TISIDB

Summary
Symbol	SPHK2
Name	sphingosine kinase 2
Aliases	SK-2; SPK 2; SPK-2; sphingosine kinase type 2
Chromosomal Location	19q13.33
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	Isoform 1: Cytoplasm. Membrane.; SUBCELLULAR LOCATION: Isoform 2: Lysosome membrane.
Domain	PF00781 Diacylglycerol kinase catalytic domain
Function	Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides.

> Gene Ontology [ TOP ]
Biological Process	GO:0003376 sphingosine-1-phosphate signaling pathway GO:0006066 alcohol metabolic process GO:0006643 membrane lipid metabolic process GO:0006644 phospholipid metabolic process GO:0006665 sphingolipid metabolic process GO:0006668 sphinganine-1-phosphate metabolic process GO:0006669 sphinganine-1-phosphate biosynthetic process GO:0006670 sphingosine metabolic process GO:0007565 female pregnancy GO:0008654 phospholipid biosynthetic process GO:0019751 polyol metabolic process GO:0030148 sphingolipid biosynthetic process GO:0030258 lipid modification GO:0034311 diol metabolic process GO:0034312 diol biosynthetic process GO:0044283 small molecule biosynthetic process GO:0044706 multi-multicellular organism process GO:0046165 alcohol biosynthetic process GO:0046173 polyol biosynthetic process GO:0046467 membrane lipid biosynthetic process GO:0046512 sphingosine biosynthetic process GO:0046519 sphingoid metabolic process GO:0046520 sphingoid biosynthetic process GO:0046834 lipid phosphorylation GO:0090520 sphingolipid mediated signaling pathway GO:1901615 organic hydroxy compound metabolic process GO:1901617 organic hydroxy compound biosynthetic process
Molecular Function	GO:0001727 lipid kinase activity GO:0008481 sphinganine kinase activity GO:0017016 Ras GTPase binding GO:0017050 D-erythro-sphingosine kinase activity GO:0031267 small GTPase binding GO:0038036 sphingosine-1-phosphate receptor activity GO:0045125 bioactive lipid receptor activity GO:0051020 GTPase binding
Cellular Component	GO:0005765 lysosomal membrane GO:0098852 lytic vacuole membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04020 Calcium signaling pathway hsa04071 Sphingolipid signaling pathway hsa04370 VEGF signaling pathway hsa04666 Fc gamma R-mediated phagocytosis hsa00600 Sphingolipid metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-1660661: Sphingolipid de novo biosynthesis R-HSA-428157: Sphingolipid metabolism

Summary
Symbol	SPHK2
Name	sphingosine kinase 2
Aliases	SK-2; SPK 2; SPK-2; sphingosine kinase type 2
Chromosomal Location	19q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SPHK2 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 SPHK2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29277894	Non-Small Cell Lung Carcinoma	Inhibit immunity; decrease the efficacy of immunotherapy; immunotherapy target	SphK2 expression predicts poor survival in NSCLC patients, and is associated with Gefitinib-resistance.
23373542	Breast Carcinoma; Osteosarcoma; Pancreatic Adenocarcinoma	Promote immunity	these findings revealed that PhotoImmunoNanoTherapy, utilizing the novel nontoxic theranostic agent ICG-CPSNP, can decrease tumor-associated inflammation and immature myeloid cells in a sphingosine kinase 2-dependent manner.

Summary
Symbol	SPHK2
Name	sphingosine kinase 2
Aliases	SK-2; SPK 2; SPK-2; sphingosine kinase type 2
Chromosomal Location	19q13.33
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 SPHK2 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	SPHK2
Name	sphingosine kinase 2
Aliases	SK-2; SPK 2; SPK-2; sphingosine kinase type 2
Chromosomal Location	19q13.33
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 SPHK2 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	0.999
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.091	0.954
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.07	0.95
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.439	0.258
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.521	0.798
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.34	0.9
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.022	0.933
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.015	0.985
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.038	0.972
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.013	0.99
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	0.056	0.969
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.105	0.28

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SPHK2 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	3.7	4.1	-0.4	1
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	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	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	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	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	SPHK2
Name	sphingosine kinase 2
Aliases	SK-2; SPK 2; SPK-2; sphingosine kinase type 2
Chromosomal Location	19q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SPHK2. 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	SPHK2
Name	sphingosine kinase 2
Aliases	SK-2; SPK 2; SPK-2; sphingosine kinase type 2
Chromosomal Location	19q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SPHK2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SPHK2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SPHK2
Name	sphingosine kinase 2
Aliases	SK-2; SPK 2; SPK-2; sphingosine kinase type 2
Chromosomal Location	19q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SPHK2. 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	SPHK2
Name	sphingosine kinase 2
Aliases	SK-2; SPK 2; SPK-2; sphingosine kinase type 2
Chromosomal Location	19q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SPHK2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SPHK2
Name	sphingosine kinase 2
Aliases	SK-2; SPK 2; SPK-2; sphingosine kinase type 2
Chromosomal Location	19q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SPHK2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SPHK2
Name	sphingosine kinase 2
Aliases	SK-2; SPK 2; SPK-2; sphingosine kinase type 2
Chromosomal Location	19q13.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SPHK2 collected from DrugBank database.

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

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