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FLASH GENE
Symbol DCTN1 contributors: mct - updated : 03-06-2015
HGNC name dynactin 1 (p150, glued homolog, Drosophila)
HGNC id 2711
DNA
TYPE functioning gene
SPECIAL FEATURE
text encoded by the same locus than SLC4A5
STRUCTURE 30.93 kb     32 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map see LGMD2B
regionally located in the PARK3 region
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
32 - 4518 141.7 1278 - 2013 23985322
  • also called p150 GLued
  • isoform 1A
  • SLK (LOSK) phosphorylates only minor isoform 1A
    • 27 - 4181 135 1144 brain only 2009 19279216
    lacking the consensus microtubule binding motif
    28 - 4433 138.6 1253 - 2013 23985322
    isoform 1B lacking 20 amino acids in the basic microtubule-binding domain
    26 - 4166 126.6 1139 - 2009 19279216
    31 - 4497 - 1271 - 2013 23985322
    28 - 4386 - 1236 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Nervousbrain   highly
     nerve    
    Reproductivemale systemtestis   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal cytoskeleton-associated protein–glycine-rich (CAP-Gly) domain having a critical role in the initiation and persistence of dynein-dependent movement of the mitotic spindle and nucleus, but is otherwise dispensable for dynein-based movement
  • the 'GKNDG' binding motif
  • three binding domains : microtubules (CAP-Gly domain), dynein and ARP1
    • mono polymer heteromer , polymer
    HOMOLOGY
    interspecies homolog to Drosophila Glued
    Homologene
    FAMILY
    CATEGORY
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome,kinetochore
    intracellular,nuclear envelope
    text
  • punctate cytoplasmic structures and centrosomes during interphase, mitotic spindle through cleavage furrow and midbodies of dividing cells
  • microtubule plus-ends
  • localizes in the nuclear envelope during prophase
  • phosphorylation is required only for centrosomal localization of DCTN1
    • basic FUNCTION
  • critical functions for NUMA1, DCTN1 and GPSM2 in mammalian development
  • NUMA1, DCTN1 and GPSM2 are involved in spindle orientation regulation
  • major component of the dynactin complex which facilitates retrograde axonal transport of cargos by the dynein complex
  • NDE1 and DCTN1 are likely associated with distinct dynein pools having specific functions
  • likely DCTN1 function and microtubule stabilization pathway could act cooperatively for protection of axons against degeneration
  • could be activating enzymes involved in the pro-survival signaling cascades that might involve MAP kinases to propagate protective signals against excitotoxicity-induced axon degeneration
  • major function of dynactin is minus end-directed transport along microtubules in a complex with dynein motor
  • dynactin phosphorylation is involved in Golgi reorientation in polarized cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • REST, DCTN1, HTT, HAP1, and RILP form a complex involved in the translocation of REST into the nucleus and HAP1 controls REST cellular localization in neurons
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction SNX6-DCTN1 for recruitment of the motor complex to the membrane-associated retromer
  • PARD6A interacts with the dynactin subunit DCTN1 and is a critical regulator of centrosomal protein recruitment
  • interacting with HTT (regulates spindle orientation by ensuring the proper localization of the DCTN1 subunit of dynactin, dynein and NUMA1)
  • TRAPPC9 mediates the interaction between DCTN1 and COPII vesicles at the target membrane
  • BICD2, DCTN1, and PAFAH1B1 cooperate in regulating dynein recruitment to cellular structures
  • AURKA is required for central spindle assembly in anaphase through phosphorylation of Ser 19 of DCTN1
    • cell & other
    REGULATION
    Phosphorylated by SLK, and SLK targets it to the centrosome, where it maintains microtubule radial organization
    Other regulated by ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which governs phosphorylation-dependent ubiquitination and subsequent proteolysis
    phosphorylation by PLK1 that might be one major pathway of nuclear envelope breakdown regulation
    ASSOCIATED DISORDERS
    corresponding disease(s) LMND , PERS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    linked to a slowly progressive form of lower motor neuron disease that resembles ALS (Moore 2009)
    constitutional     --over  
    with microtubule stabilization, functions cooperatively to protect axons from excitotoxicity-induced degeneration (pMID: 22728878)
    constitutional     --over  
    in sporadic amyotrophic lateral sclerosis (SALS) and dependent of age
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Heterozygous G59S-mutant mice are viable, and adults exhibit cellular abnormalities in lower motor neurons that are reminiscent of changes seen with human diseases, including ALS (Moore 2009)