SUCNR1 Membrane Protein Introduction

Introduction of SUCNR1

Succinate receptor 1 (SUCNR1) is a protein that in humans is encoded by the SUCNR1 gene and also belongs to the family of G protein-coupled receptors (GPCR), which represents the largest group of membrane proteins in human genome. SUCNR1 was first spotted in a megakaryocytic cell line in 1995 and called "P2U2", a name coined for its homology with the purinergic receptor P2Y2, known as P2U at that time. Later, the SUCNR1 gene re-discovered as GPR91 in 2001 on human chromosome 3q24-3q25 using an expressed sequence tag data mining strategy. Although SUCNR1 has not been crystallized yet, the information on its structure can be hypothesized by comparison with closely related proteins. Two representative purinergic receptors (P2Y1 and P2Y12) have been crystallized so far and some careful inferences can be made on SUCNR1 structure. And of important note is the possibility of two open-reading frames (ORF) for SUCNR1, one giving a protein of 330 amino acids (AA) and the other one 334 AA.

Function of SUCNR1 Membrane Protein

SSUCNR1 is involved in the promotion of hematopoietic progenitor cell development, and it has a potential role in renovascular hypertension which has known correlations to renal failure, diabetes, and atherosclerosis. SUCNR1 associated with diseases include Exudative Vitreoretinopathy 1. Among its related pathways are Peptide ligand-binding receptors and cAMP signaling pathway. OXGR1 is an important paralog of SSUCNR1. In addition, SUCNR1, just like P2Y12, 13, 14 receptors, almost exclusively couples to Gi/o in contrast with P2Y1-like receptors that preferentially activate Gq signaling and induce calcium release.

Fig.1 Structure of SUCNR1 membrane protein.

Application of SUCNR1 Membrane Protein in Literature

1. van Diepen J.A., et al. SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes. Diabetologia. 2017, 60(7):1304-13. PubMed ID: 28382382.
   
   

   This article reveals that activation of SUCNR1 in macrophages is important for both infiltration and inflammation of adipose tissue in obesity, and suggests that SUCNR1 is a promising therapeutic target in obesity-induced type 2 diabetes.

2. Gilissen J., et al. Insight into SUCNR1 (GPR91) structure and function. Pharmacology & therapeutics. 2016, 159:56-65. PubMed ID: 26808164.
   
   

   In this review, they describe the structural features of SUCNR1, its current ligands, and putative binding pocket and give an exhaustive overview of the known and hypothetical signaling partners of the receptor in different in vitro and in vivo systems. The link between SUCNR1 intracellular pathways and its pathophysiological roles are also extensively discussed.

3. Rubic-Schneider T., et al. GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice. Allergy. 2017, 72(3):444-52. PubMed ID: 27527650.
   
   

   This study reports the expression of SUCNR1 on mouse and human mast cells and reveals a hyperactive behavior of mouse SUCNR1 mast cells in a mechanistic in vivo model of skin inflammation.

4. Nguyen G., et al. Metformin ameliorates activation of hepatic stellate cells and hepatic fibrosis by succinate and GPR91 inhibition. Biochemical and biophysical research communications. 2018, 495(4):2649-56. PubMed ID: 29278707
   
   

   This article shows that metformin can attenuate activation of HSCs by activating the AMPK pathway and inhibiting the succinate- SUCNR1 pathway. Metformin has therapeutic potential for treating steatohepatitis and liver fibrosis.

5. Li Y.H., et al. Succinate causes alpha-SMA production through GPR91 activation in hepatic stellate cells. Biochemical and biophysical research communications. 2015, 463(4):853-8. PubMed ID: 26051274.
   
   

   This article results show that succinate plays an important role in HSC activation through SUCNR1 induction, and suggest that succinate and SUCNR1 may represent new therapeutic targets for modulating hepatic fibrosis.

SUCNR1 Preparation Options

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