Neuropeptide S receptor

Neuropeptide S receptor 1
Identifiers
Symbols	NPSR1; ASRT2; GPR154; GPRA; NPSR; PGR14; VRR1
External IDs	OMIM: 608595 MGI: 2441738 HomoloGene: 45515 IUPHAR: NPS GeneCards: NPSR1 Gene
Gene Ontology Molecular function • receptor activity • G-protein coupled receptor activity • vasopressin receptor activity Cellular component • cytoplasm • plasma membrane • plasma membrane • plasma membrane • integral to membrane Biological process • signal transduction • G-protein coupled receptor protein signaling pathway Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	387129	319239
Ensembl	ENSG00000187258	ENSMUSG00000043659
UniProt	Q6W5P4	Q8BZP8
RefSeq (mRNA)	NM_207172.1	NM_175678.3
RefSeq (protein)	NP_997055.1	NP_783609.1
Location (UCSC)	Chr 7: 34.7 – 34.92 Mb	Chr 9: 23.9 – 24.12 Mb
PubMed search	[1]	[2]

The neuropeptide S receptor (NPSR) is a member of the G-protein coupled receptor superfamily of integral membrane proteins^[1] which binds neuropeptide S (NPS).^[2] It was formally an orphan receptor, GPR154, until the discovery of neuropeptide S as the endogenous ligand.

In the CNS, activation of the NPSR by NPS promotes arousal and anxiolytic-like effects.^[3][4]

In addition, mututations in NPSR have been linked to a susceptibility to asthma.^[5] 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.^[6]

This gene is a member of the G protein-coupled receptor 1 family and encodes a plasma membrane protein. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. Mutations in this gene have also been associated with this disease. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.^[7]

References

1. ^ Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, Brown A, Rodriguez SS, Weller JR, Wright AC, Bergmann JE, Gaitanaris GA (2003). "The G protein-coupled receptor repertoires of human and mouse". Proc. Natl. Acad. Sci. U.S.A. 100 (8): 4903–8. doi:10.1073/pnas.0230374100. PMC 153653. PMID 12679517. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=153653. 
2. ^ Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Räisänen-Sokolowski A, Laitinen A, Laitinen LA, Kere J, Laitinen T (2005). "Characterization of GPRA, a novel G protein-coupled receptor related to asthma". Am. J. Respir. Cell Mol. Biol. 33 (3): 262–70. doi:10.1165/rcmb.2004-0405OC. PMID 15947423. 
3. ^ Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, Brucher FA, Zeng J, Ly NK, Henriksen SJ, de Lecea L, Civelli O (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. 
4. ^ Okamura N, Reinscheid RK (2007). "Neuropeptide S: a novel modulator of stress and arousal". Stress (Amsterdam, Netherlands) 10 (3): 221–6. doi:10.1080/10253890701248673. PMID 17613937. 
5. ^ Laitinen T, Polvi A, Rydman P, Vendelin J, Pulkkinen V, Salmikangas P, Mäkelä S, Rehn M, Pirskanen A, Rautanen A, Zucchelli M, Gullstén H, Leino M, Alenius H, Petäys T, Haahtela T, Laitinen A, Laprise C, Hudson TJ, Laitinen LA, Kere J (2004). "Characterization of a common susceptibility locus for asthma-related traits". Science 304 (5668): 300–4. doi:10.1126/science.1090010. PMID 15073379. 
6. ^ Vendelin J, Bruce S, Holopainen P, Pulkkinen V, Rytilä P, Pirskanen A, Rehn M, Laitinen T, Laitinen LA, Haahtela T, Saarialho-Kere U, Laitinen A, Kere J (2006). "Downstream target genes of the neuropeptide S-NPSR1 pathway". Hum. Mol. Genet. 15 (19): 2923–35. doi:10.1093/hmg/ddl234. PMID 16926187. 
7. ^ "Entrez Gene: NPSR1 neuropeptide S receptor 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=387129. 

Further reading

• Malerba G, Pignatti PF (2005). "A review of asthma genetics: gene expression studies and recent candidates.". J. Appl. Genet. 46 (1): 93–104. PMID 15741670. 
• Vassilatis DK, Hohmann JG, Zeng H, et al. (2003). "The G protein-coupled receptor repertoires of human and mouse.". Proc. Natl. Acad. Sci. U.S.A. 100 (8): 4903–8. doi:10.1073/pnas.0230374100. PMC 153653. PMID 12679517. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=153653. 
• Scherer SW, Cheung J, MacDonald JR, et al. (2003). "Human chromosome 7: DNA sequence and biology.". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2882961. 
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
• Gupte J, Cutler G, Chen JL, Tian H (2004). "Elucidation of signaling properties of vasopressin receptor-related receptor 1 by using the chimeric receptor approach.". Proc. Natl. Acad. Sci. U.S.A. 101 (6): 1508–13. doi:10.1073/pnas.0308250100. PMC 341764. PMID 14757815. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=341764. 
• Laitinen T, Polvi A, Rydman P, et al. (2004). "Characterization of a common susceptibility locus for asthma-related traits.". Science 304 (5668): 300–4. doi:10.1126/science.1090010. PMID 15073379. 
• Xu YL, Reinscheid RK, Huitron-Resendiz S, et al. (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. 
• Melén E, Bruce S, Doekes G, et al. (2005). "Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma.". Am. J. Respir. Crit. Care Med. 171 (10): 1089–95. doi:10.1164/rccm.200410-1317OC. PMID 15710598. 
• Kormann MS, Carr D, Klopp N, et al. (2005). "G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population.". Am. J. Respir. Crit. Care Med. 171 (12): 1358–62. doi:10.1164/rccm.200410-1312OC. PMID 15764725. 
• Gloriam DE, Schiöth HB, Fredriksson R (2005). "Nine new human Rhodopsin family G-protein coupled receptors: identification, sequence characterisation and evolutionary relationship.". Biochim. Biophys. Acta 1722 (3): 235–46. doi:10.1016/j.bbagen.2004.12.001. PMID 15777626. 
• Postma DS, Koppelman GH (2005). "Confirmation of GPRA: a putative drug target for asthma.". Am. J. Respir. Crit. Care Med. 171 (12): 1323–4. doi:10.1164/rccm.2503006. PMID 15941840. 
• Vendelin J, Pulkkinen V, Rehn M, et al. (2005). "Characterization of GPRA, a novel G protein-coupled receptor related to asthma.". Am. J. Respir. Cell Mol. Biol. 33 (3): 262–70. doi:10.1165/rcmb.2004-0405OC. PMID 15947423. 
• Söderhäll C, Marenholz I, Nickel R, et al. (2005). "Lack of association of the G protein-coupled receptor for asthma susceptibility gene with atopic dermatitis.". J. Allergy Clin. Immunol. 116 (1): 220–1. doi:10.1016/j.jaci.2005.03.002. PMID 15990798. 
• Veal CD, Reynolds NJ, Meggitt SJ, et al. (2005). "Absence of association between asthma and high serum immunoglobulin E associated GPRA haplotypes and adult atopic dermatitis.". J. Invest. Dermatol. 125 (2): 399–401. doi:10.1111/j.0022-202X.2005.23828.x. PMID 16098057. 
• Feng Y, Hong X, Wang L, et al. (2006). "G protein-coupled receptor 154 gene polymorphism is associated with airway hyperresponsiveness to methacholine in a Chinese population.". J. Allergy Clin. Immunol. 117 (3): 612–7. doi:10.1016/j.jaci.2005.11.045. PMID 16522461. 
• Bernier V, Stocco R, Bogusky MJ, et al. (2006). "Structure-function relationships in the neuropeptide S receptor: molecular consequences of the asthma-associated mutation N107I.". J. Biol. Chem. 281 (34): 24704–12. doi:10.1074/jbc.M603691200. PMID 16790440. 
• Allen IC, Pace AJ, Jania LA, et al. (2006). "Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease.". Am. J. Physiol. Lung Cell Mol. Physiol. 291 (5): L1005–17. doi:10.1152/ajplung.00174.2006. PMID 16829631. 
• Vendelin J, Bruce S, Holopainen P, et al. (2006). "Downstream target genes of the neuropeptide S-NPSR1 pathway.". Hum. Mol. Genet. 15 (19): 2923–35. doi:10.1093/hmg/ddl234. PMID 16926187. 
• Pulkkinen V, Haataja R, Hannelius U, et al. (2007). "G protein-coupled receptor for asthma susceptibility associates with respiratory distress syndrome.". Ann. Med. 38 (5): 357–66. doi:10.1080/07853890600756453. PMID 16938805. 

External links

• "Neuropeptide S Receptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1324. 
• MeSH NPSR1+protein,+human

Metabolites and
signaling molecules

Eicosanoid	CysLT (1, 2) · LTB4 (1, 2) · FPRL1 · OXE · Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) · Prostacyclin · Thromboxane
Other	Bile acid · Cannabinoid (CB1, CB2, GPR (18, 55, 119)) · EBI2 · Estrogen · Free fatty acid (1, 2, 3, 4) · Lactate  · Lysophosphatidic acid (1, 2, 3, 4, 5, 6)  · Lysophospholipid (1, 2, 3, 4, 5, 6, 7, 8) · Niacin (1, 2) · Oxoglutarate · PAF · Sphingosine-1-phosphate (1, 2, 3, 4, 5) · Succinate

Peptide

Neuropeptide	B/W (1, 2) · FF (1, 2) · S · Y (1, 2, 4, 5) · Neuromedin (B, U (1, 2)) · Neurotensin (1, 2)
Other	Anaphylatoxin (C3a, C5a) · Angiotensin (1, 2) · Apelin · Bombesin (BRS3, GRPR, NMBR) · Bradykinin (B1, B2) · Chemokine · Cholecystokinin (A, B) · Endothelin (A, B) · Formyl peptide (1, 2, 3) · FSH · Galanin (1, 2, 3) · GHB receptor · Gonadotropin-releasing hormone (1, 2) · Ghrelin · Kisspeptin · Luteinizing hormone/choriogonadotropin · MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) · Melanocortin (1, 2, 3, 4, 5) · MCHR (1, 2) · Motilin · Opioid (Delta, Kappa, Mu, Nociceptin & Zeta, but not Sigma) · Orexin (1, 2) · Oxytocin · Prokineticin (1, 2) · Prolactin-releasing peptide · Relaxin (1, 2, 3, 4) · Somatostatin (1, 2, 3, 4, 5) · Tachykinin (1, 2, 3) · Thyrotropin · Thyrotropin-releasing hormone · Urotensin-II · Vasopressin (1A, 1B, 2)

Miscellaneous

Orphan	GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Other	Adrenomedullin · Olfactory · Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) · Protease-activated (1, 2, 3, 4) · SREB (1, 2, 3)

Class B: Secretin like

Orphan	GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Other	Brain-specific angiogenesis inhibitor (1, 2, 3) · Cadherin (1, 2, 3) · Calcitonin · CALCRL · CD97 · Corticotropin-releasing hormone (1, 2) · EMR (1, 2, 3) · Glucagon (GR, GIPR, GLP1R, GLP2R) · Growth hormone releasing hormone · PACAPR1 · GPR · Latrophilin (1, 2, 3, ELTD1) · Methuselah-like proteins · Parathyroid hormone (1, 2) · Secretin · Vasoactive intestinal peptide (1, 2)

Class C: Metabotropic
glutamate / pheromone

Taste	TAS1R (1, 2, 3) · TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Other	Calcium-sensing receptor · GABA B (1, 2) · Glutamate receptor (Metabotropic glutamate (1, 2, 3, 4, 5, 6, 7, 8)) · GPRC6A · GPR (156, 158, 179) · RAIG (1, 2, 3, 4)

Class F:
Frizzled / Smoothened

Frizzled	Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Smoothened	Smoothened

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)