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. 

Contents

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
lpB4
Edg-8
endothelial differentiation, sphingolipid G-protein-coupled receptor, 8
S1P receptor 5
S1P receptor Edg-8
S1P5
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
lpB4
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
sphingosine 1-phosphate
sphingosylphosphorylcholine
Comments: sphingosine 1-phosphate exhibits greater potency than sphingosylphosphorylcholine
Rank order of potency
sphingosine 1-phosphate > dihydrosp​hingosine​-1-phosph​ate > sphingosylphosphorylcholine  [6]
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 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

REFERENCES

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 30/09/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=279.

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