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FLASH GENE
Symbol TOR1A contributors: npt/mct/pgu - updated : 19-04-2010
HGNC name torsin family 1, member A (torsin A)
HGNC id 3098
Corresponding disease
DYT1 dystonia 1, idiopathic torsion
Location 9q34.11      Physical location : 132.575.221 - 132.586.441
Synonym name
  • torsin 1A
  • dystonia 1 protein
  • Synonym symbol(s) DQ2, DYT2
    DNA
    TYPE functioning gene
    STRUCTURE 11.22 kb     5 Exon(s)
    regulatory sequence Promoter
    text structure
  • proximal minimal promoter within -191 bp with respect to the ATG codon with multiple transcription start sites, and presence of a highly conserved direct repeat of two Ets binding cores within -78 bp to -69 bp, which are transcriptional activators
  • MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2117 - 332 - 2009 19535332
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Nervousbraindiencephalonhypothalamus  
     brainforebraincerebral cortexfrontal 
     brainlimbic systemhippocampusdentate gyrus 
     brainmidbrain   
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Muscularstriatumskeletal  
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    NervousPurkinje cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal endoplasmic reticulum (ER)3 signal sequence
  • a 20-AA hydrophobic region followed by a conserved AAA+ (ATPases associated with a variety of cellular activities) domain (Giles 2009)
  • glycosylation and potential phosphorylation sites
  • hydrophobic potential membrane-spanning domain
  • 20-amino-acid-long hydrophobic segment remaining at the N-terminus after signal-peptide cleavage, responsible for the membrane anchoring
  • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to murine Tor1a
    intraspecies homolog to TOR1B, heat shock proteins and Clp proteases
    Homologene
    FAMILY
  • AAA ATPase superfamily of chaperone-like proteins
  • clpA/clpB family
  • torsin subfamily
  • AAA+ ATPase superfamily
  • CATEGORY chaperone/stress , enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nuclear envelope,lumen
    text
  • mostly in endoplasmic reticulum, lesser in nuclear envelope, primarily associated with the ER and nuclear envelope (NE) compartments in cells
  • found throughout the cytoplasm, neurite processes, and growth cones
  • located within the lumen of the nuclear envelope (NE) and endoplasmic reticulum (ER)
  • basic FUNCTION
  • potentially involved in synaptic functioning
  • having either a housekeeping function or a synaptic function
  • capable of self-associating into an oligomeric complex
  • may be involved in connecting the nuclear envelope to the cytoplasmic cytoskeleton
  • can regulate the cellular trafficking of the dopamine transporter, as well as other polytopic membrane-bound proteins, including G protein-coupled receptors, transporters, and ion channels
  • may contribute to maintain the appropriate site-directed polarization and control neurite outgrowth
  • acting as an ER chaperone protein in a dynamic complex of proteins that links the NE/ER/Golgi, cytoskeleton, and translational machinery
  • playing a role together with snapin (SNAPAP) in regulated exocytosis
  • role in dynamic interactions between the KASH domains of nesprins and their protein partners in the lumen of the NE (nuclear enveloppe), with TOR1A influencing the localization of nesprins and associated cytoskeletal elements and affecting their role in nuclear and cell movement
  • has a regulatory role in vesicle recycling
  • may function as a molecular chaperone
  • play a role in several cellular processes, including dopaminergic neurotransmission, nuclear envelope organization and dynamics, and protein trafficking
  • CELLULAR PROCESS protein, post translation, folding
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP binding
  • protein
  • interacting with LAP1 and LULL1
  • association between TOR1A and nesprin-3, which spans the outer nuclear membrane (ONM) of the nuclear envelope and links it to vimentin via plectin in fibroblasts
  • interacting with KLHL14 (disruption of the KLHL14- torsinA interaction by mutation could contribute to the pathophysiology of DYT1 dystonia)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DYT1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    GAG mutation, in early-onset recurrent major depression, independently of motor manifestations of dystonia
    Susceptibility to sporadic idiopathic dystonia
    Variant & Polymorphism other
  • haplotype associated with sporadic idiopathic dystonia
  • 216H allele having highly protective effect in patients with the GAG deletion (increased in carriers without dystonia and decreased in carriers with dystonia)
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologydystonia 
    specific small molecules that enhance TOR1A activity represent a promising new approach toward therapeutic development for torsion-dystonia, and potentially for other diseases involving the processing of mutant proteins
    ANIMAL & CELL MODELS
  • ectopic overexpression of both human and C. elegans torsin proteins results in a dramatic reduction of polyglutamine-dependent protein aggregation suggesting a role for torsins in managing protein folding
  • It also suggest that breakdown in a neuroprotective mechanism that is, in part, mediated by torsins may be responsible for the neuronal dysfunction associated with dystonia