Target Information
| Target General Information | Top | |||||
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| Target ID |
T70027
(Former ID: TTDI02631)
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| Target Name |
Torsin-1A (TOR1A)
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| Synonyms |
Torsin family 1 member A; Torsin ATPase-1A; TORA; TA; Dystonia 1 protein; DYT1; DQ2
Click to Show/Hide
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| Gene Name |
TOR1A
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
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. 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.
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| BioChemical Class |
Acid anhydride hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.6.4.-
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| Sequence |
MKLGRAVLGLLLLAPSVVQAVEPISLGLALAGVLTGYIYPRLYCLFAECCGQKRSLSREA
LQKDLDDNLFGQHLAKKIILNAVFGFINNPKPKKPLTLSLHGWTGTGKNFVSKIIAENIY EGGLNSDYVHLFVATLHFPHASNITLYKDQLQLWIRGNVSACARSIFIFDEMDKMHAGLI DAIKPFLDYYDLVDGVSYQKAMFIFLSNAGAERITDVALDFWRSGKQREDIKLKDIEHAL SVSVFNNKNSGFWHSSLIDRNLIDYFVPFLPLEYKHLKMCIRVEMQSRGYEIDEDIVSRV AEEMTFFPKEERVFSDKGCKTVFTKLDYYYDD Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Adenosine triphosphate | Ligand Info | |||||
| Structure Description | TorsinA-LULL1 complex, H. sapiens, bound to VHH-BS2 | PDB:5J1S | ||||
| Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | Yes | [2] |
| PDB Sequence |
SLSREALQKD
64 LDDNLFGQHL74 AKKIILNAVF84 GFINNPKPKK94 PLTLSLHGWT104 GTGKNFVSKI 114 IAENIYEGGL124 NSDYVHLFVA134 TLHFPHASNI144 TLYKDQLQLW154 IRGNVSACAR 164 SIFIFDQMDK174 MHAGLIDAIK184 PFLDYYDLVD194 GVSYQKAMFI204 FLSNAGAERI 214 TDVALDFWRS224 GKQREDIKLK234 DIEHALSVSV244 FNNKNSGFWH254 SSLIDRNLID 264 YFVPFLPLEY274 KHLKMCIRVE284 MQSRGYEIDE294 DIVSRVAEEM304 TFFPKEERVF 314 SDKGCKTVFT324 KLDYYYD
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ASN68
3.323
LEU69
3.556
PHE70
2.855
GLN72
3.932
GLY102
4.644
TRP103
3.971
THR104
2.648
GLY105
2.934
THR106
2.902
GLY107
3.095
LYS108
2.720
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| Caseinolytic peptidase B protein homolog (CLPB) | 21.186 (50/236) | 1.00E-03 |
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 4.29E-04 |
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| Closeness centrality | 2.04E-01 | Radiality | 1.35E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.10E+01 | Topological coefficient | 2.00E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Torsin 1A and the pathomechanism of torsion dystonia type 1. Postepy Biochem. 2015;61(1):35-41. | |||||
| REF 2 | Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia. Elife. 2016 Aug 4;5. pii: e17983. | |||||
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