Neuropeptide S receptor

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]

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
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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]