Browse S1PR4

Summary
SymbolS1PR4
Namesphingosine-1-phosphate receptor 4
Aliases EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location19p13.3
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.
Domain PF00001 7 transmembrane receptor (rhodopsin family)
Function

Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. May be involved in cell migration processes that are specific for lymphocytes.

> Gene Ontology
 
Biological Process GO:0003376 sphingosine-1-phosphate signaling pathway
GO:0006874 cellular calcium ion homeostasis
GO:0006875 cellular metal ion homeostasis
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:0007189 adenylate cyclase-activating G-protein coupled receptor signaling pathway
GO:0007202 activation of phospholipase C activity
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0010517 regulation of phospholipase activity
GO:0010518 positive regulation of phospholipase activity
GO:0010863 positive regulation of phospholipase C activity
GO:0051480 regulation of cytosolic calcium ion concentration
GO:0055074 calcium ion homeostasis
GO:0060191 regulation of lipase activity
GO:0060193 positive regulation of lipase activity
GO:0072503 cellular divalent inorganic cation homeostasis
GO:0072507 divalent inorganic cation homeostasis
GO:0090520 sphingolipid mediated signaling pathway
GO:1900274 regulation of phospholipase C activity
Molecular Function GO:0038036 sphingosine-1-phosphate receptor activity
GO:0045125 bioactive lipid receptor activity
Cellular Component -
> 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-418594: G alpha (i) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-500792: GPCR ligand binding
R-HSA-419408: Lysosphingolipid and LPA receptors
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
Summary
SymbolS1PR4
Namesphingosine-1-phosphate receptor 4
Aliases EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between S1PR4 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 S1PR4 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
22678911Breast CarcinomaInhibit immunity (T cell function)Immunosuppression via Treg cells was transferable and required the release of sphingosine-1-phosphate (S1P) from apoptotic cells, acting via S1P receptor 4 on DCs to induce IL-27 secretion. We propose that CD69 expression on CD39(+) Treg cells enables them to interact with CD73-expressing CD8(+) T cells to generate adenosine, thereby suppressing cytotoxicity.
Summary
SymbolS1PR4
Namesphingosine-1-phosphate receptor 4
Aliases EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location19p13.3
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 S1PR4 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
SymbolS1PR4
Namesphingosine-1-phosphate receptor 4
Aliases EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location19p13.3
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 S1PR4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.080.868
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1920.854
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0090.992
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.7580.442
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.8140.582
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 472.7520.129
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.3750.545
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.5470.546
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1130.906
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.8180.376
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-0.1440.916
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.210.276
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of S1PR4 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) 27737.42.74.70.294
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.43.440.587
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
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
SymbolS1PR4
Namesphingosine-1-phosphate receptor 4
Aliases EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of S1PR4. 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
SymbolS1PR4
Namesphingosine-1-phosphate receptor 4
Aliases EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of S1PR4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by S1PR4.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolS1PR4
Namesphingosine-1-phosphate receptor 4
Aliases EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of S1PR4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolS1PR4
Namesphingosine-1-phosphate receptor 4
Aliases EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of S1PR4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolS1PR4
Namesphingosine-1-phosphate receptor 4
Aliases EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between S1PR4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolS1PR4
Namesphingosine-1-phosphate receptor 4
Aliases EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting S1PR4 collected from DrugBank database.
> Drugs from DrugBank database
 

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