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Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 333 | 20q13.33 | NPBWR2 | neuropeptides B and W receptor 2 | 6 |
| Previous and Unofficial Names |
| GPR8 | G protein-coupled receptor 8 | neuropeptides B/W receptor 2 |
| Database Links |
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| Specialist databases | |
| GPCRdb | npbw2_human (Hs) |
| Other databases | |
| Alphafold | P48146 (Hs) |
| ChEMBL Target | CHEMBL4523864 (Hs) |
| Ensembl Gene | ENSG00000125522 (Hs) |
| Entrez Gene | 2832 (Hs) |
| Human Protein Atlas | ENSG00000125522 (Hs) |
| KEGG Gene | hsa:2832 (Hs) |
| OMIM | 600731 (Hs) |
| Pharos | P48146 (Hs) |
| RefSeq Nucleotide | NM_005286 (Hs) |
| RefSeq Protein | NP_005277 (Hs) |
| UniProtKB | P48146 (Hs) |
| Wikipedia | NPBWR2 (Hs) |
| Natural/Endogenous Ligands |
| neuropeptide B-23 {Sp: Human} |
| neuropeptide B-29 {Sp: Human} |
| neuropeptide B-23 {Sp: Mouse} |
| neuropeptide B-29 {Sp: Mouse} |
| neuropeptide B-23 {Sp: Rat} |
| neuropeptide B-29 {Sp: Rat} |
| neuropeptide W-23 {Sp: Human} |
| neuropeptide W-30 {Sp: Human} , neuropeptide W-30 {Sp: Mouse} |
| neuropeptide W-23 {Sp: Mouse, Rat} |
| neuropeptide W-30 {Sp: Rat} |
| Potency order of endogenous ligands (Human) |
| neuropeptide W-23 (NPW, Q8N729) > neuropeptide W-30 (NPW, Q8N729) > neuropeptide B-29 (NPB, Q8NG41) > neuropeptide B-23 (NPB, Q8NG41) [1] |
Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| The potency data above is found from several binding assays where the experimental conditions may not be consistent. Results from functional studies give the rank order of affinity as: NPW-23 > NPW-30 > NPB-29 > NPB-23 [1]. Deletion of the first tryptophan residue in both peptides results in significant reduction in potency suggesting that the N-terminus is involved in receptor binding and signal transduction. These peptides do not share any obvious homology to known peptides and are both equipotent at NPBW1 as well as to its human homologue NPBW2. These peptides also share high homology with other species such as rat and mouse. Immunocytochemical localisation studies have reported the presence of these peptides in discrete regions of the central nervous system [2-3]. In the periphery, NPW-like immunoreactivity has been localised to the renal glomeruli, as well as the endothelium of both the left internal mammary artery and the endocardium. It has yet to be determined whether NPB or NPW circulate in human plasma. The de-brominated forms of the endogenous ligands neuropeptide B-23 and neuropeptide B-29, des-Br-neuropeptide B-29 and des-Br-neuropeptide-23 were not found to be major components of bovine hypothalamus [4]. |
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| Antagonist Comments | ||
| No antagonists are currently available for NPBW2. |
| Allosteric Modulator Comments | ||
| It is currently unknown whether there are allosteric regulators of NPBW2. |
| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gi/Go family | Adenylyl cyclase inhibition |
| Comments: NPB has been shown to stimulate the Gq/11 phospholipase C pathway [5]. However, it has not been conclusively determined whether this is through NPBW2 activation or via another receptor. | |
| References: 1,7-8 | |
| Tissue Distribution
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| Functional Assays
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| Physiological Functions
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| General Comments |
| The gene encoding NPBW2 has not yet been identified in rat or mouse. |
1. Brezillon S, Lannoy V, Franssen JD, Le Poul E, Dupriez V, Lucchetti J, Detheux M, Parmentier M. (2003) Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8. J Biol Chem, 278 (2): 776-83. [PMID:12401809]
2. Dun SL, Brailoiu GC, Mizuo K, Yang J, Chang JK, Dun NJ. (2005) Neuropeptide B immunoreactivity in the central nervous system of the rat. Brain Res, 1045: 157-163. [PMID:15910774]
3. Dun SL, Brailoiu GC, Yang J, Chang JK, Dun NJ. (2003) Neuropeptide W-immunoreactivity in the hypothalamus and pituitary of the rat. Neurosci Lett, 349 (2): 71-4. [PMID:12946555]
4. Fujii R, Yoshida H, Fukusumi S, Habata Y, Hosoya M, Kawamata Y, Yano T, Hinuma S, Kitada C, Asami T et al.. (2002) Identification of a neuropeptide modified with bromine as an endogenous ligand for GPR7. J Biol Chem, 277 (37): 34010-6. [PMID:12118011]
5. Mazzocchi G, Rebuffat P, Ziolkowska A, Rossi GP, Malendowicz LK, Nussdorfer GG. (2005) G protein receptors 7 and 8 are expressed in human adrenocortical cells, and their endogenous ligands neuropeptides B and w enhance cortisol secretion by activating adenylate cyclase- and phospholipase C-dependent signaling cascades. J Clin Endocrinol Metab, 90 (6): 3466-71. [PMID:15797961]
6. O'Dowd BF, Scheideler MA, Nguyen T, Cheng R, Rasmussen JS, Marchese A, Zastawny R, Heng HH, Tsui LC, Shi X et al.. (1995) The cloning and chromosomal mapping of two novel human opioid-somatostatin-like receptor genes, GPR7 and GPR8, expressed in discrete areas of the brain. Genomics, 28 (1): 84-91. [PMID:7590751]
7. Shimomura Y, Harada M, Goto M, Sugo T, Matsumoto Y, Abe M, Watanabe T, Asami T, Kitada C, Mori M et al.. (2002) Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8. J Biol Chem, 277 (39): 35826-32. [PMID:12130646]
8. Tanaka H, Yoshida T, Miyamoto N, Motoike T, Kurosu H, Shibata K, Yamanaka A, Williams SC, Richardson JA, Tsujino N et al.. (2003) Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. Proc Natl Acad Sci USA, 100 (10): 6251-6. [PMID:12719537]
