GPRC6A Membrane Protein Introduction

Introduction of GPRC6A

GPRC6A is a member of the family C G protein-coupled receptors, which are characterized by the presence of a seven-transmembrane domain and an unusually long amino-terminal domain (ATD). This receptor was initially deorphanized by infusion of its large N-terminal domain to the heptahelical and C-terminal region of the related goldfish 5.24 receptor. Cell signaling studies suggest that the receptor couples primarily via the Gαq/11 pathway to increase inositol phosphate production and mobilize intracellular calcium. Besides, it may also increase cyclic AMP and/or phosphorylation of extracellular signal-regulated kinase-1/2.

Basic Information of GPRC6A
Protein Name	G-protein coupled family C group 6 member A
Gene Name	GPRC6A
Aliases	GPCR33, hGPCR33
Organism	Homo sapiens (Human)
UniProt ID	Q5T6X5
Transmembrane Times	7
Length (aa)	926
Sequence	MAFLIILITCFVIILATSQPCQTPDDFVAATSPGHIIIGGLFAIHEKMLSSEDSPRRPQI QECVGFEISVFLQTLAMIHSIEMINNSTLLPGVKLGYEIYDTCTEVTVAMAATLRFLSKF NCSRETVEFKCDYSSYMPRVKAVIGSGYSEITMAVSRMLNLQLMPQVGYESTAEILSDKI RFPSFLRTVPSDFHQIKAMAHLIQKSGWNWIGIITTDDDYGRLALNTFIIQAEANNVCIA FKEVLPAFLSDNTIEVRINRTLKKIILEAQVNVIVVFLRQFHVFDLFNKAIEMNINKMWI ASDNWSTATKITTIPNVKKIGKVVGFAFRRGNISSFHSFLQNLHLLPSDSHKLLHEYAMH LSACAYVKDTDLSQCIFNHSQRTLAYKANKAIERNFVMRNDFLWDYAEPGLIHSIQLAVF ALGYAIRDLCQARDCQNPNAFQPWELLGVLKNVTFTDGWNSFHFDAHGDLNTGYDVVLWK EINGHMTVTKMAEYDLQNDVFIIPDQETKNEFRNLKQIQSKCSKECSPGQMKKTTRSQHI CCYECQNCPENHYTNQTDMPHCLLCNNKTHWAPVRSTMCFEKEVEYLNWNDSLAILLLIL SLLGIIFVLVVGIIFTRNLNTPVVKSSGGLRVCYVILLCHFLNFASTSFFIGEPQDFTCK TRQTMFGVSFTLCISCILTKSLKILLAFSFDPKLQKFLKCLYRPILIIFTCTGIQVVICT LWLIFAAPTVEVNVSLPRVIILECEEGSILAFGTMLGYIAILAFICFIFAFKGKYENYNE AKFITFGMLIYFIAWITFIPIYATTFGKYVPAVEIIVILISNYGILYCTFIPKCYVIICK QEINTKSAFLKMIYSYSSHSVSSIALSPASLDSMSGNVTMTNPSSSGKSATWQKSKDLQA QAFAHICRENATSVSKTLPRKRMSSI

Functions of GPRC6A Membrane Protein

This receptor has a broad expression in brain and peripheral tissues with highest levels in kidney, skeletal muscle, testis, and leucocytes. It functions via binding to different ligands, including L-α-amino acids, divalent cations, osteocalcin, and steroids. However, the broad ligand recognition and tissue expression have obscured the elucidation of the specific physiological role of this receptor and the mechanisms regulating its activity and cell surface availability. Studies in GPRC6A knockout mice have revealed that loss-of-CPRC6A results in metabolic syndrome. Moreover, bone, cardiovascular, immune, and skin functions of GPRC6A have also been identified in mice. However, the function of this receptor in humans remains unclear.

GPRC6A Membrane Protein Introduction

Applications of GPRC6A in Literature

Kinsey-Jones J. S., et al. GPRC6a is not required for the effects of a high-protein diet on body weight in mice. Obesity. 2015, 23(6): 1194-1200. PubMed ID: 25958858

The study demonstrated that GPRC6A was not necessary for the effects of low- and high-protein diets on body weight and food intake in mice.
Pi M., et al. Structural and functional evidence for testosterone activation of GPRC6A in peripheral tissues. Molecular Endocrinology. 2015, 29(12): 1759. PubMed ID: 26602597

This study investigated the role of GPRC6A in Alum adjuvanticity. Results showed that Alum adjuvanticity is increased in GPRC61-deficient mice, suggesting that GPRC6A limited the humoral response to Alum.
Rueda P., et al. Murine GPRC6A mediates cellular responses to L-amino acids, but not osteocalcin variants. Plos One. 2016, 11(1): e0146846. PubMed ID: 26785252

This article studied the agonist of GPRC6A (de-carboxylatedosteocalcin) in cells and found that the reported mouse GPRC6A-dependent effects of OCN may result from indirect, rather than direct activation of the receptor.
Johansson H., et al. Selective allosteric antagonists for the G protein-coupled receptor GPRC6A based on the 2-phenylindole privileged structure scaffold. Journal of Medicinal Chemistry. 2015, 58(22): 8938-51. PubMed ID: 26516782

This article presented the structure-activity relationship study of the 2-arylindole antagonist 3 of GPRC6A, including the design, synthesis, and pharmacological information.
Toni L., et al. Polymorphism rs2274911 of GPRC6A as a novel risk factor for testis failure. Journal of Clinical Endocrinology & Metabolism. 2016, 101(4): jc20153967. PubMed ID: 26735260

This article studied the possible association between rs2274911 polymorphism and male fertility and/or cryptorchidism. The results suggested that GPRC6A inactivation or sub-function contributed to reduced exposure to androgens, resulting in cryptorchidism during fetal life and/or low sperm production in adulthood.

GPRC6A Preparation Options

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