Tbio TSC2 Tuberin

Protein Summary

Description

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). Mutations in this gene lead to tuberous sclerosis complex. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. The protein associates with hamartin in a cytosolic complex, possibly acting as a chaperone for hamartin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P49815
• A7E2E2
• B4DIL8
• B4DIQ7
• B4DRN2
• B7Z2B8
• C9J378
• O75275
• Q4LE71
• Q8TAZ1

Gene Name

• TSC2

Ensembl ID

• ENST00000219476
• ENSP00000219476
• ENSG00000103197
• ENST00000350773
• ENSP00000344383
• ENST00000382538
• ENSP00000371978
• ENST00000401874
• ENSP00000384468
• ENST00000439673
• ENSP00000399232
• ENST00000642936
• ENSP00000494514
• ENST00000644043
• ENSP00000496262

Symbol

• TSC4
• LAM
• TSC4
• PPP1R160

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
biological process	0.99
biological term	0.98
disease perturbation	0.9
kinase	0.9

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / G-protein Modulator / Tuberin

DTO Classes

Protein / Enzyme Modulator / G-protein Modulator / Tuberin

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1830.65   (req: < 5)

Gene RIFs: 254   (req: <= 3)

Antibodies: 1854   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1830.65   (req: >= 5)

Gene RIFs: 254   (req: > 3)

Antibodies: 1854   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 29

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (301)

Explore Interacting Targets

1 – 10 of 301

• See Interactions on String-DB

COL20A1

Tdark

Novelty:  0.39788946

p_int:  0.9997743

p_ni:  0.000225691

p_wrong:  9e-9

Score:  0.188

Data Source:  BioPlex,STRINGDB

CD79B

Tclin

Novelty:  0.00227414

p_int:  0.99975998

p_ni:  0.000239989

p_wrong:  3.1e-8

Data Source:  BioPlex

TBC1D7

Tbio

Novelty:  0.06502242

p_int:  0.998400748

p_ni:  0.001599251

p_wrong:  1e-9

Score:  0.997

Data Source:  BioPlex,Reactome,STRINGDB

PNKD

Tbio

Family:  Enzyme

Novelty:  0.02456078

p_int:  0.998229984

p_ni:  0.001770004

p_wrong:  1.2e-8

Data Source:  BioPlex

MORF4L1

Tbio

Family:  Epigenetic

Novelty:  0.01696001

p_int:  0.99575212

p_ni:  0.00424788

Data Source:  BioPlex

CD226

Tbio

Novelty:  0.00374102

p_int:  0.992623556

p_ni:  0.007376444

Data Source:  BioPlex

PRKCSH

Tbio

Family:  Enzyme

Novelty:  0.00787916

p_int:  0.990608065

p_ni:  0.009391648

p_wrong:  2.86e-7

Score:  0.266

Data Source:  BioPlex,STRINGDB

SEMA4C

Tbio

Novelty:  0.01237067

p_int:  0.98289715

p_ni:  0.017102849

p_wrong:  1e-9

Data Source:  BioPlex

CD83

Tbio

Novelty:  0.00138653

p_int:  0.968181557

p_ni:  0.031818443

Data Source:  BioPlex

TMEM9

Tbio

Novelty:  0.06916197

p_int:  0.967897613

p_ni:  0.032102385

p_wrong:  3e-9

Data Source:  BioPlex

Nearest Tclin Targets (3)

Explore Nearest Tclin Targets

Upstream (1)

Downstream (2)

1 – 1 of 1

MTOR

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  14

1: PI3K-Akt signaling pathway

2: mTOR signaling pathway

3: Choline metabolism in cancer

4: Longevity regulating pathway

more:  10 more common pathways

Pathways (73)

Reactome (23)

KEGG (15)

PathwayCommons (13)

WikiPathways (22)

AKT phosphorylates targets in the cytosol (R-HSA-198323)

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1 – 5 of 23

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	AKT phosphorylates targets in the cytosol	14 targets	R-HSA-198323
Reactome	Autophagy	109 targets	R-HSA-9612973
Reactome	Cellular responses to external stimuli	487 targets	R-HSA-8953897
Reactome	Constitutive Signaling by AKT1 E17K in Cancer	26 targets	R-HSA-5674400
Reactome	Disease	1105 targets	R-HSA-1643685

Name	Explore in Pharos	Explore in Source
AKT phosphorylates targets in the cytosol	14 targets	R-HSA-198323
Autophagy	109 targets	R-HSA-9612973
Cellular responses to external stimuli	487 targets	R-HSA-8953897
Constitutive Signaling by AKT1 E17K in Cancer	26 targets	R-HSA-5674400
Disease	1105 targets	R-HSA-1643685

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (38)

Functions (5)

Components (9)

Processes (24)

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1 – 5 of 5

GO Term	Evidence	Assigned by
GTPase activator activity	Inferred from Direct Assay (IDA)	UniProtKB
phosphatase binding	Inferred from Direct Assay (IDA)	UniProtKB
Hsp90 protein binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein homodimerization activity	Inferred from Physical Interaction (IPI)	UniProtKB
small GTPase binding	Inferred from Physical Interaction (IPI)	UniProtKB

Disease Associations (null)

No disease associations found

GWAS Traits (37)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 37

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
atrial fibrillation	EFO_0000275	2	3	0	1.1	90.4
glomerular filtration rate	EFO_0005208	4	4	4		87.4
appendicular lean mass	EFO_0004980	3	1	3		85.8
heel bone mineral density	EFO_0009270	2	1	2		77.9
blood protein measurement	EFO_0007937	1	1	1		77.7

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 37

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
atrial fibrillation	EFO_0000275	0	1.1	90.4
glomerular filtration rate	EFO_0005208	4		87.4
appendicular lean mass	EFO_0004980	3		85.8
heel bone mineral density	EFO_0009270	2		77.9
blood protein measurement	EFO_0007937	1		77.7

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
Alternative splicing
Complete proteome
Cytoplasm
Disease mutation
Epilepsy
GTPase activation
Host-virus interaction
Membrane
Phosphoprotein
Polymorphism

GWAS Trait Find Similar Targets

No Header	No Header
alkaline phosphatase measurement
appendicular lean mass
atrial fibrillation
blood protein measurement
BMI-adjusted hip circumference
BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio
body height
body mass index
body weight

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
integument phenotype
liver/biliary system phenotype

IDG Resources

No IDG generated resources found

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	TSC complex subunit 2	VGNC:48997	468086
Macaque	TSC complex subunit 2		694965
Mouse	tuberous sclerosis 2	MGI:102548	22084
Rat	TSC complex subunit 2	RGD:3908	24855
Dog	TSC complex subunit 2	VGNC:47891	479883

Species	Name	OMA	EggNOG	Inparanoid
Chimp	TSC complex subunit 2
Macaque	TSC complex subunit 2
Mouse	tuberous sclerosis 2
Rat	TSC complex subunit 2
Dog	TSC complex subunit 2

Publication Statistics

PubMed Score 1830.65

PubMed score by year

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PubTator Score 765.58

PubTator score by year

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Related Publications

Text Mined References (336)

GeneRif Annotations (254)

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PMID	Year	Title