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0  structures 71  species 0  interactions 72  sequences 1  architecture

Family: Neuropeptide_S (PF14993)

Summary: Neuropeptide S precursor protein

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This is the Wikipedia entry entitled "Neuropeptide S". More...

Neuropeptide S Edit Wikipedia article

Aliases NPS, neuropeptide S
External IDs MGI: 3642232 HomoloGene: 106066 GeneCards: NPS
Gene location (Human)
Chromosome 10 (human)
Chr. Chromosome 10 (human)[1]
Chromosome 10 (human)
Genomic location for NPS
Genomic location for NPS
Band 10q26.2 Start 127,549,369 bp[1]
End 127,552,639 bp[1]
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 10: 127.55 – 127.55 Mb Chr 10: 135.26 – 135.27 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse
Neuropeptide S
Symbol Neuropeptide_S
Pfam PF14993

Neuropeptide S (NPS) is a neuropeptide found in human and mammalian brain, mainly produced by neurons in the amygdala and between Barrington's nucleus and the locus coeruleus, although NPS-responsive neurons extend projections into many other brain areas.[5][6][7] NPS binds specifically to a G protein-coupled receptor, NPSR.[8][9] Animal studies show that NPS suppresses anxiety and appetite, induces wakefulness and hyperactivity, including hyper-sexuality, and plays a significant role in the extinction of conditioned fear.[10][11][12][13][14][15][16] It has also been shown to significantly enhance dopamine activity in the mesolimbic pathway,[16] and inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans.[17]

Synthetic ligands

The non-peptide NPS receptor antagonist SHA-68 blocks the effects of NPS in animals and is anxiogenic.[18] Several peptide derived NPS agonists and antagonists have also been developed.[19][20][21][22][23]

Peptide sequence

Below are the sequences of mature neuropeptide S in several representative species in which it is expressed:

species sequence MW


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000214285 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000073804 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Xu YL, Gall CM, Jackson VR, Civelli O, Reinscheid RK (Jan 2007). "Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain". The Journal of Comparative Neurology. 500 (1): 84–102. PMID 17099900. doi:10.1002/cne.21159. 
  6. ^ Jüngling K, Seidenbecher T, Sosulina L, Lesting J, Sangha S, Clark SD, Okamura N, Duangdao DM, Xu YL, Reinscheid RK, Pape HC (Jul 2008). "Neuropeptide S-mediated control of fear expression and extinction: role of intercalated GABAergic neurons in the amygdala". Neuron. 59 (2): 298–310. PMC 2610688Freely accessible. PMID 18667157. doi:10.1016/j.neuron.2008.07.002. 
  7. ^ Meis S, Bergado-Acosta JR, Yanagawa Y, Obata K, Stork O, Munsch T (2008). Grothe B, ed. "Identification of a neuropeptide S responsive circuitry shaping amygdala activity via the endopiriform nucleus". PLoS One. 3 (7): e2695. PMC 2442874Freely accessible. PMID 18628994. doi:10.1371/journal.pone.0002695.  open access publication – free to read
  8. ^ Reinscheid RK, Xu YL (Dec 2005). "Neuropeptide S and its receptor: a newly deorphanized G protein-coupled receptor system". The Neuroscientist. 11 (6): 532–8. PMID 16282594. doi:10.1177/1073858405276405. 
  9. ^ Reinscheid RK (2008). "Neuropeptide S: anatomy, pharmacology, genetics and physiological functions". Results and Problems in Cell Differentiation. 46: 145–58. PMID 18204825. doi:10.1007/400_2007_051. 
  10. ^ 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 (Aug 2004). "Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects". Neuron. 43 (4): 487–97. PMID 15312648. doi:10.1016/j.neuron.2004.08.005. 
  11. ^ Reinscheid RK, Xu YL (Nov 2005). "Neuropeptide S as a novel arousal promoting peptide transmitter". The FEBS Journal. 272 (22): 5689–93. PMID 16279934. doi:10.1111/j.1742-4658.2005.04982.x. 
  12. ^ Okamura N, Reinscheid RK (Aug 2007). "Neuropeptide S: a novel modulator of stress and arousal". Stress. 10 (3): 221–6. PMID 17613937. doi:10.1080/10253890701248673. 
  13. ^ Leonard SK, Dwyer JM, Sukoff Rizzo SJ, Platt B, Logue SF, Neal SJ, Malberg JE, Beyer CE, Schechter LE, Rosenzweig-Lipson S, Ring RH (May 2008). "Pharmacology of neuropeptide S in mice: therapeutic relevance to anxiety disorders". Psychopharmacology. 197 (4): 601–11. PMID 18311561. doi:10.1007/s00213-008-1080-4. 
  14. ^ Rizzi A, Vergura R, Marzola G, Ruzza C, Guerrini R, Salvadori S, Regoli D, Calo G (May 2008). "Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice". British Journal of Pharmacology. 154 (2): 471–9. PMC 2442439Freely accessible. PMID 18376418. doi:10.1038/bjp.2008.96. 
  15. ^ Vitale G, Filaferro M, Ruggieri V, Pennella S, Frigeri C, Rizzi A, Guerrini R, Calò G (Dec 2008). "Anxiolytic-like effect of neuropeptide S in the rat defensive burying". Peptides. 29 (12): 2286–91. PMID 18793688. doi:10.1016/j.peptides.2008.08.014. 
  16. ^ a b Mochizuki T, Kim J, Sasaki K (May 2010). "Microinjection of neuropeptide S into the rat ventral tegmental area induces hyperactivity and increases extracellular levels of dopamine metabolites in the nucleus accumbens shell". Peptides. 31 (5): 926–31. PMID 20156501. doi:10.1016/j.peptides.2010.02.006. 
  17. ^ Wan Saudi WS, Halim MA, Rudholm-Feldreich T, Gillberg L, Rosenqvist E, Tengholm A, Sundbom M, Karlbom U, Näslund E, Webb DL, Sjöblom M, Hellström PM (Oct 2015). "Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide". Am J Physiol Gastrointest Liver Physiol. 309 (9): G625–34. PMID 26206857. doi:10.1152/ajpgi.00104.2015. 
  18. ^ Okamura N, Habay SA, Zeng J, Chamberlin AR, Reinscheid RK (Jun 2008). "Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor". The Journal of Pharmacology and Experimental Therapeutics. 325 (3): 893–901. PMC 2583099Freely accessible. PMID 18337476. doi:10.1124/jpet.107.135103. 
  19. ^ Roth AL, Marzola E, Rizzi A, Arduin M, Trapella C, Corti C, Vergura R, Martinelli P, Salvadori S, Regoli D, Corsi M, Cavanni P, Caló G, Guerrini R (Jul 2006). "Structure-activity studies on neuropeptide S: identification of the amino acid residues crucial for receptor activation". The Journal of Biological Chemistry. 281 (30): 20809–16. PMID 16720571. doi:10.1074/jbc.M601846200. 
  20. ^ Camarda V, Trapella C, Calo G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S (Feb 2008). "Synthesis and biological activity of human neuropeptide S analogues modified in position 2". Journal of Medicinal Chemistry. 51 (3): 655–8. PMID 18181564. doi:10.1021/jm701204n. 
  21. ^ Camarda V, Trapella C, Calo' G, Guerrini R, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S (Oct 2008). "Structure-activity study at positions 3 and 4 of human neuropeptide S". Bioorganic & Medicinal Chemistry. 16 (19): 8841–5. PMID 18793857. doi:10.1016/j.bmc.2008.08.073. 
  22. ^ Guerrini R, Camarda V, Trapella C, Calò G, Rizzi A, Ruzza C, Fiorini S, Marzola E, Reinscheid RK, Regoli D, Salvadori S (Jan 2009). "Synthesis and biological activity of human neuropeptide S analogues modified in position 5: identification of potent and pure neuropeptide S receptor antagonists". Journal of Medicinal Chemistry. 52 (2): 524–9. PMC 2653091Freely accessible. PMID 19113861. doi:10.1021/jm8012294. 
  23. ^ Camarda V, Rizzi A, Ruzza C, Zucchini S, Marzola G, Marzola E, Guerrini R, Salvadori S, Reinscheid RK, Regoli D, Calò G (Feb 2009). "In vitro and in vivo pharmacological characterization of the neuropeptide s receptor antagonist [D-Cys(tBu)5]neuropeptide S". The Journal of Pharmacology and Experimental Therapeutics. 328 (2): 549–55. PMC 2630366Freely accessible. PMID 18971372. doi:10.1124/jpet.108.143867. 

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Neuropeptide S precursor protein Provide feedback

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Literature references

  1. Reinscheid RK, Xu YL;, FEBS J. 2005;272:5689-5693.: Neuropeptide S as a novel arousal promoting peptide transmitter. PUBMED:16279934 EPMC:16279934

  2. Beck B, Fernette B, Stricker-Krongrad A;, Biochem Biophys Res Commun. 2005;332:859-865.: Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in rats. PUBMED:15919054 EPMC:15919054

This tab holds annotation information from the InterPro database.

InterPro entry IPR028138

Neuropeptide S (NPS) is a bioactive peptide that may be involved in several biological processes, including food intake, locomotion, wakefulness, arousal, and anxiety. NPS activates its cognate G protein-coupled receptor (NPSR1) at low nanomolar agonist concentrations and induces elevation of intracellular Ca2+ and cAMP [PUBMED:15312648, PUBMED:15919054, PUBMED:17613937].

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Seed source: Jackhmmer:P0C0P6
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 7
Number in full: 72
Average length of the domain: 65.00 aa
Average identity of full alignment: 66 %
Average coverage of the sequence by the domain: 74.57 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 34.4 54.7
Noise cut-off 26.2 18.6
Model length: 65
Family (HMM) version: 6
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