CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008216
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tuberin 
Protein Synonyms/Alias
 Tuberous sclerosis 2 protein 
Gene Name
 TSC2 
Gene Synonyms/Alias
 TSC4 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
438AQSIHPAKDGWIQNLubiquitination[1]
634HRLGLPNKDGVVRFSubiquitination[1]
658PERGSEKKTSGPLSPubiquitination[1]
914DFVPFITKGLRSNVLubiquitination[1]
930SFDDTPEKDSFRARSubiquitination[1]
1068QTKEAPAKLESQAGQubiquitination[1]
Reference
 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 
Functional Description
 In complex with TSC1, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and 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 and RAB5 in vitro. Mutations in TSC2 lead to constitutive activation of RAP1A in tumors. 
Sequence Annotation
 DOMAIN 1531 1758 Rap-GAP.
 REGION 1 400 Required for interaction with TSC1.
 MOD_RES 927 927 Phosphothreonine.
 MOD_RES 939 939 Phosphoserine; by PKB/AKT1.
 MOD_RES 981 981 Phosphoserine.
 MOD_RES 1132 1132 Phosphoserine.
 MOD_RES 1155 1155 Phosphoserine.
 MOD_RES 1330 1330 Phosphothreonine; by AMPK.
 MOD_RES 1337 1337 Phosphoserine.
 MOD_RES 1338 1338 Phosphoserine.
 MOD_RES 1346 1346 Phosphoserine.
 MOD_RES 1364 1364 Phosphoserine (By similarity).
 MOD_RES 1387 1387 Phosphoserine.
 MOD_RES 1411 1411 Phosphoserine.
 MOD_RES 1418 1418 Phosphoserine.
 MOD_RES 1420 1420 Phosphoserine.
 MOD_RES 1448 1448 Phosphoserine; by AMPK.
 MOD_RES 1452 1452 Phosphoserine.
 MOD_RES 1462 1462 Phosphothreonine; by PKB/AKT1.
 MOD_RES 1798 1798 Phosphoserine; by RPS6KA1.  
Keyword
 Alternative splicing; Complete proteome; Cytoplasm; Disease mutation; GTPase activation; Membrane; Phosphoprotein; Polymorphism; Reference proteome; Tumor suppressor; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1807 AA 
Protein Sequence
MAKPTSKDSG LKEKFKILLG LGTPRPNPRS AEGKQTEFII TAEILRELSM ECGLNNRIRM 60
IGQICEVAKT KKFEEHAVEA LWKAVADLLQ PERPLEARHA VLALLKAIVQ GQGERLGVLR 120
ALFFKVIKDY PSNEDLHERL EVFKALTDNG RHITYLEEEL ADFVLQWMDV GLSSEFLLVL 180
VNLVKFNSCY LDEYIARMVQ MICLLCVRTA SSVDIEVSLQ VLDAVVCYNC LPAESLPLFI 240
VTLCRTINVK ELCEPCWKLM RNLLGTHLGH SAIYNMCHLM EDRAYMEDAP LLRGAVFFVG 300
MALWGAHRLY SLRNSPTSVL PSFYQAMACP NEVVSYEIVL SITRLIKKYR KELQVVAWDI 360
LLNIIERLLQ QLQTLDSPEL RTIVHDLLTT VEELCDQNEF HGSQERYFEL VERCADQRPE 420
SSLLNLISYR AQSIHPAKDG WIQNLQALME RFFRSESRGA VRIKVLDVLS FVLLINRQFY 480
EEELINSVVI SQLSHIPEDK DHQVRKLATQ LLVDLAEGCH THHFNSLLDI IEKVMARSLS 540
PPPELEERDV AAYSASLEDV KTAVLGLLVI LQTKLYTLPA SHATRVYEML VSHIQLHYKH 600
SYTLPIASSI RLQAFDFLLL LRADSLHRLG LPNKDGVVRF SPYCVCDYME PERGSEKKTS 660
GPLSPPTGPP GPAPAGPAVR LGSVPYSLLF RVLLQCLKQE SDWKVLKLVL GRLPESLRYK 720
VLIFTSPCSV DQLCSALCSM LSGPKTLERL RGAPEGFSRT DLHLAVVPVL TALISYHNYL 780
DKTKQREMVY CLEQGLIHRC ASQCVVALSI CSVEMPDIII KALPVLVVKL THISATASMA 840
VPLLEFLSTL ARLPHLYRNF AAEQYASVFA ISLPYTNPSK FNQYIVCLAH HVIAMWFIRC 900
RLPFRKDFVP FITKGLRSNV LLSFDDTPEK DSFRARSTSL NERPKSRIQT SLTSASLGSA 960
DENSVAQADD SLKNLHLELT ETCLDMMARY VFSNFTAVPK RSPVGEFLLA GGRTKTWLVG 1020
NKLVTVTTSV GTGTRSLLGL DSGELQSGPE SSSSPGVHVR QTKEAPAKLE SQAGQQVSRG 1080
ARDRVRSMSG GHGLRVGALD VPASQFLGSA TSPGPRTAPA AKPEKASAGT RVPVQEKTNL 1140
AAYVPLLTQG WAEILVRRPT GNTSWLMSLE NPLSPFSSDI NNMPLQELSN ALMAAERFKE 1200
HRDTALYKSL SVPAASTAKP PPLPRSNTVA SFSSLYQSSC QGQLHRSVSW ADSAVVMEEG 1260
SPGEVPVLVE PPGLEDVEAA LGMDRRTDAY SRSSSVSSQE EKSLHAEELV GRGIPIERVV 1320
SSEGGRPSVD LSFQPSQPLS KSSSSPELQT LQDILGDPGD KADVGRLSPE VKARSQSGTL 1380
DGESAAWSAS GEDSRGQPEG PLPSSSPRSP SGLRPRGYTI SDSAPSRRGK RVERDALKSR 1440
ATASNAEKVP GINPSFVFLQ LYHSPFFGDE SNKPILLPNE SQSFERSVQL LDQIPSYDTH 1500
KIAVLYVGEG QSNSELAILS NEHGSYRYTE FLTGLGRLIE LKDCQPDKVY LGGLDVCGED 1560
GQFTYCWHDD IMQAVFHIAT LMPTKDVDKH RCDKKRHLGN DFVSIVYNDS GEDFKLGTIK 1620
GQFNFVHVIV TPLDYECNLV SLQCRKDMEG LVDTSVAKIV SDRNLPFVAR QMALHANMAS 1680
QVHHSRSNPT DIYPSKWIAR LRHIKRLRQR ICEEAAYSNP SLPLVHPPSH SKAPAQTPAE 1740
PTPGYEVGQR KRLISSVEDF TEFV 1764 
Gene Ontology
 GO:0005901; C:caveola; IEA:Compara.
 GO:0030425; C:dendrite; IEA:Compara.
 GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
 GO:0030426; C:growth cone; IEA:Compara.
 GO:0016020; C:membrane; IDA:UniProtKB.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0033596; C:TSC1-TSC2 complex; IDA:UniProtKB.
 GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
 GO:0019902; F:phosphatase binding; IDA:UniProtKB.
 GO:0006953; P:acute-phase response; IEA:Compara.
 GO:0007050; P:cell cycle arrest; TAS:Reactome.
 GO:0030030; P:cell projection organization; IEA:Compara.
 GO:0006897; P:endocytosis; TAS:ProtInc.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0007507; P:heart development; ISS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; ISS:UniProtKB.
 GO:0045792; P:negative regulation of cell size; IBA:RefGenome.
 GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Compara.
 GO:0043407; P:negative regulation of MAP kinase activity; IEA:Compara.
 GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase cascade; ISS:UniProtKB.
 GO:0006469; P:negative regulation of protein kinase activity; ISS:UniProtKB.
 GO:0051898; P:negative regulation of protein kinase B signaling cascade; ISS:UniProtKB.
 GO:0032007; P:negative regulation of TOR signaling cascade; IBA:RefGenome.
 GO:0030178; P:negative regulation of Wnt receptor signaling pathway; IBA:RefGenome.
 GO:0001843; P:neural tube closure; ISS:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0014065; P:phosphatidylinositol 3-kinase cascade; IEA:Compara.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0050918; P:positive chemotaxis; ISS:UniProtKB.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0051260; P:protein homooligomerization; IEA:Compara.
 GO:0006606; P:protein import into nucleus; ISS:UniProtKB.
 GO:0043491; P:protein kinase B signaling cascade; ISS:UniProtKB.
 GO:0030100; P:regulation of endocytosis; ISS:UniProtKB.
 GO:0046626; P:regulation of insulin receptor signaling pathway; ISS:UniProtKB.
 GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
 GO:0001666; P:response to hypoxia; IEA:Compara. 
Interpro
 IPR011989; ARM-like.
 IPR016024; ARM-type_fold.
 IPR000331; Rap_GAP_dom.
 IPR003913; Tuberin.
 IPR018515; Tuberin-type_domain.
 IPR027107; Tuberin/Ral-act_asu.
 IPR024584; Tuberin_N. 
Pfam
 PF11864; DUF3384
 PF02145; Rap_GAP
 PF03542; Tuberin 
SMART
  
PROSITE
 PS50085; RAPGAP 
PRINTS
 PR01431; TUBERIN.