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FLASH GENE
Symbol DCTN1 contributors: mct - updated : 03-06-2013
HGNC name dynactin 1 (p150, glued homolog, Drosophila)
HGNC id 2711
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)
    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)