InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TSC2

Summary

InnateDB Protein

IDBP-364621.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TSC2

Protein Name

tuberous sclerosis 2

Synonyms

LAM; PPP1R160; TSC4;

Species

Homo sapiens

Ensembl Protein

ENSP00000399232

InnateDB Gene

IDBG-9819 (TSC2)

Protein Structure

UniProt Annotation

Function

In complex with TSC1, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase- activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. Stimulates weakly the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 in vitro. Mutations in TSC2 lead to constitutive activation of RAP1A in tumors. {ECO:0000269PubMed:12271141, ECO:0000269PubMed:15340059, ECO:0000269PubMed:16707451}.

Subcellular Localization

Cytoplasm. Membrane; Peripheral membrane protein. Note=At steady state found in association with membranes.

Disease Associations

Tuberous sclerosis 2 (TSC2) [MIM:613254]: An autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical manifestations include epilepsy, learning difficulties, behavioral problems, and skin lesions. Seizures can be intractable and premature death can occur from a variety of disease-associated causes. {ECO:0000269PubMed:10069705, ECO:0000269PubMed:10205261, ECO:0000269PubMed:10533067, ECO:0000269PubMed:10570911, ECO:0000269PubMed:10607950, ECO:0000269PubMed:10732801, ECO:0000269PubMed:10735580, ECO:0000269PubMed:15024740, ECO:0000269PubMed:15595939, ECO:0000269PubMed:8824881, ECO:0000269PubMed:9302281, ECO:0000269PubMed:9463313, ECO:0000269PubMed:9829910}. Note=The disease is caused by mutations affecting the gene represented in this entry.Lymphangioleiomyomatosis (LAM) [MIM:606690]: Progressive and often fatal lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. It affects almost exclusively young women and can occur as an isolated disorder or in association with tuberous sclerosis complex. {ECO:0000269PubMed:10823953}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Liver, brain, heart, lymphocytes, fibroblasts, biliary epithelium, pancreas, skeletal muscle, kidney, lung and placenta.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 115 experimentally validated interaction(s) in this database.
They are also associated with 14 interaction(s) predicted by orthology.

Experimentally validated
Total	115 [view]
Protein-Protein	112 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	14 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005096	GTPase activator activity
GO:0005488	binding
GO:0005515	protein binding
GO:0019902	phosphatase binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0001843	neural tube closure
GO:0006469	negative regulation of protein kinase activity
GO:0006606	protein import into nucleus
GO:0006897	endocytosis
GO:0007050	cell cycle arrest
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007507	heart development
GO:0008104	protein localization
GO:0008285	negative regulation of cell proliferation
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0014067	negative regulation of phosphatidylinositol 3-kinase signaling
GO:0016192	vesicle-mediated transport
GO:0030100	regulation of endocytosis
GO:0030178	negative regulation of Wnt signaling pathway
GO:0032007	negative regulation of TOR signaling
GO:0032320	positive regulation of Ras GTPase activity
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0043491	protein kinase B signaling
GO:0043547	positive regulation of GTPase activity
GO:0045087	innate immune response
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:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0050918	positive chemotaxis
GO:0051056	regulation of small GTPase mediated signal transduction
GO:0051726	regulation of cell cycle
GO:0051898	negative regulation of protein kinase B signaling

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0016020	membrane
GO:0033596	TSC1-TSC2 complex
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000331 Rap GTPase activating protein domain
IPR003913 Tuberin
IPR016024 Armadillo-type fold
IPR018515 Tuberin-type domain
IPR024584 Tuberin, N-terminal

PFAM

PF02145
PF03542
PF11864

PRINTS

PR01431

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P49815