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Protein

Torsin-1A

Gene

TOR1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protein with chaperone functions important for the control of protein folding, processing, stability and localization as well as for the reduction of misfolded protein aggregates. Involved in the regulation of synaptic vesicle recycling, controls STON2 protein stability in collaboration with the COP9 signalosome complex (CSN). In the nucleus, may link the cytoskeleton with the nuclear envelope, this mechanism seems to be crucial for the control of nuclear polarity, cell movement and, specifically in neurons, nuclear envelope integrity. Participates in the cellular trafficking and may regulate the subcellular location of multipass membrane proteins such as the dopamine transporter SLC6A3, leading to the modulation of dopamine neurotransmission. In the endoplasmic reticulum, plays a role in the quality control of protein folding by increasing clearance of misfolded proteins such as SGCE variants or holding them in an intermediate state for proper refolding. May have a redundant function with TOR1B in non-neural tissues.8 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi102 – 109ATP8

GO - Molecular functioni

  • ATPase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • cytoskeletal protein binding Source: UniProtKB
  • kinesin binding Source: UniProtKB
  • unfolded protein binding Source: ProtInc

GO - Biological processi

  • cell adhesion Source: UniProtKB
  • chaperone-mediated protein folding Source: UniProtKB
  • chaperone mediated protein folding requiring cofactor Source: InterPro
  • chaperone-mediated protein transport Source: UniProtKB
  • ER-associated misfolded protein catabolic process Source: UniProtKB
  • intermediate filament cytoskeleton organization Source: UniProtKB
  • neuron projection development Source: UniProtKB
  • nuclear envelope organization Source: UniProtKB
  • nuclear membrane organization Source: UniProtKB
  • organelle organization Source: UniProtKB
  • positive regulation of synaptic vesicle endocytosis Source: UniProtKB
  • protein deneddylation Source: UniProtKB
  • protein homooligomerization Source: MGI
  • protein localization to nucleus Source: UniProtKB
  • regulation of dopamine uptake involved in synaptic transmission Source: UniProtKB
  • regulation of protein localization to cell surface Source: UniProtKB
  • response to oxidative stress Source: Ensembl
  • synaptic vesicle transport Source: UniProtKB
  • wound healing, spreading of cells Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Hydrolase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136827-MONOMER.
ReactomeiR-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.

Names & Taxonomyi

Protein namesi
Recommended name:
Torsin-1A
Alternative name(s):
Dystonia 1 protein
Torsin ATPase-1A (EC:3.6.4.-)
Torsin family 1 member A
Gene namesi
Name:TOR1A
Synonyms:DQ2, DYT1, TA, TORA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:3098. TOR1A.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cytoplasmic vesicle membrane Source: UniProtKB
  • cytoskeleton Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: CACAO
  • endoplasmic reticulum lumen Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extrinsic component of endoplasmic reticulum membrane Source: UniProtKB
  • growth cone Source: UniProtKB
  • membrane Source: UniProtKB
  • nuclear envelope Source: UniProtKB
  • nuclear membrane Source: UniProtKB-SubCell
  • secretory granule Source: UniProtKB
  • synaptic vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Endoplasmic reticulum, Membrane, Nucleus, Synapse

Pathology & Biotechi

Involvement in diseasei

Dystonia 1, torsion, autosomal dominant (DYT1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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. Dystonia type 1 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.
See also OMIM:128100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070932205F → I in DYT1; produces intracellular misfolded protein aggregates. 1 PublicationCorresponds to variant rs267607134dbSNPEnsembl.1
Natural variantiVAR_070933288R → Q in DYT1; produces an enlarged perinuclear space. 1 PublicationCorresponds to variant rs727502811dbSNPEnsembl.1
Natural variantiVAR_010789303Missing in DYT1; dominant negative; loss of interaction with TOR1AIP1 and TOR1AIP2 with loss of ATPase activity induction; enriched in the nuclear envelope; impairs secretory pathway; produces intracellular misfolded protein aggregates; produces an enlarged perinuclear space. 12 PublicationsCorresponds to variant rs80358233dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi18V → F: Inhibits sequence signal cleavage. 1 Publication1
Mutagenesisi20A → F: Inhibits sequence signal cleavage. 1 Publication1
Mutagenesisi33V → N: N-glycosylated. 1 Publication1
Mutagenesisi108K → A: Loss of ATP-binding. No effect on interaction with KLHL14. Increases interaction with TOR1AIP1 and TOR1AIP2. Abolishes interaction with SLC6A3. 3 Publications1
Mutagenesisi143N → Q: Reduces N-glycosylation. 1 Publication1
Mutagenesisi158N → Q: Reduces N-glycosylation. 1 Publication1
Mutagenesisi171E → Q: Loss of ATP hydrolysis. Loss of interaction with KLHL14. Localizes in the nuclear envelope. 4 Publications1

Keywords - Diseasei

Disease mutation, Dystonia

Organism-specific databases

DisGeNETi1861.
MalaCardsiTOR1A.
MIMi128100. phenotype.
OpenTargetsiENSG00000136827.
Orphaneti256. Early-onset generalized limb-onset dystonia.
36899. Myoclonus-dystonia syndrome.
PharmGKBiPA27556.

Polymorphism and mutation databases

BioMutaiTOR1A.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 201 PublicationAdd BLAST20
ChainiPRO_000000550621 – 332Torsin-1AAdd BLAST312

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi143N-linked (GlcNAc...) (high mannose)1 Publication1
Glycosylationi158N-linked (GlcNAc...) (high mannose)1 Publication1

Post-translational modificationi

N-glycosylated.3 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiO14656.
MaxQBiO14656.
PaxDbiO14656.
PeptideAtlasiO14656.
PRIDEiO14656.

PTM databases

iPTMnetiO14656.
PhosphoSitePlusiO14656.

Expressioni

Tissue specificityi

Widely expressed. Highest levels in kidney and liver. 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 highly expressed in the spinal cord.3 Publications

Gene expression databases

BgeeiENSG00000136827.
CleanExiHS_TOR1A.
GenevisibleiO14656. HS.

Organism-specific databases

HPAiCAB012473.

Interactioni

Subunit structurei

Homohexamer. Interacts with TOR1B; the interaction may be specific of neural tissues. Interacts (ATP-bound) with TOR1AIP1 and TOR1AIP2; the interactions induce ATPase activity. Interacts with KLHL14; preferentially when ATP-free. Interacts with KLC1 (via TPR repeats); the interaction associates TOR1A with the kinesin oligomeric complex. Interacts with COPS4; the interaction associates TOR1A with the CSN complex. Interacts with SNAPIN; the interaction is direct and associates SNAPIN with the CSN complex. Interacts with STON2. Interacts (ATP-bound) with SYNE3 (via KASH domain); the interaction is required for SYNE3 nuclear envelope localization. Interacts with VIM; the interaction associates TOR1A with the cytoskeleton. Interacts with PLEC. Interacts (ATP-bound) with SLC6A3; regulates SLC6A3 transport to the plasma membrane.11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KRTAP10-7P604093EBI-524257,EBI-10172290

GO - Molecular functioni

  • cytoskeletal protein binding Source: UniProtKB
  • kinesin binding Source: UniProtKB
  • unfolded protein binding Source: ProtInc

Protein-protein interaction databases

BioGridi108193. 36 interactors.
DIPiDIP-34411N.
IntActiO14656. 11 interactors.
MINTiMINT-7002075.
STRINGi9606.ENSP00000345719.

Structurei

Secondary structure

1332
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi58 – 68Combined sources11
Helixi73 – 87Combined sources15
Beta strandi96 – 102Combined sources7
Helixi108 – 119Combined sources12
Helixi123 – 125Combined sources3
Beta strandi129 – 133Combined sources5
Helixi134 – 137Combined sources4
Helixi141 – 143Combined sources3
Helixi144 – 161Combined sources18
Beta strandi166 – 170Combined sources5
Helixi172 – 174Combined sources3
Helixi177 – 187Combined sources11
Beta strandi202 – 207Combined sources6
Helixi211 – 223Combined sources13
Helixi228 – 230Combined sources3
Helixi233 – 239Combined sources7
Turni240 – 245Combined sources6
Helixi247 – 252Combined sources6
Beta strandi256 – 262Combined sources7
Beta strandi264 – 269Combined sources6
Helixi274 – 287Combined sources14
Helixi294 – 303Combined sources10
Beta strandi306 – 308Combined sources3
Turni309 – 311Combined sources3
Turni316 – 322Combined sources7
Helixi323 – 328Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5J1SX-ray1.40A51-332[»]
5J1TX-ray1.40A51-332[»]
ProteinModelPortaliO14656.
SMRiO14656.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni91 – 251Interaction with SNAPINAdd BLAST161
Regioni251 – 332Interaction with KLC11 PublicationAdd BLAST82
Regioni312 – 332Interaction with SYNE31 PublicationAdd BLAST21

Sequence similaritiesi

Belongs to the ClpA/ClpB family. Torsin subfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2170. Eukaryota.
ENOG410XR06. LUCA.
GeneTreeiENSGT00390000001920.
HOGENOMiHOG000115770.
HOVERGENiHBG054188.
InParanoidiO14656.
OMAiKTTMIES.
OrthoDBiEOG091G0B5F.
PhylomeDBiO14656.
TreeFamiTF314941.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR027417. P-loop_NTPase.
IPR010448. Torsin.
IPR030549. Torsin-1A.
IPR017378. Torsin_1/2.
[Graphical view]
PANTHERiPTHR10760. PTHR10760. 1 hit.
PTHR10760:SF15. PTHR10760:SF15. 1 hit.
PfamiPF06309. Torsin. 1 hit.
[Graphical view]
PIRSFiPIRSF038079. Torsin_2A. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O14656-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKLGRAVLGL LLLAPSVVQA VEPISLGLAL AGVLTGYIYP RLYCLFAECC
60 70 80 90 100
GQKRSLSREA LQKDLDDNLF GQHLAKKIIL NAVFGFINNP KPKKPLTLSL
110 120 130 140 150
HGWTGTGKNF VSKIIAENIY EGGLNSDYVH LFVATLHFPH ASNITLYKDQ
160 170 180 190 200
LQLWIRGNVS ACARSIFIFD EMDKMHAGLI DAIKPFLDYY DLVDGVSYQK
210 220 230 240 250
AMFIFLSNAG AERITDVALD FWRSGKQRED IKLKDIEHAL SVSVFNNKNS
260 270 280 290 300
GFWHSSLIDR NLIDYFVPFL PLEYKHLKMC IRVEMQSRGY EIDEDIVSRV
310 320 330
AEEMTFFPKE ERVFSDKGCK TVFTKLDYYY DD
Length:332
Mass (Da):37,809
Last modified:January 1, 1998 - v1
Checksum:iB69B28D0B4112080
GO
Isoform 2 (identifier: O14656-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     149-332: DQLQLWIRGN...FTKLDYYYDD → ARMEVWNPFL...SQFPLERCRS

Note: No experimental confirmation available.
Show »
Length:197
Mass (Da):22,135
Checksum:iBD34184941B1B11C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti259D → H in AAP35577 (Ref. 3) Curated1
Sequence conflicti259D → H in AAH00674 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070932205F → I in DYT1; produces intracellular misfolded protein aggregates. 1 PublicationCorresponds to variant rs267607134dbSNPEnsembl.1
Natural variantiVAR_020449216D → H.Corresponds to variant rs1801968dbSNPEnsembl.1
Natural variantiVAR_010788264D → H.1 Publication1
Natural variantiVAR_070933288R → Q in DYT1; produces an enlarged perinuclear space. 1 PublicationCorresponds to variant rs727502811dbSNPEnsembl.1
Natural variantiVAR_010789303Missing in DYT1; dominant negative; loss of interaction with TOR1AIP1 and TOR1AIP2 with loss of ATPase activity induction; enriched in the nuclear envelope; impairs secretory pathway; produces intracellular misfolded protein aggregates; produces an enlarged perinuclear space. 12 PublicationsCorresponds to variant rs80358233dbSNPEnsembl.1
Natural variantiVAR_070934323 – 328Missing Found in a patient with early-onset atypical dystonia and myoclonic features. 1 PublicationCorresponds to variant rs80358235dbSNPEnsembl.6

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_026605149 – 332DQLQL…YYYDD → ARMEVWNPFLDVIGFGVSLL WDEIWEFYVEMSEPGKRFMS QFPLERCRS in isoform 2. 1 PublicationAdd BLAST184

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF007871 mRNA. Translation: AAC51732.1.
AK314505 mRNA. Translation: BAG37105.1.
BT006931 mRNA. Translation: AAP35577.1.
AL158207 Genomic DNA. Translation: CAC88168.1.
BC000674 mRNA. Translation: AAH00674.1.
BC014484 mRNA. Translation: AAH14484.1.
CCDSiCCDS6930.1. [O14656-1]
RefSeqiNP_000104.1. NM_000113.2. [O14656-1]
UniGeneiHs.534312.

Genome annotation databases

EnsembliENST00000351698; ENSP00000345719; ENSG00000136827. [O14656-1]
GeneIDi1861.
KEGGihsa:1861.
UCSCiuc004byl.4. human. [O14656-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF007871 mRNA. Translation: AAC51732.1.
AK314505 mRNA. Translation: BAG37105.1.
BT006931 mRNA. Translation: AAP35577.1.
AL158207 Genomic DNA. Translation: CAC88168.1.
BC000674 mRNA. Translation: AAH00674.1.
BC014484 mRNA. Translation: AAH14484.1.
CCDSiCCDS6930.1. [O14656-1]
RefSeqiNP_000104.1. NM_000113.2. [O14656-1]
UniGeneiHs.534312.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5J1SX-ray1.40A51-332[»]
5J1TX-ray1.40A51-332[»]
ProteinModelPortaliO14656.
SMRiO14656.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108193. 36 interactors.
DIPiDIP-34411N.
IntActiO14656. 11 interactors.
MINTiMINT-7002075.
STRINGi9606.ENSP00000345719.

PTM databases

iPTMnetiO14656.
PhosphoSitePlusiO14656.

Polymorphism and mutation databases

BioMutaiTOR1A.

Proteomic databases

EPDiO14656.
MaxQBiO14656.
PaxDbiO14656.
PeptideAtlasiO14656.
PRIDEiO14656.

Protocols and materials databases

DNASUi1861.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000351698; ENSP00000345719; ENSG00000136827. [O14656-1]
GeneIDi1861.
KEGGihsa:1861.
UCSCiuc004byl.4. human. [O14656-1]

Organism-specific databases

CTDi1861.
DisGeNETi1861.
GeneCardsiTOR1A.
GeneReviewsiTOR1A.
HGNCiHGNC:3098. TOR1A.
HPAiCAB012473.
MalaCardsiTOR1A.
MIMi128100. phenotype.
605204. gene.
neXtProtiNX_O14656.
OpenTargetsiENSG00000136827.
Orphaneti256. Early-onset generalized limb-onset dystonia.
36899. Myoclonus-dystonia syndrome.
PharmGKBiPA27556.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2170. Eukaryota.
ENOG410XR06. LUCA.
GeneTreeiENSGT00390000001920.
HOGENOMiHOG000115770.
HOVERGENiHBG054188.
InParanoidiO14656.
OMAiKTTMIES.
OrthoDBiEOG091G0B5F.
PhylomeDBiO14656.
TreeFamiTF314941.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136827-MONOMER.
ReactomeiR-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.

Miscellaneous databases

ChiTaRSiTOR1A. human.
GeneWikiiTorsin_A.
GenomeRNAii1861.
PROiO14656.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136827.
CleanExiHS_TOR1A.
GenevisibleiO14656. HS.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR027417. P-loop_NTPase.
IPR010448. Torsin.
IPR030549. Torsin-1A.
IPR017378. Torsin_1/2.
[Graphical view]
PANTHERiPTHR10760. PTHR10760. 1 hit.
PTHR10760:SF15. PTHR10760:SF15. 1 hit.
PfamiPF06309. Torsin. 1 hit.
[Graphical view]
PIRSFiPIRSF038079. Torsin_2A. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiTOR1A_HUMAN
AccessioniPrimary (citable) accession number: O14656
Secondary accession number(s): B2RB58, Q53Y64, Q96CA0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: January 1, 1998
Last modified: November 30, 2016
This is version 161 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.