Tsc2
entrez
24855
canonical
uniprot
P49816
canonical
ensembl
ENSRNOG00000011375
resolver
ensp
ENSRNOP00000016221
resolver
ensp
ENSRNOP00000087212
resolver
genesymbol
Tsc2
resolver
uniprot_entry
TSC2_RAT
resolver
amino_acid_sequence
MAKPTSKDSGLKEKFKILLGLGTSRPNPRCAEGKQTEFIITAEILRELSGECGLNNRIRMIGQICDVAKTKKLEEHAVEALWKAVSDLLQPERPPEARHAVLALLKAIVQGQGDRLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELAEFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIAPMVHMICLLCIRTVSSVDIEVSLQVLDAVVCYNCLPAESLPLFIITLCRTVNVKELCEPCWKLMRNLLGTHLGHSAIYNMCRIMENRSYMEDAPLLRGAVFFVGMALWGAHRLYSLKNSPTSVLPSFYEAMTCPNEVVSYEIVLSITRLIKKYRKELQAVTWDILLDIIERLLQQLQNLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYYELVESYADQRPESSLLNLITYRAQSIHPAKDGWIQNLQLLMERFFRNECRSAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPLELEERDLAVYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYETLISHIQLHYKHGYSLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCLCDCAELDRASEKKASGPLSPPTGPPSPVPTGPAVRLGHLPYSLLFRVLLQCLKQETDWKVLKLVLSKLPESLRYKVLIFTSPCSVDQLSSALCSMLSAPKTLERLRGTPEGFSRTDLHLAVVPVLTALISYHNYLDKTRQREMVYCLEQGLIYRCASQCVVALAICSVEMPDIIIKALPVLVVKLTHISATASMAIPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPYITKGLRSNVLLSFDDTPEKDKFRARSTSLNERPKSLRIARAPKQGLNNSPPVKEFKESCAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSMAQADDNLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGDLQGGSASSSDPGTHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGVLDTSAPYTPGGPASLGAQAAPAARPEKPCAGAQLPAAEKANLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAAGTAKPPTLPRSNTVASFSSLYQPSCQGQLHRSVSWADSAVVLEEGSPGEAHVPVEPPELEDFEAALGTDRHCQRPDAYSRSSSASSQEEKSHLEELAAGGIPIERAISSEGARPTVDLSFQPSQPLSKSSSSPELQTLQDILGDLGDKTDIGRLSPEAKVRSQSGILDGEAATWSAPGEESRITVPPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDNFKSRTAASSAEKVPGINPSFVFLQLYHSPFCGDESNKPILLPNESFERSVQLLDQIPSYDTHKIAVLYVGEGQSSSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIIYNDSGEDFKLGTIKGQFNFVHVIITPLDYKCNLLTLQCRKDMEGLVDTSVAKIVSDRNLSFVARQMALHANMASQVHHRRSNPTDIYPSKWIARLRHIKRLRQRIREEVHYSNPSLPLMHPPAHTKVPAQAPTEATPTYETGQRKRLISSVDDFTEFV
uniprot
proteins
disease_involvement
DISEASE: Note=A germline insertion in Tsc2 is the cause of the Eker rat model of inherited cancer susceptibility. Gives rise to a spectrum of epithelial and nonepithelial neoplasms. {ECO:0000269|PubMed:8519695}.
uniprot
proteins
function
FUNCTION: Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553). Within the TSC-TBC complex, TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (By similarity). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (By similarity). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (By similarity). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (PubMed:16707451). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (PubMed:9045618). {ECO:0000250|UniProtKB:P49815, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:16707451, ECO:0000269|PubMed:9045618}.
uniprot
proteins
mass_dalton
201278
uniprot
proteins
mutagenesis
MUTAGEN 314; /note="N->S: In chemically induced renal carcinoma."; /evidence="ECO:0000269|PubMed:10029074"; MUTAGEN 713; /note="L->R: In chemically induced renal carcinoma."; /evidence="ECO:0000269|PubMed:10029074"; MUTAGEN 939; /note="S->A: Decreased phosphorylation by PKB/AKT1; when associated with A-1130--1132-A and A-1422."; /evidence="ECO:0000269|PubMed:12172553"; MUTAGEN 939; /note="S->D: Mimics phosphorylation, leading to inhibit the ability of TSC2 to suppress mTORC1 signaling; when associated with D-1130--1132-E."; /evidence="ECO:0000269|PubMed:12172553"; MUTAGEN 1130..1132; /note="SMS->AMA: Decreased phosphorylation by PKB/AKT1; when associated with A-939 and A-1422."; /evidence="ECO:0000269|PubMed:12172553"; MUTAGEN 1130..1132; /note="SMS->DME: Mimics phosphorylation, leading to inhibit the ability of TSC2 to suppress mTORC1 signaling; when associated with D-939."; /evidence="ECO:0000269|PubMed:12172553"; MUTAGEN 1422; /note="S->A: Decreased phosphorylation by PKB/AKT1; when associated with A-939 and A-1130--1132-A."; /evidence="ECO:0000269|PubMed:12172553
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-939 and Thr-1466 by PKB/AKT1 in response to insulin signaling and growth factor stimulation inhibits the ability of the TSC-TBC complex to suppress mTORC1 signaling: phosphorylation promotes dissociation of the TSC-TBC complex from lysosomal membranes, leading to activation of mTORC1 by RHEB (PubMed:12172553). Phosphorylation at Ser-1388, Ser-1420 or Ser-1422 does not affect interaction with TSC1 (By similarity). Phosphorylation by AMPK activates it and leads to negative regulation of the mTORC1 complex (By similarity). Phosphorylated at Ser-1800 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling (By similarity). Phosphorylated by DAPK1 (By similarity). {ECO:0000250|UniProtKB:P49815, ECO:0000269|PubMed:12172553}.; PTM: 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. {ECO:0000250|UniProtKB:P49815}.
uniprot
proteins
pubmed
10029074
uniprot
proteins
pubmed
12172553
uniprot
proteins
pubmed
16707451
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
7651821
uniprot
proteins
pubmed
8519695
uniprot
proteins
pubmed
9045618
uniprot
proteins
sequence_length
1809
uniprot
proteins
subcellular_location
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}.
uniprot
proteins