Human Gene TOR1A (uc004byl.3) Description and Page Index
  Description: Homo sapiens torsin family 1, member A (torsin A) (TOR1A), mRNA.
RefSeq Summary (NM_000113): The protein encoded by this gene is a member of the AAA family of adenosine triphosphatases (ATPases), is related to the Clp protease/heat shock family and is expressed prominently in the substantia nigra pars compacta. Mutations in this gene result in the autosomal dominant disorder, torsion dystonia 1. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR3476690.312261.1, SRR1660807.193372.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000351698.5/ ENSP00000345719.4 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr9:132,575,221-132,586,441 Size: 11,221 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg19 chr9:132,576,251-132,586,364 Size: 10,114 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr9:132,575,221-132,586,441)mRNA (may differ from genome)Protein (332 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
H-INVHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: TOR1A_HUMAN
DESCRIPTION: RecName: Full=Torsin-1A; AltName: Full=Dystonia 1 protein; AltName: Full=Torsin family 1 member A; Flags: Precursor;
FUNCTION: May serve as a molecular chaperone assisting in the proper folding of secreted and/or membrane proteins. In the nucleus, displaces the nuclear membrane proteins SUN2, SYNE2 and nesprin-3/C14orf49, leaving nuclear pores and SUN1 unchanged.
SUBUNIT: May form homohexamers. Interacts with TOR1AIP1 and TOR1AIP2. Interacts with KLHL14, preferentially when ATP-free.
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. Nucleus membrane. Note=Mainly located in the lumen of the endoplasmic reticulum. The association with nuclear envelope is mediated by the interaction with TOR1AIP2. The Glu-303 del variant is lumenally-oriented in discrete large spheroid intracellular structures rather than in the endoplasmic reticulum.
TISSUE SPECIFICITY: Widely expressed. Highest levels in kidney and liver. Not detected in spleen. In the brain, high levels found in the dopaminergic neurons of the substantia nigra pars compacta, as well as in the neocortex, hippocampus and cerebellum. Also high expression in the spinal cord.
DISEASE: Defects in TOR1A are the cause of dystonia type 1 (DYT1) [MIM:128100]. DYT1 is a primary torsion dystonia, and the most common and severe form. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT1 is characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body, in the absence of other neurological symptoms. Typically, symptoms develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. 'Torsion' refers to the twisting nature of body movements observed in DYT1, often affecting the trunk. Distribution and severity of symptoms vary widely between affected individuals, ranging from mild focal dystonia to severe generalized dystonia, even within families.
SIMILARITY: Belongs to the clpA/clpB family. Torsin subfamily.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TOR1A";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TOR1A
CDC HuGE Published Literature: TOR1A
Positive Disease Associations: Coronary Artery Disease , dystonia , idiopathic torsion dystonia
Related Studies:
  1. Coronary Artery Disease
    , , . [PubMed 0]
  2. dystonia
    Kamm, C. et al. 2006, Strong genetic evidence for association of TOR1A/TOR1B with idiopathic dystonia, Neurology 2006 67(10) 1857-9. [PubMed 17130424]
  3. idiopathic torsion dystonia
    Ozelius LJ et al. 1992, Strong allelic association between the torsion dystonia gene (DYT1) andloci on chromosome 9q34 in Ashkenazi Jews., American journal of human genetics. 1992 Mar;50(3). [PubMed 1347197]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: TOR1A
Diseases sorted by gene-association score: dystonia-1, torsion* (1270), early-onset generalized dystonia* (518), dystonia* (471), early-onset generalized limb-onset dystonia* (350), focal dystonia (47), movement disease (30), segmental dystonia (25), focal hand dystonia (24), blepharospasm (23), cervical dystonia (18), autoimmune disease of gastrointestinal tract (14), dystonia-11, myoclonic (14), dystonia-12 (14), spasmodic dysphonia (13), wheat allergy (11), multifocal dystonia (10), dystonia 24 (8), child syndrome (8), spasmodic dystonia (7), oromandibular dystonia (7), adie pupil (6), acute endophthalmitis (6), hypersensitivity reaction disease (5), immunoglobulin alpha deficiency (5), cranio-facial dystonia (5), meige syndrome (5), hemidystonia (5), autoimmune disease of skin and connective tissue (5), thiamine metabolism dysfunction syndrome 2 (5), extratemporal epilepsy (5), dystonia, dopa-responsive, with or without hyperphenylalaninemia (5), functional diarrhea (4), purulent endophthalmitis (4), leukodystrophy, hypomyelinating, 2 (4), kleine-levin hibernation syndrome (4), dyschromatosis symmetrica hereditaria (3), immune system disease (1), diabetes mellitus, insulin-dependent (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 16.05 RPKM in Cells - Transformed fibroblasts
Total median expression: 417.07 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -34.4077-0.447 Picture PostScript Text
3' UTR -320.451030-0.311 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR010448 - Torsin
IPR017378 - Torsin_subgr

Pfam Domains:
PF06309 - Torsin

SCOP Domains:
52540 - P-loop containing nucleoside triphosphate hydrolases

ModBase Predicted Comparative 3D Structure on O14656
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologGenome BrowserGenome BrowserNo ortholog
Gene DetailsGene Details Gene DetailsGene Details 
Gene SorterGene Sorter Gene SorterGene Sorter 
 RGD FlyBaseWormBase 
 Protein Sequence Protein SequenceProtein Sequence 
 Alignment AlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008092 cytoskeletal protein binding
GO:0016787 hydrolase activity
GO:0016887 ATPase activity
GO:0019894 kinesin binding
GO:0051082 unfolded protein binding
GO:0051787 misfolded protein binding

Biological Process:
GO:0000338 protein deneddylation
GO:0006979 response to oxidative stress
GO:0006996 organelle organization
GO:0006998 nuclear envelope organization
GO:0007155 cell adhesion
GO:0031175 neuron projection development
GO:0034504 protein localization to nucleus
GO:0044319 wound healing, spreading of cells
GO:0045104 intermediate filament cytoskeleton organization
GO:0048489 synaptic vesicle transport
GO:0051085 chaperone mediated protein folding requiring cofactor
GO:0051260 protein homooligomerization
GO:0051584 regulation of dopamine uptake involved in synaptic transmission
GO:0061077 chaperone-mediated protein folding
GO:0071712 ER-associated misfolded protein catabolic process
GO:0071763 nuclear membrane organization
GO:0072321 chaperone-mediated protein transport
GO:1900244 positive regulation of synaptic vesicle endocytosis
GO:2000008 regulation of protein localization to cell surface

Cellular Component:
GO:0005634 nucleus
GO:0005635 nuclear envelope
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005788 endoplasmic reticulum lumen
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0008021 synaptic vesicle
GO:0016020 membrane
GO:0030054 cell junction
GO:0030133 transport vesicle
GO:0030141 secretory granule
GO:0030426 growth cone
GO:0030659 cytoplasmic vesicle membrane
GO:0031410 cytoplasmic vesicle
GO:0031965 nuclear membrane
GO:0042406 extrinsic component of endoplasmic reticulum membrane
GO:0042995 cell projection
GO:0043005 neuron projection
GO:0043231 intracellular membrane-bounded organelle
GO:0045202 synapse
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AK130769 - Homo sapiens cDNA FLJ27259 fis, clone TMS00113, highly similar to Torsin A precursor.
AK075343 - Homo sapiens cDNA PSEC0022 fis, clone NT2RP1000349, highly similar to Homo sapiens torsinA (DYT1) mRNA.
AK056062 - Homo sapiens cDNA FLJ31500 fis, clone NT2NE2005517, highly similar to Torsin A precursor.
AF007871 - Homo sapiens torsinA (DYT1) mRNA, complete cds.
JD082447 - Sequence 63471 from Patent EP1572962.
JD530664 - Sequence 511688 from Patent EP1572962.
JD484502 - Sequence 465526 from Patent EP1572962.
JD048653 - Sequence 29677 from Patent EP1572962.
BC000674 - Homo sapiens torsin family 1, member A (torsin A), mRNA (cDNA clone MGC:1558 IMAGE:3347611), complete cds.
JD116632 - Sequence 97656 from Patent EP1572962.
JD054707 - Sequence 35731 from Patent EP1572962.
JD193789 - Sequence 174813 from Patent EP1572962.
JD114042 - Sequence 95066 from Patent EP1572962.
JD516380 - Sequence 497404 from Patent EP1572962.
AK294677 - Homo sapiens cDNA FLJ56343 complete cds, highly similar to Torsin A precursor.
JD539286 - Sequence 520310 from Patent EP1572962.
JD141783 - Sequence 122807 from Patent EP1572962.
JD268461 - Sequence 249485 from Patent EP1572962.
AK314505 - Homo sapiens cDNA, FLJ95323, Homo sapiens dystonia 1, torsion (autosomal dominant; torsin A)(DYT1), mRNA.
KJ896739 - Synthetic construct Homo sapiens clone ccsbBroadEn_06133 TOR1A gene, encodes complete protein.
KR709744 - Synthetic construct Homo sapiens clone CCSBHm_00005671 TOR1A (TOR1A) mRNA, encodes complete protein.
KR709745 - Synthetic construct Homo sapiens clone CCSBHm_00005672 TOR1A (TOR1A) mRNA, encodes complete protein.
BT006931 - Homo sapiens dystonia 1, torsion (autosomal dominant; torsin A) mRNA, complete cds.
DQ892657 - Synthetic construct clone IMAGE:100005287; FLH188714.01X; RZPDo839F0473D torsin family 1, member A (torsin A) (TOR1A) gene, encodes complete protein.
DQ895897 - Synthetic construct Homo sapiens clone IMAGE:100010357; FLH188710.01L; RZPDo839F0463D torsin family 1, member A (torsin A) (TOR1A) gene, encodes complete protein.
AB590352 - Synthetic construct DNA, clone: pFN21AE1352, Homo sapiens TOR1A gene for torsin family 1, member A, without stop codon, in Flexi system.
JD023527 - Sequence 4551 from Patent EP1572962.
JD029305 - Sequence 10329 from Patent EP1572962.
JD031983 - Sequence 13007 from Patent EP1572962.
BC014484 - Homo sapiens torsin family 1, member A (torsin A), mRNA (cDNA clone MGC:23205 IMAGE:4869856), complete cds.
KJ901397 - Synthetic construct Homo sapiens clone ccsbBroadEn_10791 TOR1A gene, encodes complete protein.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O14656 (Reactome details) participates in the following event(s):

R-HSA-8863721 NEDD8-STON binds TOR1 hexamer and COP9 complex
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-199991 Membrane Trafficking
R-HSA-5653656 Vesicle-mediated transport

-  Other Names for This Gene
  Alternate Gene Symbols: B2RB58, DQ2, DYT1, NM_000113, NP_000104, O14656, Q53Y64, Q96CA0, TOR1A_HUMAN
UCSC ID: uc004byl.3
RefSeq Accession: NM_000113
Protein: O14656 (aka TOR1A_HUMAN or TO1A_HUMAN)
CCDS: CCDS6930.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TOR1A:
dystonia (DYT1 Early-Onset Isolated Dystonia)
dystonia-ov (Hereditary Dystonia Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000113.2
exon count: 5CDS single in 3' UTR: no RNA size: 2117
ORF size: 999CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2020.00frame shift in genome: no % Coverage: 99.48
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.