8wp1

Structural highlights

Function

SUCR1_HUMAN G protein-coupled receptor for succinate able to mediate signaling through Gq/GNAQ or Gi/GNAI second messengers depending on the cell type and the processes regulated (By similarity) (PubMed:15141213, PubMed:23770096, PubMed:34133934). Succinate-SUCNR1 signaling serves as a link between metabolic stress, inflammation and energy homeostasis (PubMed:18820681, PubMed:34133934). In macrophages, plays a range of immune-regulatory roles. During inflammation, succinate-SUCNR1 signaling may act as an anti-inflammatory mediator or boost inflammation depending on the inflammatory status of cells (By similarity). Hyperpolarizes M2 macrophages versus M1 phenotype through Gq signaling by regulating the transcription of genes involoved in immune function (PubMed:34133934). In activated M1 macrophages, plays a pro-inflammatory role in response to LPS (By similarity). Expressed in dendritic cells, where it is involved in the sensing of immunological danger and enhances immunity. Mediates succinate triggered intracelleular calcium mobilization, induces migratory responses and acts in synergy with Toll-like receptor ligands for the production of proinflammatory cytokines as well as an enhancement of antigen-specific activation of helper T cells (PubMed:18820681). In the small intestine, mediates the activation of tuft cells by dietary succinate and triggers type 2 immunity (By similarity). In adipocytes, plays an important role in the control of energy metabolism. In response to succinate, controls leptin expression in an AMPK-JNK-CEBPA-dependent as well as circadian clock-regulated manner (By similarity). In muscle tissue, is expressed in non-muscle cells and coordinates muscle remodeling in response to the succinate produced during exercise training in a paracrine manner (By similarity). In retina, acts as a mediator of vessel growth during retinal development. In response to succinate, regulates the production of angiogenic factors, including VEGF, by retinal ganglion neurons (By similarity).[UniProtKB:Q6IYF9][UniProtKB:Q99MT6]^{[1] [2] [3] [4]}

References

1. ↑ He W, Miao FJ, Lin DC, Schwandner RT, Wang Z, Gao J, Chen JL, Tian H, Ling L. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature. 2004 May 13;429(6988):188-93. PMID:15141213 doi:10.1038/nature02488
2. ↑ Rubic T, Lametschwandtner G, Jost S, Hinteregger S, Kund J, Carballido-Perrig N, Schwärzler C, Junt T, Voshol H, Meingassner JG, Mao X, Werner G, Rot A, Carballido JM. Triggering the succinate receptor GPR91 on dendritic cells enhances immunity. Nat Immunol. 2008 Nov;9(11):1261-9. PMID:18820681 doi:10.1038/ni.1657
3. ↑ Sundström L, Greasley PJ, Engberg S, Wallander M, Ryberg E. Succinate receptor GPR91, a Gα(i) coupled receptor that increases intracellular calcium concentrations through PLCβ. FEBS Lett. 2013 Aug 2;587(15):2399-404. PMID:23770096 doi:10.1016/j.febslet.2013.05.067
4. ↑ Trauelsen M, Hiron TK, Lin D, Petersen JE, Breton B, Husted AS, Hjorth SA, Inoue A, Frimurer TM, Bouvier M, O'Callaghan CA, Schwartz TW. Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling. Cell Rep. 2021 Jun 15;35(11):109246. PMID:34133934 doi:10.1016/j.celrep.2021.109246