GPR176 Membrane Protein Introduction

Introduction of GPR176

GPR176 belongs to the G-protein-coupled receptor (GPCR) family which contains important regulators of various cellular functions via activation of intracellular signaling events. GPR176 is an evolutionally conserved, vertebrate class A orphan GPCR. Amino-acid sequence analysis reveals that GPR176 contains four putative glycosylation sites at the N-terminal part. A relatively large, C-terminal domain of about 200 amino acids also characterizes GPR176.

Basic Information of GPR176
Protein Name G-protein coupled receptor 176
Gene Name GPR176
Aliases HB-954
Organism Homo sapiens (Human)
UniProt ID Q14439
Transmembrane Times 7
Length (aa) 515

Function of GPR176 Membrane Protein

GPR176 is mainly expressed in the brain, with prominent expression in the suprachiasmatic nucleus (SCN), and its protein abundance fluctuates in a circadian fashion. GPR176 is identified as an SCN-enriched orphan GPCR that sets the pace of circadian behavior. GPR176 is expressed in a circadian manner by SCN neurons. Molecular characterization further revealed that this orphan receptor has an agonist-independent basal activity to repress cAMP production. Besides, GPR176 acts independently of, and in parallel to, the Vipr2 GPCR, not through the canonical Gi, but via the unique G-protein subclass Gz, which is a unique Gi/G0 subfamily member that can repress adenylyl cyclases in a PTX-insensitive manner, and its expression is known to be high particularly in the brain and in several specific tissues or cells in the periphery. GPR176/Gz is a new signaling module in the control of SCN circadian time-keeping, it provides a new class of GPCR signaling as a potential drug target to modulate the central clock in the brain.

G protein-coupled receptor activation and reactivation. Fig.1 G protein-coupled receptor activation and reactivation. (Sato, 2014)

Application of GPR176 Membrane Protein in Literature

  1. Goto K., et al. G-protein-coupled receptor signaling through GPR176, Gz, and RGS16 tunes time in the center of the circadian clock [Review]. Endocrine Journal. 2017, PubMed ID: 28502923

    This article reviews a recently identified role of GPR176 in the SCN. GPR176 is an SCN-enriched orphan GPCR that sets the pace of the circadian clock in the SCN. GPR176 has an agonist-independent basal activity to reduce cAMP signaling. A unique cAMP-repressing G-protein subclass Gz is required for the activity of GPR176.

  2. Masao D., et al. GPR176 is a Gz-linked orphan G-protein-coupled receptor that sets the pace of circadian behaviour. Nature Communications. 2016, 7, 10583. PubMed ID: 26882873

    This article identifies GPR176 as an SCN-enriched orphan GPCR that sets the pace of circadian behavior. GPR176 is expressed in a circadian manner by SCN neurons, and molecular characterization reveals that it represses cAMP signaling in an agonist-independent manner.

  3. David J.S., et al. Transcriptomic response of breast cancer cells to anacardic acid. Scientific Reports. 2018, 8, 8036. PubMed ID: 29795261

    Authors in this group find that GPR176 is altered by Anacardic acid, which is a potential dietary agent for preventing and treating breast cancer, inhibited the proliferation of estrogen receptor α (ERα) positive MCF-7 and MDA-MB-231 triple negative breast cancer cells.

GPR176 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-GPR176 antibody development services.

As a forward-looking research institute as well as a leading customer service provider in the field of membrane protein, Creative Biolabs has won good reputation among our worldwide customers for successfully accomplishing numerous challenging projects including generation of many functional membrane proteins. Please feel free to contact us for more information.


  1. Sato P Y, et al. (2014). The Evolving Impact of G Protein-Coupled Receptor Kinases in Cardiac Health and Disease. Physiological Reviews. 95(2), 377–404.

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