Neuropeptide S receptor

Protein-coding gene in the species Homo sapiens

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

[edit]

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

[edit]

1. ^ a b c GRCh38: Ensembl release 89: ENSG00000187258 - Ensembl, May 2017
2. ^ a b c 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

[edit]

* 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

[edit]

* "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.

* v
* t
* e

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin-like

| Neurotransmitter|

| Adrenergic|

* α1 (A
* B
* D)
* α2 (A
* B
* C)
* β1
* β2
* β3

|

Purinergic|

* Adenosine (A1
* A2A
* A2B
* A3)
* P2Y (1
* 2
* 4
* 5
* 6
* 8
* 9
* 10
* 11
* 12
* 13
* 14)

Serotonin|

* (all but 5-HT3) 5-HT1 (A
* B
* D
* E
* F)
* 5-HT2 (A
* B
* C)
* 5-HT (4
* 5A
* 6
* 7)

Other|

* Acetylcholine (M1
* M2
* M3
* M4
* M5)
* Dopamine
* D1
* D2
* D3
* D4
* D5
* GHB receptor
* Histamine
* H1
* H2
* H3
* H4
* Melatonin (1A
* 1B
* 1C)
* TAAR (1
* 2
* 5
* 6
* 8
* 9)

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)
* Hydroxycarboxylic acids
* 1
* 2
* 3
* Lysophosphatidic acid (1
* 2
* 3
* 4
* 5
* 6)
* Lysophospholipid (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8)
* 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 (1
* 2))
* 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)
* 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|

| Taste, bitter|

* TAS2R
* 1
* 3
* 4
* 5
* 7
* 8
* 9
* 10
* 13
* 14
* 16
* 19
* 20
* 30
* 31
* 38
* 39
* 40
* 41
* 42
* 43
* 45
* 46
* 50
* 60
* Vomeronasal receptor type 1

|

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
* 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

| Adhesion|

* ADGRB
* Brain-specific angiogenesis inhibitor
* 1
* 2
* 3
* ADGRC
* Cadherin
* 1
* 2
* 3
* ADGRE
* EMR
* 1
* 2
* 3
* CD97
* ADGRG
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* ADGRL
* Latrophilin
* 1
* 2
* 3
* ELTD1

|

Orphan|

* GPR (56
* 64
* 97
* 98
* 110
* 111
* 112
* 113
* 114
* 115
* 116
* 123
* 124
* 125
* 126
* 128
* 133
* 143
* 144
* 155
* 157)

Other|

* Calcitonin
* CALCRL
* Corticotropin-releasing hormone (1
* 2)
* Glucagon (GR
* GIPR
* GLP1R
* GLP2R)
* Growth-hormone-releasing hormone
* PACAPR1
* GPR
* Methuselah-like proteins
* Parathyroid hormone (1
* 2)
* Secretin
* Vasoactive intestinal peptide (1
* 2)

Class C: Metabotropic glutamate / pheromone

| Taste, sweet|

* TAS1R
* 1
* 2
* 3
* Vomeronasal receptor, type 2

|

Other|

* Calcium-sensing receptor
* GABAB (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

* v
* t
* e

Neuropeptide receptors

G protein-coupled receptor|

| Hormone receptors|

| Hypothalamic|

* CRH
* FSH
* LHRH
* TRH
* Somatostatin

|

Pituitary|

* Vasopressin
* 1A
* 1B
* 2
* Oxytocin
* LHCG
* TSH

Other|

* Atrial natriuretic factor
* NPR3
* Calcitonin
* Cholecystokinin
* A
* B
* VIP

Opioid receptors|

* Delta
* Kappa
* Mu
* Nociceptin

Other neuropeptide receptors|

* Angiotensin
* Bradykinin
* B1
* B2
* Tachykinin
* TACR1
* Calcitonin gene-related peptide
* Galanin
* GPCR neuropeptide
* B/W
* FF
* S
* Y
* Neurotensin

Type I cytokine receptor|

* GH
* Prolactin

Enzyme-linked receptor|

* Atrial natriuretic factor
* NPR1
* NPR2

Other|

* Sigma
* 1
* 2

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