TISIDB

Summary
Symbol	RRAGA
Name	Ras-related GTP binding A
Aliases	RAGA; FIP-1; adenovirus E3 14.7 kDa-interacting protein 1; adenovirus E3-14.7K interacting protein 1; rag A; ......
Chromosomal Location	9p21.3
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	Cytoplasm Nucleus Lysosome Note=Predominantly cytoplasmic. May shuttle between the cytoplasm and nucleus, depending on the bound nucleotide state (PubMed:8995684, PubMed:9394008). Colocalizes in vivo with adenovirus E3-14.7K mainly to the cytoplasm especially near the nuclear membrane and in discrete foci on or near the plasma membrane (PubMed:8995684).
Domain	PF04670 Gtr1/RagA G protein conserved region
Function	Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RRAGC or RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form. In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. Involved in the RCC1/Ran-GTPase pathway. May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death. May alternatively act as a cellular target for adenovirus E3-14.7K, an inhibitor of TNF-alpha functions, thereby affecting cell death.

> Gene Ontology [ TOP ]
Biological Process	GO:0001101 response to acid chemical GO:0006914 autophagy GO:0007050 cell cycle arrest GO:0009267 cellular response to starvation GO:0009991 response to extracellular stimulus GO:0010506 regulation of autophagy GO:0010507 negative regulation of autophagy GO:0016236 macroautophagy GO:0019048 modulation by virus of host morphology or physiology GO:0019835 cytolysis GO:0031667 response to nutrient levels GO:0031668 cellular response to extracellular stimulus GO:0031669 cellular response to nutrient levels GO:0031929 TOR signaling GO:0032006 regulation of TOR signaling GO:0032008 positive regulation of TOR signaling GO:0034198 cellular response to amino acid starvation GO:0035821 modification of morphology or physiology of other organism GO:0038202 TORC1 signaling GO:0042268 regulation of cytolysis GO:0042594 response to starvation GO:0043200 response to amino acid GO:0044003 modification by symbiont of host morphology or physiology GO:0045786 negative regulation of cell cycle GO:0045919 positive regulation of cytolysis GO:0051701 interaction with host GO:0051817 modification of morphology or physiology of other organism involved in symbiotic interaction GO:0071229 cellular response to acid chemical GO:0071230 cellular response to amino acid stimulus GO:0071417 cellular response to organonitrogen compound GO:0071496 cellular response to external stimulus GO:1903432 regulation of TORC1 signaling GO:1904263 positive regulation of TORC1 signaling
Molecular Function	GO:0003924 GTPase activity GO:0005525 GTP binding GO:0019001 guanyl nucleotide binding GO:0031625 ubiquitin protein ligase binding GO:0032561 guanyl ribonucleotide binding GO:0044389 ubiquitin-like protein ligase binding GO:0046982 protein heterodimerization activity GO:0051219 phosphoprotein binding
Cellular Component	GO:0005765 lysosomal membrane GO:0034448 EGO complex GO:0035859 Seh1-associated complex GO:0044440 endosomal part GO:0098852 lytic vacuole membrane GO:1990130 Iml1 complex GO:1990131 Gtr1-Gtr2 GTPase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04140 Regulation of autophagy hsa04150 mTOR signaling pathway
Reactome	R-HSA-2262752: Cellular responses to stress R-HSA-8866654: E3 ubiquitin ligases ubiquitinate target proteins 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-392499: Metabolism of proteins R-HSA-109704: PI3K Cascade R-HSA-109703: PKB-mediated events R-HSA-597592: Post-translational protein modification R-HSA-8852135: Protein ubiquitination 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-165159: mTOR signalling R-HSA-166208: mTORC1-mediated signalling

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04140 Regulation of autophagy
hsa04150 mTOR signaling pathway

Reactome

R-HSA-2262752: Cellular responses to stress
R-HSA-8866654: E3 ubiquitin ligases ubiquitinate target proteins
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-392499: Metabolism of proteins
R-HSA-109704: PI3K Cascade
R-HSA-109703: PKB-mediated events
R-HSA-597592: Post-translational protein modification
R-HSA-8852135: Protein ubiquitination
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-165159: mTOR signalling
R-HSA-166208: mTORC1-mediated signalling

Summary
Symbol	RRAGA
Name	Ras-related GTP binding A
Aliases	RAGA; FIP-1; adenovirus E3 14.7 kDa-interacting protein 1; adenovirus E3-14.7K interacting protein 1; rag A; ......
Chromosomal Location	9p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between RRAGA 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	RRAGA
Name	Ras-related GTP binding A
Aliases	RAGA; FIP-1; adenovirus E3 14.7 kDa-interacting protein 1; adenovirus E3-14.7K interacting protein 1; rag A; ......
Chromosomal Location	9p21.3
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 RRAGA 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	logFC: -2.76; FDR: 0.02860	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.59	Sensitive to T cell-mediated killing
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	RRAGA
Name	Ras-related GTP binding A
Aliases	RAGA; FIP-1; adenovirus E3 14.7 kDa-interacting protein 1; adenovirus E3-14.7K interacting protein 1; rag A; ......
Chromosomal Location	9p21.3
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 RRAGA 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	0.088	0.637
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.325	0.903
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.083	0.965
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.136	0.623
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.012	0.994
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.293	0.884
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.162	0.701
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.162	0.924
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.13	0.944
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.007	0.997
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	0.439	0.875
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.007	0.919

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of RRAGA in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	RRAGA
Name	Ras-related GTP binding A
Aliases	RAGA; FIP-1; adenovirus E3 14.7 kDa-interacting protein 1; adenovirus E3-14.7K interacting protein 1; rag A; ......
Chromosomal Location	9p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RRAGA. 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	RRAGA
Name	Ras-related GTP binding A
Aliases	RAGA; FIP-1; adenovirus E3 14.7 kDa-interacting protein 1; adenovirus E3-14.7K interacting protein 1; rag A; ......
Chromosomal Location	9p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RRAGA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RRAGA. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	RRAGA
Name	Ras-related GTP binding A
Aliases	RAGA; FIP-1; adenovirus E3 14.7 kDa-interacting protein 1; adenovirus E3-14.7K interacting protein 1; rag A; ......
Chromosomal Location	9p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RRAGA. 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	RRAGA
Name	Ras-related GTP binding A
Aliases	RAGA; FIP-1; adenovirus E3 14.7 kDa-interacting protein 1; adenovirus E3-14.7K interacting protein 1; rag A; ......
Chromosomal Location	9p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of RRAGA expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	RRAGA
Name	Ras-related GTP binding A
Aliases	RAGA; FIP-1; adenovirus E3 14.7 kDa-interacting protein 1; adenovirus E3-14.7K interacting protein 1; rag A; ......
Chromosomal Location	9p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between RRAGA and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	RRAGA
Name	Ras-related GTP binding A
Aliases	RAGA; FIP-1; adenovirus E3 14.7 kDa-interacting protein 1; adenovirus E3-14.7K interacting protein 1; rag A; ......
Chromosomal Location	9p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting RRAGA collected from DrugBank database.

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

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