Target Information
| Target General Information | Top | |||||
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| Target ID |
T88547
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| Target Name |
HUMAN opioid receptor sigma 1 (OPRS1)
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| Synonyms |
hSigmaR1; Sigma1R; Sigma1-receptor; Sigma non-opioid intracellular receptor 1; Sigma 1-type opioid receptor; SRBP; SR31747-binding protein; SR31747 binding protein 1; SR-BP; SIG-1R; Opioid receptor, sigma 1, isoform 1; OPRS1 protein; Aging-associated gene 8 protein; AAG8
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| Gene Name |
SIGMAR1
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| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Schizophrenia [ICD-11: 6A20] | |||||
| Function |
Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration. Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria. Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112. Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MQWAVGRRWAWAALLLAVAAVLTQVVWLWLGTQSFVFQREEIAQLARQYAGLDHELAFSR
LIVELRRLHPGHVLPDEELQWVFVNAGGWMGAMCLLHASLSEYVLLFGTALGSRGHSGRY WAEISDTIISGTFHQWREGTTKSEVFYPGETVVHGPGEATAVEWGPNTWMVEYGRGVIPS TLAFALADTVFSTQDFLTLFYTLRSYARGLRLELTTYLFGQDP Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Investigative Agents | [+] 1 | + | ||||
| 1 | Haloperidol | Drug Info | Approved | Schizophrenia | [2] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | E-52862 | Drug Info | [1] | |||
| 2 | PD-144418 | Drug Info | [1] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Haloperidol | Drug Info | [1] | |||
| 2 | PB28 | Drug Info | [1] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | RS-PPCC | Drug Info | [1] | |||
| 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: Haloperidol | Ligand Info | |||||
| Structure Description | Human sigma-1 receptor bound to haloperidol | PDB:6DJZ | ||||
| Method | X-ray diffraction | Resolution | 3.08 Å | Mutation | No | [3] |
| PDB Sequence |
RWAWAALLLA
17 VAAVLTQVVW27 LWLGTQSFVF37 QREEIAQLAR47 QYAGLDHELA57 FSRLIVELRR 67 LHPGHVLPDE77 ELQWVFVNAG87 GWMGAMCLLH97 ASLSEYVLLF107 GTALGSRGHS 117 GRYWAEISDT127 IISGTFHQWR137 EGTTKSEVFY147 PGETVVHGPG157 EATAVEWGPN 167 TWMVEYGRGV177 IPSTLAFALA187 DTVFSTQDFL197 TLFYTLRSYA207 RGLRLELTTY 217 LF
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VAL84
4.653
TRP89
4.113
MET93
3.576
LEU95
4.728
TYR103
3.588
LEU105
3.719
PHE107
4.605
HIS116
4.788
SER117
3.315
TYR120
3.113
ILE124
3.917
ASP126
2.818
PHE133
3.811
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| Ligand Name: PD-144418 | Ligand Info | |||||
| Structure Description | Human sigma-1 receptor bound to PD144418 | PDB:5HK1 | ||||
| Method | X-ray diffraction | Resolution | 2.51 Å | Mutation | No | [4] |
| PDB Sequence |
RWAWAALLLA
17 VAAVLTQVVW27 LWLGTQSFVF37 QREEIAQLAR47 QYAGLDHELA57 FSRLIVELRR 67 LHPGHVLPDE77 ELQWVFVNAG87 GWMGAMCLLH97 ASLSEYVLLF107 GTALGSRGHS 117 GRYWAEISDT127 IISGTFHQWR137 EGTTKSEVFY147 PGETVVHGPG157 EATAVEWGPN 167 TWMVEYGRGV177 IPSTLAFALA187 DTVFSTQDFL197 TLFYTLRSYA207 RGLRLELTTY 217 LF
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VAL84
3.971
TRP89
3.866
MET93
3.828
LEU95
4.451
ALA98
4.674
TYR103
3.988
LEU105
3.531
PHE107
3.577
SER117
3.796
TYR120
3.374
ILE124
3.639
ASP126
3.067
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| 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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There is no similarity protein (E value < 0.005) for this target
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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 | 7 | Degree centrality | 7.52E-04 | Betweenness centrality | 3.73E-04 |
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| Closeness centrality | 2.09E-01 | Radiality | 1.36E+01 | Clustering coefficient | 4.76E-02 |
| Neighborhood connectivity | 1.56E+01 | Topological coefficient | 1.58E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | A SARS-CoV-2 protein interaction map reveals targets for drug repurposing | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 076035. | |||||
| REF 3 | Structural basis for Sigma(1) receptor ligand recognition. Nat Struct Mol Biol. 2018 Oct;25(10):981-987. | |||||
| REF 4 | Crystal structure of the human Sigma1 receptor. Nature. 2016 Apr 28;532(7600):527-30. | |||||
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