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Gene and Protein Information ![]() |
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class A G protein-coupled receptor | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 7 | 398 | 19p13.2 | S1PR5 | sphingosine-1-phosphate receptor 5 | |
Mouse | 7 | 400 | 9 A3 | S1pr5 | sphingosine-1-phosphate receptor 5 | |
Rat | 7 | 400 | 8q13 | S1pr5 | sphingosine-1-phosphate receptor 5 |
Previous and Unofficial Names ![]() |
edg8 | NRG-1 | endothelial differentiation G protein-coupled receptor 8 | nerve growth factor-regulated G-protein-coupled receptor 1 |
Database Links ![]() |
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Specialist databases | |
GPCRDB | s1pr5_human (Hs), s1pr5_mouse (Mm), s1pr5_rat (Rn) |
Other databases | |
Alphafold | Q9H228 (Hs), Q91X56 (Mm), Q9JKM5 (Rn) |
ChEMBL Target | CHEMBL2274 (Hs) |
DrugBank Target | Q9H228 (Hs) |
Ensembl Gene | ENSG00000180739 (Hs), ENSMUSG00000045087 (Mm), ENSRNOG00000020901 (Rn) |
Entrez Gene | 53637 (Hs), 94226 (Mm), 60399 (Rn) |
Human Protein Atlas | ENSG00000180739 (Hs) |
KEGG Gene | hsa:53637 (Hs), mmu:94226 (Mm), rno:60399 (Rn) |
OMIM | 605146 (Hs) |
Pharos | Q9H228 (Hs) |
RefSeq Nucleotide | NM_030760 (Hs), NM_053190 (Mm), NM_021775 (Rn) |
RefSeq Protein | NP_110387 (Hs), NP_444420 (Mm), NP_068543 (Rn) |
UniProtKB | Q9H228 (Hs), Q91X56 (Mm), Q9JKM5 (Rn) |
Wikipedia | S1PR5 (Hs) |
Natural/Endogenous Ligands ![]() |
dihydrosphingosine 1-phosphate |
sphingosine 1-phosphate |
sphingosylphosphorylcholine |
Comments: Sphingosine 1-phosphate exhibits greater potency than sphingosylphosphorylcholine |
Potency order of endogenous ligands |
sphingosine 1-phosphate > dihydrosphingosine 1-phosphate [15] |
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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific agonist tables |
Immunopharmacology Comments |
In the immune system S1P receptors regulate immune cell trafficking and mitogenesis, are involved in immune-modulation, and suppression of innate immune T cell responses. |
Primary Transduction Mechanisms ![]() |
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Transducer | Effector/Response |
Gi/Go family G12/G13 family |
Adenylyl cyclase inhibition |
Comments: Activation of MAPK [20]. | |
References: 15,20 |
Tissue Distribution ![]() |
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Expression Datasets ![]() |
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Functional Assays ![]() |
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Physiological Consequences of Altering Gene Expression ![]() |
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Phenotypes, Alleles and Disease Models ![]() |
Mouse data from MGI | ||||||||||||||||||
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1. Andrieu G, Ledoux A, Branka S, Bocquet M, Gilhodes J, Walzer T, Kasahara K, Inagaki M, Sabbadini RA, Cuvillier O et al.. (2017) Sphingosine 1-phosphate signaling through its receptor S1P5 promotes chromosome segregation and mitotic progression. Sci Signal, 10 (472). [PMID:28351953]
2. Bolli MH, Abele S, Binkert C, Bravo R, Buchmann S, Bur D, Gatfield J, Hess P, Kohl C, Mangold C et al.. (2010) 2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists. J Med Chem, 53 (10): 4198-211. [PMID:20446681]
3. Brinkmann V, Davis MD, Heise CE, Albert R, Cottens S, Hof R, Bruns C, Prieschl E, Baumruker T, Hiestand P et al.. (2002) The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem, 277 (24): 21453-7. [PMID:11967257]
4. Buzard DJ, Kim SH, Lopez L, Kawasaki A, Zhu X, Moody J, Thoresen L, Calderon I, Ullman B, Han S et al.. (2014) Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor. ACS Med Chem Lett, 5 (12): 1313-7. [PMID:25516790]
5. Debien E, Mayol K, Biajoux V, Daussy C, De Aguero MG, Taillardet M, Dagany N, Brinza L, Henry T, Dubois B et al.. (2013) S1PR5 is pivotal for the homeostasis of patrolling monocytes. Eur J Immunol, 43 (6): 1667-75. [PMID:23519784]
6. Demont EH, Bailey JM, Bit RA, Brown JA, Campbell CA, Deeks N, Dowell SJ, Eldred C, Gaskin P, Gray JR et al.. (2016) Discovery of Tetrahydropyrazolopyridine as Sphingosine 1-Phosphate Receptor 3 (S1P3)-Sparing S1P1 Agonists Active at Low Oral Doses. J Med Chem, 59 (3): 1003-20. [PMID:26751273]
7. Di Pardo A, Castaldo S, Amico E, Pepe G, Marracino F, Capocci L, Giovannelli A, Madonna M, van Bergeijk J, Buttari F et al.. (2018) Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington's disease. Hum Mol Genet, 27 (14): 2490-2501. [PMID:29688337]
8. Forrest M, Sun SY, Hajdu R, Bergstrom J, Card D, Doherty G, Hale J, Keohane C, Meyers C, Milligan J et al.. (2004) Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J Pharmacol Exp Ther, 309 (2): 758-68. [PMID:14747617]
9. Foss FW, Snyder AH, Davis MD, Rouse M, Okusa MD, Lynch KR, Macdonald TL. (2007) Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists. Bioorg Med Chem, 15 (2): 663-77. [PMID:17113298]
10. Gates E. (1998) A complement to care. Nurs Times, 94 (9): 55-7. [PMID:9735753]
11. Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG et al.. (2012) The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. Br J Pharmacol, 167 (5): 1035-47. [PMID:22646698]
12. Hale JJ, Lynch CL, Neway W, Mills SG, Hajdu R, Keohane CA, Rosenbach MJ, Milligan JA, Shei GJ, Parent SA et al.. (2004) A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonists. J Med Chem, 47 (27): 6662-5. [PMID:15615513]
13. Hobson AD, Harris CM, van der Kam EL, Turner SC, Abibi A, Aguirre AL, Bousquet P, Kebede T, Konopacki DB, Gintant G et al.. (2015) Discovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P5) Agonist for the Potential Treatment of Neurodegenerative Disorders. J Med Chem, 58 (23): 9154-70. [PMID:26509640]
14. Im DS, Clemens J, Macdonald TL, Lynch KR. (2001) Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): structure-activity relationship of sphingosine1-phosphate receptors. Biochemistry, 40 (46): 14053-60. [PMID:11705398]
15. Im DS, Heise CE, Ancellin N, O'Dowd BF, Shei GJ, Heavens RP, Rigby MR, Hla T, Mandala S, McAllister G et al.. (2000) Characterization of a novel sphingosine 1-phosphate receptor, Edg-8. J Biol Chem, 275 (19): 14281-6. [PMID:10799507]
16. Jaillard C, Harrison S, Stankoff B, Aigrot MS, Calver AR, Duddy G, Walsh FS, Pangalos MN, Arimura N, Kaibuchi K et al.. (2005) Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival. J Neurosci, 25 (6): 1459-69. [PMID:15703400]
17. Jenne CN, Enders A, Rivera R, Watson SR, Bankovich AJ, Pereira JP, Xu Y, Roots CM, Beilke JN, Banerjee A et al.. (2009) T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow. J Exp Med, 206 (11): 2469-81. [PMID:19808259]
18. Kennedy PC, Zhu R, Huang T, Tomsig JL, Mathews TP, David M, Peyruchaud O, Macdonald TL, Lynch KR. (2011) Characterization of a sphingosine 1-phosphate receptor antagonist prodrug. J Pharmacol Exp Ther, 338 (3): 879-89. [PMID:21632869]
19. Li Z, Chen W, Hale JJ, Lynch CL, Mills SG, Hajdu R, Keohane CA, Rosenbach MJ, Milligan JA, Shei GJ et al.. (2005) Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3. J Med Chem, 48 (20): 6169-73. [PMID:16190743]
20. Malek RL, Toman RE, Edsall LC, Wong S, Chiu J, Letterle CA, Van Brocklyn JR, Milstien S, Spiegel S, Lee NH. (2001) Nrg-1 belongs to the endothelial differentiation gene family of G protein-coupled sphingosine-1-phosphate receptors. J Biol Chem, 276 (8): 5692-9. [PMID:11069896]
21. Martinborough E, Boehm MF, Yeager AR, Tamiya J, Huang L, Brahmachary E, Moorjani M, Timony GA, Brooks JL, Peach R et al.. (2011) Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis. Patent number: US20110172202 A1. Assignee: Martinborough E, Boehm MF, Yeager AR, Tamiya J, Huang L, Brahmachary E, Moorjani M, Timony GA, Brooks JL, Peach R et al.. Priority date: 13/11/2009. Publication date: 14/07/2011.
22. Pan S, Mi Y, Pally C, Beerli C, Chen A, Guerini D, Hinterding K, Nuesslein-Hildesheim B, Tuntland T, Lefebvre S et al.. (2006) A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model. Chem Biol, 13 (11): 1227-34. [PMID:17114004]
23. Sanna MG, Liao J, Jo E, Alfonso C, Ahn MY, Peterson MS, Webb B, Lefebvre S, Chun J, Gray N et al.. (2004) Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem, 279 (14): 13839-48. [PMID:14732717]
24. Scott FL, Clemons B, Brooks J, Brahmachary E, Powell R, Dedman H, Desale HG, Timony GA, Martinborough E, Rosen H et al.. (2016) Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity. Br J Pharmacol, 173 (11): 1778-92. [PMID:26990079]
25. Taylor Meadows KR, Steinberg MW, Clemons B, Stokes ME, Opiteck GJ, Peach R, Scott FL. (2018) Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus. PLoS ONE, 13 (4): e0193236. [PMID:29608575]
26. Terai K, Soga T, Takahashi M, Kamohara M, Ohno K, Yatsugi S, Okada M, Yamaguchi T. (2003) Edg-8 receptors are preferentially expressed in oligodendrocyte lineage cells of the rat CNS. Neuroscience, 116 (4): 1053-62. [PMID:12617946]
27. Urbano M, Guerrero M, Rosen H, Roberts E. (2013) Modulators of the Sphingosine 1-phosphate receptor 1. Bioorg Med Chem Lett, 23 (23): 6377-89. [PMID:24125884]
28. Walzer T, Chiossone L, Chaix J, Calver A, Carozzo C, Garrigue-Antar L, Jacques Y, Baratin M, Tomasello E, Vivier E. (2007) Natural killer cell trafficking in vivo requires a dedicated sphingosine 1-phosphate receptor. Nat Immunol, 8 (12): 1337-44. [PMID:17965716]
29. Xu J, Gray F, Henderson A, Hicks K, Yang J, Thompson P, Oliver J. (2014) Safety, pharmacokinetics, pharmacodynamics, and bioavailability of GSK2018682, a sphingosine-1-phosphate receptor modulator, in healthy volunteers. Clin Pharmacol Drug Dev, 3 (3): 170-8. [PMID:27128606]
30. Yamamoto R, Okada Y, Hirose J, Koshika T, Kawato Y, Maeda M, Saito R, Hattori K, Harada H, Nagasaka Y et al.. (2014) ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile. PLoS ONE, 9 (10): e110819. [PMID:25347187]