Nomenclature: S1P5 receptor

Family: Lysophospholipid (S1P) receptors

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing. 


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
endothelial differentiation, sphingolipid G-protein-coupled receptor, 8
S1P receptor 5
S1P receptor Edg-8
endothelial differentiation G-protein-coupled receptor 8
nerve growth factor-regulated G-protein-coupled receptor 1
sphingosine 1-phosphate receptor
sphingosine 1-phosphate receptor 5
sphingosine 1-phosphate receptor Edg-8
sphingosine-1-phosphate receptor 5
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Reference Database
PharmGKB Gene
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
UniGene Hs.
Natural/Endogenous Ligands
sphingosine 1-phosphate
Comments: sphingosine 1-phosphate exhibits greater potency than sphingosylphosphorylcholine
Rank order of potency
sphingosine 1-phosphate > dihydrosp​hingosine​-1-phosph​ate > sphingosylphosphorylcholine  [6]
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 6
pKd 8.7 [6]
VPC03090-P Hs Partial agonist 8.64 pKd 9
pKd 8.64 (Kd 2.3x10-9 M) [9]
FTY720-phosphate Hs Agonist 8.2 – 9.52 pEC50 1,3,12
pEC50 8.2 – 9.52 [1,3,12]
AFD(R) Hs Agonist 8.0 – 9.7 pEC50 1,13
pEC50 8.0 – 9.7 [1,13]
VPC03090-P Hs Partial agonist 8.62 pEC50 9
pEC50 8.62 (EC50 2.4x10-9 M) [9]
sphingosine 1-phosphate Hs Agonist 7.4 – 8.9 pEC50 1,5,12-13
pEC50 7.4 – 8.9 [1,5,12-13]
sphingosine 1-phosphate Mm Agonist 7.8 – 7.9 pEC50 5,13
pEC50 7.8 – 7.9 (EC50 1.6x10-8 M) [5,13]
VPC44116 Hs Partial agonist 7.5 pEC50 4
pEC50 7.5 [4]
AUY954 Mm Agonist 6.5 pEC50 12
pEC50 6.5 [12]
AUY954 Hs Agonist 6.47 pEC50 12
pEC50 6.47 (EC50 3.4x10-7 M) [12]
FTY720-phosphate Hs Agonist 9.22 pIC50 3
pIC50 9.22 (IC50 6x10-10 M) [3]
compound 26 [PMID:16190743] Hs Agonist 9.0 pIC50 10
pIC50 9.0 [10]
View species-specific agonist tables
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
G12/G13 family
Adenylate cyclase inhibition
Comments:  Activation of MAPK [11].
References:  6,11
Tissue Distribution
Brain, spleen, peripheral blood leukocytes, placenta, lung, aorta, and fetal spleen
Species:  Human
Technique:  Northern blot
References:  5
Brain, spleen, embryo (day 7 and 17)
Species:  Human
Technique:  Northern blot
References:  5
CD56dim NK cells
Species:  Human
Technique:  RT-PCR
References:  15
Ly6C− monocytes
Species:  Mouse
Technique:  RT-PCR
References:  2
Spleen, intestine, brain, vas def, testis, adrenal
Species:  Mouse
Technique:  Northern blot, in situ hybridisation
References:  6
Corpus callosum, anterior commissure, fimbria, and white matter of the cerebellum
Species:  Mouse
Technique:  in situ hybridisation
References:  7
NK cell
Species:  Mouse
Technique:  RT-PCR
References:  15
NG2-positive oligodendrocyte progenitor cells
Species:  Rat
Technique:  Immunocytochemistry
References:  14
Brain, spleen
Species:  Rat
Technique:  Northern blot
References:  6
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 migration
Species:  Mouse
Tissue:  Oligodendrocytes, NK cells, monocytes
Response measured:  Migration
References:  2,7,15
Cell survival
Species:  Mouse
Tissue:  Oligodendrocytes
Response measured:  Survival
References:  7
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:  15
Loss of process retraction in knockout pre-oligodendrocytes
Species:  Mouse
Tissue:  Preoligodendrocytes
Technique:  Gene knockouts
References:  7
Lacking the egress of Ly6C− monocytes from the bone marrow in knockout mice
Species:  Mouse
Tissue:  Peripheral Ly6C− monocytes
Technique:  Gene knockouts
References:  2
Egress of NK cells from lymph nodes and bone marrow
Species:  Mouse
Tissue:  NK cells
Technique:  Gene knockouts
References:  8
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 
Available Assays
DiscoveRx PathHunter® CHO-K1 EDG8 β-Arrestin Cell Line (Cat no. 93-0583C2) more info


1. 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]

2. 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]

3. 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]

4. 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]

5. 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. Biochemistry40 (46): 14053-60. [PMID:11705398]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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. Neuroscience116 (4): 1053-62. [PMID:12617946]

15. 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]

To cite this database page, please use the following:

Jerold Chun, Yasuyuki Kihara, Chido Mpamhanga.
Lysophospholipid (S1P) receptors: S1P5 receptor. Last modified on 27/01/2014. Accessed on 30/10/2014. IUPHAR database (IUPHAR-DB),

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