ID   TSC2_RAT                Reviewed;        1809 AA.
AC   P49816;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=Tuberin {ECO:0000303|PubMed:9045618};
DE   AltName: Full=Tuberous sclerosis 2 protein homolog {ECO:0000303|PubMed:8519695};
GN   Name=Tsc2 {ECO:0000303|PubMed:8519695, ECO:0000312|RGD:3908};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), TISSUE SPECIFICITY,
RP   AND DISEASE.
RC   STRAIN=Wistar; TISSUE=Kidney;
RX   PubMed=8519695;
RA   Xiao G.-H., Jin F., Yeung R.S.;
RT   "Identification of tuberous sclerosis 2 messenger RNA splice variants that
RT   are conserved and differentially expressed in rat and human tissues.";
RL   Cell Growth Differ. 6:1185-1191(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   STRAIN=Long Evans; TISSUE=Brain, and Kidney;
RX   PubMed=7651821; DOI=10.1093/nar/23.14.2608;
RA   Kobayashi T., Nishizawa M., Hirayama Y., Kobayashi E., Hino O.;
RT   "cDNA structure, alternative splicing and exon-intron organization of the
RT   predisposing tuberous sclerosis (Tsc2) gene of the Eker rat model.";
RL   Nucleic Acids Res. 23:2608-2613(1995).
RN   [3]
RP   FUNCTION, AND INTERACTION WITH RABEP1.
RX   PubMed=9045618; DOI=10.1074/jbc.272.10.6097;
RA   Xiao G.-H., Shoarinejad F., Jin F., Golemis E.A., Yeung R.S.;
RT   "The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase
RT   activating protein (GAP) in modulating endocytosis.";
RL   J. Biol. Chem. 272:6097-6100(1997).
RN   [4]
RP   MUTAGENESIS OF ASN-314 AND LEU-713.
RX   PubMed=10029074;
RA   Satake N., Kobayashi T., Kobayashi E., Izumi K., Hino O.;
RT   "Isolation and characterization of a rat homologue of the human tuberous
RT   sclerosis 1 gene (Tsc1) and analysis of its mutations in rat renal
RT   carcinomas.";
RL   Cancer Res. 59:849-855(1999).
RN   [5]
RP   FUNCTION, PHOSPHORYLATION AT SER-939; SER-1130; SER-1132; SER-1422 AND
RP   THR-1466, AND MUTAGENESIS OF SER-939; 1130-SER--SER-1132 AND SER-1422.
RX   PubMed=12172553; DOI=10.1038/ncb839;
RA   Inoki K., Li Y., Zhu T., Wu J., Guan K.L.;
RT   "TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR
RT   signalling.";
RL   Nat. Cell Biol. 4:648-657(2002).
RN   [6]
RP   FUNCTION.
RX   PubMed=16707451; DOI=10.1158/0008-5472.can-05-4510;
RA   Jiang X., Yeung R.S.;
RT   "Regulation of microtubule-dependent protein transport by the
RT   TSC2/mammalian target of rapamycin pathway.";
RL   Cancer Res. 66:5258-5269(2006).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1389 AND SER-1413, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Catalytic component of the TSC-TBC complex, a multiprotein
CC       complex that acts as a negative regulator of the canonical mTORC1
CC       complex, an evolutionarily conserved central nutrient sensor that
CC       stimulates anabolic reactions and macromolecule biosynthesis to promote
CC       cellular biomass generation and growth (PubMed:12172553). Within the
CC       TSC-TBC complex, TSC2 acts as a GTPase-activating protein (GAP) for the
CC       small GTPase RHEB, a direct activator of the protein kinase activity of
CC       mTORC1 (By similarity). In absence of nutrients, the TSC-TBC complex
CC       inhibits mTORC1, thereby preventing phosphorylation of ribosomal
CC       protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the
CC       mTORC1 signaling (By similarity). The TSC-TBC complex is inactivated in
CC       response to nutrients, relieving inhibition of mTORC1 (By similarity).
CC       Involved in microtubule-mediated protein transport via its ability to
CC       regulate mTORC1 signaling (PubMed:16707451). Also stimulates the
CC       intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5
CC       (PubMed:9045618). {ECO:0000250|UniProtKB:P49815,
CC       ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:16707451,
CC       ECO:0000269|PubMed:9045618}.
CC   -!- SUBUNIT: Component of the TSC-TBC complex (also named Rhebulator
CC       complex), composed of 2 molecules of TSC1, 2 molecules of TSC2 and 1
CC       molecule of TBC1D7 (By similarity). Probably forms a complex composed
CC       of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C,
CC       PTGES3/p23, TSC1 and client protein TSC2 (By similarity). Probably
CC       forms a complex composed of chaperones HSP90 and HSP70, co-chaperones
CC       CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1;
CC       this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23
CC       (By similarity). Forms a complex containing HSP90AA1, TSC1 and TSC2;
CC       TSC1 is required to recruit TCS2 to the complex thereby stabilizing
CC       TSC2 (By similarity). Interacts with TSC1 and HERC1; the interaction
CC       with TSC1 stabilizes TSC2 and prevents the interaction with HERC1 (By
CC       similarity). May also interact with the adapter molecule RABEP1
CC       (PubMed:9045618). The final complex may contain TSC2 and RABEP1 linked
CC       to RAB5 (PubMed:9045618). Interacts with HSPA1 and HSPA8 (By
CC       similarity). Interacts with NAA10 (via C-terminal domain) (By
CC       similarity). Interacts with RRAGA (polyubiquitinated) (By similarity).
CC       Interacts with WDR45B (By similarity). Interacts with RPAP3 and URI1
CC       (By similarity). Interacts with YWHAG (By similarity).
CC       {ECO:0000250|UniProtKB:P49815, ECO:0000269|PubMed:9045618}.
CC   -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:P49815};
CC       Peripheral membrane protein {ECO:0000250|UniProtKB:P49815}. Cytoplasm,
CC       cytosol {ECO:0000250|UniProtKB:P49815}. Note=Recruited to lysosomal
CC       membranes in a RHEB-dependent process in absence of nutrients (By
CC       similarity). In response to insulin signaling and phosphorylation by
CC       PKB/AKT1, the complex dissociates from lysosomal membranes and
CC       relocalizes to the cytosol (By similarity).
CC       {ECO:0000250|UniProtKB:P49815}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC         Comment=Additional isoforms seem to exist.;
CC       Name=1;
CC         IsoId=P49816-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P49816-2; Sequence=VSP_004481;
CC       Name=3;
CC         IsoId=P49816-3; Sequence=VSP_004482;
CC       Name=4;
CC         IsoId=P49816-4; Sequence=VSP_004481, VSP_004482;
CC   -!- TISSUE SPECIFICITY: CNS, uterus, heart, skeletal muscle, kidney and
CC       spleen. {ECO:0000269|PubMed:8519695}.
CC   -!- PTM: Phosphorylation at Ser-939 and Thr-1466 by PKB/AKT1 in response to
CC       insulin signaling and growth factor stimulation inhibits the ability of
CC       the TSC-TBC complex to suppress mTORC1 signaling: phosphorylation
CC       promotes dissociation of the TSC-TBC complex from lysosomal membranes,
CC       leading to activation of mTORC1 by RHEB (PubMed:12172553).
CC       Phosphorylation at Ser-1388, Ser-1420 or Ser-1422 does not affect
CC       interaction with TSC1 (By similarity). Phosphorylation by AMPK
CC       activates it and leads to negative regulation of the mTORC1 complex (By
CC       similarity). Phosphorylated at Ser-1800 by RPS6KA1; phosphorylation
CC       inhibits TSC2 ability to suppress mTORC1 signaling (By similarity).
CC       Phosphorylated by DAPK1 (By similarity). {ECO:0000250|UniProtKB:P49815,
CC       ECO:0000269|PubMed:12172553}.
CC   -!- PTM: Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase
CC       complex, leading to its subsequent degradation. Ubiquitinated by MYCBP2
CC       independently of its phosphorylation status leading to subsequent
CC       degradation; association with TSC1 protects from ubiquitination.
CC       {ECO:0000250|UniProtKB:P49815}.
CC   -!- DISEASE: Note=A germline insertion in Tsc2 is the cause of the Eker rat
CC       model of inherited cancer susceptibility. Gives rise to a spectrum of
CC       epithelial and nonepithelial neoplasms. {ECO:0000269|PubMed:8519695}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; U24150; AAC52289.1; -; mRNA.
DR   EMBL; D50413; BAA08914.1; -; mRNA.
DR   PIR; S57329; S57329.
DR   RefSeq; NP_036812.2; NM_012680.3. [P49816-1]
DR   RefSeq; XP_006245971.2; XM_006245909.3.
DR   AlphaFoldDB; P49816; -.
DR   SMR; P49816; -.
DR   BioGRID; 246972; 9.
DR   IntAct; P49816; 4.
DR   MINT; P49816; -.
DR   STRING; 10116.ENSRNOP00000016221; -.
DR   iPTMnet; P49816; -.
DR   PhosphoSitePlus; P49816; -.
DR   PaxDb; 10116-ENSRNOP00000016221; -.
DR   GeneID; 24855; -.
DR   KEGG; rno:24855; -.
DR   UCSC; RGD:3908; rat. [P49816-1]
DR   AGR; RGD:3908; -.
DR   CTD; 7249; -.
DR   RGD; 3908; Tsc2.
DR   eggNOG; KOG3687; Eukaryota.
DR   InParanoid; P49816; -.
DR   OrthoDB; 20915at2759; -.
DR   PhylomeDB; P49816; -.
DR   TreeFam; TF324484; -.
DR   Reactome; R-RNO-1632852; Macroautophagy.
DR   Reactome; R-RNO-165181; Inhibition of TSC complex formation by PKB.
DR   Reactome; R-RNO-198323; AKT phosphorylates targets in the cytosol.
DR   Reactome; R-RNO-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR   Reactome; R-RNO-5628897; TP53 Regulates Metabolic Genes.
DR   Reactome; R-RNO-8854214; TBC/RABGAPs.
DR   PRO; PR:P49816; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005901; C:caveola; IDA:RGD.
DR   GO; GO:0042995; C:cell projection; IDA:RGD.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0030425; C:dendrite; IDA:RGD.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR   GO; GO:0030426; C:growth cone; IDA:RGD.
DR   GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR   GO; GO:0005764; C:lysosome; ISO:RGD.
DR   GO; GO:0016020; C:membrane; ISO:RGD.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR   GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR   GO; GO:0045202; C:synapse; ISO:RGD.
DR   GO; GO:0033596; C:TSC1-TSC2 complex; ISS:UniProtKB.
DR   GO; GO:0071889; F:14-3-3 protein binding; ISO:RGD.
DR   GO; GO:0005096; F:GTPase activator activity; IDA:RGD.
DR   GO; GO:0051879; F:Hsp90 protein binding; ISO:RGD.
DR   GO; GO:0019902; F:phosphatase binding; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR   GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR   GO; GO:0043276; P:anoikis; ISO:RGD.
DR   GO; GO:0042100; P:B cell proliferation; ISO:RGD.
DR   GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR   GO; GO:0030030; P:cell projection organization; IMP:MGI.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; ISO:RGD.
DR   GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
DR   GO; GO:0030010; P:establishment of cell polarity; IMP:RGD.
DR   GO; GO:0098976; P:excitatory chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0046323; P:glucose import; ISO:RGD.
DR   GO; GO:0007507; P:heart development; ISO:RGD.
DR   GO; GO:0098977; P:inhibitory chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISO:RGD.
DR   GO; GO:0050771; P:negative regulation of axonogenesis; IMP:RGD.
DR   GO; GO:0030889; P:negative regulation of B cell proliferation; ISO:RGD.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:RGD.
DR   GO; GO:0045792; P:negative regulation of cell size; IMP:MGI.
DR   GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:RGD.
DR   GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IMP:RGD.
DR   GO; GO:0048147; P:negative regulation of fibroblast proliferation; IDA:RGD.
DR   GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0016242; P:negative regulation of macroautophagy; IMP:RGD.
DR   GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR   GO; GO:0048550; P:negative regulation of pinocytosis; IMP:RGD.
DR   GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:RGD.
DR   GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:RGD.
DR   GO; GO:0032007; P:negative regulation of TOR signaling; IDA:RGD.
DR   GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB.
DR   GO; GO:1905563; P:negative regulation of vascular endothelial cell proliferation; IMP:RGD.
DR   GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:RGD.
DR   GO; GO:0001843; P:neural tube closure; ISO:RGD.
DR   GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR   GO; GO:0050918; P:positive chemotaxis; ISO:RGD.
DR   GO; GO:0010508; P:positive regulation of autophagy; ISO:RGD.
DR   GO; GO:0045785; P:positive regulation of cell adhesion; IMP:RGD.
DR   GO; GO:0060999; P:positive regulation of dendritic spine development; IMP:RGD.
DR   GO; GO:0010763; P:positive regulation of fibroblast migration; IMP:RGD.
DR   GO; GO:0016239; P:positive regulation of macroautophagy; ISO:RGD.
DR   GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR   GO; GO:0008104; P:protein localization; ISO:RGD.
DR   GO; GO:0034394; P:protein localization to cell surface; IMP:RGD.
DR   GO; GO:0044861; P:protein transport into plasma membrane raft; ISO:RGD.
DR   GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
DR   GO; GO:0030100; P:regulation of endocytosis; ISO:RGD.
DR   GO; GO:0046626; P:regulation of insulin receptor signaling pathway; ISO:RGD.
DR   GO; GO:0099175; P:regulation of postsynapse organization; IDA:SynGO.
DR   GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
DR   GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR   GO; GO:0035176; P:social behavior; IMP:RGD.
DR   GO; GO:0042098; P:T cell proliferation; ISO:RGD.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; ISO:RGD.
DR   Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1.
DR   Gene3D; 3.40.50.11210; Rap/Ran-GAP; 1.
DR   InterPro; IPR011989; ARM-like.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR035974; Rap/Ran-GAP_sf.
DR   InterPro; IPR000331; Rap/Ran_GAP_dom.
DR   InterPro; IPR003913; Tuberin.
DR   InterPro; IPR018515; Tuberin-type_domain.
DR   InterPro; IPR027107; Tuberin/Ral-act_asu.
DR   InterPro; IPR024584; Tuberin_N.
DR   PANTHER; PTHR10063; TUBERIN; 1.
DR   PANTHER; PTHR10063:SF0; TUBERIN; 1.
DR   Pfam; PF11864; DUF3384; 1.
DR   Pfam; PF02145; Rap_GAP; 1.
DR   Pfam; PF03542; Tuberin; 1.
DR   PRINTS; PR01431; TUBERIN.
DR   SUPFAM; SSF48371; ARM repeat; 1.
DR   SUPFAM; SSF111347; Rap/Ran-GAP; 1.
DR   PROSITE; PS50085; RAPGAP; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; GTPase activation; Lysosome; Membrane;
KW   Phosphoprotein; Reference proteome; Tumor suppressor; Ubl conjugation.
FT   CHAIN           1..1809
FT                   /note="Tuberin"
FT                   /id="PRO_0000065656"
FT   DOMAIN          1533..1760
FT                   /note="Rap-GAP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00165"
FT   REGION          1078..1136
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1330..1359
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1373..1392
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1405..1492
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1764..1793
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1088..1102
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1473..1488
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         540
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         664
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         927
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         939
FT                   /note="Phosphoserine; by PKB/AKT1"
FT                   /evidence="ECO:0000269|PubMed:12172553"
FT   MOD_RES         981
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         1130
FT                   /note="Phosphoserine; by PKB/AKT1"
FT                   /evidence="ECO:0000269|PubMed:12172553"
FT   MOD_RES         1132
FT                   /note="Phosphoserine; by PKB/AKT1"
FT                   /evidence="ECO:0000269|PubMed:12172553"
FT   MOD_RES         1155
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         1271
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         1340
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         1341
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         1349
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         1366
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         1389
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         1413
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         1420
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         1422
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:12172553"
FT   MOD_RES         1456
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         1466
FT                   /note="Phosphothreonine; by PKB/AKT1"
FT                   /evidence="ECO:0000269|PubMed:12172553"
FT   MOD_RES         1766
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61037"
FT   MOD_RES         1800
FT                   /note="Phosphoserine; by RPS6KA1"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   MOD_RES         1801
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P49815"
FT   VAR_SEQ         947..989
FT                   /note="Missing (in isoform 2 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:8519695"
FT                   /id="VSP_004481"
FT   VAR_SEQ         1272..1294
FT                   /note="Missing (in isoform 3 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:8519695"
FT                   /id="VSP_004482"
FT   MUTAGEN         314
FT                   /note="N->S: In chemically induced renal carcinoma."
FT                   /evidence="ECO:0000269|PubMed:10029074"
FT   MUTAGEN         713
FT                   /note="L->R: In chemically induced renal carcinoma."
FT                   /evidence="ECO:0000269|PubMed:10029074"
FT   MUTAGEN         939
FT                   /note="S->A: Decreased phosphorylation by PKB/AKT1; when
FT                   associated with A-1130--1132-A and A-1422."
FT                   /evidence="ECO:0000269|PubMed:12172553"
FT   MUTAGEN         939
FT                   /note="S->D: Mimics phosphorylation, leading to inhibit the
FT                   ability of TSC2 to suppress mTORC1 signaling; when
FT                   associated with D-1130--1132-E."
FT                   /evidence="ECO:0000269|PubMed:12172553"
FT   MUTAGEN         1130..1132
FT                   /note="SMS->AMA: Decreased phosphorylation by PKB/AKT1;
FT                   when associated with A-939 and A-1422."
FT                   /evidence="ECO:0000269|PubMed:12172553"
FT   MUTAGEN         1130..1132
FT                   /note="SMS->DME: Mimics phosphorylation, leading to inhibit
FT                   the ability of TSC2 to suppress mTORC1 signaling; when
FT                   associated with D-939."
FT                   /evidence="ECO:0000269|PubMed:12172553"
FT   MUTAGEN         1422
FT                   /note="S->A: Decreased phosphorylation by PKB/AKT1; when
FT                   associated with A-939 and A-1130--1132-A."
FT                   /evidence="ECO:0000269|PubMed:12172553"
FT   CONFLICT        932
FT                   /note="K -> S (in Ref. 2; BAA08914)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1514
FT                   /note="C -> F (in Ref. 2; BAA08914)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1730
FT                   /note="R -> S (in Ref. 2; BAA08914)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1809 AA;  201278 MW;  6190BEFB45272664 CRC64;
     MAKPTSKDSG LKEKFKILLG LGTSRPNPRC AEGKQTEFII TAEILRELSG ECGLNNRIRM
     IGQICDVAKT KKLEEHAVEA LWKAVSDLLQ PERPPEARHA VLALLKAIVQ GQGDRLGVLR
     ALFFKVIKDY PSNEDLHERL EVFKALTDNG RHITYLEEEL AEFVLQWMDV GLSSEFLLVL
     VNLVKFNSCY LDEYIAPMVH MICLLCIRTV SSVDIEVSLQ VLDAVVCYNC LPAESLPLFI
     ITLCRTVNVK ELCEPCWKLM RNLLGTHLGH SAIYNMCRIM ENRSYMEDAP LLRGAVFFVG
     MALWGAHRLY SLKNSPTSVL PSFYEAMTCP NEVVSYEIVL SITRLIKKYR KELQAVTWDI
     LLDIIERLLQ QLQNLDSPEL RTIVHDLLTT VEELCDQNEF HGSQERYYEL VESYADQRPE
     SSLLNLITYR AQSIHPAKDG WIQNLQLLME RFFRNECRSA VRIKVLDVLS FVLLINRQFY
     EEELINSVVI SQLSHIPEDK DHQVRKLATQ LLVDLAEGCH THHFNSLLDI IEKVMARSLS
     PPLELEERDL AVYSASLEDV KTAVLGLLVI LQTKLYTLPA SHATRVYETL ISHIQLHYKH
     GYSLPIASSI RLQAFDFLLL LRADSLHRLG LPNKDGVVRF SPYCLCDCAE LDRASEKKAS
     GPLSPPTGPP SPVPTGPAVR LGHLPYSLLF RVLLQCLKQE TDWKVLKLVL SKLPESLRYK
     VLIFTSPCSV DQLSSALCSM LSAPKTLERL RGTPEGFSRT DLHLAVVPVL TALISYHNYL
     DKTRQREMVY CLEQGLIYRC ASQCVVALAI CSVEMPDIII KALPVLVVKL THISATASMA
     IPLLEFLSTL ARLPHLYRNF AAEQYASVFA ISLPYTNPSK FNQYIVCLAH HVIAMWFIRC
     RLPFRKDFVP YITKGLRSNV LLSFDDTPEK DKFRARSTSL NERPKSLRIA RAPKQGLNNS
     PPVKEFKESC AAEAFRCRSI SVSEHVVRSR IQTSLTSASL GSADENSMAQ ADDNLKNLHL
     ELTETCLDMM ARYVFSNFTA VPKRSPVGEF LLAGGRTKTW LVGNKLVTVT TSVGTGTRSL
     LGLDSGDLQG GSASSSDPGT HVRQTKEAPA KLESQAGQQV SRGARDRVRS MSGGHGLRVG
     VLDTSAPYTP GGPASLGAQA APAARPEKPC AGAQLPAAEK ANLAAYVPLL TQGWAEILVR
     RPTGNTSWLM SLENPLSPFS SDINNMPLQE LSNALMAAER FKEHRDTALY KSLSVPAAGT
     AKPPTLPRSN TVASFSSLYQ PSCQGQLHRS VSWADSAVVL EEGSPGEAHV PVEPPELEDF
     EAALGTDRHC QRPDAYSRSS SASSQEEKSH LEELAAGGIP IERAISSEGA RPTVDLSFQP
     SQPLSKSSSS PELQTLQDIL GDLGDKTDIG RLSPEAKVRS QSGILDGEAA TWSAPGEESR
     ITVPPEGPLP SSSPRSPSGL RPRGYTISDS APSRRGKRVE RDNFKSRTAA SSAEKVPGIN
     PSFVFLQLYH SPFCGDESNK PILLPNESFE RSVQLLDQIP SYDTHKIAVL YVGEGQSSSE
     LAILSNEHGS YRYTEFLTGL GRLIELKDCQ PDKVYLGGLD VCGEDGQFTY CWHDDIMQAV
     FHIATLMPTK DVDKHRCDKK RHLGNDFVSI IYNDSGEDFK LGTIKGQFNF VHVIITPLDY
     KCNLLTLQCR KDMEGLVDTS VAKIVSDRNL SFVARQMALH ANMASQVHHR RSNPTDIYPS
     KWIARLRHIK RLRQRIREEV HYSNPSLPLM HPPAHTKVPA QAPTEATPTY ETGQRKRLIS
     SVDDFTEFV
//