Homologene
    FAMILY
  • dynamin family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,peroxisome
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    basic FUNCTION
  • involved in mitochondrial morphology in distrituting mitochondrial tubules throughout the cytoplasm and in vesicle trafficking
  • involved in the formation and trafficking of coated vesicles
  • involved in mitochondrial fusion/fission and modulating apoptotic cell death at the mitochondrial level
  • playing a role in the mitochondrial fission in mitotic cells when phosphorylated on Ser-585
  • key components in mitochondrial membrane fusion and division
  • its expression level constitutively regulate mitochondrial dynamics and cell survival in cortical neurons
  • function of the gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner
  • its posttranslational and dynamic modifications, contribute not only to the normal regulation of mitochondrial division, but also to neuropathologic processes
  • required for mitochondrial fission
  • stimulates BID-induced BAX oligomerization and cytochrome c release by promoting tethering and hemifusion of membranes
  • master regulator of mitochondrial fission (
  • mitochondrial fission requires the dynamin-like protein DNM1L that is recruited to the mitochondrial surface, possibly through the membrane-anchored protein FIS1 or MFF
  • may act as a regulatory factor for efficient execution of both fusion and fission of mitochondria
  • DNM1L, and FIS1 are two key players of mitochondrial fission
  • PIM1 activity prevents DNM1L compartmentalization to the mitochondria and preserves reticular mitochondrial morphology in response to simulated ischemia (sI)
  • may thus function as a node integrating signals from stress regulators, such as AMPK, to coordinate organelle shape and function
  • is required for TP53 translocation to the mitochondria under conditions of oxidative stress
  • GTPase that mediates mitochondrial and peroxisomal division in a process dependent on self-assembly and coupled to GTP hydrolysis
  • role not only in the formation of lipid tubes but also on the stabilization of tightly apposed membranes, which are intermediate states in the process of mitochondrial fission
  • DNM1L and parkin play synergistic roles in neuronal mitochondrial homeostasis and survival
  • astrocytic mitochondrial DNM1L is a key protein in mitochondrial dynamics and decreased DNM1L may interfere with neuron survival in Parkinson disease by disrupting Ca(2+)-coupled glutamate uptake
  • DNM1L and PARK2/Parkin work likely in a synergistic manner to maintain mitochondrial function and structural integrity in the heart and brain
  • in dividing mitochondria, membrane scission is accomplished by a dynamin-related GTPase, DNM1L, that oligomerizes at the site of fission and constricts in a GTP-dependent manner
  • DNM1l is a GTPase protein responsible for mitochondrial division, and SAMM50 is responsible for protein sorting and assembly
  • mitochondrial morphology is governed by the balance of mitochondrial fusion, mediated by mitofusins and optic atrophy 1 (OPA1), and fission, mediated by dynamin-related protein 1 (DNM1L)
  • role of DNM1L adaptor proteins MIEF2 and MIEF1 in mitochondrial fission
  • is a dynamin guanosine triphosphatase important for mitochondrial and peroxisomal division
  • mitochondrial inheritance, genome maintenance and metabolic adaptation depend on organelle fission by dynamin-related protein 1 (DNM1L) and its mitochondrial receptors
  • cytosolic protein responsible for mitochondrial fission and essential in the initiation and development of several human diseases, including cancer
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • glycogen synthetase kinase3, beta
  • interacyting with MARCH5 and MFN2
  • FIS1 plays important roles in peroxisome division and maintenance of peroxisome morphology in mammalian cells, possibly in a concerted manner with PEX11B and DNM1L
  • GFER-DNM1L link in preserving mitochondrial dynamics and function in pluripotent stem cells
  • DNM1L and possibly other proteins are thought to interact with the FIS1 TPR region during the fission process (
  • ER-specific BNIP1 plays an important role in mitochondrial dynamics by modulating the mitochondrial fission protein DNM1L in a BH3 domain-dependent fashion
  • LRRK2 interacted with DNM1L, interaction enhanced by PD-associated mutations that probably results in increased mitochondrial DNM1L level
  • PGAM5 dephosphorylates and activates mitochondrial fission protein DNM1L
  • ANXA6 inhibits DNM1L activity, and Ca2+-binding to ANXA6 relieves this inhibition to permit DNM1L-mediated mitochondrial fission
  • key target for SENP3-mediated deSUMOylation is the GTPase DNM1L, which plays a major role in regulating mitochondrial fission
  • DNM1L-binding to TP53 induced mitochondria-related necrosis
  • STX17 promotes mitochondrial fission by determining DNM1L localization and activity
  • regulation of DNM1L phosphorylation by PRKAA1 activation contributed to suppression of ER stress and thus presented a potential therapeutic strategy for PRKAA1 activation in the regulation of endothelium homeostasis
  • MARCH5 controls dynamin-related protein 1 (DNM1L)-dependent mitochondrial fission and cell sensitivity to stress-induced apoptosis
  • DNM1L-dependent mitochondrial fission through MIEF1 MIEF2 regulates cristae remodeling during intrinsic apoptosis
  • SAMM50 interacts with DNM1L
  • FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM (ER-mitochondrial contact site (MAM)) by working in concert with DNM1L and CANX under hypoxic conditions in mammalian cells
  • mitochondrial fission proteins DNM1L and MFF negatively regulate MARCH5 activity toward MIEF2 and MCL1
  • SENP3-mediated deSUMOylation of DNM1L facilitates interaction with MFF to promote cell death
  • DNM1L receptors include the paralogues mitochondrial dynamics proteins of 49 and 51 kDa (MIEF1 and MIEF2) and mitochondrial fission factor (MFF)
  • OTUD6A promotes proliferation of cancer cells via regulating DNM1L stability and mitochondrial fission
  • cell & other
    REGULATION
    Other calcineurin-dependent dephosphorylation, in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis
    ASSOCIATED DISORDERS
    corresponding disease(s) EMPF
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    during senescence exacerbates endothelial cells dysfunction by increasing mitochondrial reactive oxygen species and subsequently inhibiting autophagic flux
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mouse mutant, Python, which develops dilated cardiomyopathy, attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l)