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Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 371 | 7p14.3 | NPSR1 | neuropeptide S receptor 1 | 26,39,76,90 |
| Mouse | 7 | 371 | 9 A3-A4 | Npsr1 | neuropeptide S receptor 1 | 55 |
| Rat | 7 | 372 | 8q13 | Npsr1 | neuropeptide S receptor 1 | |
| Previous and Unofficial Names |
| VRR1 | GPR154 | PGR14 | G protein-coupled receptor 154 | vasopressin receptor-related receptor 1 |
| Database Links |
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| Specialist databases | |
| GPCRdb | npsr1_human (Hs), npsr1_mouse (Mm), npsr1_rat (Rn) |
| Other databases | |
| Alphafold | Q6W5P4 (Hs), Q8BZP8 (Mm), P0C0L6 (Rn) |
| ChEMBL Target | CHEMBL5162 (Hs), CHEMBL5497 (Mm), CHEMBL3308949 (Rn) |
| Ensembl Gene | ENSG00000187258 (Hs), ENSMUSG00000043659 (Mm), ENSRNOG00000015863 (Rn) |
| Entrez Gene | 387129 (Hs), 319239 (Mm), 300458 (Rn) |
| Human Protein Atlas | ENSG00000187258 (Hs) |
| KEGG Gene | hsa:387129 (Hs), mmu:319239 (Mm), rno:300458 (Rn) |
| OMIM | 608595 (Hs) |
| Pharos | Q6W5P4 (Hs) |
| RefSeq Nucleotide | NM_207172 (Hs), NM_175678 (Mm), NM_001106808 (Rn) |
| RefSeq Protein | NP_997056 (Hs), NP_997055 (Hs), NP_783609 (Mm), NP_001100278 (Rn) |
| UniProtKB | Q6W5P4 (Hs), Q8BZP8 (Mm), P0C0L6 (Rn) |
| Wikipedia | NPSR1 (Hs) |
| Natural/Endogenous Ligands |
| neuropeptide S {Sp: Human} , neuropeptide S {Sp: Mouse} , neuropeptide S {Sp: Rat} |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| [125I]-Tyr10-hNPS = [125I]-Tyr10 Neuropeptide S (human). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific antagonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonist SHA 68 has been tested against human Asn107 and Ile107 NPS receptor variants exhibiting pA2 values of 7.8 and 7.5 respectively [53]. The value for antagonist RTI-118 in the table above refers to human NPSR Ile107. The ligand has been tested also at the human NPSR Asn107 with pKe value of 6.31 [92]. NCGC 84 has also been tested in calcium mobilization and ERK phosphorylation assays where it displays pIC50 values of 7.44 and 8.03 respectively [84]. |
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gq/G11 family | Phospholipase C stimulation |
| References: 4,82,90 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| Gs family | Adenylyl cyclase stimulation |
| References: 26,64 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| NPS receptor knockout mice have been investigated in different laboratories. Of note, the anxious-like phenotype, the memory deficit and the reduced sensitivity to the hypnotic effect of diazepam and EtOH have not been replicated in other laboratories [7,20,71,94]. More importantly, the NPS stimulant [17,20,71,94] and arousal promoting [71] effects, the NPS anxiolytic-like [71,94] and anti-aggressiveness [69] actions are no longer evident in NPS receptor knockout mice. | ||||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Gene Expression and Pathophysiology
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| Biologically Significant Variants
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| General Comments |
| NPS precursor mRNA is highly expressed in a cluster of neurons located adjacent to the Locus coeruleus [90]. |
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23. Ghazal P, Corsi M, Roth A, Faggioni F, Corti C, Merlo Pick E, Pucciarelli S, Ciccocioppo R, Ubaldi M. (2014) Paradoxical response to the sedative effects of diazepam and alcohol in C57BL/6J mice lacking the neuropeptide S receptor. Peptides, 61: 107-13. [PMID:25240770]
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30. Han RW, Zhang RS, Xu HJ, Chang M, Peng YL, Wang R. (2013) Neuropeptide S enhances memory and mitigates memory impairment induced by MK801, scopolamine or Aβ₁₋₄₂ in mice novel object and object location recognition tasks. Neuropharmacology, 70: 261-7. [PMID:23454528]
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47. Liu X, Si W, Garau C, Jüngling K, Pape HC, Schulz S, Reinscheid RK. (2017) Neuropeptide S precursor knockout mice display memory and arousal deficits. Eur J Neurosci, 46 (1): 1689-1700. [PMID:28548278]
48. Lukas M, Neumann ID. (2012) Nasal application of neuropeptide S reduces anxiety and prolongs memory in rats: social versus non-social effects. Neuropharmacology, 62 (1): 398-405. [PMID:21871467]
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