TISIDB

Summary
Symbol	S1PR4
Name	sphingosine-1-phosphate receptor 4
Aliases	EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location	19p13.3
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	S1PR4
Name	sphingosine-1-phosphate receptor 4
Aliases	EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location	19p13.3
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

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Literatures describing the relation between S1PR4 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
22678911	Breast Carcinoma	Inhibit 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
Symbol	S1PR4
Name	sphingosine-1-phosphate receptor 4
Aliases	EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location	19p13.3
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	S1PR4
Name	sphingosine-1-phosphate receptor 4
Aliases	EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location	19p13.3
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.08	0.868
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.192	0.854
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.009	0.992
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.758	0.442
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.814	0.582
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	2.752	0.129
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.375	0.545
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.547	0.546
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.113	0.906
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.818	0.376
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-0.144	0.916
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.21	0.276

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	2.7	4.7	0.294
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	3.4	4	0.587
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	S1PR4
Name	sphingosine-1-phosphate receptor 4
Aliases	EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location	19p13.3
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 [ TOP ]

Summary
Symbol	S1PR4
Name	sphingosine-1-phosphate receptor 4
Aliases	EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location	19p13.3
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	S1PR4
Name	sphingosine-1-phosphate receptor 4
Aliases	EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location	19p13.3
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	S1PR4
Name	sphingosine-1-phosphate receptor 4
Aliases	EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of S1PR4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	S1PR4
Name	sphingosine-1-phosphate receptor 4
Aliases	EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between S1PR4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	S1PR4
Name	sphingosine-1-phosphate receptor 4
Aliases	EDG6; endothelial differentiation, G-protein-coupled receptor 6; endothelial differentiation, lysophosphatid ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting S1PR4 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse S1PR4