Q9ER39 (TOR1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 106. History...
Names and origin
|Protein names||Recommended name:|
Dystonia 1 protein
Torsin ATPase 1
Torsin family 1 member A
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||333 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Ref.3 Ref.4 Ref.5 Ref.6 Ref.9
ATP + H2O = ADP + phosphate.
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. Ref.6 Ref.7 Ref.9
Endoplasmic reticulum lumen. Nucleus membrane; Peripheral membrane protein. Cell projection › growth cone. Cytoplasmic vesicle membrane By similarity. Cell junction › synapse › synaptosome By similarity. Cytoplasm › cytoskeleton By similarity. Cytoplasmic vesicle › secretory vesicle By similarity. Cytoplasmic vesicle › secretory vesicle › synaptic vesicle By similarity. Note: Upon oxidative stress, redistributes to protusions from the cell surface By similarity. Peripherally associated with the inner face of the ER membrane, probably mediated by the interaction with TOR1AIP1. The association with nucleus membrane is mediated by the interaction with TOR1AIP2. Ref.8 Ref.9
At E16 and E18, widely expressed with higher expression levels in neural tissues. In the spinal cord, expressed as early as E12 until p21, the expression levels decrease in the adulthood (at protein level). Ref.3 Ref.8 Ref.9
Animals fail to feed or vocalize and die within 48 hours of birth. At E18, the global structure of the central nervous system is normal. However, at the cellular level, nuclear envelope abnormalities, with membranous vesicle-appearing structures in the perinuclear space, are observed in multiple areas of the central nervous system, including neurons of the spinal cord, pons, frontal cortex, and hippocampus. Ref.3 Ref.9
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 20||20||By similarity|
|Chain||21 – 333||313||Torsin-1A||PRO_0000005508|
|Nucleotide binding||103 – 110||8||ATP Potential|
|Region||92 – 252||161||Interaction with SNAPIN By similarity|
|Region||252 – 333||82||Interaction with KLC1 By similarity|
|Region||313 – 333||21||Interaction with SYNE3 By similarity|
Amino acid modifications
|Glycosylation||144||1||N-linked (GlcNAc...) By similarity|
|Glycosylation||159||1||N-linked (GlcNAc...) By similarity|
|Mutagenesis||304||1||Missing: Nuclear envelope abnormalities specific to neurons. Ref.3|
|||"Characterization of the mouse torsinA gene."|
Kuner R., Teismann P., Trutzel A., Naim J., Richter A., Bach A., Ferger B., Schneider A.
Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||"Loss of the dystonia-associated protein torsinA selectively disrupts the neuronal nuclear envelope."|
Goodchild R.E., Kim C.E., Dauer W.T.
Neuron 48:923-932(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NUCLEAR ENVELOPE INTEGRITY, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, MUTAGENESIS OF GLU-304.
|||"SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA."|
Esapa C.T., Waite A., Locke M., Benson M.A., Kraus M., McIlhinney R.A., Sillitoe R.V., Beesley P.W., Blake D.J.
Hum. Mol. Genet. 16:327-342(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEGRADATION OF MISFOLDED PROTEINS.
|||"Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells."|
Hewett J.W., Tannous B., Niland B.P., Nery F.C., Zeng J., Li Y., Breakefield X.O.
Proc. Natl. Acad. Sci. U.S.A. 104:7271-7276(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PROTEIN PROCESSING.
|||"TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton."|
Nery F.C., Zeng J., Niland B.P., Hewett J., Farley J., Irimia D., Li Y., Wiche G., Sonnenberg A., Breakefield X.O.
J. Cell Sci. 121:3476-3486(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NUCLEAR POLARITY, INTERACTION WITH SYNE3; PLEC AND VIM.
|||"Printor, a novel torsinA-interacting protein implicated in dystonia pathogenesis."|
Giles L.M., Li L., Chin L.S.
J. Biol. Chem. 284:21765-21775(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KLHL14.
|||"Relative tissue expression of homologous torsinB correlates with the neuronal specific importance of DYT1 dystonia-associated torsinA."|
Jungwirth M., Dear M.L., Brown P., Holbrook K., Goodchild R.
Hum. Mol. Genet. 19:888-900(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, GLYCOSYLATION, DEVELOPMENTAL STAGE.
|||"A molecular mechanism underlying the neural-specific defect in torsinA mutant mice."|
Kim C.E., Perez A., Perkins G., Ellisman M.H., Dauer W.T.
Proc. Natl. Acad. Sci. U.S.A. 107:9861-9866(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NUCLEAR ENVELOPE INTEGRITY, INTERACTION WITH TOR1AIP1, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION.
|+||Additional computationally mapped references.|
|AJ298841 mRNA. Translation: CAC12785.1.|
BC017683 mRNA. Translation: AAH17683.1.
|RefSeq||NP_659133.1. NM_144884.2. |
3D structure databases
|SMR||Q9ER39. Positions 95-122. |
Protein-protein interaction databases
|BioGrid||206008. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000028200; ENSMUSP00000028200; ENSMUSG00000026849. |
|UCSC||uc008jdc.2. mouse. |
|MGI||MGI:1353568. Tor1a. |
Gene expression databases
Family and domain databases
|Gene3D||188.8.131.520. 1 hit. |
|InterPro||IPR027417. P-loop_NTPase. |
|PANTHER||PTHR10760. PTHR10760. 1 hit. |
|Pfam||PF06309. Torsin. 1 hit. |
|PIRSF||PIRSF038079. Torsin_2A. 1 hit. |
|SUPFAM||SSF52540. SSF52540. 1 hit. |
|ChiTaRS||TOR1A. mouse. |
|Accession||Primary (citable) accession number: Q9ER39|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|