succinate receptor | Succinate receptor | IUPHAR/BPS Guide to PHARMACOLOGY

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succinate receptor

Target id: 166

Nomenclature: succinate receptor

Family: Succinate receptor

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for succinate receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 330 3q24-3q25.1 SUCNR1 succinate receptor 1 24
Mouse 7 317 3 D Sucnr1 succinate receptor 1
Rat 7 317 2q31 Sucnr1 succinate receptor 1
Gene and Protein Information Comments
In humans, there is the possibility of two open-reading frames (ORFs) for SUCNR1, one giving a protein of 330 amino acids (aa) and the other one 334-aa. Wittenberger et al. [24] noted that the 330-aa protein was more likely to be expressed given the Kozak sequence surrounding the second ATG. Some databases report SUCNR1 as being 334-aa long.
Previous and Unofficial Names
succinate receptor 1 | GPR91 | P2Y purinoceptor 1 | SUCNR1 | G protein-coupled receptor 91
Database Links
Specialist databases
GPCRDB sucr1_human (Hs), sucr1_mouse (Mm), sucr1_rat (Rn)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
succinic acid

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
cis-epoxysuccinic acid Hs Full agonist 5.6 pEC50 6
pEC50 5.6 (EC50 2.7x10-6 M) [6]
cis-1,2-cyclopropanedicarboxylic acid Hs Full agonist 4.3 pEC50 6
pEC50 4.3 (EC50 4.9x10-5 M) [6]
(S)-chlorosuccinic acid Hs Full agonist 4.1 pEC50 6
pEC50 4.1 (EC50 7.2x10-5 M) [6]
maleic acid Hs Full agonist 3.9 – 4.2 pEC50 6-7,10
pEC50 4.2 (EC50 5.7x10-5 M) [6]
pEC50 4.0 (EC50 9.4x10-5 M) [7]
pEC50 3.9 (EC50 1.34x10-4 M) [10]
succinic acid Hs Full agonist 3.1 – 4.7 pEC50 10,20
pEC50 3.1 – 4.7 (EC50 9.1x10-5 – 2x10-5 M) [10,20]
methylmalonic acid Hs Full agonist 3.5 – 3.8 pEC50 6,10
pEC50 3.8 (EC50 1.69x10-4 M) [6]
pEC50 3.5 (EC50 2.84x10-4 M) [10]
Agonist Comments
Using molecular docking calculations, it is predicted that SUCNR1 may interact with gamma-hydroxybutyrate [15].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
compound 5g [PMID: 21571530] Hs Antagonist 7.5 pIC50 3
pIC50 7.5 (IC50 3.5x10-8 M) [3]
compound 5g [PMID: 21571530] Rn Antagonist 6.9 pIC50 3
pIC50 6.9 (IC50 1.35x10-7 M) [3]
compound 7e [PMID: 21571530] Hs Antagonist 6.7 pIC50 3
pIC50 6.7 (IC50 1.8x10-7 M) [3]
View species-specific antagonist tables
Antagonist Comments
There are several synthetic antagonists against SUCNR1 discovered from a systematic structure-activity relationship study [3]. Among these antagonists, N-[{3-(3-trifluoromethyl-4-fluorophenyl)isoxazol-5-yl}methyl]-4-([1,8]naphthyridin-2-yl)butyramide (5g) and 2-{4-[5-(3-Chloro-4-trifluoromethoxyphenyl)-[1,3,4]oxadiazol-2-yl]butyl}-[1,8]naphthyridine (7e) are identified to have high pharmaceutical and clinical importance. 5g demonstrated satisfactory oral bioavailability in rats (%F: 26), very good plasma concentration (Cmax: 37uM, AUC0-24h: 69uM at 30mg/kg p.o. dose) and low plasma clearance. Similarly, 7e demonstrates low plasma clearance (2.0mL/min/kg), excellent bioavailability (%F: 87) and drug exposure (Cmax: 72uM, AUC0-24h: 471uMh, t1/2: 3.4h) upon oral admistration (30mg/kg p.o.) in rats.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Phospholipase C stimulation
Other - See Comments
Comments:  The Succinate receptor can recruit arrestins [7] and is internalized upon stimulation [7,10]. The precise mechanism for internalization has not been elucidated.
References:  7,10,21
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  Several authors were unable to confirm the activation of the Gq/G11 in transfected HEK293 cells [7,21]. It has been suggested that the Phospholipase C-β activation by Succinate receptor was mediated by Gβγ [21].
References:  10
Tissue Distribution
Kidney
Species:  Human
Technique:  Northen blot
References:  24
Present in platelets, T cells, B cells and monocytes. Absent in granulocytes.
Species:  Human
Technique:  Western blot
References:  14
Immature monocyte-derived DCs (MoDCs), macrophages, T cells, B cells
Species:  Human
Technique:  RT-PCR
References:  17
Platelets
Species:  Human
Technique:  RT-PCR, western blot and confocal immunofluorescene microscopy
References:  1
CD34+ haematopoietic stem cells, megakaryocytes, erythroid progenitor cultures, bone marrow-derived stromal cell cultures.
Species:  Human
Technique:  RT-PCR and immunoblot
References:  9
Megakaryocytes, platelets, monocytes
Species:  Human
Technique:  RT-PCR
References:  14
Isolated adipocytes, white adipose tissues, kidney, liver, gall bladder, vena cava, skin, spleen, thyroid
Species:  Mouse
Technique:  RT-PCR
References:  16
Cortical region of mouse kidney, including proximal tubules, distal tubules, juxtaglomerular apparatus
Species:  Mouse
Technique:  in situ hybridisation
References:  10
Kidney, liver, spleen
Species:  Mouse
Technique:  RT-PCR
References:  9-10
Kidney, liver
Species:  Mouse
Technique:  Northen blot
References:  24
Kidney and glomerular endothelial cells. No transcripts of SUCNR1 were detected in vascular smooth muscle cell and juxtaglomerular cell.
Species:  Mouse
Technique:  RT-PCR
References:  22
Apical membrane of retinal pigment epithelium
Species:  Mouse
Technique:  in situ hybridisation
References:  8
Ventricular cardiomyocytes
Species:  Rat
Technique:  RT-PCR, western blot and confocal microscopy
References:  1
Cell bodies of retinal ganglion cell layer and cells of the inner nuclear layer and outer retina
Species:  Rat
Technique:  Immunohistochemistry
References:  8
Quiescent hepatic stellate cells. The transcipts of SUCNR1 were not detected in hepatocytes, cholangiocytes, Kuppffer cells, sinusoidal endothelial cells and portal fibroblasts
Species:  Rat
Technique:  RT-PCR and confocal immunofluorescence
References:  5
Apical membrane of macula densa cells
Species:  Rat
Technique:  Immunohistochemistry
References:  23
Vascular endothelial cells in the afferent arteriole and glomerulus. No expression of SUCR1 was detected in juxtaglomerular cell.
Species:  Rat
Technique:  Immunohistochemistry
References:  22-23
Tissue Distribution Comments
No transcripts of SUCNR1 were detected in the brain when examined by Northern blot analysis [4]. SUCNR1 is functionally expressed by immature dendritic cells after differentiation from monocytes and was rapidly downregulated after dendritic cell maturation [17]. SUCNR1 expression is enriched in both early and late-stage haematopoietic progenitor cells [9].
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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