Torsin A Explained

Torsin-1A (TorA) also known as dystonia 1 protein (DYT1) is a protein that in humans is encoded by the TOR1A gene (also known as DQ2 or DYT1).^[1] TorA localizes to the endoplasmic reticulum and contiguous perinuclear space, where its ATPase activity is activated by either LULL1 or LAP1, respectively.

Function

The protein encoded by this gene is a member of the AAA family of adenosine triphosphatases (ATPases), is related to the Clp protease/heat shock family.

Clinical significance

Mutations in this gene result in the autosomal dominant disorder, torsion dystonia 1.^[2]

Further reading

• Ozelius LJ, Hewett JW, Page CE, etal . The gene (DYT1) for early-onset torsion dystonia encodes a novel protein related to the Clp protease/heat shock family. . Advances in Neurology . 78 . 93–105 . 1998 . 9750906 .
• Ferrari Toninelli G, Spano P, Memo M . TorsinA, microtubules and cell polarity. . Funct. Neurol. . 18 . 1 . 7–10 . 2003 . 12760408 .
• Rothwell JC, Edwards M, Huang YZ, Bhatia KP . Physiological studies in carriers of the DYT1 gene mutation. . Rev. Neurol. (Paris) . 159 . 10 Pt 1 . 880–4 . 2004 . 14615676 .
• Ozelius LJ, Hewett JW, Page CE, etal . The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein. . Nat. Genet. . 17 . 1 . 40–8 . 1997 . 9288096 . 10.1038/ng0997-40 . 29095964 .
• Augood SJ, Penney JB, Friberg IK, etal . Expression of the early-onset torsion dystonia gene (DYT1) in human brain. . Ann. Neurol. . 43 . 5 . 669–73 . 1998 . 9585364 . 10.1002/ana.410430518 . 30238231 .
• Kamm C, Castelon-Konkiewitz E, Naumann M, etal . GAG deletion in the DYT1 gene in early limb-onset idiopathic torsion dystonia in Germany. . Mov. Disord. . 14 . 4 . 681–3 . 1999 . 10435508 . 10.1002/1531-8257(199907)14:4<681::AID-MDS1020>3.0.CO;2-M . 20194006 .
• Ikeuchi T, Shimohata T, Nakano R, etal . A case of primary torsion dystonia in Japan with the 3-bp (GAG) deletion in the DYT1 gene with a unique clinical presentation. . Neurogenetics . 2 . 3 . 189–90 . 1999 . 10541594 . 10.1007/s100480050082 . 27834129 .
• Shashidharan P, Kramer BC, Walker RH, etal . Immunohistochemical localization and distribution of torsinA in normal human and rat brain. . Brain Res. . 853 . 2 . 197–206 . 2000 . 10640617 . 10.1016/S0006-8993(99)02232-5 . 7112316 .
• Hewett J, Gonzalez-Agosti C, Slater D, etal . Mutant torsinA, responsible for early-onset torsion dystonia, forms membrane inclusions in cultured neural cells. . Hum. Mol. Genet. . 9 . 9 . 1403–13 . 2000 . 10814722 . 10.1093/hmg/9.9.1403 .
• Kustedjo K, Bracey MH, Cravatt BF . Torsin A and its torsion dystonia-associated mutant forms are lumenal glycoproteins that exhibit distinct subcellular localizations. . J. Biol. Chem. . 275 . 36 . 27933–9 . 2000 . 10871631 . 10.1074/jbc.M910025199 . free .
• Suzuki Y, Tsunoda T, Sese J, etal . Identification and characterization of the potential promoter regions of 1031 kinds of human genes. . Genome Res. . 11 . 5 . 677–84 . 2001 . 11337467 . 10.1101/gr.gr-1640r. 311086 .
• Konakova M, Huynh DP, Yong W, Pulst SM . Cellular distribution of torsin A and torsin B in normal human brain. . Arch. Neurol. . 58 . 6 . 921–7 . 2001 . 11405807 . 10.1001/archneur.58.6.921 .
• Sharma N, Hewett J, Ozelius LJ, etal . A close association of torsinA and alpha-synuclein in Lewy bodies: a fluorescence resonance energy transfer study. . Am. J. Pathol. . 159 . 1 . 339–44 . 2001 . 11438481 . 10.1016/s0002-9440(10)61700-2. 1850427 .
• Leung JC, Klein C, Friedman J, etal . Novel mutation in the TOR1A (DYT1) gene in atypical early onset dystonia and polymorphisms in dystonia and early onset parkinsonism. . Neurogenetics . 3 . 3 . 133–43 . 2002 . 11523564 . 10.1007/s100480100111 . 11713438 .
• Tuffery-Giraud S, Cavalier L, Roubertie A, etal . No evidence of allelic heterogeneity in the DYT1 gene of European patients with early onset torsion dystonia. . J. Med. Genet. . 38 . 10 . 35e–35 . 2002 . 11584049 . 10.1136/jmg.38.10.e35 . 1734733 .
• Major T, Svetel M, Romac S, Kostić VS . DYT1 mutation in primary torsion dystonia in a Serbian population. . J. Neurol. . 248 . 11 . 940–3 . 2002 . 11757956 . 10.1007/s004150170045 . 10128440 .
• Walker RH, Morgello S, Davidoff-Feldman B, etal . Autosomal dominant chorea-acanthocytosis with polyglutamine-containing neuronal inclusions. . Neurology . 58 . 7 . 1031–7 . 2002 . 11940688 . 10.1212/wnl.58.7.1031. 38388934 .
• Hjermind LE, Werdelin LM, Sørensen SA . Inherited and de novo mutations in sporadic cases of DYT1-dystonia. . Eur. J. Hum. Genet. . 10 . 3 . 213–6 . 2002 . 11973627 . 10.1038/sj.ejhg.5200782 . free .

External links

• GeneReview/NIH/UW entry on Early-Onset Primary Dystonia

Notes and References

1. Ozelius LJ, Page CE, Klein C, Hewett JW, Mineta M, Leung J, Shalish C, Bressman SB, de Leon D, Brin MF, Fahn S, Corey DP, Breakefield XO . The TOR1A (DYT1) gene family and its role in early onset torsion dystonia . Genomics . 62 . 3 . 377–84 . Mar 2000 . 10644435 . 10.1006/geno.1999.6039 .
2. Web site: Entrez Gene: TOR1A torsin family 1, member A (torsin A).