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GPR146 Membrane Protein Introduction

Introduction of GPR146

GPR146 is encoded by gene Gpr146, and it belongs to G protein-coupled receptor (GPCR) family, which is the most abundant receptor family residing in the cell surface. Participation in various physiological processes makes GPCR become the potential targets for numerous diseases, such as diabetes, Parkinson’s disease, infectious diseases, etc. GPR146 has the typical structure of GPCRs, consisted of an extracellular N terminus, seven transmembrane helices, and an intracellular C terminus. It is acknowledged that GPR146 is a possible receptor for proinsulin C-peptide.

Basic Information of GPR146
Protein Name G-protein coupled receptor 146
Gene Name GPR146
Aliases PGR8
Organism Homo sapiens (Human)
UniProt ID Q96CH1
Transmembrane Times 7
Length (aa) 333
Sequence MWSCSWFNGTGLVEELPACQDLQLGLSLLSLLGLVVGVPVGLCYNALLVLANLHSKASMTMPDVYFVNMAVAGLVLSALAPVHLLGPPSSRWALWSVGGEVHVALQIPFNVSSLVAMYSTALLSLDHYIERALPRTYMASVYNTRHVCGFVWGGALLTSFSSLLFYICSHVSTRALECAKMQNAEAADATLVFIGYVVPALATLYALVLLSRVRREDTPLDRDTGRLEPSAHRLLVATVCTQFGLWTPHYLILLGHTVIISRGKPVDAHYLGLLHFVKDFSKLLAFSSSFVTPLLYRYMNQSFPSKLQRLMKKLPCGDRHCSPDHMGVQQVLA

Function of GPR146 Membrane Protein

GPR146 was demonstrated to be the receptor of proinsulin C-peptide, which has emerged as a promising target for the treatment of diabetes-associated microvascular complications. The binding of GPR146 and C-peptide can regulate the function of retinal pigment epithelium, a monolayer of cells in the retina. In diabetic macular edema, the blood-retinal barrier consisted of retinal pigment epithelium is disrupted. Knockdown of GPR146 will block C-peptide-induced cFos expression in KATOIII cells. Additionally, the binding of C-peptide and GPR146 has therapeutic potency in the treatment of retinopathies, neuropathies, and nephropathy. GPR146 is identified as an antiviral factor specific to RNA-virus infection, such as Vesicular stomatitis virus and Newcastle disease virus. So GPR146 may be a potential target for antiviral drugs development.

The model of viruses escape from GPR146-mediated antiviral function. Fig.1 The model of viruses escape from GPR146-mediated antiviral function. (Huang, 2017)

Application of GPR146 Membrane Protein in Literature

  1. Kolar G.R., et al. Targeting orphan G protein-coupled receptors for the treatment of diabetes and its complications: C-peptide and GPR146. Journal of internal medicine. 2017, 281(1): 25-40. PubMed ID: 27306986

    In this review, the authors discuss GPR146, the putative receptor of proinsulin C-peptide has the therapeutic potency in the treatment of diabetes-associated complications. They describe various strategies, such as deorphanization strategy, to study the ‘deorphanize’ of this diverse family of receptors.

  2. Yosten G.L.C., et al. Evidence for an interaction between proinsulin C-peptide and GPR146. Journal of Endocrinology. 2013, 218(2): B1-B8. PubMed ID: 23980258

    Using a unique Deductive Ligand-Receptor Matching Strategy, the authors first demonstrate that GPR146 is potential a part of the C-peptide signaling complex. In the C-peptide signalosome, GPR146 may be a platform for the elucidation.

  3. Huang H., et al. Elimination of GPR146-mediated antiviral function through IRF3/HES1-signaling pathway. Immunology. 2017, 152(1):102-114. PubMed ID: 28464285

    This article verifies that GPR146 distributes on the erythrocytes of healthy humans and type 2 diabetes patients. And it can mediate the effects of C-peptide on ATP release from human erythrocytes, especially in the exposure of low O2 tension in humans with type 2 diabetes.

  4. Richards J.P., et al. Low O2-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin. American Journal of Physiology-Regulatory Integrative and Comparative Physiology. 2014, 307(7): R862-R868. PubMed ID: 25080497

    This article reveals the antiviral role of GPR146 in fighting viral infection. But GPR146-mediated protection is eliminated by IRF3/HES1-signalling, which suggests a potential therapeutic significance of both GPR146 and HES1 signaling in viral infection.

GPR146 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-GPR146 antibody development services.


Over years, Creative Biolabs has successfully generated many functional membrane proteins for our customers. We are happy to tailor one-stop, custom-oriented service packages regarding a variety of membrane protein targets. Please feel free to contact us for more information.

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