TISIDB

Summary
Symbol	DGKA
Name	diacylglycerol kinase, alpha 80kDa
Aliases	DGK-alpha; DAGK1; diacylglycerol kinase, alpha (80kD); 80 kDa diacylglycerol kinase; DAG kinase alpha; digly ......
Chromosomal Location	12q13.3
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	-
Domain	PF00130 Phorbol esters/diacylglycerol binding domain (C1 domain) PF14513 Diacylglycerol kinase N-terminus PF00609 Diacylglycerol kinase accessory domain PF00781 Diacylglycerol kinase catalytic domain
Function	Upon cell stimulation converts the second messenger diacylglycerol into phosphatidate, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity.

> Gene Ontology [ TOP ]
Biological Process	GO:0006638 neutral lipid metabolic process GO:0006639 acylglycerol metabolic process GO:0006654 phosphatidic acid biosynthetic process GO:0007205 protein kinase C-activating G-protein coupled receptor signaling pathway GO:0007596 blood coagulation GO:0007599 hemostasis GO:0030168 platelet activation GO:0030258 lipid modification GO:0046339 diacylglycerol metabolic process GO:0046473 phosphatidic acid metabolic process GO:0046486 glycerolipid metabolic process GO:0046834 lipid phosphorylation GO:0050817 coagulation GO:0050878 regulation of body fluid levels
Molecular Function	GO:0004143 diacylglycerol kinase activity GO:0005543 phospholipid binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04070 Phosphatidylinositol signaling system hsa00561 Glycerolipid metabolism hsa00564 Glycerophospholipid metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-114508: Effects of PIP2 hydrolysis R-HSA-416476: G alpha (q) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-109582: Hemostasis R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	DGKA
Name	diacylglycerol kinase, alpha 80kDa
Aliases	DGK-alpha; DAGK1; diacylglycerol kinase, alpha (80kD); 80 kDa diacylglycerol kinase; DAG kinase alpha; digly ......
Chromosomal Location	12q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between DGKA 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 DGKA and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26768655	Hepatocellular Carcinoma; Cervical Carcinoma	Inhibit immunity (T cell function)	A novel diacylglycerol kinase α-selective inhibitor, CU-3, induces cancer cell apoptosis and enhances immune response. CU-3 competitively reduced the affinity of DGKα for ATP, but not diacylglycerol or phosphatidylserine. Moreover, this compound induced apoptosis in HepG2 hepatocellular carcinoma and HeLa cervical cancer cells while simultaneously enhancing the interleukin-2 production of Jurkat T cells.
29572701	melanoma	Inhibit immunity (T cell function); decrease the efficacy of immunotherapy	Diacylglycerol kinase α Diacylglycerol kinase α inactivation is an integral component of the costimulatory pathway that amplifies TCR signals.

Summary
Symbol	DGKA
Name	diacylglycerol kinase, alpha 80kDa
Aliases	DGK-alpha; DAGK1; diacylglycerol kinase, alpha (80kD); 80 kDa diacylglycerol kinase; DAG kinase alpha; digly ......
Chromosomal Location	12q13.3
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 DGKA 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	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	Total # shRNA with >= 4-fold: 4	Resistant to T-cell proliferation

Summary
Symbol	DGKA
Name	diacylglycerol kinase, alpha 80kDa
Aliases	DGK-alpha; DAGK1; diacylglycerol kinase, alpha (80kD); 80 kDa diacylglycerol kinase; DAG kinase alpha; digly ......
Chromosomal Location	12q13.3
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 DGKA 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	-0.278	0.507
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.708	0.607
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.047	0.959
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.03	0.915
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.238	0.923
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.237	0.937
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.392	0.367
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.37	0.768
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.416	0.766
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.498	0.295
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	1.826	0.401
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.179	0.13

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of DGKA 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
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	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	DGKA
Name	diacylglycerol kinase, alpha 80kDa
Aliases	DGK-alpha; DAGK1; diacylglycerol kinase, alpha (80kD); 80 kDa diacylglycerol kinase; DAG kinase alpha; digly ......
Chromosomal Location	12q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DGKA. 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	DGKA
Name	diacylglycerol kinase, alpha 80kDa
Aliases	DGK-alpha; DAGK1; diacylglycerol kinase, alpha (80kD); 80 kDa diacylglycerol kinase; DAG kinase alpha; digly ......
Chromosomal Location	12q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DGKA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DGKA. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DGKA
Name	diacylglycerol kinase, alpha 80kDa
Aliases	DGK-alpha; DAGK1; diacylglycerol kinase, alpha (80kD); 80 kDa diacylglycerol kinase; DAG kinase alpha; digly ......
Chromosomal Location	12q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DGKA. 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	DGKA
Name	diacylglycerol kinase, alpha 80kDa
Aliases	DGK-alpha; DAGK1; diacylglycerol kinase, alpha (80kD); 80 kDa diacylglycerol kinase; DAG kinase alpha; digly ......
Chromosomal Location	12q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DGKA expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DGKA
Name	diacylglycerol kinase, alpha 80kDa
Aliases	DGK-alpha; DAGK1; diacylglycerol kinase, alpha (80kD); 80 kDa diacylglycerol kinase; DAG kinase alpha; digly ......
Chromosomal Location	12q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DGKA and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DGKA
Name	diacylglycerol kinase, alpha 80kDa
Aliases	DGK-alpha; DAGK1; diacylglycerol kinase, alpha (80kD); 80 kDa diacylglycerol kinase; DAG kinase alpha; digly ......
Chromosomal Location	12q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DGKA collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting DGKA.

ID	Name	Drug Type	Targets	#Targets
DB00163	Vitamin E	Small Molecule	ALOX5, DGKA, NR1I2, PPP2CA, PPP2CB, PRKCA, PRKCB, SEC14L2, SEC14L3 ......	10
DB14001	alpha-Tocopherol succinate	Small Molecule	ALOX5, DGKA, NR1I2, PPP2CA, PPP2CB, PRKCA, PRKCB, SEC14L2, SEC14L3 ......	10
DB14002	D-alpha-Tocopherol acetate	Small Molecule	ALOX5, DGKA, NR1I2, PPP2CA, PPP2CB, PRKCA, PRKCB, SEC14L2, SEC14L3 ......	10

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