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tuberin; tuberous sclerosis 2 protein (TSC2 TSC4)
Function:
- in complex with TSC1, inhibits nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 & 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 & RAB5 in vitro
- phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect interaction with TSC1
- phosphorylation at Ser-939 & Thr-1462 by PKB/AKT1 is induced by growth factor stimulation
- interacts with TSC1 & HERC1; the interaction with TSC1 stabilizes TSC2 & prevents the interaction with HERC1
- may also interact with the adapter molecule RABEP1
- component of a complex containing TSC2 & RABEP1 linked to RAB5 (probable)
- interacts with HSPA1 & HSPA8
Structure:
- contains 1 rap-GAP domain
Compartment:
- cytoplasm. membrane
- peripheral membrane protein.
- at steady state, found in association with membranes
Alternative splicing: named isoforms=6
Expression:
- expressed in liver, brain, heart, lymphocytes, fibroblasts, biliary epithelium, pancreas, skeletal muscle, kidney, lung & placenta
Pathology:
- mutations in TSC2 lead to constitutive activation of RAP1A in tumors
- defects in TSC2 are a cause of
a) tuberous sclerosis
b) lymphangioleiomyomatosis
Interactions
molecular events
Related
TSC2 gene
TSC2 gene mutation; tuberin gene mutation
tuberous sclerosis (Bourneville disease, epiloia)
General
membrane protein
phosphoprotein
Properties
SIZE: entity length = 1807 aa
MW = 201 kD
COMPARTMENT: cytoplasm
MOTIF: TSC1 interaction {1-400}
Thr phosphorylation site {T927}
Ser phosphorylation site {S939}
Ser phosphorylation site {S981}
Ser phosphorylation site {S1097}
Ser phosphorylation site {S1132}
Ser phosphorylation site {S1155}
Ser phosphorylation site {S1334}
Ser phosphorylation site {S1337}
Ser phosphorylation site {S1338}
Ser phosphorylation site {S1341}
Ser phosphorylation site {S1364}
Ser phosphorylation site {S1387}
Ser phosphorylation site {S1388}
Ser phosphorylation site {S1411}
Ser phosphorylation site {S1418}
Ser phosphorylation site {S1420}
Ser phosphorylation site {S1449}
Ser phosphorylation site {S1452}
Thr phosphorylation site {T1462}
rap-GAP domain
NAME: rap-GAP domain
SITE: 1531-1758
Ser phosphorylation site {S1798}
References
- UniProt :accession P49815
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/TSC2ID184.html
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/TSC2
- European Chromosome 16 Tuberous Sclerosis Consortium.
Identification and characterization of the tuberous sclerosis
gene on chromosome 16.
Cell 75:1305-1315 1993
PMID: 8269512
Component-of
molecular complex
Databases & Figures
OMIM correlations
MORBIDMAP 191092
UniProt P49815
Pfam PF02145
Entrez Gene 7249
Kegg hsa:7249
RTK -> PI-3-kinase -> Akt -> ...