TOR1A_MOUSE
ID TOR1A_MOUSE Reviewed; 333 AA.
AC Q9ER39;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Torsin-1A;
DE AltName: Full=Dystonia 1 protein;
DE AltName: Full=Torsin ATPase 1;
DE EC=3.6.4.-;
DE AltName: Full=Torsin family 1 member A;
DE Flags: Precursor;
GN Name=Tor1a; Synonyms=Dyt1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Kuner R., Teismann P., Trutzel A., Naim J., Richter A., Bach A., Ferger B.,
RA Schneider A.;
RT "Characterization of the mouse torsinA gene.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION IN NUCLEAR ENVELOPE INTEGRITY, DISRUPTION PHENOTYPE, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF GLU-304.
RX PubMed=16364897; DOI=10.1016/j.neuron.2005.11.010;
RA Goodchild R.E., Kim C.E., Dauer W.T.;
RT "Loss of the dystonia-associated protein torsinA selectively disrupts the
RT neuronal nuclear envelope.";
RL Neuron 48:923-932(2005).
RN [4]
RP FUNCTION IN DEGRADATION OF MISFOLDED PROTEINS.
RX PubMed=17200151; DOI=10.1093/hmg/ddl472;
RA Esapa C.T., Waite A., Locke M., Benson M.A., Kraus M., McIlhinney R.A.,
RA Sillitoe R.V., Beesley P.W., Blake D.J.;
RT "SGCE missense mutations that cause myoclonus-dystonia syndrome impair
RT epsilon-sarcoglycan trafficking to the plasma membrane: modulation by
RT ubiquitination and torsinA.";
RL Hum. Mol. Genet. 16:327-342(2007).
RN [5]
RP FUNCTION IN PROTEIN PROCESSING.
RX PubMed=17428918; DOI=10.1073/pnas.0701185104;
RA Hewett J.W., Tannous B., Niland B.P., Nery F.C., Zeng J., Li Y.,
RA Breakefield X.O.;
RT "Mutant torsinA interferes with protein processing through the secretory
RT pathway in DYT1 dystonia cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:7271-7276(2007).
RN [6]
RP FUNCTION IN NUCLEAR POLARITY, AND INTERACTION WITH SYNE3; PLEC AND VIM.
RX PubMed=18827015; DOI=10.1242/jcs.029454;
RA Nery F.C., Zeng J., Niland B.P., Hewett J., Farley J., Irimia D., Li Y.,
RA Wiche G., Sonnenberg A., Breakefield X.O.;
RT "TorsinA binds the KASH domain of nesprins and participates in linkage
RT between nuclear envelope and cytoskeleton.";
RL J. Cell Sci. 121:3476-3486(2008).
RN [7]
RP INTERACTION WITH KLHL14.
RX PubMed=19535332; DOI=10.1074/jbc.m109.004838;
RA Giles L.M., Li L., Chin L.S.;
RT "Printor, a novel torsinA-interacting protein implicated in dystonia
RT pathogenesis.";
RL J. Biol. Chem. 284:21765-21775(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, GLYCOSYLATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=20015956; DOI=10.1093/hmg/ddp557;
RA Jungwirth M., Dear M.L., Brown P., Holbrook K., Goodchild R.;
RT "Relative tissue expression of homologous torsinB correlates with the
RT neuronal specific importance of DYT1 dystonia-associated torsinA.";
RL Hum. Mol. Genet. 19:888-900(2010).
RN [10]
RP FUNCTION IN NUCLEAR ENVELOPE INTEGRITY, INTERACTION WITH TOR1AIP1,
RP DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=20457914; DOI=10.1073/pnas.0912877107;
RA Kim C.E., Perez A., Perkins G., Ellisman M.H., Dauer W.T.;
RT "A molecular mechanism underlying the neural-specific defect in torsinA
RT mutant mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:9861-9866(2010).
CC -!- FUNCTION: Protein with chaperone functions important for the control of
CC protein folding, processing, stability and localization as well as for
CC the reduction of misfolded protein aggregates. Involved in the
CC regulation of synaptic vesicle recycling, controls STON2 protein
CC stability in collaboration with the COP9 signalosome complex (CSN). In
CC the nucleus, may link the cytoskeleton with the nuclear envelope, this
CC mechanism seems to be crucial for the control of nuclear polarity, cell
CC movement and, specifically in neurons, nuclear envelope integrity.
CC Participates in the cellular trafficking and may regulate the
CC subcellular location of multipass membrane proteins such as the
CC dopamine transporter SLC6A3, leading to the modulation of dopamine
CC neurotransmission. In the endoplasmic reticulum, plays a role in the
CC quality control of protein folding by increasing clearance of misfolded
CC proteins such as SGCE variants or holding them in an intermediate state
CC for proper refolding. May have a redundant function with TOR1B in non-
CC neural tissues. {ECO:0000269|PubMed:16364897,
CC ECO:0000269|PubMed:17200151, ECO:0000269|PubMed:17428918,
CC ECO:0000269|PubMed:18827015, ECO:0000269|PubMed:20457914}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC -!- SUBUNIT: Homohexamer. Interacts with TOR1B; the interaction may be
CC specific of neural tissues. Interacts (ATP-bound) with TOR1AIP1 and
CC TOR1AIP2; the interactions induce ATPase activity. Interacts with
CC KLHL14; preferentially when ATP-free. Interacts with KLC1 (via TPR
CC repeats); the interaction associates TOR1A with the kinesin oligomeric
CC complex. Interacts with COPS4; the interaction associates TOR1A with
CC the CSN complex. Interacts with SNAPIN; the interaction is direct and
CC associates SNAPIN with the CSN complex. Interacts with STON2. Interacts
CC (ATP-bound) with SYNE3 (via KASH domain); the interaction is required
CC for SYNE3 nuclear envelope localization. Interacts with VIM; the
CC interaction associates TOR1A with the cytoskeleton. Interacts with
CC PLEC. Interacts (ATP-bound) with SLC6A3; regulates SLC6A3 transport to
CC the plasma membrane. {ECO:0000269|PubMed:18827015,
CC ECO:0000269|PubMed:19535332, ECO:0000269|PubMed:20457914}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:O14656}. Nucleus membrane; Peripheral membrane
CC protein. Cell projection, growth cone. Cytoplasmic vesicle membrane
CC {ECO:0000250}. Synapse, synaptosome {ECO:0000250}. Cytoplasm,
CC cytoskeleton {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC {ECO:0000250}. Note=Upon oxidative stress, redistributes to protusions
CC from the cell surface (By similarity). Peripherally associated with the
CC inner face of the ER membrane, probably mediated by the interaction
CC with TOR1AIP1. The association with nucleus membrane is mediated by the
CC interaction with TOR1AIP2. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed (at protein level).
CC {ECO:0000269|PubMed:16364897, ECO:0000269|PubMed:20015956}.
CC -!- DEVELOPMENTAL STAGE: At 16 dpc and 18 dpc, widely expressed with higher
CC expression levels in neural tissues. In the spinal cord, expressed as
CC early as 12 dpc until P21, the expression levels decrease in the
CC adulthood (at protein level). {ECO:0000269|PubMed:16364897,
CC ECO:0000269|PubMed:20015956, ECO:0000269|PubMed:20457914}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:20015956}.
CC -!- DISRUPTION PHENOTYPE: Animals fail to feed or vocalize and die within
CC 48 hours of birth. At 18 dpc, the global structure of the central
CC nervous system is normal. However, at the cellular level, nuclear
CC envelope abnormalities, with membranous vesicle-appearing structures in
CC the perinuclear space, are observed in multiple areas of the central
CC nervous system, including neurons of the spinal cord, pons, frontal
CC cortex, and hippocampus. {ECO:0000269|PubMed:16364897,
CC ECO:0000269|PubMed:20457914}.
CC -!- SIMILARITY: Belongs to the ClpA/ClpB family. Torsin subfamily.
CC {ECO:0000305}.
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DR EMBL; AJ298841; CAC12785.1; -; mRNA.
DR EMBL; BC017683; AAH17683.1; -; mRNA.
DR CCDS; CCDS15891.1; -.
DR RefSeq; NP_659133.1; NM_144884.2.
DR PDB; 6FV0; X-ray; 2.29 A; A=322-333.
DR PDBsum; 6FV0; -.
DR AlphaFoldDB; Q9ER39; -.
DR SMR; Q9ER39; -.
DR BioGRID; 206008; 2.
DR STRING; 10090.ENSMUSP00000028200; -.
DR GlyGen; Q9ER39; 2 sites.
DR iPTMnet; Q9ER39; -.
DR PhosphoSitePlus; Q9ER39; -.
DR EPD; Q9ER39; -.
DR jPOST; Q9ER39; -.
DR MaxQB; Q9ER39; -.
DR PaxDb; Q9ER39; -.
DR PRIDE; Q9ER39; -.
DR ProteomicsDB; 258952; -.
DR Antibodypedia; 31437; 273 antibodies from 32 providers.
DR DNASU; 30931; -.
DR Ensembl; ENSMUST00000028200; ENSMUSP00000028200; ENSMUSG00000026849.
DR GeneID; 30931; -.
DR KEGG; mmu:30931; -.
DR UCSC; uc008jdc.2; mouse.
DR CTD; 1861; -.
DR MGI; MGI:1353568; Tor1a.
DR VEuPathDB; HostDB:ENSMUSG00000026849; -.
DR eggNOG; KOG2170; Eukaryota.
DR GeneTree; ENSGT00950000182888; -.
DR HOGENOM; CLU_053537_0_0_1; -.
DR InParanoid; Q9ER39; -.
DR OMA; RGYETNE; -.
DR OrthoDB; 1453168at2759; -.
DR PhylomeDB; Q9ER39; -.
DR TreeFam; TF314941; -.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR BioGRID-ORCS; 30931; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Tor1a; mouse.
DR PRO; PR:Q9ER39; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9ER39; protein.
DR Bgee; ENSMUSG00000026849; Expressed in primary oocyte and 259 other tissues.
DR ExpressionAtlas; Q9ER39; baseline and differential.
DR Genevisible; Q9ER39; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:MGI.
DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005635; C:nuclear envelope; IDA:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0030141; C:secretory granule; ISS:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; ISS:UniProtKB.
DR GO; GO:0008092; F:cytoskeletal protein binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0019894; F:kinesin binding; ISO:MGI.
DR GO; GO:0051787; F:misfolded protein binding; IPI:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IEA:InterPro.
DR GO; GO:0061077; P:chaperone-mediated protein folding; ISS:UniProtKB.
DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; IDA:UniProtKB.
DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0006998; P:nuclear envelope organization; IMP:MGI.
DR GO; GO:0071763; P:nuclear membrane organization; IMP:MGI.
DR GO; GO:0006996; P:organelle organization; IMP:UniProtKB.
DR GO; GO:1900244; P:positive regulation of synaptic vesicle endocytosis; ISS:UniProtKB.
DR GO; GO:0000338; P:protein deneddylation; ISS:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0051584; P:regulation of dopamine uptake involved in synaptic transmission; ISS:UniProtKB.
DR GO; GO:2000008; P:regulation of protein localization to cell surface; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
DR GO; GO:0048499; P:synaptic vesicle membrane organization; ISS:UniProtKB.
DR GO; GO:0048489; P:synaptic vesicle transport; ISS:UniProtKB.
DR GO; GO:0044319; P:wound healing, spreading of cells; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR010448; Torsin.
DR InterPro; IPR030549; Torsin-1A.
DR InterPro; IPR017378; Torsin_1/2.
DR PANTHER; PTHR10760; PTHR10760; 1.
DR PANTHER; PTHR10760:SF15; PTHR10760:SF15; 1.
DR Pfam; PF06309; Torsin; 1.
DR PIRSF; PIRSF038079; Torsin_2A; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell projection; Chaperone; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Endoplasmic reticulum; Glycoprotein;
KW Hydrolase; Membrane; Nucleotide-binding; Nucleus; Reference proteome;
KW Signal; Synapse; Synaptosome.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT CHAIN 21..333
FT /note="Torsin-1A"
FT /id="PRO_0000005508"
FT REGION 92..252
FT /note="Interaction with SNAPIN"
FT /evidence="ECO:0000250"
FT REGION 252..333
FT /note="Interaction with KLC1"
FT /evidence="ECO:0000250"
FT REGION 313..333
FT /note="Interaction with SYNE3"
FT /evidence="ECO:0000250"
FT BINDING 103..110
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT MUTAGEN 304
FT /note="Missing: Nuclear envelope abnormalities specific to
FT neurons."
FT /evidence="ECO:0000269|PubMed:16364897"
SQ SEQUENCE 333 AA; 37830 MW; CD2D7B97E3F03274 CRC64;
MKLGRAALAL LLLAPCVVRA VEPISLSLAL AGVLTTYISY PRLYCLFAEC CGQMRSLSRE
ALQKDLDNKL FGQHLAKKVI LNAVSGFLSN PKPKKPLTLS LHGWTGTGKN FASKIIAENI
YEGGLNSDYV HLFVATLHFP HASNITQYKD QLQMWIRGNV SACARSIFIF DEMDKMHAGL
IDAIKPFLDY YDVVDEVSYQ KAIFIFLSNA GAERITDVAL DFWKSGKQRE EIKLRDMEPA
LAVSVFNNKN SGFWHSSLID RNLIDYFVPF LPLEYKHLKM CIRVEMQSRG YEVDEDIISK
VAEEMTFFPK EEKVFSDKGC KTVFTKLDYY LDD
