GPR27 Membrane Protein Introduction

Introduction of GPR27

GPR27 is encoded by the GPR27 gene. It belongs to the G-protein-coupled receptor (GPCR) family which has been extensively studied during the past few decades because it offers abundant drug targets for many diseases. It is one of the three subtypes of super conserved receptors expressed in the brain (SREB) subfamily, GPR27 (SREB1), GPR85 (SREB2), and GPR173 (SREB3). Meanwhile, they share 52%-63% amino acid identity and are highly conserved throughout vertebrate evolution.

Basic Information of GPR27
Protein Name	Probable G-protein coupled receptor 27
Gene Name	GPR27
Aliases	Super conserved receptor expressed in brain 1, SREB1
Organism	Homo sapiens (Human)
UniProt ID	Q9NS67
Transmembrane Times	7
Length (aa)	375
Sequence	MANASEPGGSGGGEAAALGLKLATLSLLLCVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGAPPGALGCKLLAFLAALFCFHAAFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAMLVCAAWALALAAAFPPVLDGGGDDEDAPCALEQRPDGAPGALGFLLLLAVVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAANWTAGFGRGPTPPALVGIRPAGPGRGARLLVLEEFKTEKRLCKMFYARVTLLFLLLWGPYVASYLRVLVRPGAVPVQAYLTASVWLTFAQAGINPVVCFLFNRELRDCFRAQFPCCQSPRTTQATHPCDLKGIGL

Function of GPR27 Membrane Protein

GPR27 is one of orphan receptors, whose endogenous ligand remains unidentified. GPR27 has a predominant expression in the central nervous system, suggesting its important function in the development of nervous system. In addition, GPR27 has reported being involved in regulation the insulin secretion and insulin promoter activity. Inconsistent with these findings, the mouse insulin promoter activity as well as the glucose-stimulated insulin secretion decrease in the GPR27 knockout mice. Furthermore, some studies reveal that the activity of Pdx1 has an important role in regulating the effects of GPR27 on the insulin promoter and insulin secretion. On the other side, the 293T cells overexpressed with GPR27 shows an elevation of inositol phosphate levels, while knockdown the expression of GPR27 in MIN26 cells results in the decreasing of inositol phosphate levels. GPR27 has positive and negative regulation of insulin promoter activity and insulin secretion.

Fig.1 The proposed signaling pathway of GPR27. (Dupuis, 2017)

Application of GPR27 Membrane Protein in Literature

Dupuis N., et al. Activation of the Orphan G Protein-Coupled Receptor GPR27 by Surrogate Ligands Promotes β-Arrestin 2 Recruitment. Mol. Pharmacol. 2017, 91(6):595. PubMed ID: 28314853

This article reports the molecular analysis of the signaling pathways of GPR27 and provides some selective compounds with agonist properties for GPR27 for the first time.
Ku G.M., et al. An siRNA Screen in Pancreatic Beta Cells Reveals a Role for Gpr27 in Insulin Production. PLoS Genet. 2012, 8(1):e1002449. PubMed ID: 22253604

This article reveals that GPR27 is a novel regulator in both insulin secretion and insulin promoter activity, suggesting GPR27 may be a potential target for diabetes treatment.
Yanai T., et al. Identification and molecular docking studies for novel inverse agonists of SREB, super conserved receptor expressed in brain. Genes Cells. 2016, 21(7):717-727. PubMed ID: 27184081

This article reveals that the SREB family, consisting of GPR27, GPR85, and GPR173, could couple G_s-type G proteins, and the coupled protein complexes show significant constitutive activities in the central nervous system.
O'Dowd B.F., et al. Discovery of Three Novel G-Protein-Coupled Receptor Genes. Genomics. 1998, 47(2):310-313. PubMed ID: 9479505

Authors in this group use degenerate PCR primers based on GPR1 to amplify the sequence of GRP27 from mouse genomic library, and the transcripts of GPR27 are detected in several regions of human and rat central nervous system.
Ribrioux S., et al. Bioinformatics prediction of overlapping frameshifted translation products in mammalian transcripts. BMC Genomics. 2008, 9:122-122. PubMed ID: 18325113

This article focuses on a novel bioinformatics method for genome-wide analysis to provide more evidence to prove the existing of large overlapping coding sequences of GPR27.

GPR27 Preparation Options

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Reference

Dupuis N., et al. (2017) Activation of the Orphan G Protein-Coupled Receptor GPR27 by Surrogate Ligands Promotes β-Arrestin 2 Recruitment. Mol. Pharmacol. 91(6):595.

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