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
Sequence	MGHNGSWISPNASEPHNASGAEAAGVNRSALGEFGEAQLYRQFTTTVQVVIFIGSLLGNFMVLWSTCRTTVFKSVTNRFIKNLACSGICASLVCVPFDIILSTSPHCCWWIYTMLFCKVVKFLHKVFCSVTILSFPAIALDRYYSVLYPLERKISDAKSRELVMYIWAHAVVASVPVFAVTNVADIYATSTCTEVWSNSLGHLVYVLVYNITTVIVPVVVVFLFLILIRRALSASQKKKVIIAALRTPQNTISIPYASQREAELHATLLSMVMVFILCSVPYATLVVYQTVLNVPDTSVFLLLTAVWLPKVSLLANPVLFLTVNKSVRKCLIGTLVQLHHRYSRRNVVSTGSGMAEASLEPSIRSGSQLLEMFHIGQQQIFKPTEDEEESEAKYIGSADFQAKEIFSTCLEGEQGPQFAPSAPPLSTVDSVSQVAPAAPVEPETFPDKYSLQFGFGPFELPPQWLSETRNSKKRLLPPLGNTPEELIQTKVPKVGRVERKMSRNNKVSIFPKVDS

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 G_i, but via the unique G-protein subclass G_z, which is a unique G_i/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/G_z 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.

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

Application of GPR176 Membrane Protein in Literature

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 G_z is required for the activity of GPR176.
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.
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

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Reference

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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