Browse TSC1

Summary
SymbolTSC1
Nametuberous sclerosis 1
Aliases KIAA0243; hamartin; tuberous sclerosis 1 protein; tumor suppressor
Chromosomal Location9q34
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 PF04388 Hamartin protein
Function

In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling (PubMed:12271141, PubMed:28215400). Seems not to be required for TSC2 GAP activity towards RHEB (PubMed:15340059). Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling (By similarity). Acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (PubMed:29127155). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (PubMed:16464865, PubMed:29127155).

> Gene Ontology
 
Biological Process GO:0001655 urogenital system development
GO:0001822 kidney development
GO:0001838 embryonic epithelial tube formation
GO:0001841 neural tube formation
GO:0001843 neural tube closure
GO:0001952 regulation of cell-matrix adhesion
GO:0001954 positive regulation of cell-matrix adhesion
GO:0002250 adaptive immune response
GO:0002263 cell activation involved in immune response
GO:0002285 lymphocyte activation involved in immune response
GO:0002286 T cell activation involved in immune response
GO:0002292 T cell differentiation involved in immune response
GO:0002366 leukocyte activation involved in immune response
GO:0002521 leukocyte differentiation
GO:0006403 RNA localization
GO:0006405 RNA export from nucleus
GO:0006407 rRNA export from nucleus
GO:0006417 regulation of translation
GO:0006470 protein dephosphorylation
GO:0006813 potassium ion transport
GO:0006913 nucleocytoplasmic transport
GO:0006914 autophagy
GO:0007015 actin filament organization
GO:0007044 cell-substrate junction assembly
GO:0007045 cell-substrate adherens junction assembly
GO:0007050 cell cycle arrest
GO:0007159 leukocyte cell-cell adhesion
GO:0007160 cell-matrix adhesion
GO:0007272 ensheathment of neurons
GO:0007507 heart development
GO:0007626 locomotory behavior
GO:0008286 insulin receptor signaling pathway
GO:0008344 adult locomotory behavior
GO:0008361 regulation of cell size
GO:0008366 axon ensheathment
GO:0008643 carbohydrate transport
GO:0008645 hexose transport
GO:0009991 response to extracellular stimulus
GO:0010506 regulation of autophagy
GO:0010507 negative regulation of autophagy
GO:0010608 posttranscriptional regulation of gene expression
GO:0010810 regulation of cell-substrate adhesion
GO:0010811 positive regulation of cell-substrate adhesion
GO:0010921 regulation of phosphatase activity
GO:0014020 primary neural tube formation
GO:0014706 striated muscle tissue development
GO:0015672 monovalent inorganic cation transport
GO:0015749 monosaccharide transport
GO:0015758 glucose transport
GO:0015931 nucleobase-containing compound transport
GO:0016236 macroautophagy
GO:0016241 regulation of macroautophagy
GO:0016242 negative regulation of macroautophagy
GO:0016311 dephosphorylation
GO:0016331 morphogenesis of embryonic epithelium
GO:0017148 negative regulation of translation
GO:0021537 telencephalon development
GO:0021543 pallium development
GO:0021761 limbic system development
GO:0021766 hippocampus development
GO:0021915 neural tube development
GO:0021987 cerebral cortex development
GO:0022613 ribonucleoprotein complex biogenesis
GO:0030038 contractile actin filament bundle assembly
GO:0030098 lymphocyte differentiation
GO:0030217 T cell differentiation
GO:0030534 adult behavior
GO:0030900 forebrain development
GO:0031032 actomyosin structure organization
GO:0031589 cell-substrate adhesion
GO:0031647 regulation of protein stability
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:0032231 regulation of actin filament bundle assembly
GO:0032535 regulation of cellular component size
GO:0032868 response to insulin
GO:0032869 cellular response to insulin stimulus
GO:0032956 regulation of actin cytoskeleton organization
GO:0032970 regulation of actin filament-based process
GO:0034248 regulation of cellular amide metabolic process
GO:0034249 negative regulation of cellular amide metabolic process
GO:0034329 cell junction assembly
GO:0034330 cell junction organization
GO:0034332 adherens junction organization
GO:0034333 adherens junction assembly
GO:0035051 cardiocyte differentiation
GO:0035148 tube formation
GO:0035239 tube morphogenesis
GO:0035303 regulation of dephosphorylation
GO:0035304 regulation of protein dephosphorylation
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0042110 T cell activation
GO:0042254 ribosome biogenesis
GO:0042552 myelination
GO:0042692 muscle cell differentiation
GO:0043149 stress fiber assembly
GO:0043379 memory T cell differentiation
GO:0043434 response to peptide hormone
GO:0043666 regulation of phosphoprotein phosphatase activity
GO:0044089 positive regulation of cellular component biogenesis
GO:0044708 single-organism behavior
GO:0045216 cell-cell junction organization
GO:0045785 positive regulation of cell adhesion
GO:0045786 negative regulation of cell cycle
GO:0045792 negative regulation of cell size
GO:0046323 glucose import
GO:0046626 regulation of insulin receptor signaling pathway
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0048041 focal adhesion assembly
GO:0048738 cardiac muscle tissue development
GO:0050657 nucleic acid transport
GO:0050658 RNA transport
GO:0050808 synapse organization
GO:0050821 protein stabilization
GO:0051017 actin filament bundle assembly
GO:0051029 rRNA transport
GO:0051146 striated muscle cell differentiation
GO:0051168 nuclear export
GO:0051169 nuclear transport
GO:0051236 establishment of RNA localization
GO:0051259 protein oligomerization
GO:0051291 protein heterooligomerization
GO:0051492 regulation of stress fiber assembly
GO:0051493 regulation of cytoskeleton organization
GO:0051893 regulation of focal adhesion assembly
GO:0051894 positive regulation of focal adhesion assembly
GO:0055007 cardiac muscle cell differentiation
GO:0060537 muscle tissue development
GO:0060562 epithelial tube morphogenesis
GO:0060606 tube closure
GO:0061572 actin filament bundle organization
GO:0070482 response to oxygen levels
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070997 neuron death
GO:0071166 ribonucleoprotein complex localization
GO:0071375 cellular response to peptide hormone stimulus
GO:0071417 cellular response to organonitrogen compound
GO:0071426 ribonucleoprotein complex export from nucleus
GO:0071428 rRNA-containing ribonucleoprotein complex export from nucleus
GO:0071453 cellular response to oxygen levels
GO:0071496 cellular response to external stimulus
GO:0071593 lymphocyte aggregation
GO:0072001 renal system development
GO:0072175 epithelial tube formation
GO:0090066 regulation of anatomical structure size
GO:0090109 regulation of cell-substrate junction assembly
GO:0090630 activation of GTPase activity
GO:0090649 response to oxygen-glucose deprivation
GO:0090650 cellular response to oxygen-glucose deprivation
GO:1900076 regulation of cellular response to insulin stimulus
GO:1900077 negative regulation of cellular response to insulin stimulus
GO:1901214 regulation of neuron death
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:1901888 regulation of cell junction assembly
GO:1901890 positive regulation of cell junction assembly
GO:1902532 negative regulation of intracellular signal transduction
GO:1903391 regulation of adherens junction organization
GO:1903393 positive regulation of adherens junction organization
Molecular Function GO:0030695 GTPase regulator activity
GO:0032794 GTPase activating protein binding
GO:0047485 protein N-terminus binding
GO:0051087 chaperone binding
GO:0060589 nucleoside-triphosphatase regulator activity
Cellular Component GO:0005884 actin filament
GO:0005938 cell cortex
GO:0015629 actin cytoskeleton
GO:0030027 lamellipodium
GO:0030426 growth cone
GO:0030427 site of polarized growth
GO:0031252 cell leading edge
GO:0033596 TSC1-TSC2 complex
GO:0044445 cytosolic part
GO:0099568 cytoplasmic region
> KEGG and Reactome Pathway
 
KEGG hsa04140 Regulation of autophagy
hsa04150 mTOR signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04152 AMPK signaling pathway
hsa04910 Insulin signaling pathway
Reactome 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-165181: Inhibition of TSC complex formation by PKB
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-1632852: Macroautophagy
R-HSA-199991: Membrane Trafficking
R-HSA-109704: PI3K Cascade
R-HSA-109703: PKB-mediated events
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-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
SymbolTSC1
Nametuberous sclerosis 1
Aliases KIAA0243; hamartin; tuberous sclerosis 1 protein; tumor suppressor
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TSC1 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
 
  Literatures describing the relation between TSC1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
24532578MelanomaInhibit immunity (T cell function); immunotherapy targetTuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cell-mediated antitumor immunity. We report in this study that the tuberous sclerosis 1 (TSC1), a negative regulator of mTOR signaling, plays a crucial role in iNKT cell anergy. Deficiency of TSC1 in iNKT cells results in resistance to α-GalCer-induced anergy, manifested by increased expansion of and cytokine production by iNKT cells in response to secondary Ag stimulation. It is correlated with impaired upregulation of programmed death-1, Egr2, and Grail. TSC1-deficient iNKT cells display enhanced antitumor immunity in a melanoma lung metastasis model. Our data suggest targeting TSC1/2 as a strategy for boosting antitumor immune therapy.
Summary
SymbolTSC1
Nametuberous sclerosis 1
Aliases KIAA0243; hamartin; tuberous sclerosis 1 protein; tumor suppressor
Chromosomal Location9q34
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 TSC1 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 NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 STARS Score: 3.66; FDR: 0.035 Resistant to T cell-mediated killing
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
SymbolTSC1
Nametuberous sclerosis 1
Aliases KIAA0243; hamartin; tuberous sclerosis 1 protein; tumor suppressor
Chromosomal Location9q34
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 TSC1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0570.753
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1390.884
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2030.79
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1830.503
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0310.988
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4610.875
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1770.594
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2830.853
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0710.967
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.0520.952
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.690.55
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0650.253
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TSC1 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) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277314.85.59.30.206
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275914.86.880.252
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211714.3014.30.238
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.4015.40.482
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.16.24.91
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 592011.18.91
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 111307.7-7.71
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 51208.3-8.31
Summary
SymbolTSC1
Nametuberous sclerosis 1
Aliases KIAA0243; hamartin; tuberous sclerosis 1 protein; tumor suppressor
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TSC1. 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
SymbolTSC1
Nametuberous sclerosis 1
Aliases KIAA0243; hamartin; tuberous sclerosis 1 protein; tumor suppressor
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TSC1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TSC1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTSC1
Nametuberous sclerosis 1
Aliases KIAA0243; hamartin; tuberous sclerosis 1 protein; tumor suppressor
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TSC1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTSC1
Nametuberous sclerosis 1
Aliases KIAA0243; hamartin; tuberous sclerosis 1 protein; tumor suppressor
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TSC1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTSC1
Nametuberous sclerosis 1
Aliases KIAA0243; hamartin; tuberous sclerosis 1 protein; tumor suppressor
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TSC1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTSC1
Nametuberous sclerosis 1
Aliases KIAA0243; hamartin; tuberous sclerosis 1 protein; tumor suppressor
Chromosomal Location9q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TSC1 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.