NPBWR2 Membrane Protein Introduction

Introduction of NPBWR2

Encoded by NPBWR2 gene which is located on chromosome 20q13.3 in human, neuropeptide B/W receptor-2 (NPBWR1) has been known as orphan receptor GPR8. Human NPBWR2 has 333 amino acid residues and presents approximately 64% sequence homology with NPBWR1. In general, both NPW and NPB bind and activate NPBWR2 with varying degrees of affinity. Compared with NPBWR1, the potency rank order of NPBWR2 is NPW23 > NPW30 > NPB. The recent research showed that high expression of NPBWR2 mRNA has been found in the human hippocampus and amygdala, whereas it has not been found in rodents.

Basic Information of NPBWR2
Protein Name	Neuropeptides B/W receptor type 2
Gene Name	NPBWR2
Aliases	GPR8
Organism	Homo sapiens (Human)
UniProt ID	P48146
Transmembrane Times	7
Length (aa)	333
Sequence	MQAAGHPEPLDSRGSFSLPTMGANVSQDNGTGHNATFSEPLPFLYVLLPAVYSGICAVGLTGNTAVILVILRAPKMKTVTNVFILNLAVADGLFTLVLPVNIAEHLLQYWPFGELLCKLVLAVDHYNIFSSIYFLAVMSVDRYLVVLATVRSRHMPWRTYRGAKVASLCVWLGVTVLVLPFFSFAGVYSNELQVPSCGLSFPWPEQVWFKASRVYTLVLGFVLPVCTICVLYTDLLRRLRAVRLRSGAKALGKARRKVTVLVLVVLAVCLLCWTPFHLASVVALTTDLPQTPLVISMSYVITSLSYANSCLNPFLYAFLDDNFRKNFRSILRC

Function of NPBWR2 Membrane Protein

Neuropeptide B (NPB) and neuropeptide W (NPW) are two endogenous peptide ligands of NPBWR2. In recent years, many studies have shown that NPB/W system is associated with the modulation of inflammatory pain. Due to the physiological role of NPB in pain regulation, the agonists for NPBWR2 present great potential for the treatment of chronic inflammatory pain. The binding of NPBWR2 to Gi-class of G-proteins suggests the inhibitory properties of these neuropeptides on neurons according to the activation of GIRK. It is worth mentioning that NPW is released from the hypothalamus and acts on adenohypophyseal cells via NPBWR2. In contrast, the effects of NPB and NPW might be mediated by the high expression of NPBWR1 in the hypothalamus.

Fig.1 Structure of NPB/W and their receptors.

Application of NPBWR2 Membrane Protein in Literature

Zhihai L. Cloning and mRNA expression of NPB and its effect on hormone secretion of the reproductive cells in the pig. Gen Comp Endocrinol. 2018, 261: 97-103. PubMed ID: 29481768

NPB is an endogenous ligand for the orphan G protein-coupled receptors NPBWR1 and NPBWR2. This article reports the important roles of NPB/NPBWR1 or NPBWR2 system in modulating the reproductive activity in the pig.
Motoike T., et al. Mesolimbic neuropeptide W coordinates stress responses under novel environments. Proceedings of the National Academy of Sciences of the United States of America. 2016, 113(21): 6023. PubMed ID: 27140610

NPB and NPW are two endogenous neuropeptide ligands for the G protein-coupled receptors NPBWR1 and NPBWR2. This article reveals the critical roles of NPW/NPBWR1 system in the gating of stressful stimuli during exposure to novel environments.
Scanes C.G. Opening a New Door: Neuropeptide W (NPW) Is a Novel Inhibitory Secretagogue for GH and Prolactin Acting via the Gi Protein-Coupled NPBWR2. Endocrinology. 2016, 157(9): 3394-3397. PubMed ID: 27580806

Authors in this group perform a series of studies characterizing the NPB and NPW and their receptors in chickens, geese, mammals, and vertebrates. Finally, they get the conclusion that NPW might be a novel inhibitory hypophysiotropic or releasing factor.
Sakurai T. NPBWR1 and NPBWR2: Implications in Energy Homeostasis, Pain, and Emotion. Frontiers in Endocrinology. 2013, 4: 23. PubMed ID: 23515889

This article reports that NPB and NPW are associated with the regulation of energy homeostasis, feeding behavior, neuroendocrine function, and modulating inflammatory pain. The recent studies also support their potential applications in regulating stress responses, emotion, anxiety, and fear.
Takenoya F. Neuropeptide W: a key player in the homeostatic regulation of feeding and energy metabolism? Ann N Y Acad Sci. 2010, 1200(1): 162-169. PubMed ID: 20633144

NPW has been identified as the endogenous ligand for both NPBWR1 and NPBWR2. This article reveals the distribution of NPW and the neuronal interactions between NPW. In addition, the dichotomous actions of NPW have also been discussed.

NPBWR2 Preparation Options

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