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O14656 (TOR1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 16, 2012. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Torsin-1A
Alternative name(s):
Dystonia 1 protein
Torsin family 1 member A
Gene names
Name:TOR1A
Synonyms:DQ2, DYT1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length332 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May serve as a molecular chaperone assisting in the proper folding of secreted and/or membrane proteins. In the nucleus, displaces the nuclear membrane proteins SUN2, SYNE2 and nesprin-3/C14orf49, leaving nuclear pores and SUN1 unchanged. Ref.10

Subunit structure

May form homohexamers. Interacts with TOR1AIP1 and TOR1AIP2. Interacts with KLHL14, preferentially when ATP-free. Ref.8 Ref.9

Subcellular location

Endoplasmic reticulum lumen. Nucleus membrane. Note: Mainly located in the lumen of the endoplasmic reticulum. The association with nuclear envelope is mediated by the interaction with TOR1AIP2. The Glu-303 del variant is lumenally-oriented in discrete large spheroid intracellular structures rather than in the endoplasmic reticulum. Ref.6 Ref.9 Ref.10

Tissue specificity

Widely expressed. Highest levels in kidney and liver. Not detected in spleen. In the brain, high levels found in the dopaminergic neurons of the substantia nigra pars compacta, as well as in the neocortex, hippocampus and cerebellum. Also high expression in the spinal cord. Ref.7

Involvement in disease

Defects in TOR1A are the cause of dystonia type 1 (DYT1) [MIM:128100]. DYT1 is a primary torsion dystonia, and the most common and severe form. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT1 is characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body, in the absence of other neurological symptoms. Typically, symptoms develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. 'Torsion' refers to the twisting nature of body movements observed in DYT1, often affecting the trunk. Distribution and severity of symptoms vary widely between affected individuals, ranging from mild focal dystonia to severe generalized dystonia, even within families. Ref.1

Sequence similarities

Belongs to the clpA/clpB family. Torsin subfamily.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14656-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O14656-2)

The sequence of this isoform differs from the canonical sequence as follows:
     149-332: DQLQLWIRGN...FTKLDYYYDD → ARMEVWNPFL...SQFPLERCRS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 332312Torsin-1A
PRO_0000005506

Regions

Nucleotide binding102 – 1098ATP

Amino acid modifications

Glycosylation1431N-linked (GlcNAc...) (high mannose)
Glycosylation1581N-linked (GlcNAc...) (high mannose)

Natural variations

Alternative sequence149 – 332184DQLQL…YYYDD → ARMEVWNPFLDVIGFGVSLL WDEIWEFYVEMSEPGKRFMS QFPLERCRS in isoform 2.
VSP_026605
Natural variant2161D → H.
Corresponds to variant rs1801968 [ dbSNP | Ensembl ].
VAR_020449
Natural variant2641D → H. Ref.1
VAR_010788
Natural variant3031Missing in DYT1; enriched in the nuclear envelope compared to wild-type, but affects nuclear envelope components less efficiently. Ref.1
VAR_010789

Experimental info

Mutagenesis1081K → A: Loss of ATP-binding. No effect on KLHL14-binding. Loss of relocalization to the nuclear envelope in the presence of TOR1AIP2. Ref.9 Ref.10
Mutagenesis1711E → Q: Loss of ATP hydrolysis. Loss of KLHL14-binding. Loss of relocalization to the nuclear envelope in the presence of TOR1AIP2. Ref.9 Ref.10
Sequence conflict2591D → H in AAP35577. Ref.3
Sequence conflict2591D → H in AAH00674. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: B69B28D0B4112080

FASTA33237,809
        10         20         30         40         50         60 
MKLGRAVLGL LLLAPSVVQA VEPISLGLAL AGVLTGYIYP RLYCLFAECC GQKRSLSREA 

        70         80         90        100        110        120 
LQKDLDDNLF GQHLAKKIIL NAVFGFINNP KPKKPLTLSL HGWTGTGKNF VSKIIAENIY 

       130        140        150        160        170        180 
EGGLNSDYVH LFVATLHFPH ASNITLYKDQ LQLWIRGNVS ACARSIFIFD EMDKMHAGLI 

       190        200        210        220        230        240 
DAIKPFLDYY DLVDGVSYQK AMFIFLSNAG AERITDVALD FWRSGKQRED IKLKDIEHAL 

       250        260        270        280        290        300 
SVSVFNNKNS GFWHSSLIDR NLIDYFVPFL PLEYKHLKMC IRVEMQSRGY EIDEDIVSRV 

       310        320        330 
AEEMTFFPKE ERVFSDKGCK TVFTKLDYYY DD

« Hide

Isoform 2 [UniParc].

Checksum: BD34184941B1B11C
Show »

FASTA19722,135

References

« Hide 'large scale' references
[1]"The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein."
Ozelius L.J., Hewett J.W., Page C.E., Bressman S.B., Kramer P.L., Shalish C., de Leon D., Brin M.F., Raymond D., Corey D.P., Fahn S., Risch N.J., Buckler A.J., Gusella J.F., Breakefield X.O.
Nat. Genet. 17:40-48(1997) [PubMed: 9288096] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT DYT1 GLU-303 DEL, VARIANT HIS-264.
Tissue: Brain cortex, Hippocampus and Substantia nigra.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed: 15164053] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Kidney and Skin.
[6]"Torsin A and its torsion dystonia-associated mutant forms are lumenal glycoproteins that exhibit distinct subcellular localizations."
Kustedjo K., Bracey M.H., Cravatt B.F.
J. Biol. Chem. 275:27933-27939(2000) [PubMed: 10871631] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"Immunohistochemical localization and distribution of torsinA in normal human and rat brain."
Shashidharan P., Kramer B.C., Walker R.H., Olanow C.W., Brin M.F.
Brain Res. 853:197-206(2000) [PubMed: 10640617] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein."
Goodchild R.E., Dauer W.T.
J. Cell Biol. 168:855-862(2005) [PubMed: 15767459] [Abstract]
Cited for: INTERACTION WITH TOR1AIP1 AND TOR1AIP2.
[9]"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: 19535332] [Abstract]
Cited for: INTERACTION WITH KLHL14, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-108 AND GLU-171.
[10]"LULL1 retargets TorsinA to the nuclear envelope revealing an activity that is impaired by the DYT1 dystonia mutation."
Vander Heyden A.B., Naismith T.V., Snapp E.L., Hodzic D., Hanson P.I.
Mol. Biol. Cell 20:2661-2672(2009) [PubMed: 19339278] [Abstract]
Cited for: FUNCTION, HEXAMER FORMATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-108 AND GLU-171.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF007871 mRNA. Translation: AAC51732.1.
AK314505 mRNA. Translation: BAG37105.1.
BT006931 mRNA. Translation: AAP35577.1.
AL158207 Genomic DNA. Translation: CAC88168.1.
BC000674 mRNA. Translation: AAH00674.1.
BC014484 mRNA. Translation: AAH14484.1.
IPIIPI00386422.
IPI00413293.
RefSeqNP_000104.1. NM_000113.2.
UniGeneHs.534312.

3D structure databases

ProteinModelPortalO14656.
SMRO14656. Positions 94-119.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-34411N.
IntActO14656. 3 interactions.
STRINGO14656.

Proteomic databases

PRIDEO14656.

Protocols and materials databases

DNASU1861.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000351698; ENSP00000345719; ENSG00000136827.
ENST00000437532; ENSP00000412574; ENSG00000136827.
GeneID1861.
KEGGhsa:1861.
UCSCuc004byl.3. human.
uc004byn.3. human.

Organism-specific databases

CTD1861.
GeneCardsGC09M132575.
H-InvDBHIX0008457.
HGNCHGNC:3098. TOR1A.
HPACAB012473.
MIM128100. phenotype.
605204. gene.
neXtProtNX_O14656.
Orphanet256. Early onset torsion dystonia.
36899. Myoclonic dystonia.
PharmGKBPA27556.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG283963.
GeneTreeENSGT00390000001920.
HOGENOMHOG000115770.
HOVERGENHBG054188.
InParanoidO14656.
OrthoDBEOG4RBQK4.
PhylomeDBO14656.

Enzyme and pathway databases

Pathway_Interaction_DBalphasynuclein_pathway. Alpha-synuclein signaling.

Gene expression databases

ArrayExpressO14656.
BgeeO14656.
CleanExHS_TOR1A.
GenevestigatorO14656.
GermOnlineENSG00000136827. Homo sapiens.

Family and domain databases

InterProIPR010448. Torsin.
IPR017378. Torsin_subgr.
[Graphical view]
PANTHERPTHR10760. Torsin. 1 hit.
PfamPF06309. Torsin. 1 hit.
[Graphical view]
PIRSFPIRSF038079. Torsin_2A. 1 hit.
ProtoNetSearch...

Other

NextBio7627.
SOURCESearch...

Entry information

Entry nameTOR1A_HUMAN
AccessionPrimary (citable) accession number: O14656
Secondary accession number(s): B2RB58, Q53Y64, Q96CA0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: January 1, 1998
Last modified: May 16, 2012
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

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