Protein: Tuberin (Tuberous sclerosis 2 protein homolog) (P49816)
Organism: Rattus norvegicus (Rat)
Function: 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 (By similarity). Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (By similarity). May also play a role in microtubule-mediated protein transport. Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5.
Subcellular location: Lysosome membrane {ECO:0000250|UniProtKB:P49815}; Peripheral membrane protein {ECO:0000250|UniProtKB:P49815}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P49815}. Note=Recruited to lysosomal membranes in a RHEB-dependent process in absence of nutrients (By similarity). In response to insulin signaling and phosphorylation by PKB/AKT1, the complex dissociates from lysosomal membranes and relocalizes to the cytosol (By similarity). {ECO:0000250|UniProtKB:P49815}.
Interaction partners:
- TBC1 domain family member 7
- Hamartin
- GTP-binding protein Rheb
- Glycogen synthase kinase-3 beta
- RAC-alpha serine/threonine-protein kinase
- Serine/threonine-protein kinase mTOR
- DNA damage-inducible transcript 4 protein
- 5'-AMP-activated protein kinase catalytic subunit alpha-1
- Ribosomal protein S6 kinase alpha-1
- RAC-beta serine/threonine-protein kinase
Sequence:
MAKPTSKDSGLKEKFKILLGLGTSRPNPRCAEGKQTEFIITAEILRELSGECGLNNRIRMIGQICDVAKTKKLEEHAVEALWKAVSDLLQPERPPEARHAVLALLKAIVQGQGDRLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELAEFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIAPMVHMICLLCIRTVSSVDIEVSLQVLDAVVCYNCLPAESLPLFIITLCRTVNVKELCEPCWKLMRNLLGTHLGHSAIYNMCRIMENRSYMEDAPLLRGAVFFVGMALWGAHRLYSLKNSPTSVLPSFYEAMTCPNEVVSYEIVLSITRLIKKYRKELQAVTWDILLDIIERLLQQLQNLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYYELVESYADQRPESSLLNLITYRAQSIHPAKDGWIQNLQLLMERFFRNECRSAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPLELEERDLAVYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYETLISHIQLHYKHGYSLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCLCDCAELDRASEKKASGPLSPPTGPPSPVPTGPAVRLGHLPYSLLFRVLLQCLKQETDWKVLKLVLSKLPESLRYKVLIFTSPCSVDQLSSALCSMLSAPKTLERLRGTPEGFSRTDLHLAVVPVLTALISYHNYLDKTRQREMVYCLEQGLIYRCASQCVVALAICSVEMPDIIIKALPVLVVKLTHISATASMAIPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPYITKGLRSNVLLSFDDTPEKDKFRARSTSLNERPKSLRIARAPKQGLNNSPPVKEFKESCAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSMAQADDNLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGDLQGGSASSSDPGTHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGVLDTSAPYTPGGPASLGAQAAPAARPEKPCAGAQLPAAEKANLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAAGTAKPPTLPRSNTVASFSSLYQPSCQGQLHRSVSWADSAVVLEEGSPGEAHVPVEPPELEDFEAALGTDRHCQRPDAYSRSSSASSQEEKSHLEELAAGGIPIERAISSEGARPTVDLSFQPSQPLSKSSSSPELQTLQDILGDLGDKTDIGRLSPEAKVRSQSGILDGEAATWSAPGEESRITVPPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDNFKSRTAASSAEKVPGINPSFVFLQLYHSPFCGDESNKPILLPNESFERSVQLLDQIPSYDTHKIAVLYVGEGQSSSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIIYNDSGEDFKLGTIKGQFNFVHVIITPLDYKCNLLTLQCRKDMEGLVDTSVAKIVSDRNLSFVARQMALHANMASQVHHRRSNPTDIYPSKWIARLRHIKRLRQRIREEVHYSNPSLPLMHPPAHTKVPAQAPTEATPTYETGQRKRLISSVDDFTEFV