Homo sapiens Protein: TSC2
InnateDB Protein IDBP-9825.7
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 ENSP00000344383
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.
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]
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
InterPro IPR000331 Rap GTPase activating protein domain
IPR003913 Tuberin
IPR016024 Armadillo-type fold
IPR018515 Tuberin-type domain
IPR024584 Tuberin, N-terminal
PFAM PF02145
Post-translational Modifications
SwissProt P49815
PhosphoSite PhosphoSite-P49815
UniProt Splice Variant
Entrez Gene 7249
UniGene Hs.90303
RefSeq NP_001107854
OMIM 191092
HPRD 01850
EMBL AB014460 AB210000 AC005600 AC093513 AK295672 AK295728 AK299343 BC025364 BC046929 BC150300 CH471112 L48517 L48518 L48519 L48521 L48522 L48523 L48524 L48525 L48526 L48527 L48528 L48529 L48530 L48531 L48532 L48533 L48534 L48535 L48536 L48537 L48538 L48539 L48540 L48541 L48542 L48543 L48544 L48545 L48546 X75621
GenPept AAB41564 AAC34210 AAH25364 AAH46929 AAI50301 BAA32694 BAE06082 BAG58530 BAG58569 BAG61344 CAA53287 EAW85556