ID TOR1A_HUMAN Reviewed; 332 AA. AC O14656; B2RB58; Q53Y64; Q96CA0; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 11-NOV-2015, entry version 150. DE RecName: Full=Torsin-1A; DE AltName: Full=Dystonia 1 protein; DE AltName: Full=Torsin ATPase-1A; DE EC=3.6.4.-; DE AltName: Full=Torsin family 1 member A; DE Flags: Precursor; GN Name=TOR1A; Synonyms=DQ2, DYT1, TA, TORA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT DYT1 GLU-303 DEL, AND RP VARIANT HIS-264. RC TISSUE=Brain cortex, Hippocampus, and Substantia nigra; RX PubMed=9288096; DOI=10.1038/ng0997-40; RA Ozelius L.J., Hewett J.W., Page C.E., Bressman S.B., Kramer P.L., RA Shalish C., de Leon D., Brin M.F., Raymond D., Corey D.P., Fahn S., RA Risch N.J., Buckler A.J., Gusella J.F., Breakefield X.O.; RT "The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding RT protein."; RL Nat. Genet. 17:40-48(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Kidney, and Skin; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-143 AND ASN-158, AND RP MUTAGENESIS OF ASN-143 AND ASN-158. RX PubMed=10871631; DOI=10.1074/jbc.M910025199; RA Kustedjo K., Bracey M.H., Cravatt B.F.; RT "Torsin A and its torsion dystonia-associated mutant forms are lumenal RT glycoproteins that exhibit distinct subcellular localizations."; RL J. Biol. Chem. 275:27933-27939(2000). RN [7] RP TISSUE SPECIFICITY. RX PubMed=10640617; DOI=10.1016/S0006-8993(99)02232-5; RA Shashidharan P., Kramer B.C., Walker R.H., Olanow C.W., Brin M.F.; RT "Immunohistochemical localization and distribution of torsinA in RT normal human and rat brain."; RL Brain Res. 853:197-206(2000). RN [8] RP INTERACTION WITH TOR1B, TISSUE SPECIFICITY, GLYCOSYLATION, AND RP SUBCELLULAR LOCATION. RX PubMed=15147511; DOI=10.1111/j.1471-4159.2004.02404.x; RA Hewett J.W., Kamm C., Boston H., Beauchamp R., Naismith T., RA Ozelius L., Hanson P.I., Breakefield X.O., Ramesh V.; RT "TorsinB--perinuclear location and association with torsinA."; RL J. Neurochem. 89:1186-1194(2004). RN [9] RP INTERACTION WITH KLC1, TISSUE SPECIFICITY, AND CHARACTERIZATION OF RP VARIANT DYT1 GLU-303 DEL. RX PubMed=14970196; DOI=10.1074/jbc.M401332200; RA Kamm C., Boston H., Hewett J., Wilbur J., Corey D.P., Hanson P.I., RA Ramesh V., Breakefield X.O.; RT "The early onset dystonia protein torsinA interacts with kinesin light RT chain 1."; RL J. Biol. Chem. 279:19882-19892(2004). RN [10] RP FUNCTION IN CELLULAR TRAFFICKING, SUBUNIT, INTERACTION WITH SLC6A3, RP CHARACTERIZATION OF VARIANT DYT1 GLU-303 DEL, AND MUTAGENESIS OF RP LYS-108. RX PubMed=15505207; DOI=10.1073/pnas.0308088101; RA Torres G.E., Sweeney A.L., Beaulieu J.M., Shashidharan P., Caron M.G.; RT "Effect of torsinA on membrane proteins reveals a loss of function and RT a dominant-negative phenotype of the dystonia-associated DeltaE- RT torsinA mutant."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15650-15655(2004). RN [11] RP INTERACTION WITH TOR1AIP1 AND TOR1AIP2. RX PubMed=15767459; DOI=10.1083/jcb.200411026; RA Goodchild R.E., Dauer W.T.; RT "The AAA+ protein torsinA interacts with a conserved domain present in RT LAP1 and a novel ER protein."; RL J. Cell Biol. 168:855-862(2005). RN [12] RP FUNCTION IN CYTOSKELETON ORGANIZATION, CHARACTERIZATION OF VARIANT RP DYT1 GLU-303 DEL, SUBCELLULAR LOCATION, AND INTERACTION WITH VIM. RX PubMed=16361107; DOI=10.1016/j.nbd.2005.10.012; RA Hewett J.W., Zeng J., Niland B.P., Bragg D.C., Breakefield X.O.; RT "Dystonia-causing mutant torsinA inhibits cell adhesion and neurite RT extension through interference with cytoskeletal dynamics."; RL Neurobiol. Dis. 22:98-111(2006). RN [13] RP SUBCELLULAR LOCATION, SIGNAL SEQUENCE CLEAVAGE SITE, GLYCOSYLATION, RP AND MUTAGENESIS OF VAL-18; ALA-20 AND VAL-33. RX PubMed=17037984; DOI=10.1042/BJ20061313; RA Callan A.C., Bunning S., Jones O.T., High S., Swanton E.; RT "Biosynthesis of the dystonia-associated AAA+ ATPase torsinA at the RT endoplasmic reticulum."; RL Biochem. J. 401:607-612(2007). RN [14] RP FUNCTION IN PROTEIN PROCESSING, AND CHARACTERIZATION OF VARIANT DYT1 RP GLU-303 DEL. 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 RT secretory pathway in DYT1 dystonia cells."; RL Proc. Natl. Acad. Sci. U.S.A. 104:7271-7276(2007). RN [15] RP FUNCTION IN VESICLE RECYCLING, INTERACTION WITH SNAPIN, AND RP CHARACTERIZATION OF VARIANT DYT1 GLU-303 DEL. RX PubMed=18167355; DOI=10.1074/jbc.M704097200; RA Granata A., Watson R., Collinson L.M., Schiavo G., Warner T.T.; RT "The dystonia-associated protein torsinA modulates synaptic vesicle RT recycling."; RL J. Biol. Chem. 283:7568-7579(2008). RN [16] RP FUNCTION IN NUCLEAR POLARITY, INTERACTION WITH PLEC; SYNE3 AND VIM, RP AND CHARACTERIZATION OF VARIANT DYT1 GLU-303 DEL. RX PubMed=18827015; DOI=10.1242/jcs.029454; RA Nery F.C., Zeng J., Niland B.P., Hewett J., Farley J., Irimia D., RA Li Y., 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 [17] RP INTERACTION WITH KLHL14, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP LYS-108 AND GLU-171. 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 [18] RP FUNCTION, HEXAMERIZATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP LYS-108 AND GLU-171. RX PubMed=19339278; DOI=10.1091/mbc.E09-01-0094; RA Vander Heyden A.B., Naismith T.V., Snapp E.L., Hodzic D., Hanson P.I.; RT "LULL1 retargets TorsinA to the nuclear envelope revealing an activity RT that is impaired by the DYT1 dystonia mutation."; RL Mol. Biol. Cell 20:2661-2672(2009). RN [19] RP FUNCTION AS CHAPERONE, AND CHARACTERIZATION OF VARIANT DYT1 GLU-303 RP DEL. RX PubMed=20169475; DOI=10.1007/s12192-010-0173-2; RA Burdette A.J., Churchill P.F., Caldwell G.A., Caldwell K.A.; RT "The early-onset torsion dystonia-associated protein, torsinA, RT displays molecular chaperone activity in vitro."; RL Cell Stress Chaperones 15:605-617(2010). RN [20] RP SUBUNIT, AND MUTAGENESIS OF GLU-171. 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 [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [22] RP INTERACTION WITH CSN4; SNAPIN AND STON2, SUBCELLULAR LOCATION, AND RP CHARACTERIZATION OF VARIANT DYT1 GLU-303 DEL. RX PubMed=21102408; DOI=10.1038/emboj.2010.285; RA Granata A., Koo S.J., Haucke V., Schiavo G., Warner T.T.; RT "CSN complex controls the stability of selected synaptic proteins via RT a torsinA-dependent process."; RL EMBO J. 30:181-193(2011). RN [23] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TOR1AIP1 AND TOR1AIP2, RP CHARACTERIZATION OF VARIANT GLU-303 DEL, AND MUTAGENESIS OF GLU-171. RX PubMed=23569223; DOI=10.1073/pnas.1300676110; RA Zhao C., Brown R.S., Chase A.R., Eisele M.R., Schlieker C.; RT "Regulation of Torsin ATPases by LAP1 and LULL1."; RL Proc. Natl. Acad. Sci. U.S.A. 110:E1545-1554(2013). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [25] RP VARIANT 323-PHE--TYR-328 DEL. RX PubMed=11523564; DOI=10.1007/s100480100111; RA Leung J.C., Klein C., Friedman J., Vieregge P., Jacobs H., Doheny D., RA Kamm C., DeLeon D., Pramstaller P.P., Penney J.B., Eisengart M., RA Jankovic J., Gasser T., Bressman S.B., Corey D.P., Kramer P., RA Brin M.F., Ozelius L.J., Breakefield X.O.; RT "Novel mutation in the TOR1A (DYT1) gene in atypical early onset RT dystonia and polymorphisms in dystonia and early onset parkinsonism."; RL Neurogenetics 3:133-143(2001). RN [26] RP VARIANT DYT1 GLN-288, AND CHARACTERIZATION OF VARIANTS DYT1 GLN-288 RP AND GLU-303 DEL. RX PubMed=18477710; DOI=10.1136/jnnp.2008.148270; RA Zirn B., Grundmann K., Huppke P., Puthenparampil J., Wolburg H., RA Riess O., Muller U.; RT "Novel TOR1A mutation p.Arg288Gln in early-onset dystonia (DYT1)."; RL J. Neurol. Neurosurg. Psych. 79:1327-1330(2008). RN [27] RP VARIANT DYT1 ILE-205, AND CHARACTERIZATION OF VARIANTS DYT1 ILE-205 RP AND GLU-303 DEL. RX PubMed=19955557; DOI=10.1136/jmg.2009.072082; RA Calakos N., Patel V.D., Gottron M., Wang G., Tran-Viet K.N., RA Brewington D., Beyer J.L., Steffens D.C., Krishnan R.R., Zuechner S.; RT "Functional evidence implicating a novel TOR1A mutation in idiopathic, RT late-onset focal dystonia."; RL J. Med. Genet. 47:646-650(2010). CC -!- FUNCTION: Protein with chaperone functions important for the CC control of protein folding, processing, stability and localization CC as well as for the reduction of misfolded protein aggregates. CC Involved in the regulation of synaptic vesicle recycling, controls CC STON2 protein stability in collaboration with the COP9 signalosome CC complex (CSN). In the nucleus, may link the cytoskeleton with the CC nuclear envelope, this mechanism seems to be crucial for the CC control of nuclear polarity, cell movement and, specifically in CC neurons, nuclear envelope integrity. Participates in the cellular CC trafficking and may regulate the subcellular location of multipass CC membrane proteins such as the dopamine transporter SLC6A3, leading CC to the modulation of dopamine neurotransmission. In the CC endoplasmic reticulum, plays a role in the quality control of CC protein folding by increasing clearance of misfolded proteins such CC as SGCE variants or holding them in an intermediate state for CC proper refolding. May have a redundant function with TOR1B in non- CC neural tissues. {ECO:0000269|PubMed:15505207, CC ECO:0000269|PubMed:16361107, ECO:0000269|PubMed:17428918, CC ECO:0000269|PubMed:18167355, ECO:0000269|PubMed:18827015, CC ECO:0000269|PubMed:19339278, ECO:0000269|PubMed:20169475, CC ECO:0000269|PubMed:23569223}. CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. CC {ECO:0000269|PubMed:23569223}. CC -!- SUBUNIT: Homohexamer. Interacts with TOR1B; the interaction may be CC specific of neural tissues. Interacts (ATP-bound) with TOR1AIP1 CC and TOR1AIP2; the interactions induce ATPase activity. Interacts CC with KLHL14; preferentially when ATP-free. Interacts with KLC1 CC (via TPR repeats); the interaction associates TOR1A with the CC kinesin oligomeric complex. Interacts with COPS4; the interaction CC associates TOR1A with the CSN complex. Interacts with SNAPIN; the CC interaction is direct and associates SNAPIN with the CSN complex. CC Interacts with STON2. Interacts (ATP-bound) with SYNE3 (via KASH CC domain); the interaction is required for SYNE3 nuclear envelope CC localization. Interacts with VIM; the interaction associates TOR1A CC with the cytoskeleton. Interacts with PLEC. Interacts (ATP-bound) CC with SLC6A3; regulates SLC6A3 transport to the plasma membrane. CC {ECO:0000269|PubMed:14970196, ECO:0000269|PubMed:15147511, CC ECO:0000269|PubMed:15505207, ECO:0000269|PubMed:15767459, CC ECO:0000269|PubMed:16361107, ECO:0000269|PubMed:18167355, CC ECO:0000269|PubMed:18827015, ECO:0000269|PubMed:19535332, CC ECO:0000269|PubMed:20015956, ECO:0000269|PubMed:21102408, CC ECO:0000269|PubMed:23569223}. CC -!- INTERACTION: CC P60409:KRTAP10-7; NbExp=3; IntAct=EBI-524257, EBI-10172290; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. Nucleus CC membrane; Peripheral membrane protein. Cell projection, growth CC cone {ECO:0000250}. Cytoplasmic vesicle membrane {ECO:0000250}. CC Cytoplasmic vesicle, secretory vesicle {ECO:0000250}. Cytoplasmic CC vesicle, secretory vesicle, synaptic vesicle. Cytoplasm, CC cytoskeleton. Note=Upon oxidative stress, redistributes to CC protusions from the cell surface (By similarity). Peripherally CC associated with the inner face of the ER membrane, probably CC mediated by the interaction with TOR1AIP1. The association with CC nucleus membrane is mediated by the interaction with TOR1AIP2. CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O14656-1; Sequence=Displayed; CC Name=2; CC IsoId=O14656-2; Sequence=VSP_026605; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Widely expressed. Highest levels in kidney and CC liver. In the brain, high levels found in the dopaminergic neurons CC of the substantia nigra pars compacta, as well as in the CC neocortex, hippocampus and cerebellum. Also highly expressed in CC the spinal cord. {ECO:0000269|PubMed:10640617, CC ECO:0000269|PubMed:14970196, ECO:0000269|PubMed:15147511}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10871631, CC ECO:0000269|PubMed:15147511, ECO:0000269|PubMed:17037984}. CC -!- DISEASE: Dystonia 1, torsion, autosomal dominant (DYT1) CC [MIM:128100]: A primary torsion dystonia, and the most common and CC severe form. Dystonia is defined by the presence of sustained CC involuntary muscle contractions, often leading to abnormal CC postures. Dystonia type 1 is characterized by involuntary, CC repetitive, sustained muscle contractions or postures involving CC one or more sites of the body, in the absence of other CC neurological symptoms. Typically, symptoms develop first in an arm CC or leg in middle to late childhood and progress in approximately CC 30% of patients to other body regions (generalized dystonia) CC within about five years. 'Torsion' refers to the twisting nature CC of body movements observed in DYT1, often affecting the trunk. CC Distribution and severity of symptoms vary widely between affected CC individuals, ranging from mild focal dystonia to severe CC generalized dystonia, even within families. CC {ECO:0000269|PubMed:18477710, ECO:0000269|PubMed:19955557, CC ECO:0000269|PubMed:9288096}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ClpA/ClpB family. Torsin subfamily. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF007871; AAC51732.1; -; mRNA. DR EMBL; AK314505; BAG37105.1; -; mRNA. DR EMBL; BT006931; AAP35577.1; -; mRNA. DR EMBL; AL158207; CAC88168.1; -; Genomic_DNA. DR EMBL; BC000674; AAH00674.1; -; mRNA. DR EMBL; BC014484; AAH14484.1; -; mRNA. DR CCDS; CCDS6930.1; -. [O14656-1] DR RefSeq; NP_000104.1; NM_000113.2. [O14656-1] DR UniGene; Hs.534312; -. DR ProteinModelPortal; O14656; -. DR SMR; O14656; 93-125. DR BioGrid; 108193; 35. DR DIP; DIP-34411N; -. DR IntAct; O14656; 8. DR MINT; MINT-7002075; -. DR STRING; 9606.ENSP00000345719; -. DR PhosphoSite; O14656; -. DR BioMuta; TOR1A; -. DR MaxQB; O14656; -. DR PaxDb; O14656; -. DR PRIDE; O14656; -. DR DNASU; 1861; -. DR Ensembl; ENST00000351698; ENSP00000345719; ENSG00000136827. [O14656-1] DR GeneID; 1861; -. DR KEGG; hsa:1861; -. DR UCSC; uc004byl.3; human. [O14656-1] DR UCSC; uc004byn.3; human. [O14656-2] DR CTD; 1861; -. DR GeneCards; TOR1A; -. DR GeneReviews; TOR1A; -. DR HGNC; HGNC:3098; TOR1A. DR HPA; CAB012473; -. DR HPA; HPA051195; -. DR MIM; 128100; phenotype. DR MIM; 605204; gene. DR neXtProt; NX_O14656; -. DR Orphanet; 256; Early-onset generalized limb-onset dystonia. DR Orphanet; 36899; Myoclonus-dystonia syndrome. DR PharmGKB; PA27556; -. DR eggNOG; KOG2170; Eukaryota. DR eggNOG; ENOG410XR06; LUCA. DR GeneTree; ENSGT00390000001920; -. DR HOGENOM; HOG000115770; -. DR HOVERGEN; HBG054188; -. DR InParanoid; O14656; -. DR OMA; MIESHVI; -. DR OrthoDB; EOG7TF791; -. DR PhylomeDB; O14656; -. DR TreeFam; TF314941; -. DR ChiTaRS; TOR1A; human. DR GeneWiki; Torsin_A; -. DR GenomeRNAi; 1861; -. DR NextBio; 7627; -. DR PRO; PR:O14656; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; O14656; -. DR CleanEx; HS_TOR1A; -. DR Genevisible; O14656; HS. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. 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:CACAO. DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0030426; C:growth cone; ISS:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0030141; C:secretory granule; ISS:UniProtKB. DR GO; GO:0008021; C:synaptic vesicle; IDA:UniProtKB. DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATPase activity; IDA:UniProtKB. DR GO; GO:0008092; F:cytoskeletal protein binding; IPI:UniProtKB. DR GO; GO:0019894; F:kinesin binding; IPI:UniProtKB. DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc. DR GO; GO:0007155; P:cell adhesion; IMP:UniProtKB. DR GO; GO:0051085; P:chaperone mediated protein folding requiring cofactor; IEA:InterPro. DR GO; GO:0061077; P:chaperone-mediated protein folding; IDA:UniProtKB. DR GO; GO:0072321; P:chaperone-mediated protein transport; IDA:UniProtKB. DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; ISS:UniProtKB. DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0031175; P:neuron projection development; IMP:UniProtKB. DR GO; GO:0006998; P:nuclear envelope organization; ISS:UniProtKB. DR GO; GO:0071763; P:nuclear membrane organization; ISS:UniProtKB. DR GO; GO:0006996; P:organelle organization; ISS:UniProtKB. DR GO; GO:1900244; P:positive regulation of synaptic vesicle endocytosis; IMP:UniProtKB. DR GO; GO:0000338; P:protein deneddylation; IMP:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:MGI. DR GO; GO:0034504; P:protein localization to nucleus; IMP:UniProtKB. DR GO; GO:0051584; P:regulation of dopamine uptake involved in synaptic transmission; IDA:UniProtKB. DR GO; GO:2000008; P:regulation of protein localization to cell surface; IMP:UniProtKB. DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl. DR GO; GO:0048489; P:synaptic vesicle transport; IMP:UniProtKB. DR GO; GO:0044319; P:wound healing, spreading of cells; ISS:UniProtKB. DR Gene3D; 3.40.50.300; -; 2. 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 Alternative splicing; ATP-binding; Cell junction; Cell projection; KW Chaperone; Complete proteome; Cytoplasm; Cytoplasmic vesicle; KW Cytoskeleton; Disease mutation; Dystonia; Endoplasmic reticulum; KW Glycoprotein; Hydrolase; Membrane; Nucleotide-binding; Nucleus; KW Polymorphism; Reference proteome; Signal; Synapse. FT SIGNAL 1 20 {ECO:0000305|PubMed:17037984}. FT CHAIN 21 332 Torsin-1A. FT /FTId=PRO_0000005506. FT NP_BIND 102 109 ATP. FT REGION 91 251 Interaction with SNAPIN. FT REGION 251 332 Interaction with KLC1. FT REGION 312 332 Interaction with SYNE3. FT CARBOHYD 143 143 N-linked (GlcNAc...) (high mannose). FT {ECO:0000269|PubMed:10871631}. FT CARBOHYD 158 158 N-linked (GlcNAc...) (high mannose). FT {ECO:0000269|PubMed:10871631}. FT VAR_SEQ 149 332 DQLQLWIRGNVSACARSIFIFDEMDKMHAGLIDAIKPFLDY FT YDLVDGVSYQKAMFIFLSNAGAERITDVALDFWRSGKQRED FT IKLKDIEHALSVSVFNNKNSGFWHSSLIDRNLIDYFVPFLP FT LEYKHLKMCIRVEMQSRGYEIDEDIVSRVAEEMTFFPKEER FT VFSDKGCKTVFTKLDYYYDD -> ARMEVWNPFLDVIGFGV FT SLLWDEIWEFYVEMSEPGKRFMSQFPLERCRS (in FT isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_026605. FT VARIANT 205 205 F -> I (in DYT1; produces intracellular FT misfolded protein aggregates). FT {ECO:0000269|PubMed:19955557}. FT /FTId=VAR_070932. FT VARIANT 216 216 D -> H (in dbSNP:rs1801968). FT /FTId=VAR_020449. FT VARIANT 264 264 D -> H. {ECO:0000269|PubMed:9288096}. FT /FTId=VAR_010788. FT VARIANT 288 288 R -> Q (in DYT1; produces an enlarged FT perinuclear space). FT {ECO:0000269|PubMed:18477710}. FT /FTId=VAR_070933. FT VARIANT 303 303 Missing (in DYT1; dominant negative; loss FT of interaction with TOR1AIP1 and TOR1AIP2 FT with loss of ATPase activity induction; FT enriched in the nuclear envelope; impairs FT secretory pathway; produces intracellular FT misfolded protein aggregates; produces an FT enlarged perinuclear space; FT dbSNP:rs80358233). FT {ECO:0000269|PubMed:14970196, FT ECO:0000269|PubMed:15505207, FT ECO:0000269|PubMed:16361107, FT ECO:0000269|PubMed:17428918, FT ECO:0000269|PubMed:18167355, FT ECO:0000269|PubMed:18477710, FT ECO:0000269|PubMed:18827015, FT ECO:0000269|PubMed:19955557, FT ECO:0000269|PubMed:20169475, FT ECO:0000269|PubMed:21102408, FT ECO:0000269|PubMed:23569223, FT ECO:0000269|PubMed:9288096}. FT /FTId=VAR_010789. FT VARIANT 323 328 Missing (found in a patient with early- FT onset atypical dystonia and myoclonic FT features; dbSNP:rs80358235). FT {ECO:0000269|PubMed:11523564}. FT /FTId=VAR_070934. FT MUTAGEN 18 18 V->F: Inhibits sequence signal cleavage. FT {ECO:0000269|PubMed:17037984}. FT MUTAGEN 20 20 A->F: Inhibits sequence signal cleavage. FT {ECO:0000269|PubMed:17037984}. FT MUTAGEN 33 33 V->N: N-glycosylated. FT {ECO:0000269|PubMed:17037984}. FT MUTAGEN 108 108 K->A: Loss of ATP-binding. No effect on FT interaction with KLHL14. Increases FT interaction with TOR1AIP1 and TOR1AIP2. FT Abolishes interaction with SLC6A3. FT {ECO:0000269|PubMed:15505207, FT ECO:0000269|PubMed:19339278, FT ECO:0000269|PubMed:19535332}. FT MUTAGEN 143 143 N->Q: Reduces N-glycosylation. FT {ECO:0000269|PubMed:10871631}. FT MUTAGEN 158 158 N->Q: Reduces N-glycosylation. FT {ECO:0000269|PubMed:10871631}. FT MUTAGEN 171 171 E->Q: Loss of ATP hydrolysis. Loss of FT interaction with KLHL14. Localizes in the FT nuclear envelope. FT {ECO:0000269|PubMed:19339278, FT ECO:0000269|PubMed:19535332, FT ECO:0000269|PubMed:20015956, FT ECO:0000269|PubMed:23569223}. FT CONFLICT 259 259 D -> H (in Ref. 3; AAP35577 and 5; FT AAH00674). {ECO:0000305}. SQ SEQUENCE 332 AA; 37809 MW; B69B28D0B4112080 CRC64; MKLGRAVLGL LLLAPSVVQA VEPISLGLAL AGVLTGYIYP RLYCLFAECC GQKRSLSREA LQKDLDDNLF GQHLAKKIIL NAVFGFINNP KPKKPLTLSL HGWTGTGKNF VSKIIAENIY EGGLNSDYVH LFVATLHFPH ASNITLYKDQ LQLWIRGNVS ACARSIFIFD EMDKMHAGLI DAIKPFLDYY DLVDGVSYQK AMFIFLSNAG AERITDVALD FWRSGKQRED IKLKDIEHAL SVSVFNNKNS GFWHSSLIDR NLIDYFVPFL PLEYKHLKMC IRVEMQSRGY EIDEDIVSRV AEEMTFFPKE ERVFSDKGCK TVFTKLDYYY DD //