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NPFFR2 Membrane Protein Introduction

Introduction of NPFFR2

Neuropeptide FF receptor 2, also known as NPFF2, is a human protein encoded by the NPFFR2 gene and is the member of the Neuropeptide FF receptor family. The Neuropeptide FF receptor family belongs to the G-protein-coupled receptor (GPCR) superfamily which contains two subtypes, NPFFR1 and NPFFR2. They exhibit high affinities for Rfamide related peptides (RFRP) and Neuropeptide FF (NPFF). NPFFR2 is present in high density, particularly in mammals in the superficial layers of the spinal cord where it is involved in nociception and modulation of opioid functions.

Basic Information of NPFFR2
Protein Name Neuropeptide FF receptor 2
Gene Name NPFFR2
Aliases G-protein coupled receptor 74, G-protein coupled receptor HLWAR77, Neuropeptide G-protein coupled receptor
Organism Homo sapiens (Human)
UniProt ID Q9Y5X5
Transmembrane Times 7
Length (aa) 522
Sequence MNSFFGTPAASWCLLESDVSSAPDKEAGRERRALSVQQRGGPAWSGSLEWSRQSAGDRRRLGLSRQTAKSSWSRSRDRTCCCRRAWWILVPAADRARRERFIMNEKWDTNSSENWHPIWNVNDTKHHLYSDINITYVNYYLHQPQVAAIFIISYFLIFFLCMMGNTVVCFIVMRNKHMHTVTNLFILNLAISDLLVGIFCMPITLLDNIIAGWPFGNTMCKISGLVQGISVAASVFTLVAIAVDRFQCVVYPFKPKLTIKTAFVIIMIIWVLAITIMSPSAVMLHVQEEKYYRVRLNSQNKTSPVYWCREDWPNQEMRKIYTTVLFANIYLAPLSLIVIMYGRIGISLFRAAVPHTGRKNQEQWHVVSRKKQKIIKMLLIVALLFILSWLPLWTLMMLSDYADLSPNELQIINIYIYPFAHWLAFGNSSVNPIIYGFFNENFRRGFQEAFQLQLCQKRAKPMEAYALKAKSHVLINTSNQLVQESTFQNPHGETLLYRKSAEKPQQELVMEELKETTNSSEI

Function of NPFFR2 Membrane Protein

Numerous studies indicated that NPFF played an important role to modulate opioid-induced analgesia, tolerance, and dependence. The NPFF2 receptor belongs to the rhodopsin family of G protein-coupled receptors and mediates the effects of several related RFamide neuropeptides. One of the main pharmacological interests of this system resides in its ability to regulate endogenous opioid systems, making it a potential target to reduce the negative effects of chronic opioid use. Phosphorylation of intracellular residues is the most extensively studied post-translational modification regulating G proteincoupled receptor activity. However, until now, no information concerning NPFF2 receptor phosphorylation is available. What’s more, Study has shown that phosphorylation plays the key role in the regulation of NPFF2 receptor activity and trafficking.

Structure of NPFFR2 membrane protein. Fig.1 Structure of NPFFR2 membrane protein.

Application of NPFFR2 Membrane Protein in Literature

  1. Lyubimov Y., et al. Human kisspeptins activate neuropeptide FF2 receptor. Neuroscience. 2010, 170(1): 117-22. PubMed ID: 20600636.

    This article studied the possible activation of NPFF2R by kisspeptins, neuropeptides derived from the mouse and human metastin or Kiss-1 precurso. The results suggested that, besides regulation of reproduction, kisspeptins have a potential to mediate physiological effects on, for example, autonomic regulation and nociception in man via the NPFF2R pathways.

  2. Lin Y.T., et al. Activation of NPFFR2 leads to hyperalgesia through the spinal inflammatory mediator CGRP in mice. Experimental neurology. 2017, 291: 62-73. PubMed ID: 28179153.

    This aim of this study was to delineate the role of NPFFR2 in pain transmission. And results demonstrated that NPFFR2 activation modulates pain transmission by up-regulating the pain mediator CGRP, leading to hyperalgesia.

  3. Lin Y.T., et al. NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents. International journal of molecular sciences. 2017, 18(8). PubMed ID: 28825666.

    Authors in this group used NPFFR2 agonists to examine the role of NPFFR2 in activating the HPA axis in rodents and treatment with NPFFR2 agonist (AC-263093, IP) increased c-Fos protein expression in the hypothalamic paraventricular nucleus and induced an anxiogenic effect, which was evaluated in mice using an elevated plus maze. These findings revealed that the direct action of hypothalamic NPFFR2 stimulates the HPA axis and triggers anxiety-like behaviors.

  4. Mouledous L., et al. GRK2 protein-mediated transphosphorylation contributes to loss of function of mu-opioid receptors induced by neuropeptide FF (NPFF2) receptors. The Journal of biological chemistry. 2012, 287(16): 12736-49. PubMed ID: 22375000.

    This article helps us to understand the molecular mechanism involved in the anti-opioid activity of NPFF. The data showed that NPFF induced heterologous desensitization of MOP receptor signaling is mediated by GRK2 and could involve transphosphorylation within the heteromeric receptor complex.

  5. Waqas S.F.H., et al. Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages. The Journal of clinical investigation. 2017, 127(9): 3559. PubMed ID: 28758905.

    This article revealed that human and mouse ATMs express NPFFR2, a receptor for the appetite-reducing NPFF and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine. NPFF promoted M2 activation and increased the proliferation of murine and human ATMs, both M2 activation and increased ATM proliferation were abolished in NPFFR2-deficient ATMs. NPFF thus plays an important role in supporting healthy adipose tissue via the maintenance of metabolically beneficial ATMs.

NPFFR2 Preparation Options

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