TISIDB

Summary
Symbol	NPRL2
Name	NPR2-like, GATOR1 complex subunit
Aliases	NPR2L; TUSC4; tumor suppressor candidate 4; nitrogen permease regulator-like 2 (S. cerevisiae); 2810446G01Ri ......
Chromosomal Location	3p21.3
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	Lysosome membrane Note=Localization to lysosomes is amino acid-independent.
Domain	PF06218 Nitrogen permease regulator 2
Function	As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway. ; FUNCTION: Suppresses Src-dependent tyrosine phosphorylation and activation of PDPK1 and its downstream signaling. Down-regulates PDPK1 kinase activity by interfering with tyrosine phosphorylation at 'Tyr-9', 'Tyr-373' and 'Tyr-376' residues. May act as a tumor suppressor. Suppresses cell growth and enhances sensitivity to various anticancer drugs.

> Gene Ontology [ TOP ]
Biological Process	GO:0000045 autophagosome assembly GO:0006914 autophagy GO:0006995 cellular response to nitrogen starvation GO:0007033 vacuole organization GO:0009267 cellular response to starvation GO:0009991 response to extracellular stimulus GO:0010506 regulation of autophagy GO:0010508 positive regulation of autophagy GO:0016236 macroautophagy GO:0016241 regulation of macroautophagy 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:0032007 negative regulation of TOR signaling GO:0033673 negative regulation of kinase activity GO:0034198 cellular response to amino acid starvation GO:0042326 negative regulation of phosphorylation GO:0042594 response to starvation GO:0043562 cellular response to nitrogen levels GO:0044088 regulation of vacuole organization GO:0051348 negative regulation of transferase activity GO:0071496 cellular response to external stimulus GO:1902115 regulation of organelle assembly GO:1902532 negative regulation of intracellular signal transduction GO:1905037 autophagosome organization GO:2000785 regulation of autophagosome assembly
Molecular Function	GO:0005096 GTPase activator activity GO:0008047 enzyme activator activity GO:0030695 GTPase regulator activity GO:0060589 nucleoside-triphosphatase regulator activity
Cellular Component	GO:0035859 Seh1-associated complex GO:1990130 Iml1 complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04150 mTOR signaling pathway
Reactome	-

Summary
Symbol	NPRL2
Name	NPR2-like, GATOR1 complex subunit
Aliases	NPR2L; TUSC4; tumor suppressor candidate 4; nitrogen permease regulator-like 2 (S. cerevisiae); 2810446G01Ri ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between NPRL2 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	NPRL2
Name	NPR2-like, GATOR1 complex subunit
Aliases	NPR2L; TUSC4; tumor suppressor candidate 4; nitrogen permease regulator-like 2 (S. cerevisiae); 2810446G01Ri ......
Chromosomal Location	3p21.3
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

[ TOP ]

Statistical results of NPRL2 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: -3.20; FDR: 0.00700	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	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	NPRL2
Name	NPR2-like, GATOR1 complex subunit
Aliases	NPR2L; TUSC4; tumor suppressor candidate 4; nitrogen permease regulator-like 2 (S. cerevisiae); 2810446G01Ri ......
Chromosomal Location	3p21.3
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 NPRL2 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	-0.072	0.753
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.068	0.967
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.076	0.951
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.151	0.698
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.084	0.956
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.236	0.903
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.197	0.475
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.206	0.86
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.177	0.891
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.892	0.489
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	-0.472	0.793
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.116	0.143

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of NPRL2 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	14.8	1.4	13.4	0.0181
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	14.8	1.7	13.1	0.032
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	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	NPRL2
Name	NPR2-like, GATOR1 complex subunit
Aliases	NPR2L; TUSC4; tumor suppressor candidate 4; nitrogen permease regulator-like 2 (S. cerevisiae); 2810446G01Ri ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NPRL2. 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	NPRL2
Name	NPR2-like, GATOR1 complex subunit
Aliases	NPR2L; TUSC4; tumor suppressor candidate 4; nitrogen permease regulator-like 2 (S. cerevisiae); 2810446G01Ri ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NPRL2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NPRL2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NPRL2
Name	NPR2-like, GATOR1 complex subunit
Aliases	NPR2L; TUSC4; tumor suppressor candidate 4; nitrogen permease regulator-like 2 (S. cerevisiae); 2810446G01Ri ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NPRL2. 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	NPRL2
Name	NPR2-like, GATOR1 complex subunit
Aliases	NPR2L; TUSC4; tumor suppressor candidate 4; nitrogen permease regulator-like 2 (S. cerevisiae); 2810446G01Ri ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NPRL2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NPRL2
Name	NPR2-like, GATOR1 complex subunit
Aliases	NPR2L; TUSC4; tumor suppressor candidate 4; nitrogen permease regulator-like 2 (S. cerevisiae); 2810446G01Ri ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NPRL2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NPRL2
Name	NPR2-like, GATOR1 complex subunit
Aliases	NPR2L; TUSC4; tumor suppressor candidate 4; nitrogen permease regulator-like 2 (S. cerevisiae); 2810446G01Ri ......
Chromosomal Location	3p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NPRL2 collected from DrugBank database.

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

Browse NPRL2