Browse S1PR1

Summary
SymbolS1PR1
Namesphingosine-1-phosphate receptor 1
Aliases edg-1; D1S3362; CD363; endothelial differentiation, sphingolipid G-protein-coupled receptor, 1; CHEDG1; S1P1 ......
Chromosomal Location1p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane; Multi-pass membrane protein. Endosome. Membrane raft. Note=Recruited to caveolin-enriched plasma membrane microdomains in response to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine. Ligand binding leads to receptor internalization.
Domain PF00001 7 transmembrane receptor (rhodopsin family)
Function

G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis (By similarity). Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury.

> Gene Ontology
 
Biological Process GO:0001503 ossification
GO:0001525 angiogenesis
GO:0001894 tissue homeostasis
GO:0001955 blood vessel maturation
GO:0003007 heart morphogenesis
GO:0003158 endothelium development
GO:0003241 growth involved in heart morphogenesis
GO:0003245 cardiac muscle tissue growth involved in heart morphogenesis
GO:0003376 sphingosine-1-phosphate signaling pathway
GO:0006874 cellular calcium ion homeostasis
GO:0006875 cellular metal ion homeostasis
GO:0007015 actin filament organization
GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway
GO:0007193 adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway
GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007507 heart development
GO:0007517 muscle organ development
GO:0010639 negative regulation of organelle organization
GO:0014706 striated muscle tissue development
GO:0019226 transmission of nerve impulse
GO:0021700 developmental maturation
GO:0030031 cell projection assembly
GO:0030032 lamellipodium assembly
GO:0030038 contractile actin filament bundle assembly
GO:0030278 regulation of ossification
GO:0030282 bone mineralization
GO:0030335 positive regulation of cell migration
GO:0030500 regulation of bone mineralization
GO:0030595 leukocyte chemotaxis
GO:0031032 actomyosin structure organization
GO:0031214 biomineral tissue development
GO:0031532 actin cytoskeleton reorganization
GO:0032103 positive regulation of response to external stimulus
GO:0032231 regulation of actin filament bundle assembly
GO:0032232 negative regulation of actin filament bundle assembly
GO:0032844 regulation of homeostatic process
GO:0032956 regulation of actin cytoskeleton organization
GO:0032970 regulation of actin filament-based process
GO:0033002 muscle cell proliferation
GO:0034103 regulation of tissue remodeling
GO:0035265 organ growth
GO:0035637 multicellular organismal signaling
GO:0040017 positive regulation of locomotion
GO:0043149 stress fiber assembly
GO:0045124 regulation of bone resorption
GO:0045446 endothelial cell differentiation
GO:0045453 bone resorption
GO:0046849 bone remodeling
GO:0046850 regulation of bone remodeling
GO:0048514 blood vessel morphogenesis
GO:0048644 muscle organ morphogenesis
GO:0048659 smooth muscle cell proliferation
GO:0048660 regulation of smooth muscle cell proliferation
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0048738 cardiac muscle tissue development
GO:0048771 tissue remodeling
GO:0048871 multicellular organismal homeostasis
GO:0050900 leukocyte migration
GO:0050918 positive chemotaxis
GO:0050920 regulation of chemotaxis
GO:0050921 positive regulation of chemotaxis
GO:0050926 regulation of positive chemotaxis
GO:0050927 positive regulation of positive chemotaxis
GO:0051017 actin filament bundle assembly
GO:0051272 positive regulation of cellular component movement
GO:0051480 regulation of cytosolic calcium ion concentration
GO:0051482 positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway
GO:0051492 regulation of stress fiber assembly
GO:0051493 regulation of cytoskeleton organization
GO:0051494 negative regulation of cytoskeleton organization
GO:0051497 negative regulation of stress fiber assembly
GO:0055008 cardiac muscle tissue morphogenesis
GO:0055017 cardiac muscle tissue growth
GO:0055074 calcium ion homeostasis
GO:0060249 anatomical structure homeostasis
GO:0060326 cell chemotaxis
GO:0060415 muscle tissue morphogenesis
GO:0060419 heart growth
GO:0060537 muscle tissue development
GO:0060560 developmental growth involved in morphogenesis
GO:0061383 trabecula morphogenesis
GO:0061384 heart trabecula morphogenesis
GO:0061572 actin filament bundle organization
GO:0070167 regulation of biomineral tissue development
GO:0071695 anatomical structure maturation
GO:0072503 cellular divalent inorganic cation homeostasis
GO:0072507 divalent inorganic cation homeostasis
GO:0072676 lymphocyte migration
GO:0072678 T cell migration
GO:0090520 sphingolipid mediated signaling pathway
GO:0097581 lamellipodium organization
GO:2000147 positive regulation of cell motility
Molecular Function GO:0001664 G-protein coupled receptor binding
GO:0038036 sphingosine-1-phosphate receptor activity
GO:0045125 bioactive lipid receptor activity
GO:0046625 sphingolipid binding
Cellular Component GO:0009897 external side of plasma membrane
GO:0045121 membrane raft
GO:0098552 side of membrane
GO:0098589 membrane region
GO:0098857 membrane microdomain
> KEGG and Reactome Pathway
 
KEGG hsa04068 FoxO signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04080 Neuroactive ligand-receptor interaction
Reactome R-HSA-373076: Class A/1 (Rhodopsin-like receptors)
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-418594: G alpha (i) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-500792: GPCR ligand binding
R-HSA-168256: Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-419408: Lysosphingolipid and LPA receptors
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-449147: Signaling by Interleukins
Summary
SymbolS1PR1
Namesphingosine-1-phosphate receptor 1
Aliases edg-1; D1S3362; CD363; endothelial differentiation, sphingolipid G-protein-coupled receptor, 1; CHEDG1; S1P1 ......
Chromosomal Location1p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between S1PR1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between S1PR1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29036438Gastric CarcinomaInhibit immunity (T cell function)We generated a xenograft mouse model and used SEW-2871, a S1P1 specific agonist to activate S1P1 signalling. SEW-2871 promoted tumor growth in our mouse model, and induced a higher level of MDSC and a reduced level of CD8+CD69+ T cells within tumor. Additionally, SEW-2871 enhanced expression of several MDSC recruitment-associated chemokines (CXCL12, CXCL5 and CCL2) in tumor cells. These chemokines facilitated MDSC migration by interaction with CCR2, CXCR2 and CXCR4. S1P1 signalling promoted gastric cancer by enhancing chemokine expression in tumor cells and recruiting MDSC to tumor microenvironment, which impaired anti-tumoral function of TILs.
28878352Hodgkin LymphomaInhibit immunityS1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells. S1P activates phosphatidylinositide 3-kinase (PI3-K) in these cells that is mediated by the increased expression of S1PR1 and the decreased expression of S1PR2. Genes upregulated by the PI3-K pathway included the basic leucine zipper transcription factor, ATF-like 3 (BATF3), which is normally associated with the development of dendritic cells. Knockdown of BATF3 in HL cell lines revealed that BATF3 contributed to the transcriptional programme of primary HRS cells, including the upregulation of S1PR1.
22745305Diffuse Large B-Cell LymphomaInhibit immunityS1PR1 is an effective target to block STAT3 signaling in activated B cell-like diffuse large B-cell lymphoma. Here we demonstrate that persistent activated STAT3 colocalizes with elevated expression of S1PR1, a G-protein-coupled receptor for sphingosine-1-phosphate (S1P), in the tumor cells of the activated B cell-like subtype of diffuse large B-cell lymphoma patient specimens.Inhibition of S1PR1 expression by shRNA in the lymphoma cells validates that blocking S1PR1 affects expression of STAT3 downstream genes critically involved in tumor cell survival, proliferation, tumor invasion, and/or immunosuppression.
Summary
SymbolS1PR1
Namesphingosine-1-phosphate receptor 1
Aliases edg-1; D1S3362; CD363; endothelial differentiation, sphingolipid G-protein-coupled receptor, 1; CHEDG1; S1P1 ......
Chromosomal Location1p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of S1PR1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolS1PR1
Namesphingosine-1-phosphate receptor 1
Aliases edg-1; D1S3362; CD363; endothelial differentiation, sphingolipid G-protein-coupled receptor, 1; CHEDG1; S1P1 ......
Chromosomal Location1p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of S1PR1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.3770.277
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2440.848
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.4760.628
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.2680.511
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.310.841
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.9980.61
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.470.287
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.5080.676
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3910.779
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9630.494
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.7220.403
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.3080.029
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of S1PR1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.811.8-70.577
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.516.7-4.21
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 382703.7-3.70.415
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221307.7-7.70.371
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolS1PR1
Namesphingosine-1-phosphate receptor 1
Aliases edg-1; D1S3362; CD363; endothelial differentiation, sphingolipid G-protein-coupled receptor, 1; CHEDG1; S1P1 ......
Chromosomal Location1p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of S1PR1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolS1PR1
Namesphingosine-1-phosphate receptor 1
Aliases edg-1; D1S3362; CD363; endothelial differentiation, sphingolipid G-protein-coupled receptor, 1; CHEDG1; S1P1 ......
Chromosomal Location1p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of S1PR1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by S1PR1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolS1PR1
Namesphingosine-1-phosphate receptor 1
Aliases edg-1; D1S3362; CD363; endothelial differentiation, sphingolipid G-protein-coupled receptor, 1; CHEDG1; S1P1 ......
Chromosomal Location1p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of S1PR1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolS1PR1
Namesphingosine-1-phosphate receptor 1
Aliases edg-1; D1S3362; CD363; endothelial differentiation, sphingolipid G-protein-coupled receptor, 1; CHEDG1; S1P1 ......
Chromosomal Location1p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of S1PR1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolS1PR1
Namesphingosine-1-phosphate receptor 1
Aliases edg-1; D1S3362; CD363; endothelial differentiation, sphingolipid G-protein-coupled receptor, 1; CHEDG1; S1P1 ......
Chromosomal Location1p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between S1PR1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolS1PR1
Namesphingosine-1-phosphate receptor 1
Aliases edg-1; D1S3362; CD363; endothelial differentiation, sphingolipid G-protein-coupled receptor, 1; CHEDG1; S1P1 ......
Chromosomal Location1p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting S1PR1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting S1PR1.
ID Name Drug Type Targets #Targets
DB09105Asfotase AlfaBiotechS1PR11