TISIDB

Summary
Symbol	PRKAG3
Name	protein kinase, AMP-activated, gamma 3 non-catalytic subunit
Aliases	AMPKG3; 5'-AMP-activated protein kinase, gamma-3 subunit; AMPK gamma-3 chain; AMPK gamma3; AMPK subunit gamm ......
Chromosomal Location	2q35
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	PF00571 CBS domain
Function	AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.

> Gene Ontology [ TOP ]
Biological Process	GO:0000271 polysaccharide biosynthetic process GO:0005976 polysaccharide metabolic process GO:0005977 glycogen metabolic process GO:0005978 glycogen biosynthetic process GO:0006073 cellular glucan metabolic process GO:0006091 generation of precursor metabolites and energy GO:0006112 energy reserve metabolic process GO:0006631 fatty acid metabolic process GO:0006633 fatty acid biosynthetic process GO:0006914 autophagy GO:0007050 cell cycle arrest GO:0008643 carbohydrate transport GO:0008645 hexose transport GO:0009250 glucan biosynthetic process GO:0015749 monosaccharide transport GO:0015758 glucose transport GO:0015980 energy derivation by oxidation of organic compounds GO:0016051 carbohydrate biosynthetic process GO:0016053 organic acid biosynthetic process GO:0016236 macroautophagy GO:0033692 cellular polysaccharide biosynthetic process GO:0034637 cellular carbohydrate biosynthetic process GO:0044042 glucan metabolic process GO:0044262 cellular carbohydrate metabolic process GO:0044264 cellular polysaccharide metabolic process GO:0044283 small molecule biosynthetic process GO:0044723 single-organism carbohydrate metabolic process GO:0045786 negative regulation of cell cycle GO:0046394 carboxylic acid biosynthetic process GO:0072330 monocarboxylic acid biosynthetic process GO:0072331 signal transduction by p53 class mediator GO:1901796 regulation of signal transduction by p53 class mediator
Molecular Function	GO:0004674 protein serine/threonine kinase activity GO:0004679 AMP-activated protein kinase activity
Cellular Component	GO:0031588 nucleotide-activated protein kinase complex GO:0061695 transferase complex, transferring phosphorus-containing groups GO:1902911 protein kinase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04068 FoxO signaling pathway hsa04152 AMPK signaling pathway hsa04530 Tight junction hsa04710 Circadian rhythm hsa04910 Insulin signaling pathway hsa04920 Adipocytokine signaling pathway hsa04921 Oxytocin signaling pathway hsa04922 Glucagon signaling pathway
Reactome	R-HSA-2151209: Activation of PPARGC1A (PGC-1alpha) by phosphorylation R-HSA-2262752: Cellular responses to stress R-HSA-380972: Energy dependent regulation of mTOR by LKB1-AMPK R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-2428924: IGF1R signaling cascade R-HSA-112399: IRS-mediated signalling R-HSA-2428928: IRS-related events triggered by IGF1R R-HSA-74751: Insulin receptor signalling cascade R-HSA-1632852: Macroautophagy R-HSA-199991: Membrane Trafficking R-HSA-1592230: Mitochondrial biogenesis R-HSA-1852241: Organelle biogenesis and maintenance R-HSA-109704: PI3K Cascade R-HSA-109703: PKB-mediated events R-HSA-5633007: Regulation of TP53 Activity R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation R-HSA-162582: Signal Transduction R-HSA-74752: Signaling by Insulin receptor R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) R-HSA-5628897: TP53 Regulates Metabolic Genes R-HSA-3700989: Transcriptional Regulation by TP53 R-HSA-1445148: Translocation of GLUT4 to the plasma membrane R-HSA-5653656: Vesicle-mediated transport R-HSA-165159: mTOR signalling

> KEGG and Reactome Pathway

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KEGG

hsa04068 FoxO signaling pathway
hsa04152 AMPK signaling pathway
hsa04530 Tight junction
hsa04710 Circadian rhythm
hsa04910 Insulin signaling pathway
hsa04920 Adipocytokine signaling pathway
hsa04921 Oxytocin signaling pathway
hsa04922 Glucagon signaling pathway

Reactome

R-HSA-2151209: Activation of PPARGC1A (PGC-1alpha) by phosphorylation
R-HSA-2262752: Cellular responses to stress
R-HSA-380972: Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-1632852: Macroautophagy
R-HSA-199991: Membrane Trafficking
R-HSA-1592230: Mitochondrial biogenesis
R-HSA-1852241: Organelle biogenesis and maintenance
R-HSA-109704: PI3K Cascade
R-HSA-109703: PKB-mediated events
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation
R-HSA-162582: Signal Transduction
R-HSA-74752: Signaling by Insulin receptor
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-5628897: TP53 Regulates Metabolic Genes
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-1445148: Translocation of GLUT4 to the plasma membrane
R-HSA-5653656: Vesicle-mediated transport
R-HSA-165159: mTOR signalling

Summary
Symbol	PRKAG3
Name	protein kinase, AMP-activated, gamma 3 non-catalytic subunit
Aliases	AMPKG3; 5'-AMP-activated protein kinase, gamma-3 subunit; AMPK gamma-3 chain; AMPK gamma3; AMPK subunit gamm ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PRKAG3 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 [ TOP ]
There is no record.

Summary
Symbol	PRKAG3
Name	protein kinase, AMP-activated, gamma 3 non-catalytic subunit
Aliases	AMPKG3; 5'-AMP-activated protein kinase, gamma-3 subunit; AMPK gamma-3 chain; AMPK gamma3; AMPK subunit gamm ......
Chromosomal Location	2q35
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 PRKAG3 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	PRKAG3
Name	protein kinase, AMP-activated, gamma 3 non-catalytic subunit
Aliases	AMPKG3; 5'-AMP-activated protein kinase, gamma-3 subunit; AMPK gamma-3 chain; AMPK gamma3; AMPK subunit gamm ......
Chromosomal Location	2q35
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 PRKAG3 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	0.166	0.362
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.057	0.914
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.247	0.565
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.93	0.0191
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-2.964	0.017
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.631	0.662
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.167	0.699
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	-0.167	0.796
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.154	0.571

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PRKAG3 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	0	7.4	0.0709
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	0	7.4	0.096
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	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	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	12.5	-1.4	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	22.2	-22.2	0.505
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
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	PRKAG3
Name	protein kinase, AMP-activated, gamma 3 non-catalytic subunit
Aliases	AMPKG3; 5'-AMP-activated protein kinase, gamma-3 subunit; AMPK gamma-3 chain; AMPK gamma3; AMPK subunit gamm ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PRKAG3. 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	PRKAG3
Name	protein kinase, AMP-activated, gamma 3 non-catalytic subunit
Aliases	AMPKG3; 5'-AMP-activated protein kinase, gamma-3 subunit; AMPK gamma-3 chain; AMPK gamma3; AMPK subunit gamm ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PRKAG3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PRKAG3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PRKAG3
Name	protein kinase, AMP-activated, gamma 3 non-catalytic subunit
Aliases	AMPKG3; 5'-AMP-activated protein kinase, gamma-3 subunit; AMPK gamma-3 chain; AMPK gamma3; AMPK subunit gamm ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PRKAG3. 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	PRKAG3
Name	protein kinase, AMP-activated, gamma 3 non-catalytic subunit
Aliases	AMPKG3; 5'-AMP-activated protein kinase, gamma-3 subunit; AMPK gamma-3 chain; AMPK gamma3; AMPK subunit gamm ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PRKAG3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PRKAG3
Name	protein kinase, AMP-activated, gamma 3 non-catalytic subunit
Aliases	AMPKG3; 5'-AMP-activated protein kinase, gamma-3 subunit; AMPK gamma-3 chain; AMPK gamma3; AMPK subunit gamm ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PRKAG3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PRKAG3
Name	protein kinase, AMP-activated, gamma 3 non-catalytic subunit
Aliases	AMPKG3; 5'-AMP-activated protein kinase, gamma-3 subunit; AMPK gamma-3 chain; AMPK gamma3; AMPK subunit gamm ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PRKAG3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PRKAG3.

ID	Name	Drug Type	Targets	#Targets
DB00945	Acetylsalicylic acid	Small Molecule	AKR1C1, EDNRA, HSPA5, IKBKB, NFKB1, NFKB2, NFKBIA, PRKAA1, PRKAA2, ......	18

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