S1P<sub>5</sub> receptor | Lysophospholipid (S1P) receptors | IUPHAR/BPS Guide to PHARMACOLOGY

S1P5 receptor

Target id: 279

Nomenclature: S1P5 receptor

Family: Lysophospholipid (S1P) receptors

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 :     S1P5 receptor has curated GtoImmuPdb data

Gene and Protein Information
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 A4 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
Specialist databases
GPCRDB s1pr5_human (Hs), s1pr5_mouse (Mm), s1pr5_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
sphingosine 1-phosphate
sphingosylphosphorylcholine
Comments: Sphingosine 1-phosphate exhibits greater potency than sphingosylphosphorylcholine
Potency order of endogenous ligands
sphingosine 1-phosphate > dihydrosphingosine 1-phosphate > sphingosylphosphorylcholine  [12]

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
sphingosine 1-phosphate Rn Agonist 8.7 pKd 12
pKd 8.7 [12]
VPC03090-P Hs Partial agonist 8.6 pKd 15
pKd 8.6 (Kd 2.3x10-9 M) [15]
siponimod Hs Agonist 9.0 pEC50 24
pEC50 9.0 (EC50 9.8x10-10 M) [24]
Description: In a GTPγS binding assay
FTY720-phosphate Hs Agonist 8.2 – 9.5 pEC50 2,6,19
pEC50 8.2 – 9.5 [2,6,19]
AFD(R) Hs Agonist 8.0 – 9.7 pEC50 2,20
pEC50 8.0 – 9.7 [2,20]
VPC03090-P Hs Partial agonist 8.6 pEC50 15
pEC50 8.6 (EC50 2.4x10-9 M) [15]
A-971432 Hs Agonist 8.2 – 8.4 pEC50 9
pEC50 8.4 (EC50 4.1x10-9 M) [9]
Description: In a forskolin-induced cAMP inhibition assay in S1P5-transfected CHO cells.
pEC50 8.2 (EC50 5.7x10-9 M) [9]
Description: In a GTPγS assay using membranes from S1P5-transfected HEK293 cells.
RP-101075 Hs Agonist 8.2 pEC50 22
pEC50 8.2 (EC50 5.9x10-9 M) [22]
Description: As measured in a GTPγS assay.
sphingosine 1-phosphate Hs Agonist 7.4 – 8.9 pEC50 2,11,19-20
pEC50 7.4 – 8.9 [2,11,19-20]
ASP4058 Hs Agonist 8.1 pEC50 26
pEC50 8.1 (EC50 7.5x10-9 M) [26]
Description: In a GTPγS binding assay.
sphingosine 1-phosphate Mm Agonist 7.8 – 7.9 pEC50 11,20
pEC50 7.8 – 7.9 (EC50 1.6x10-8 M) [11,20]
compound 43 [PMID: 26751273] Hs Agonist 7.8 pEC50 5
pEC50 7.8 (EC50 1.66x10-8 M) [5]
Description: In an aequorin calcium accumulation assay.
ozanimod Hs Agonist 7.3 – 8.0 pEC50 18,21
pEC50 8.0 (EC50 1.1x10-8 M) [21]
Description: In a GTPγS assay.
pEC50 7.3 (EC50 5.52x10-8 M) [18]
etrasimod Hs Agonist 7.6 pEC50 3
pEC50 7.6 (EC50 2.44x10-8 M) [3]
Description: In a β-arrestin recruitment assay.
VPC44116 Hs Partial agonist 7.5 pEC50 7
pEC50 7.5 [7]
AUY954 Mm Agonist 6.5 pEC50 19
pEC50 6.5 [19]
AUY954 Hs Agonist 6.5 pEC50 19
pEC50 6.5 (EC50 3.4x10-7 M) [19]
FTY720-phosphate Hs Agonist 9.2 pIC50 6
pIC50 9.2 (IC50 6x10-10 M) [6]
compound 26 [PMID: 16190743] Hs Agonist 9.0 pIC50 16
pIC50 9.0 [16]
ponesimod Hs Partial agonist 6.8 pIC50 1
pIC50 6.8 (IC50 1.42x10-7 M) [1]
Description: In a radioligand binding assay using membranes from CHO cells expressing human S1P5
fingolimod Hs Agonist 5.7 pIC50 8
pIC50 5.7 (IC50 2.1x10-6 M) [8]
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.
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
Comment:  Eosinophils express all S1P receptors except S1P2R.
References:  10
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
G12/G13 family
Adenylate cyclase inhibition
Comments:  Activation of MAPK [17].
References:  12,17
Tissue Distribution
Brain, spleen, embryo (day 7 and 17)
Species:  Human
Technique:  Northern blot
References:  11
CD56dim NK cells
Species:  Human
Technique:  RT-PCR
References:  25
Brain, spleen, peripheral blood leukocytes, placenta, lung, aorta, and fetal spleen
Species:  Human
Technique:  Northern blot
References:  11
Ly6C− monocytes
Species:  Mouse
Technique:  RT-PCR
References:  4
Corpus callosum, anterior commissure, fimbria, and white matter of the cerebellum
Species:  Mouse
Technique:  in situ hybridisation
References:  13
Spleen, intestine, brain, vas def, testis, adrenal
Species:  Mouse
Technique:  Northern blot, in situ hybridisation
References:  12
NK cell
Species:  Mouse
Technique:  RT-PCR
References:  25
NG2-positive oligodendrocyte progenitor cells
Species:  Rat
Technique:  Immunocytochemistry
References:  23
Brain, spleen
Species:  Rat
Technique:  Northern blot
References:  12
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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Functional Assays
Cell survival
Species:  Mouse
Tissue:  Oligodendrocytes
Response measured:  Survival
References:  13
Cell migration
Species:  Mouse
Tissue:  Oligodendrocytes, NK cells, monocytes
Response measured:  Migration
References:  4,13,25
Physiological Consequences of Altering Gene Expression
Aberrant NK cell homing during steady-state conditions in knockout mice.
Species:  Mouse
Tissue:  NK cell
Technique:  Gene knockouts
References:  25
Loss of process retraction in knockout pre-oligodendrocytes
Species:  Mouse
Tissue:  Preoligodendrocytes
Technique:  Gene knockouts
References:  13
Lacking the egress of Ly6C− monocytes from the bone marrow in knockout mice
Species:  Mouse
Tissue:  Peripheral Ly6C− monocytes
Technique:  Gene knockouts
References:  4
Egress of NK cells from lymph nodes and bone marrow
Species:  Mouse
Tissue:  NK cells
Technique:  Gene knockouts
References:  14
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
S1pr5tm1Club S1pr5tm1Club/S1pr5tm1Club
involves: 129P2/OlaHsd * C57BL/6J
MGI:2150641  MP:0003690 abnormal glial cell physiology PMID: 15703400 
S1pr5tm1Jch S1pr5tm1Jch/S1pr5tm1Jch
involves: 129P2/OlaHsd * C57BL/6
MGI:2150641  MP:0008053 abnormal NK cell differentiation PMID: 19808259 

References

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1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. Idzko M, Panther E, Corinti S, Morelli A, Ferrari D, Herouy Y, Dichmann S, Mockenhaupt M, Gebicke-Haerter P, Di Virgilio F et al.. (2002) Sphingosine 1-phosphate induces chemotaxis of immature and modulates cytokine-release in mature human dendritic cells for emergence of Th2 immune responses. FASEB J., 16 (6): 625-7. [PMID:11919175]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]

16. 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]

17. 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]

18. 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.

19. 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]

20. 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]

21. 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]

22. 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]

23. 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]

24. 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]

25. 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]

26. 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]

Contributors

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How to cite this page

Yasuyuki Kihara, Victoria Blaho, Hirotaka Mizuno, Jerold Chun.
Lysophospholipid (S1P) receptors: S1P5 receptor. Last modified on 06/04/2018. Accessed on 19/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=279.