Neuropeptide S receptor

NPSR1
Identifiers
Aliases	NPSR1 , ASRT2, GPR154, GPRA, NPSR, PGR14, VRR1, neuropeptide S receptor 1
External IDs	OMIM: 608595; MGI: 2441738; HomoloGene: 45515; GeneCards: NPSR1; OMA:NPSR1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7p14.3 Start 34,658,218 bp [1] End 34,878,332 bp [1]
Gene location (Mouse) Chr. Chromosome 9 (mouse) [2] Band 9|9 A3- A4 Start 24,009,292 bp [2] End 24,227,694 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle gonad ganglionic eminence hypothalamus prefrontal cortex mucosa of transverse colon anterior cingulate cortex ventricular zone Brodmann area 9 rectum Top expressed in dentate gyrus of hippocampal formation granule cell cerebellar cortex primary visual cortex superior frontal gyrus hypothalamus neural layer of retina hippocampus proper thymus lens olfactory bulb More reference expression data BioGPS n/a
Gene ontology Molecular function G protein-coupled receptor activity vasopressin receptor activity signal transducer activity neuropeptide receptor activity Cellular component cytoplasm integral component of membrane plasma membrane integral component of plasma membrane membrane Biological process positive regulation of release of sequestered calcium ion into cytosol neuropeptide signaling pathway signal transduction G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 387129 319239 Ensembl ENSG00000187258 ENSMUSG00000043659 UniProt Q6W5P4 Q8BZP8 RefSeq (mRNA) NM_207173 NM_001300933 NM_001300934 NM_001300935 NM_207172 NM_175678 RefSeq (protein) NP_001287862 NP_001287863 NP_001287864 NP_997055 NP_997056 NP_783609 Location (UCSC) Chr 7: 34.66 – 34.88 Mb Chr 9: 24.01 – 24.23 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The neuropeptide S receptor (NPSR) is a member of the G-protein coupled receptor superfamily of integral membrane proteins ^[5] which binds neuropeptide S (NPS). ^[6] It was formerly an orphan receptor, GPR154, until the discovery of neuropeptide S as the endogenous ligand. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. This gene is a member of the G protein-coupled receptor 1 family and encodes a plasma membrane protein. Mutations in this gene have also been associated with this disease. ^[7]

Clinical significance

In the CNS, activation of the NPSR by NPS promotes arousal and anxiolytic-like effects. ^{[8] [9]}

In addition, mututations in NPSR have been linked to a susceptibility to asthma (rs3249801, A107I). ^[10] Hence NPSR has also been called GPRA (G protein-coupled receptor for asthma susceptibility). Activation of NPSR in the airway epithelium has a number of effects including upregulation of matrix metalloproteinases which are involved in the pathogenesis of asthma. ^[11] It has been shown that activation of NPSR by NPS affects both gastrointestinal motility and mucosal permeability simultaneously. Aberrant signaling and upregulation of NPSR1 could potentially exacerbate dysmotility and hyperpermeability by local mechanisms in gastrointestinal functional and inflammatory reactions. ^[12]

The very rare NPSR mutation Y206H, which makes the receptor more sensitive to NPS, may cause familial natural short sleep. ^[13] This finding has not been investigated in animal models, and is sufficiently rare that a biobank study was unable to find other carriers to attempt a replication of the association with sleep duration. ^[14]

References

1. GRCh38: Ensembl release 89: ENSG00000187258 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000043659 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, et al. (Apr 2003). "The G protein-coupled receptor repertoires of human and mouse". Proceedings of the National Academy of Sciences of the United States of America. 100 (8): 4903–8. Bibcode:2003PNAS..100.4903V. doi: 10.1073/pnas.0230374100 . PMC   153653 . PMID   12679517.
6. Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Räisänen-Sokolowski A, Laitinen A, et al. (Sep 2005). "Characterization of GPRA, a novel G protein-coupled receptor related to asthma". American Journal of Respiratory Cell and Molecular Biology. 33 (3): 262–70. doi:10.1165/rcmb.2004-0405OC. PMID   15947423.
7. "Entrez Gene: NPSR1 neuropeptide S receptor 1".
8. Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, et al. (Aug 2004). "Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects". Neuron. 43 (4): 487–97. doi: 10.1016/j.neuron.2004.08.005 . PMID   15312648. S2CID   15601843.
9. Okamura N, Reinscheid RK (Aug 2007). "Neuropeptide S: a novel modulator of stress and arousal". Stress. 10 (3): 221–6. doi:10.1080/10253890701248673. PMID   17613937. S2CID   39068808.
10. Laitinen T, Polvi A, Rydman P, Vendelin J, Pulkkinen V, Salmikangas P, et al. (Apr 2004). "Characterization of a common susceptibility locus for asthma-related traits". Science. 304 (5668): 300–4. Bibcode:2004Sci...304..300L. doi:10.1126/science.1090010. PMID   15073379. S2CID   9149671.
11. Vendelin J, Bruce S, Holopainen P, Pulkkinen V, Rytilä P, Pirskanen A, et al. (Oct 2006). "Downstream target genes of the neuropeptide S-NPSR1 pathway". Human Molecular Genetics. 15 (19): 2923–35. doi: 10.1093/hmg/ddl234 . PMID   16926187.
12. Wan Saudi WS, Halim MA, Rudholm-Feldreich T, Gillberg L, Rosenqvist E, Tengholm A, et al. (Oct 2015). "Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide". Am J Physiol Gastrointest Liver Physiol. 309 (9): G625-34. doi: 10.1152/ajpgi.00104.2015 . PMID   26206857.
13. Xing L, Shi G, Mostovoy Y, Gentry NW, Fan Z, McMahon TB, et al. (October 2019). "Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation". Science Translational Medicine. 11 (514) eaax2014. doi:10.1126/scitranslmed.aax2014. PMC   7587149 . PMID   31619542. S2CID   204756335.
14. Weedon MN, Jones SE, Lane JM, Lee J, Ollila HM, Dawes A, et al. (September 2022). "The impact of Mendelian sleep and circadian genetic variants in a population setting". PLoS Genetics. 18 (9) e1010356. doi: 10.1371/journal.pgen.1010356 . PMC   9499244 . PMID   36137075.

Further reading

• Malerba G, Pignatti PF (2005). "A review of asthma genetics: gene expression studies and recent candidates". Journal of Applied Genetics. 46 (1): 93–104. PMID   15741670.
• Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, et al. (Apr 2003). "The G protein-coupled receptor repertoires of human and mouse". Proceedings of the National Academy of Sciences of the United States of America. 100 (8): 4903–8. Bibcode:2003PNAS..100.4903V. doi: 10.1073/pnas.0230374100 . PMC   153653 . PMID   12679517.
• Gupte J, Cutler G, Chen JL, Tian H (Feb 2004). "Elucidation of signaling properties of vasopressin receptor-related receptor 1 by using the chimeric receptor approach". Proceedings of the National Academy of Sciences of the United States of America. 101 (6): 1508–13. Bibcode:2004PNAS..101.1508G. doi: 10.1073/pnas.0308250100 . PMC   341764 . PMID   14757815.
• Laitinen T, Polvi A, Rydman P, Vendelin J, Pulkkinen V, Salmikangas P, et al. (Apr 2004). "Characterization of a common susceptibility locus for asthma-related traits". Science. 304 (5668): 300–4. Bibcode:2004Sci...304..300L. doi:10.1126/science.1090010. PMID   15073379. S2CID   9149671.
• Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, et al. (Aug 2004). "Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects". Neuron. 43 (4): 487–97. doi: 10.1016/j.neuron.2004.08.005 . PMID   15312648. S2CID   15601843.
• Melén E, Bruce S, Doekes G, Kabesch M, Laitinen T, Lauener R, et al. (May 2005). "Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma". American Journal of Respiratory and Critical Care Medicine. 171 (10): 1089–95. doi:10.1164/rccm.200410-1317OC. PMID   15710598.
• Kormann MS, Carr D, Klopp N, Illig T, Leupold W, Fritzsch C, et al. (Jun 2005). "G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population". American Journal of Respiratory and Critical Care Medicine. 171 (12): 1358–62. doi:10.1164/rccm.200410-1312OC. PMID   15764725.
• Gloriam DE, Schiöth HB, Fredriksson R (Apr 2005). "Nine new human Rhodopsin family G-protein coupled receptors: identification, sequence characterisation and evolutionary relationship". Biochimica et Biophysica Acta (BBA) - General Subjects. 1722 (3): 235–46. doi:10.1016/j.bbagen.2004.12.001. PMID   15777626.
• Postma DS, Koppelman GH (Jun 2005). "Confirmation of GPRA: a putative drug target for asthma". American Journal of Respiratory and Critical Care Medicine. 171 (12): 1323–4. doi:10.1164/rccm.2503006. PMID   15941840.
• Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Räisänen-Sokolowski A, Laitinen A, et al. (Sep 2005). "Characterization of GPRA, a novel G protein-coupled receptor related to asthma". American Journal of Respiratory Cell and Molecular Biology. 33 (3): 262–70. doi:10.1165/rcmb.2004-0405OC. PMID   15947423.
• Söderhäll C, Marenholz I, Nickel R, Grüber C, Kehrt R, Rohde K, et al. (Jul 2005). "Lack of association of the G protein-coupled receptor for asthma susceptibility gene with atopic dermatitis". The Journal of Allergy and Clinical Immunology. 116 (1): 220–1. doi:10.1016/j.jaci.2005.03.002. hdl:11573/114973. PMID   15990798.
• Veal CD, Reynolds NJ, Meggitt SJ, Allen MH, Lindgren CM, Kere J, et al. (Aug 2005). "Absence of association between asthma and high serum immunoglobulin E associated GPRA haplotypes and adult atopic dermatitis". The Journal of Investigative Dermatology. 125 (2): 399–401. doi: 10.1111/j.0022-202X.2005.23828.x . PMID   16098057.
• Feng Y, Hong X, Wang L, Jiang S, Chen C, Wang B, et al. (Mar 2006). "G protein-coupled receptor 154 gene polymorphism is associated with airway hyperresponsiveness to methacholine in a Chinese population". The Journal of Allergy and Clinical Immunology. 117 (3): 612–7. doi: 10.1016/j.jaci.2005.11.045 . PMID   16522461.
• Bernier V, Stocco R, Bogusky MJ, Joyce JG, Parachoniak C, Grenier K, et al. (Aug 2006). "Structure-function relationships in the neuropeptide S receptor: molecular consequences of the asthma-associated mutation N107I". The Journal of Biological Chemistry. 281 (34): 24704–12. doi: 10.1074/jbc.M603691200 . PMID   16790440.
• Allen IC, Pace AJ, Jania LA, Ledford JG, Latour AM, Snouwaert JN, et al. (Nov 2006). "Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease". American Journal of Physiology. Lung Cellular and Molecular Physiology. 291 (5): L1005-17. doi:10.1152/ajplung.00174.2006. PMID   16829631. S2CID   5888233.
• Vendelin J, Bruce S, Holopainen P, Pulkkinen V, Rytilä P, Pirskanen A, et al. (Oct 2006). "Downstream target genes of the neuropeptide S-NPSR1 pathway". Human Molecular Genetics. 15 (19): 2923–35. doi: 10.1093/hmg/ddl234 . PMID   16926187.
• Pulkkinen V, Haataja R, Hannelius U, Helve O, Pitkänen OM, Karikoski R, et al. (2007). "G protein-coupled receptor for asthma susceptibility associates with respiratory distress syndrome". Annals of Medicine. 38 (5): 357–66. doi:10.1080/07853890600756453. PMID   16938805. S2CID   10090669.

External links

• "Neuropeptide S Receptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-02-06. Retrieved 2007-11-03.
• NPSR1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.