O14656 (TOR1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Torsin-1A

Alternative name(s):
Dystonia 1 protein
Torsin family 1 member A

Gene names

Name:	TOR1A
Synonyms:	DQ2, DYT1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	332 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May serve as a molecular chaperone assisting in the proper folding of secreted and/or membrane proteins.
Subunit structure	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. Also found associated with the nuclear envelope. The Glu-303 del variant is lumenally-oriented in discrete large spheroid intracellular structures rather than in the endoplasmic reticulum. Ref.6 Ref.9
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.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Dystonia
Domain	Signal
Ligand	ATP-binding Nucleotide-binding
Molecular function	Chaperone
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	chaperone mediated protein folding requiring cofactor Inferred from electronic annotation. Source: InterPro response to unfolded protein Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Traceable author statement. Source: ProtInc serine-type endopeptidase activity Traceable author statement. Source: ProtInc unfolded protein binding Traceable author statement. Source: ProtInc
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 332	312	Torsin-1A		PRO_0000005506
Regions
	Nucleotide binding	102 – 109	8	ATP
Amino acid modifications
	Glycosylation	143	1	N-linked (GlcNAc...) (high mannose)
	Glycosylation	158	1	N-linked (GlcNAc...) (high mannose)
Natural variations
	Alternative sequence	149 – 332	184	DQLQL…YYYDD → ARMEVWNPFLDVIGFGVSLL WDEIWEFYVEMSEPGKRFMS QFPLERCRS in isoform 2.		VSP_026605
	Natural variant	216	1	D → H. Corresponds to variant rs1801968 [ dbSNP | Ensembl ].		VAR_020449
	Natural variant	264	1	D → H. Ref.1		VAR_010788
	Natural variant	303	1	Missing in DYT1.		VAR_010789
Experimental info
	Mutagenesis	108	1	K → A: Loss of ATP-binding. No effect on KLHL14-binding. Ref.9
	Mutagenesis	171	1	E → Q: Loss of ATP hydrolysis. Loss of KLHL14-binding. Ref.9
	Sequence conflict	259	1	D → H in AAP35577. Ref.3
	Sequence conflict	259	1	D → H in AAH00674. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: B69B28D0B4112080	FASTA	332	37,809
	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
	Isoform 2 [UniParc]. Checksum: BD34184941B1B11C	FASTA	197	22,135
	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 ASNITLYKAR MEVWNPFLDV IGFGVSLLWD EIWEFYVEMS 190 EPGKRFMSQF PLERCRS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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.
IPI	IPI00386422. IPI00413293.
RefSeq	NP_000104.1. NM_000113.2.
UniGene	Hs.534312.
3D structure databases
ProteinModelPortal	O14656.
SMR	O14656. Positions 94-119.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14656. 3 interactions.
STRING	O14656.
Proteomic databases
PRIDE	O14656.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000351698; ENSP00000345719; ENSG00000136827. ENST00000437532; ENSP00000412574; ENSG00000136827.
GeneID	1861.
KEGG	hsa:1861.
UCSC	uc004byl.1. human. uc004byn.1. human.
Organism-specific databases
CTD	1861.
GeneCards	GC09M132575.
H-InvDB	HIX0008457.
HGNC	HGNC:3098. TOR1A.
HPA	CAB012473.
MIM	128100. phenotype. 605204. gene.
neXtProt	NX_O14656.
Orphanet	256. Early onset torsion dystonia. 36899. Myoclonic dystonia.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13997.
GeneTree	ENSGT00390000001920.
HOVERGEN	HBG054188.
InParanoid	O14656.
OrthoDB	EOG4RBQK4.
PhylomeDB	O14656.
Enzyme and pathway databases
Pathway_Interaction_DB	alphasynuclein_pathway. Alpha-synuclein signaling.
Gene expression databases
ArrayExpress	O14656.
Bgee	O14656.
CleanEx	HS_TOR1A.
Genevestigator	O14656.
GermOnline	ENSG00000136827. Homo sapiens.
Family and domain databases
InterPro	IPR010448. Torsin. IPR017378. Torsin_subgr. [Graphical view]
PANTHER	PTHR10760. Torsin. 1 hit.
Pfam	PF06309. Torsin. 1 hit. [Graphical view]
PIRSF	PIRSF038079. Torsin_2A. 1 hit.
ProtoNet	Search...
Other
NextBio	7627.
SOURCE	Search...

Entry information

Entry name

TOR1A_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.