tuberin; tuberous sclerosis 2 protein (TSC2 TSC4)
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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
More general terms
Additional terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P49815.html
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/8269512
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7249
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7249
- OMIM: https://mirror.omim.org/entry/191092
- OMIM: https://mirror.omim.org/entry/191100
- OMIM: https://mirror.omim.org/entry/606690
- UniProt: http://www.uniprot.org/uniprot/P49815.html