TOR1A_HUMAN
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 03-AUG-2022, entry version 202.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 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., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., 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., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., 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., Rogers J.,
RA 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 project:
RT 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 MUTAGENESIS
RP 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 normal
RT human and rat brain.";
RL Brain Res. 853:197-206(2000).
RN [8]
RP INTERACTION WITH TOR1B, TISSUE SPECIFICITY, GLYCOSYLATION, AND SUBCELLULAR
RP 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., Ozelius L.,
RA 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, CHARACTERIZATION OF VARIANT DYT1
RP GLU-303 DEL, AND SUBCELLULAR LOCATION.
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 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 a
RT dominant-negative phenotype of the dystonia-associated DeltaE-torsinA
RT 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 LAP1
RT and a novel ER protein.";
RL J. Cell Biol. 168:855-862(2005).
RN [12]
RP FUNCTION IN CYTOSKELETON ORGANIZATION, CHARACTERIZATION OF VARIANT DYT1
RP 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, AND
RP 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 secretory
RT 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, AND
RP 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., 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 [17]
RP INTERACTION WITH KLHL14, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-108
RP 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 LYS-108
RP 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 that
RT 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 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, displays
RT 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., Buerckstuemmer T.,
RA 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 a
RT 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., Ayoub D.,
RA 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 INVOLVEMENT IN AMC5, VARIANTS AMC5 GLU-303 DEL AND SER-318,
RP CHARACTERIZATION OF VARIANT AMC5 SER-318, AND SUBCELLULAR LOCATION.
RX PubMed=29053766; DOI=10.1093/brain/awx230;
RA Kariminejad A., Dahl-Halvarsson M., Ravenscroft G., Afroozan F.,
RA Keshavarz E., Goullee H., Davis M.R., Faraji Zonooz M., Najmabadi H.,
RA Laing N.G., Tajsharghi H.;
RT "TOR1A variants cause a severe arthrogryposis with developmental delay,
RT strabismus and tremor.";
RL Brain 140:2851-2859(2017).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 51-332 IN COMPLEX WITH TOR1AIP2,
RP CHARACTERIZATION OF VARIANT DYT1 GLU-303 DEL, AND MUTAGENESIS OF GLU-171.
RX PubMed=27490483; DOI=10.7554/elife.17983;
RA Demircioglu F.E., Sosa B.A., Ingram J., Ploegh H.L., Schwartz T.U.;
RT "Structures of TorsinA and its disease-mutant complexed with an activator
RT reveal the molecular basis for primary dystonia.";
RL Elife 5:0-0(2016).
RN [27]
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., Brin M.F.,
RA Ozelius L.J., Breakefield X.O.;
RT "Novel mutation in the TOR1A (DYT1) gene in atypical early onset dystonia
RT and polymorphisms in dystonia and early onset parkinsonism.";
RL Neurogenetics 3:133-143(2001).
RN [28]
RP VARIANT DYT1 GLN-288, AND CHARACTERIZATION OF VARIANTS DYT1 GLN-288 AND
RP GLU-303 DEL.
RX PubMed=18477710; DOI=10.1136/jnnp.2008.148270;
RA Zirn B., Grundmann K., Huppke P., Puthenparampil J., Wolburg H., Riess O.,
RA Muller U.;
RT "Novel TOR1A mutation p.Arg288Gln in early-onset dystonia (DYT1).";
RL J. Neurol. Neurosurg. Psych. 79:1327-1330(2008).
RN [29]
RP VARIANT DYT1 ILE-205, AND CHARACTERIZATION OF VARIANTS DYT1 ILE-205 AND
RP 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., Brewington D.,
RA 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).
RN [30]
RP CHARACTERIZATION OF VARIANTS DYT1 ILE-205; GLN-288 AND GLU-303 DEL,
RP FUNCTION, AND SUBUNIT.
RX PubMed=24930953; DOI=10.1002/humu.22602;
RA Hettich J., Ryan S.D., de Souza O.N., Saraiva Macedo Timmers L.F., Tsai S.,
RA Atai N.A., da Hora C.C., Zhang X., Kothary R., Snapp E., Ericsson M.,
RA Grundmann K., Breakefield X.O., Nery F.C.;
RT "Biochemical and cellular analysis of human variants of the DYT1 dystonia
RT protein, TorsinA/TOR1A.";
RL Hum. Mutat. 35:1101-1113(2014).
RN [31]
RP VARIANT HIS-216.
RX PubMed=26940431; DOI=10.1111/ane.12579;
RA Piovesana L.G., Torres F.R., Azevedo P.C., Amaral T.P., Lopes-Cendes I.,
RA D'Abreu A.;
RT "New THAP1 mutation and role of putative modifier in TOR1A.";
RL Acta Neurol. Scand. 135:183-188(2017).
RN [32]
RP VARIANT AMC5 GLU-303 DEL.
RX PubMed=28516161; DOI=10.1212/nxg.0000000000000154;
RA Reichert S.C., Gonzalez-Alegre P., Scharer G.H.;
RT "Biallelic TOR1A variants in an infant with severe arthrogryposis.";
RL Neurol. Genet. 3:e154-e154(2017).
RN [33]
RP VARIANT AMC5 288-ARG--ASP-332 DEL.
RX PubMed=30244176; DOI=10.1016/j.ejmg.2018.09.011;
RA Isik E., Aykut A., Atik T., Cogulu O., Ozkinay F.;
RT "Biallelic TOR1A mutations cause severe arthrogryposis: A case requiring
RT reverse phenotyping.";
RL Eur. J. Med. Genet. 62:103544-103544(2019).
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: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, ECO:0000269|PubMed:24930953}.
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 Evidence={ECO:0000269|PubMed:23569223};
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:14970196,
CC ECO:0000269|PubMed:15147511, ECO:0000269|PubMed:15505207,
CC ECO:0000269|PubMed:15767459, ECO:0000269|PubMed:16361107,
CC ECO:0000269|PubMed:18167355, ECO:0000269|PubMed:18827015,
CC ECO:0000269|PubMed:19535332, ECO:0000269|PubMed:20015956,
CC ECO:0000269|PubMed:21102408, ECO:0000269|PubMed:23569223,
CC ECO:0000269|PubMed:24930953, ECO:0000269|PubMed:27490483}.
CC -!- INTERACTION:
CC O14656; Q6PCB6: ABHD17C; NbExp=3; IntAct=EBI-524257, EBI-22011868;
CC O14656; P05067: APP; NbExp=3; IntAct=EBI-524257, EBI-77613;
CC O14656; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-524257, EBI-9089489;
CC O14656; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-524257, EBI-350590;
CC O14656; P22692: IGFBP4; NbExp=3; IntAct=EBI-524257, EBI-2831948;
CC O14656; P60409: KRTAP10-7; NbExp=6; IntAct=EBI-524257, EBI-10172290;
CC O14656; Q99750: MDFI; NbExp=3; IntAct=EBI-524257, EBI-724076;
CC O14656; Q5JTV8: TOR1AIP1; NbExp=2; IntAct=EBI-524257, EBI-2559665;
CC O14656; Q8NFQ8: TOR1AIP2; NbExp=3; IntAct=EBI-524257, EBI-524567;
CC O14656-2; Q6PCB6: ABHD17C; NbExp=3; IntAct=EBI-25847109, EBI-22011868;
CC O14656-2; P63010-2: AP2B1; NbExp=3; IntAct=EBI-25847109, EBI-11529439;
CC O14656-2; P05067: APP; NbExp=3; IntAct=EBI-25847109, EBI-77613;
CC O14656-2; Q9UII2: ATP5IF1; NbExp=3; IntAct=EBI-25847109, EBI-718459;
CC O14656-2; Q5JTY5: CBWD3; NbExp=3; IntAct=EBI-25847109, EBI-723434;
CC O14656-2; Q9UJX2: CDC23; NbExp=3; IntAct=EBI-25847109, EBI-396137;
CC O14656-2; Q53EZ4: CEP55; NbExp=3; IntAct=EBI-25847109, EBI-747776;
CC O14656-2; Q96FZ7: CHMP6; NbExp=3; IntAct=EBI-25847109, EBI-1049648;
CC O14656-2; Q92478: CLEC2B; NbExp=3; IntAct=EBI-25847109, EBI-13350535;
CC O14656-2; P35222: CTNNB1; NbExp=3; IntAct=EBI-25847109, EBI-491549;
CC O14656-2; Q9NR90-2: DAZ3; NbExp=3; IntAct=EBI-25847109, EBI-25830216;
CC O14656-2; Q9UHI6: DDX20; NbExp=3; IntAct=EBI-25847109, EBI-347658;
CC O14656-2; Q14154: DELE1; NbExp=3; IntAct=EBI-25847109, EBI-2805660;
CC O14656-2; Q9H147: DNTTIP1; NbExp=3; IntAct=EBI-25847109, EBI-2795449;
CC O14656-2; O75616: ERAL1; NbExp=3; IntAct=EBI-25847109, EBI-6393536;
CC O14656-2; Q9UI08-2: EVL; NbExp=3; IntAct=EBI-25847109, EBI-6448852;
CC O14656-2; Q6PIV2: FOXR1; NbExp=3; IntAct=EBI-25847109, EBI-10253815;
CC O14656-2; Q9H4A5: GOLPH3L; NbExp=3; IntAct=EBI-25847109, EBI-4403434;
CC O14656-2; P0C0S5: H2AZ1; NbExp=3; IntAct=EBI-25847109, EBI-1199859;
CC O14656-2; Q6DN90-2: IQSEC1; NbExp=3; IntAct=EBI-25847109, EBI-21911304;
CC O14656-2; Q8NA54: IQUB; NbExp=3; IntAct=EBI-25847109, EBI-10220600;
CC O14656-2; Q92993: KAT5; NbExp=3; IntAct=EBI-25847109, EBI-399080;
CC O14656-2; Q8IUB9: KRTAP19-1; NbExp=3; IntAct=EBI-25847109, EBI-12811111;
CC O14656-2; A2RU56: LOC401296; NbExp=3; IntAct=EBI-25847109, EBI-9088215;
CC O14656-2; Q8TDB4: MGARP; NbExp=3; IntAct=EBI-25847109, EBI-4397720;
CC O14656-2; P41218: MNDA; NbExp=3; IntAct=EBI-25847109, EBI-2829677;
CC O14656-2; Q9Y605: MRFAP1; NbExp=3; IntAct=EBI-25847109, EBI-995714;
CC O14656-2; O43196-2: MSH5; NbExp=3; IntAct=EBI-25847109, EBI-25844576;
CC O14656-2; O00746: NME4; NbExp=3; IntAct=EBI-25847109, EBI-744871;
CC O14656-2; Q96CV9-2: OPTN; NbExp=3; IntAct=EBI-25847109, EBI-9091423;
CC O14656-2; Q99497: PARK7; NbExp=3; IntAct=EBI-25847109, EBI-1164361;
CC O14656-2; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-25847109, EBI-716063;
CC O14656-2; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-25847109, EBI-9090282;
CC O14656-2; P12273: PIP; NbExp=3; IntAct=EBI-25847109, EBI-1049746;
CC O14656-2; O75626-3: PRDM1; NbExp=3; IntAct=EBI-25847109, EBI-25829882;
CC O14656-2; P57729: RAB38; NbExp=3; IntAct=EBI-25847109, EBI-6552718;
CC O14656-2; Q96QF0-7: RAB3IP; NbExp=3; IntAct=EBI-25847109, EBI-11984839;
CC O14656-2; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-25847109, EBI-25837959;
CC O14656-2; Q15019-3: SEPTIN2; NbExp=3; IntAct=EBI-25847109, EBI-11525407;
CC O14656-2; Q9NQ40: SLC52A3; NbExp=3; IntAct=EBI-25847109, EBI-25845274;
CC O14656-2; Q12824: SMARCB1; NbExp=3; IntAct=EBI-25847109, EBI-358419;
CC O14656-2; Q05C28: SPACA3; NbExp=3; IntAct=EBI-25847109, EBI-25845337;
CC O14656-2; Q7Z6I5: SPATA12; NbExp=3; IntAct=EBI-25847109, EBI-10696971;
CC O14656-2; O75558: STX11; NbExp=3; IntAct=EBI-25847109, EBI-714135;
CC O14656-2; P21980-2: TGM2; NbExp=3; IntAct=EBI-25847109, EBI-25842075;
CC O14656-2; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-25847109, EBI-3650647;
CC O14656-2; Q9NX07-2: TRNAU1AP; NbExp=3; IntAct=EBI-25847109, EBI-21894090;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:29053766}. Nucleus membrane
CC {ECO:0000269|PubMed:14970196, ECO:0000269|PubMed:29053766}; Peripheral
CC membrane protein {ECO:0000305}. Cell projection, growth cone
CC {ECO:0000250}. Cytoplasmic vesicle membrane {ECO:0000250}. Cytoplasmic
CC vesicle, secretory vesicle {ECO:0000250}. Cytoplasmic vesicle,
CC secretory vesicle, synaptic vesicle. Cytoplasm, cytoskeleton. Note=Upon
CC oxidative stress, redistributes to protusions from the cell surface (By
CC similarity). Peripherally associated with the inner face of the ER
CC membrane, probably mediated by the interaction with TOR1AIP1. The
CC association with nucleus membrane is mediated by the interaction with
CC TOR1AIP2. {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 -!- TISSUE SPECIFICITY: Widely expressed. Highest levels in kidney and
CC liver. In the brain, high levels found in the dopaminergic neurons of
CC the substantia nigra pars compacta, as well as in the neocortex,
CC hippocampus and cerebellum. Also highly expressed in the spinal cord.
CC {ECO:0000269|PubMed:10640617, ECO:0000269|PubMed:14970196,
CC 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) [MIM:128100]: A
CC primary torsion dystonia, and the most common and severe form. Dystonia
CC is defined by the presence of sustained involuntary muscle
CC contractions, often leading to abnormal postures. Dystonia type 1 is
CC characterized by involuntary, repetitive, sustained muscle contractions
CC or postures involving one or more sites of the body, in the absence of
CC other neurological symptoms. Typically, symptoms develop first in an
CC arm or leg in middle to late childhood and progress in approximately
CC 30% of patients to other body regions (generalized dystonia) within
CC about five years. 'Torsion' refers to the twisting nature of body
CC movements observed in DYT1, often affecting the trunk. Distribution and
CC severity of symptoms vary widely between affected individuals, ranging
CC from mild focal dystonia to severe generalized dystonia, even within
CC families. {ECO:0000269|PubMed:14970196, ECO:0000269|PubMed:15505207,
CC ECO:0000269|PubMed:16361107, ECO:0000269|PubMed:17428918,
CC ECO:0000269|PubMed:18167355, ECO:0000269|PubMed:18477710,
CC ECO:0000269|PubMed:18827015, ECO:0000269|PubMed:19955557,
CC ECO:0000269|PubMed:20169475, ECO:0000269|PubMed:21102408,
CC ECO:0000269|PubMed:24930953, ECO:0000269|PubMed:27490483,
CC ECO:0000269|PubMed:9288096}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Arthrogryposis multiplex congenita 5 (AMC5) [MIM:618947]: A
CC form of arthrogryposis multiplex congenita, a developmental condition
CC characterized by multiple joint contractures resulting from reduced or
CC absent fetal movements. AMC5 is an autosomal recessive form
CC characterized by severe congenital contractures, developmental delay,
CC strabismus and tremor. {ECO:0000269|PubMed:28516161,
CC ECO:0000269|PubMed:29053766, ECO:0000269|PubMed:30244176}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the ClpA/ClpB family. Torsin subfamily.
CC {ECO:0000305}.
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DR EMBL; AF007871; AAC51732.1; -; mRNA.
DR EMBL; AK314505; BAG37105.1; -; mRNA.
DR EMBL; BT006931; AAP35577.1; -; mRNA.
DR EMBL; AL158207; -; NOT_ANNOTATED_CDS; 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 PDB; 5J1S; X-ray; 1.40 A; A=51-332.
DR PDB; 5J1T; X-ray; 1.40 A; A=51-332.
DR PDB; 6OIF; EM; 4.40 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y=51-332.
DR PDBsum; 5J1S; -.
DR PDBsum; 5J1T; -.
DR PDBsum; 6OIF; -.
DR AlphaFoldDB; O14656; -.
DR SMR; O14656; -.
DR BioGRID; 108193; 100.
DR CORUM; O14656; -.
DR DIP; DIP-34411N; -.
DR IntAct; O14656; 73.
DR MINT; O14656; -.
DR STRING; 9606.ENSP00000345719; -.
DR GlyConnect; 1821; 2 N-Linked glycans (1 site).
DR GlyGen; O14656; 3 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; O14656; -.
DR PhosphoSitePlus; O14656; -.
DR BioMuta; TOR1A; -.
DR EPD; O14656; -.
DR jPOST; O14656; -.
DR MassIVE; O14656; -.
DR MaxQB; O14656; -.
DR PaxDb; O14656; -.
DR PeptideAtlas; O14656; -.
DR PRIDE; O14656; -.
DR ProteomicsDB; 48152; -. [O14656-1]
DR ProteomicsDB; 48153; -. [O14656-2]
DR ABCD; O14656; 1 sequenced antibody.
DR Antibodypedia; 31437; 273 antibodies from 32 providers.
DR DNASU; 1861; -.
DR Ensembl; ENST00000351698.5; ENSP00000345719.4; ENSG00000136827.12. [O14656-1]
DR GeneID; 1861; -.
DR KEGG; hsa:1861; -.
DR MANE-Select; ENST00000351698.5; ENSP00000345719.4; NM_000113.3; NP_000104.1.
DR UCSC; uc004byl.4; human. [O14656-1]
DR CTD; 1861; -.
DR DisGeNET; 1861; -.
DR GeneCards; TOR1A; -.
DR GeneReviews; TOR1A; -.
DR HGNC; HGNC:3098; TOR1A.
DR HPA; ENSG00000136827; Low tissue specificity.
DR MalaCards; TOR1A; -.
DR MIM; 128100; phenotype.
DR MIM; 605204; gene.
DR MIM; 618947; phenotype.
DR neXtProt; NX_O14656; -.
DR OpenTargets; ENSG00000136827; -.
DR Orphanet; 256; Early-onset generalized limb-onset dystonia.
DR Orphanet; 36899; Myoclonus-dystonia syndrome.
DR PharmGKB; PA27556; -.
DR VEuPathDB; HostDB:ENSG00000136827; -.
DR eggNOG; KOG2170; Eukaryota.
DR GeneTree; ENSGT00950000182888; -.
DR HOGENOM; CLU_053537_0_0_1; -.
DR InParanoid; O14656; -.
DR OMA; RGYETNE; -.
DR PhylomeDB; O14656; -.
DR TreeFam; TF314941; -.
DR PathwayCommons; O14656; -.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR SignaLink; O14656; -.
DR SIGNOR; O14656; -.
DR BioGRID-ORCS; 1861; 12 hits in 1087 CRISPR screens.
DR ChiTaRS; TOR1A; human.
DR GeneWiki; Torsin_A; -.
DR GenomeRNAi; 1861; -.
DR Pharos; O14656; Tbio.
DR PRO; PR:O14656; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O14656; protein.
DR Bgee; ENSG00000136827; Expressed in stromal cell of endometrium and 191 other tissues.
DR ExpressionAtlas; O14656; baseline and differential.
DR Genevisible; O14656; HS.
DR GO; GO:0070161; C:anchoring 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:0005829; C:cytosol; TAS:Reactome.
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; HDA: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:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IDA:UniProtKB.
DR GO; GO:0008092; F:cytoskeletal protein binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IMP:UniProtKB.
DR GO; GO:0019894; F:kinesin binding; IPI:UniProtKB.
DR GO; GO:0051787; F:misfolded protein binding; IEA:Ensembl.
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 cofactor-dependent protein refolding; IEA:InterPro.
DR GO; GO:0061077; P:chaperone-mediated protein folding; 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: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:GO_Central.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0048499; P:synaptic vesicle membrane organization; IMP:UniProtKB.
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; -; 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; Alternative splicing; ATP-binding; Cell projection;
KW Chaperone; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Disease variant;
KW Dystonia; Endoplasmic reticulum; Glycoprotein; Hydrolase; Membrane;
KW Nucleotide-binding; Nucleus; Reference proteome; Signal; Synapse.
FT SIGNAL 1..20
FT /evidence="ECO:0000305|PubMed:17037984"
FT CHAIN 21..332
FT /note="Torsin-1A"
FT /id="PRO_0000005506"
FT REGION 91..251
FT /note="Interaction with SNAPIN"
FT REGION 251..332
FT /note="Interaction with KLC1"
FT /evidence="ECO:0000269|PubMed:14970196"
FT REGION 312..332
FT /note="Interaction with SYNE3"
FT /evidence="ECO:0000269|PubMed:18827015"
FT BINDING 102..109
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000269|PubMed:10871631"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000269|PubMed:10871631"
FT VAR_SEQ 149..332
FT /note="DQLQLWIRGNVSACARSIFIFDEMDKMHAGLIDAIKPFLDYYDLVDGVSYQK
FT AMFIFLSNAGAERITDVALDFWRSGKQREDIKLKDIEHALSVSVFNNKNSGFWHSSLID
FT RNLIDYFVPFLPLEYKHLKMCIRVEMQSRGYEIDEDIVSRVAEEMTFFPKEERVFSDKG
FT CKTVFTKLDYYYDD -> ARMEVWNPFLDVIGFGVSLLWDEIWEFYVEMSEPGKRFMSQ
FT FPLERCRS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026605"
FT VARIANT 205
FT /note="F -> I (in DYT1; increased identical protein
FT binding; decreased ATP-dependent chaperone mediated protein
FT folding; changed nuclear membrane organization; decreased
FT neuron projection development; dbSNP:rs267607134)"
FT /evidence="ECO:0000269|PubMed:19955557,
FT ECO:0000269|PubMed:24930953"
FT /id="VAR_070932"
FT VARIANT 216
FT /note="D -> H (in dbSNP:rs1801968)"
FT /evidence="ECO:0000269|PubMed:26940431"
FT /id="VAR_020449"
FT VARIANT 264
FT /note="D -> H"
FT /evidence="ECO:0000269|PubMed:9288096"
FT /id="VAR_010788"
FT VARIANT 288..332
FT /note="Missing (in AMC5)"
FT /evidence="ECO:0000269|PubMed:30244176"
FT /id="VAR_084705"
FT VARIANT 288
FT /note="R -> Q (in DYT1; increased identical protein
FT binding; decreased ATP-dependent chaperone mediated protein
FT folding; changed nuclear membrane organization;
FT dbSNP:rs727502811)"
FT /evidence="ECO:0000269|PubMed:18477710,
FT ECO:0000269|PubMed:24930953"
FT /id="VAR_070933"
FT VARIANT 303
FT /note="Missing (in DYT1 and AMC5; acts as a dominant
FT negative; increased identical protein binding; loss of
FT interaction with TOR1AIP1 and TOR1AIP2 with loss of ATPase
FT activity induction; increased localization to the nuclear
FT membrane; decreased ATP-dependent chaperone mediated
FT protein folding; changed nuclear membrane organization;
FT dbSNP:rs80358233)"
FT /evidence="ECO:0000269|PubMed:14970196,
FT ECO:0000269|PubMed:15505207, ECO:0000269|PubMed:16361107,
FT ECO:0000269|PubMed:17428918, ECO:0000269|PubMed:18167355,
FT ECO:0000269|PubMed:18477710, ECO:0000269|PubMed:18827015,
FT ECO:0000269|PubMed:19955557, ECO:0000269|PubMed:20169475,
FT ECO:0000269|PubMed:21102408, ECO:0000269|PubMed:23569223,
FT ECO:0000269|PubMed:24930953, ECO:0000269|PubMed:27490483,
FT ECO:0000269|PubMed:28516161, ECO:0000269|PubMed:29053766,
FT ECO:0000269|PubMed:9288096"
FT /id="VAR_010789"
FT VARIANT 318
FT /note="G -> S (in AMC5; increased localization to the
FT nuclear membrane; induces the formation of spheroid bodies
FT in cells)"
FT /evidence="ECO:0000269|PubMed:29053766"
FT /id="VAR_084706"
FT VARIANT 323..328
FT /note="Missing (found in a patient with early-onset
FT atypical dystonia and myoclonic features; unknown
FT pathological significance; dbSNP:rs80358235)"
FT /evidence="ECO:0000269|PubMed:11523564"
FT /id="VAR_070934"
FT MUTAGEN 18
FT /note="V->F: Inhibits sequence signal cleavage."
FT /evidence="ECO:0000269|PubMed:17037984"
FT MUTAGEN 20
FT /note="A->F: Inhibits sequence signal cleavage."
FT /evidence="ECO:0000269|PubMed:17037984"
FT MUTAGEN 33
FT /note="V->N: N-glycosylated."
FT /evidence="ECO:0000269|PubMed:17037984"
FT MUTAGEN 108
FT /note="K->A: Loss of ATP-binding. No effect on interaction
FT with KLHL14. Increases interaction with TOR1AIP1 and
FT TOR1AIP2. Abolishes interaction with SLC6A3."
FT /evidence="ECO:0000269|PubMed:15505207,
FT ECO:0000269|PubMed:19339278, ECO:0000269|PubMed:19535332"
FT MUTAGEN 143
FT /note="N->Q: Reduces N-glycosylation."
FT /evidence="ECO:0000269|PubMed:10871631"
FT MUTAGEN 158
FT /note="N->Q: Reduces N-glycosylation."
FT /evidence="ECO:0000269|PubMed:10871631"
FT MUTAGEN 171
FT /note="E->Q: Loss of ATP hydrolysis. Loss of interaction
FT with KLHL14. Localizes in the nuclear envelope. No effect
FT on interaction with TOR1AIP1."
FT /evidence="ECO:0000269|PubMed:19339278,
FT ECO:0000269|PubMed:19535332, ECO:0000269|PubMed:20015956,
FT ECO:0000269|PubMed:23569223, ECO:0000269|PubMed:27490483"
FT CONFLICT 259
FT /note="D -> H (in Ref. 3; AAP35577 and 5; AAH00674)"
FT /evidence="ECO:0000305"
FT HELIX 58..68
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 73..87
FT /evidence="ECO:0007829|PDB:5J1S"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 108..119
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:5J1S"
FT STRAND 129..133
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 134..137
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 144..161
FT /evidence="ECO:0007829|PDB:5J1S"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 177..187
FT /evidence="ECO:0007829|PDB:5J1S"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 211..223
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 233..239
FT /evidence="ECO:0007829|PDB:5J1S"
FT TURN 240..245
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 247..252
FT /evidence="ECO:0007829|PDB:5J1S"
FT STRAND 256..262
FT /evidence="ECO:0007829|PDB:5J1S"
FT STRAND 264..269
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 274..287
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 294..303
FT /evidence="ECO:0007829|PDB:5J1S"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:5J1S"
FT TURN 309..311
FT /evidence="ECO:0007829|PDB:5J1S"
FT TURN 316..322
FT /evidence="ECO:0007829|PDB:5J1S"
FT HELIX 323..328
FT /evidence="ECO:0007829|PDB:5J1S"
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
