GPR33 Membrane Protein Introduction

Introduction of GPR33

GPR33 is a protein that is encoded by the GPR33 gene. It was found to be transcribed during the late phase of rat cytomegalovirus infection in rat embryo fibroblasts. In the past years, GPR33, a member of the G-protein-coupled receptor family, has been identified as a pseudogene in humans. It has been reported that the human GPR33 gene contains a premature stop codon within the coding sequence of the second intracellular loop but no other obvious structural defects, suggesting a recent inactivation of the receptor.

Basic Information of GPR33
Protein Name Putative G-protein coupled receptor GPR33
Gene Name GPR33
Aliases N/A
Organism Homo sapiens (Human)
UniProt ID Q49SQ1
Transmembrane Times 7
Length (aa) 333

Function of GPR33 Membrane Protein

Studies have shown that all G-protein-coupled receptors (GPCR) share a common molecular architecture consisting of seven transmembrane domains (TMD) connected by three extra- and three intracellular loops (ICL). As an orphan member of the chemokine-like receptor family, GPR33 was identified as a pseudogene in human but as an intact gene in mouse. The human GPR33 gene contains a premature stop codon within the coding sequence of the second intracellular loop but no other obvious structural defects, which suggests a recent inactivation of the receptor. It has been reported that the inactivation of this chemoattractant GPCR not only occurs in humans but also in several great ape and rodent species. GPR33 also plays an important role in signal transduction through cell membranes. What’s more, it has a similar structure of ChemR23, a chemokine receptor for chemerin and SIV coreceptor, indicating that GPR33 has a potential role in the cellular defense that was lost during human evolution.

GPCR structure. Fig.1 GPCR structure.

Application of GPR33 Membrane Protein in Literature

  1. Bohnekamp J., Involvement of the chemokine-like receptor GPR33 in innate immunity. Biochemical and biophysical research communications. 2010, 396(2):272-7. PubMed ID: 20399748

    This article finds that GPR33 is highly expressed in dendritic cells (DC). Murine GPR33 expression is regulated by the activity of toll-like receptors (TLR) and AP-1/NF-kappaB signaling pathways in cell culture and in vivo. It indicates that GPR33 plays an important role in innate immunity which became dispensable during human evolution most likely due to past or balancing selection.

  2. Römpler H., Functional consequences of naturally occurring DRY motif variants in the mammalian chemoattractant receptor GPR33. Genomics. 2006, 87(6):724-32. PubMed ID: 16595170

    This article indicates that different receptor- and context-specific consequences of Asp-Arg-Tyr (DRY) mutations. It also reveals GPR33 as a new example illustrating missense mutations as a first step in the pseudogenization process.

  3. Rompler H., The rise and fall of the chemoattractant receptor GPR33. Journal of Biological Chemistry. 2005. PubMed ID: 15987686

    This article suggests that the coincidental inactivation and its fixation in several species of distantly related mammalian orders indicating a selective pressure on this chemoattractant receptor gene.

GPR33 Preparation Options

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