TSC2

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]

tuberous sclerosis 2

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).

AnoikisManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
EndocytosisManual Assertion Based On ExperimentTAS:ProtInc
Heart developmentISS:UniProtKB
Insulin-like growth factor receptor signaling pathwayISS:UniProtKB
Negative regulation of cell population proliferationISS:UniProtKB
Negative regulation of insulin receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of mitophagy1 PublicationNAS:ParkinsonsUK-UCL
Negative regulation of phosphatidylinositol 3-kinase signalingISS:UniProtKB
Negative regulation of protein kinase activityISS:UniProtKB
Negative regulation of protein kinase B signalingISS:UniProtKB
Negative regulation of TOR signalingManual Assertion Based On ExperimentIDA:ComplexPortal
Negative regulation of Wnt signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Neural tube closureISS:UniProtKB
Positive chemotaxisISS:UniProtKB
Positive regulation of GTPase activityIEA:InterPro
Positive regulation of macroautophagyManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Protein import into nucleusISS:UniProtKB
Protein kinase B signalingISS:UniProtKB
Protein localizationISS:UniProtKB
Regulation of cell cycleManual Assertion Based On ExperimentIBA:GO_Central
Regulation of endocytosisISS:UniProtKB
Regulation of insulin receptor signaling pathwayISS:UniProtKB
Regulation of small GTPase mediated signal transductionIEA:InterPro
Vesicle-mediated transportManual Assertion Based On ExperimentTAS:ProtInc

Cytoplasm
Membrane
At steady state found in association with membranes.

Tuberous sclerosis 2 (TSC2):
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.
Lymphangioleiomyomatosis (LAM):
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.
Focal cortical dysplasia 2 (FCORD2):
A form of focal cortical dysplasia, a malformation of cortical development that results in medically refractory epilepsy in the pediatric population and in adults. FCORD2 is a severe form, with onset usually in childhood, characterized by disrupted cortical lamination and specific cytological abnormalities. It is classified in 2 subtypes: type IIA characterized by dysmorphic neurons and lack of balloon cells; type IIB with dysmorphic neurons and balloon cells.

Phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect interaction with TSC1. Phosphorylation at Ser-939 and Thr-1462 by PKB/AKT1 is induced by growth factor stimulation. Phosphorylation by AMPK activates it and leads to negative regulation of the mTORC1 complex. Phosphorylated at Ser-1798 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling. Phosphorylated by DAPK1.
Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase complex, leading to its subsequent degradation. Ubiquitinated by MYCBP2 independently of its phosphorylation status leading to subsequent degradation; association with TSC1 protects from ubiquitination.