Browse TSC2

Summary
SymbolTSC2
Nametuberous sclerosis 2
Aliases tuberin; PPP1R160; protein phosphatase 1, regulatory subunit 160; TSC4; tuberous sclerosis 2 protein
Chromosomal Location16p13.3
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
 
Subcellular Location Cytoplasm. Membrane; Peripheral membrane protein. Note=At steady state found in association with membranes.
Domain PF11864 Domain of unknown function (DUF3384)
PF02145 Rap/ran-GAP
PF03542 Tuberin
Function

In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling (PubMed:12271141, PubMed:28215400). Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:15340059). May also play a role in microtubule-mediated protein transport (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity).

> Gene Ontology
 
Biological Process GO:0001838 embryonic epithelial tube formation
GO:0001841 neural tube formation
GO:0001843 neural tube closure
GO:0001933 negative regulation of protein phosphorylation
GO:0006469 negative regulation of protein kinase activity
GO:0006606 protein import into nucleus
GO:0006913 nucleocytoplasmic transport
GO:0007050 cell cycle arrest
GO:0007507 heart development
GO:0008286 insulin receptor signaling pathway
GO:0014020 primary neural tube formation
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0014066 regulation of phosphatidylinositol 3-kinase signaling
GO:0014067 negative regulation of phosphatidylinositol 3-kinase signaling
GO:0016055 Wnt signaling pathway
GO:0016331 morphogenesis of embryonic epithelium
GO:0017038 protein import
GO:0021915 neural tube development
GO:0030100 regulation of endocytosis
GO:0030111 regulation of Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0031929 TOR signaling
GO:0032006 regulation of TOR signaling
GO:0032007 negative regulation of TOR signaling
GO:0032868 response to insulin
GO:0032869 cellular response to insulin stimulus
GO:0033673 negative regulation of kinase activity
GO:0034504 protein localization to nucleus
GO:0035148 tube formation
GO:0035239 tube morphogenesis
GO:0042326 negative regulation of phosphorylation
GO:0043434 response to peptide hormone
GO:0043491 protein kinase B signaling
GO:0044744 protein targeting to nucleus
GO:0045786 negative regulation of cell cycle
GO:0046626 regulation of insulin receptor signaling pathway
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0048009 insulin-like growth factor receptor signaling pathway
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048017 inositol lipid-mediated signaling
GO:0050918 positive chemotaxis
GO:0051056 regulation of small GTPase mediated signal transduction
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051348 negative regulation of transferase activity
GO:0051896 regulation of protein kinase B signaling
GO:0051898 negative regulation of protein kinase B signaling
GO:0060562 epithelial tube morphogenesis
GO:0060606 tube closure
GO:0060627 regulation of vesicle-mediated transport
GO:0071375 cellular response to peptide hormone stimulus
GO:0071417 cellular response to organonitrogen compound
GO:0072175 epithelial tube formation
GO:0198738 cell-cell signaling by wnt
GO:1900076 regulation of cellular response to insulin stimulus
GO:1900077 negative regulation of cellular response to insulin stimulus
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:1902532 negative regulation of intracellular signal transduction
GO:1902593 single-organism nuclear import
Molecular Function GO:0005096 GTPase activator activity
GO:0008047 enzyme activator activity
GO:0019902 phosphatase binding
GO:0030695 GTPase regulator activity
GO:0031267 small GTPase binding
GO:0051020 GTPase binding
GO:0060589 nucleoside-triphosphatase regulator activity
Cellular Component GO:0033596 TSC1-TSC2 complex
GO:0044445 cytosolic part
> KEGG and Reactome Pathway
 
KEGG hsa04115 p53 signaling pathway
hsa04140 Regulation of autophagy
hsa04150 mTOR signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04152 AMPK signaling pathway
hsa04910 Insulin signaling pathway
hsa04919 Thyroid hormone signaling pathway
Reactome R-HSA-198323: AKT phosphorylates targets in the cytosol
R-HSA-1280218: Adaptive Immune System
R-HSA-2262752: Cellular responses to stress
R-HSA-5674400: Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-380972: Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-180292: GAB1 signalosome
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-168256: Immune System
R-HSA-165181: Inhibition of TSC complex formation by PKB
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-1632852: Macroautophagy
R-HSA-199991: Membrane Trafficking
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-109704: PI3K Cascade
R-HSA-2219528: PI3K/AKT Signaling in Cancer
R-HSA-198203: PI3K/AKT activation
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-109703: PKB-mediated events
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
R-HSA-8854214: TBC/RABGAPs
R-HSA-5628897: TP53 Regulates Metabolic Genes
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-5653656: Vesicle-mediated transport
R-HSA-165159: mTOR signalling
Summary
SymbolTSC2
Nametuberous sclerosis 2
Aliases tuberin; PPP1R160; protein phosphatase 1, regulatory subunit 160; TSC4; tuberous sclerosis 2 protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TSC2 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
 

There is no record.
Summary
SymbolTSC2
Nametuberous sclerosis 2
Aliases tuberin; PPP1R160; protein phosphatase 1, regulatory subunit 160; TSC4; tuberous sclerosis 2 protein
Chromosomal Location16p13.3
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
  Statistical results of TSC2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: -2.59; FDR: 0.04630 Resistant to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolTSC2
Nametuberous sclerosis 2
Aliases tuberin; PPP1R160; protein phosphatase 1, regulatory subunit 160; TSC4; tuberous sclerosis 2 protein
Chromosomal Location16p13.3
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
 
Points in the above scatter plot represent the expression difference of TSC2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0410.838
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2750.876
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.1310.92
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.2650.42
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.3330.909
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1780.961
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2490.447
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2340.877
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2360.892
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.220.892
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.0180.651
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.040.421
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TSC2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.41.460.177
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.41.75.70.231
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.55.93.61
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.49.16.31
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91644.46.238.20.0403
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 594011.128.90.505
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47500500.109
1329033130MelanomaallAnti-PD-1 (nivolumab) 38277.907.90.26
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.109.10.519
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolTSC2
Nametuberous sclerosis 2
Aliases tuberin; PPP1R160; protein phosphatase 1, regulatory subunit 160; TSC4; tuberous sclerosis 2 protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TSC2. 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
 
Summary
SymbolTSC2
Nametuberous sclerosis 2
Aliases tuberin; PPP1R160; protein phosphatase 1, regulatory subunit 160; TSC4; tuberous sclerosis 2 protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TSC2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TSC2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTSC2
Nametuberous sclerosis 2
Aliases tuberin; PPP1R160; protein phosphatase 1, regulatory subunit 160; TSC4; tuberous sclerosis 2 protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TSC2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTSC2
Nametuberous sclerosis 2
Aliases tuberin; PPP1R160; protein phosphatase 1, regulatory subunit 160; TSC4; tuberous sclerosis 2 protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TSC2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTSC2
Nametuberous sclerosis 2
Aliases tuberin; PPP1R160; protein phosphatase 1, regulatory subunit 160; TSC4; tuberous sclerosis 2 protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TSC2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTSC2
Nametuberous sclerosis 2
Aliases tuberin; PPP1R160; protein phosphatase 1, regulatory subunit 160; TSC4; tuberous sclerosis 2 protein
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TSC2 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.