InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TOR1A

Summary

InnateDB Protein

IDBP-89278.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TOR1A

Protein Name

torsin family 1, member A (torsin A)

Synonyms

DQ2; DYT1;

Species

Homo sapiens

Ensembl Protein

ENSP00000345719

InnateDB Gene

IDBG-89274 (TOR1A)

Protein Structure

UniProt Annotation

Function

Protein with chaperone functions important for the control of protein folding, processing, stability and localization as well as for the reduction of misfolded protein aggregates. Involved in the regulation of synaptic vesicle recycling, controls STON2 protein stability in collaboration with the COP9 signalosome complex (CSN). In the nucleus, may link the cytoskeleton with the nuclear envelope, this mechanism seems to be crucial for the control of nuclear polarity, cell movement and, specifically in neurons, nuclear envelope integrity. Participates in the cellular trafficking and may regulate the subcellular location of multipass membrane proteins such as the dopamine transporter SLC6A3, leading to the modulation of dopamine neurotransmission. In the endoplasmic reticulum, plays a role in the quality control of protein folding by increasing clearance of misfolded proteins such as SGCE variants or holding them in an intermediate state for proper refolding. May have a redundant function with TOR1B in non- neural tissues. {ECO:0000269PubMed:15505207, ECO:0000269PubMed:16361107, ECO:0000269PubMed:17428918, ECO:0000269PubMed:18167355, ECO:0000269PubMed:18827015, ECO:0000269PubMed:19339278, ECO:0000269PubMed:20169475, ECO:0000269PubMed:23569223}.

Subcellular Localization

Endoplasmic reticulum lumen. Nucleus membrane; Peripheral membrane protein. Cell projection, growth cone {ECO:0000250}. Cytoplasmic vesicle membrane {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle. Cytoplasm, cytoskeleton. Note=Upon oxidative stress, redistributes to protusions from the cell surface (By similarity). Peripherally associated with the inner face of the ER membrane, probably mediated by the interaction with TOR1AIP1. The association with nucleus membrane is mediated by the interaction with TOR1AIP2. {ECO:0000250}.

Disease Associations

Dystonia 1, torsion, autosomal dominant (DYT1) [MIM:128100]: 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. Dystonia type 1 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. {ECO:0000269PubMed:18477710, ECO:0000269PubMed:19955557, ECO:0000269PubMed:9288096}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Widely expressed. Highest levels in kidney and liver. 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 highly expressed in the spinal cord. {ECO:0000269PubMed:10640617, ECO:0000269PubMed:14970196, ECO:0000269PubMed:15147511}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 25 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	25 [view]
Protein-Protein	25 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008092	cytoskeletal protein binding
GO:0016887	ATPase activity
GO:0019894	kinesin binding
GO:0051082	unfolded protein binding
GO:0051787	misfolded protein binding

Biological Process

GO:0000338	protein deneddylation
GO:0006200	ATP catabolic process
GO:0006979	response to oxidative stress
GO:0006996	organelle organization
GO:0006998	nuclear envelope organization
GO:0007155	cell adhesion
GO:0031175	neuron projection development
GO:0034504	protein localization to nucleus
GO:0044319	wound healing, spreading of cells
GO:0045104	intermediate filament cytoskeleton organization
GO:0048489	synaptic vesicle transport
GO:0051085	chaperone mediated protein folding requiring cofactor
GO:0051260	protein homooligomerization
GO:0051584	regulation of dopamine uptake involved in synaptic transmission
GO:0061077	chaperone-mediated protein folding
GO:0071712	ER-associated misfolded protein catabolic process
GO:0071763	nuclear membrane organization
GO:0072321	chaperone-mediated protein transport
GO:1900244	positive regulation of synaptic vesicle endocytosis
GO:2000008	regulation of protein localization to cell surface

Cellular Component

GO:0005634	nucleus
GO:0005635	nuclear envelope
GO:0005737	cytoplasm
GO:0005783	endoplasmic reticulum
GO:0005788	endoplasmic reticulum lumen
GO:0005856	cytoskeleton
GO:0008021	synaptic vesicle
GO:0016020	membrane
GO:0030054	cell junction
GO:0030133	transport vesicle
GO:0030141	secretory granule
GO:0030426	growth cone
GO:0030659	cytoplasmic vesicle membrane
GO:0031965	nuclear membrane
GO:0042406	extrinsic component of endoplasmic reticulum membrane
GO:0043005	neuron projection
GO:0043231	intracellular membrane-bounded organelle
GO:0070062	extracellular vesicular exosome