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GPR34 Membrane Protein Introduction

Introduction of GPR34

Probable G-protein coupled receptor 34 is a protein encoded by the human GPR34 gene. It is a 7-transmembrane receptor that belongs to the G protein-coupled receptor family. Based on sequence similarities to the platelet-activating factor (PAF) receptor, the human GPR34 was already discovered in 1997 (AF039686.1) and found to be widely expressed in human and mouse tissues.

Basic Information of GPR34
Protein Name Putative G-protein coupled receptor GPR34
Gene Name GPR34
Aliases N/A
Organism Homo sapiens (Human)
UniProt ID Q9UPC5
Transmembrane Times 7
Length (aa) 381
Sequence MRSHTITMTTTSVSSWPYSSHRMRFITNHSDQPPQNFSATPNVTTCPMDEKLLSTVLTTSYSVIFIVGLVGNIIALYVFLGIHRKRNSIQIYLLNVAIADLLLIFCLPFRIMYHINQNKWTLGVILCKVVGTLFYMNMYISIILLGFISLDRYIKINRSIQQRKAITTKQSIYVCCIVWMLALGGFLTMIILTLKKGGHNSTMCFHYRDKHNAKGEAIFNFILVVMFWLIFLLIILSYIKIGKNLLRISKRRSKFPNSGKYATTARNSFIVLIIFTICFVPYHAFRFIYISSQLNVSSCYWKEIVHKTNEIMLVLSSFNSCLDPVMYFLMSSNIRKIMCQLLFRRFQGEPSRSESTSEFKPGYSLHDTSVAVKIQSSSKST

Function of GPR34 Membrane Protein

G protein-coupled receptors (GPR) is one of the largest gene families whose primary function is to transmit extracellular stimuli such as light, hormones, neurotransmitters, peptides, and nucleotides, into intracellular signals via interaction of their intracellular domains with heterotrimeric G proteins. As a member of the GPR family, GPR34 was confirmed as a lysophosphatidylserine receptor in 2012. Originally, GPR34 was isolated from a human fetal brain cDNA library in 1999. The expression of GPR34 has been determined in different human tissues. Besides, it has been reported that GPR34 is highly expressed in several solid tumors, such as metastatic melanoma and MALT lymphoma. And it has an essential role in tumor development and progression. Studies have suggested that increased expression of GPR34 in the membrane of gastric cancer tissues was likely associated with metastatic ability, as well as invasion of NCI-N87 gastric cancer cells. What’s more, GPR34 could mediate signals to the interior of the cell via activation of heterotrimeric G proteins which in turn activate various effector proteins, ultimately resulting in a physiologic response.

Structure of an archetypal GPCR. Fig.1 Structure of an archetypal GPCR.

Application of GPR34 Membrane Protein in Literature

  1. Schöneberg T., et.al. The G protein-coupled receptor GPR34-the past 20 years of a grownup. Pharmacology & therapeutics. 2018. PubMed ID: 29684466

    This article summarizes the current knowledge of GPR34 on its evolution, genomic and structural organization, physiology, pharmacology and relevance in human diseases including neurodegenerative diseases and cancer, which accumulated over the last 20 years.

  2. Sayama M., et.al. Probing the Hydrophobic Binding Pocket of G-Protein-Coupled Lysophosphatidylserine Receptor GPR34/LPS1 by Docking-Aided Structure-Activity Analysis. Journal of medicinal chemistry. 2017, 60(14):6384-99. PubMed ID: 28715213

    This article focuses on the molecular basis of the structure-activity relationship of ligands of GPR34. It indicates that a kink in the benzene-based lipid surrogates matches the L-shaped hydrophobic pocket of GPR34. A tetrabenazine-based lipid analog bearing a bulky tert-butyl group at the 4-position of the terminal benzene ring exhibited potent GPR34 agonistic activity, validating the present hydrophobic binding pocket model.

  3. Spicer L.J., et.al. G protein-coupled receptor 34 in ovarian granulosa cells of cattle: changes during follicular development and potential functional implications. Domestic animal endocrinology. 2017, 59:90-9. PubMed ID: 28040605

    The research is conducted to determine if GPR34 mRNA in granulosa cell [GC] changes during selection and growth of dominant follicles in cattle as well as to investigate the hormonal regulation of GPR34 mRNA in bovine GC in vitro. It comes to a conclusion that GPR34 is a developmentally and hormonally regulated gene in GC, and its presumed ligands enhance IGF1-induced proliferation and steroidogenesis of bovine GC.

  4. Hasegawa H., et.al. Topogenesis and cell surface trafficking of GPR34 are facilitated by positive-inside rule that effects through a tri-basic motif in the first intracellular loop. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2016, 1863(7):1534-51. PubMed ID: 27086875

    This article investigates the process of membrane topology determination and how it relates to the acquisition of cell surface trafficking competence in human GPR34. It has shown that the underlying biochemical properties of the conformational epitope were, therefore, the key to understanding mechanistic processes propelled by positive-inside rule that simultaneously regulate the topogenesis and intracellular trafficking of GPR34.

  5. Jäger E., et.al. Dendritic cells regulate GPR34 through mitogenic signals and undergo apoptosis in its absence. The Journal of Immunology. 2016, 196(6):2504-13. PubMed ID: 26851221

    This report reveals a novel role of GPR34 in the fate of DCs and identifies a regulatory mechanism that could be relevant for the treatment of GPR34-overexpressing pathologies, such as neuroinflammatory or cancer conditions.

GPR34 Preparation Options

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