CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-014295
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tuberin 
Protein Synonyms/Alias
 Tuberous sclerosis 2 protein homolog 
Gene Name
 Tsc2 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
914DFVPYITKGLRSNVLubiquitination[1]
930SFDDTPEKDSFRARSubiquitination[1]
1043SNFTAVPKRSPVGEFubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
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 (By similarity). Specifically stimulates the intrinsic GTPase activity of the Ras-related protein RAP1A and RAB5. Suggesting a possible mechanism for its role in regulating cellular growth (By similarity). 
Sequence Annotation
 DOMAIN 1532 1766 Rap-GAP.
 MOD_RES 927 927 Phosphothreonine (By similarity).
 MOD_RES 939 939 Phosphoserine; by PKB/AKT1 (By
 MOD_RES 981 981 Phosphoserine.
 MOD_RES 1132 1132 Phosphoserine (By similarity).
 MOD_RES 1155 1155 Phosphoserine (By similarity).
 MOD_RES 1339 1339 Phosphoserine (By similarity).
 MOD_RES 1340 1340 Phosphoserine (By similarity).
 MOD_RES 1348 1348 Phosphoserine (By similarity).
 MOD_RES 1365 1365 Phosphoserine.
 MOD_RES 1388 1388 Phosphoserine (By similarity).
 MOD_RES 1412 1412 Phosphoserine.
 MOD_RES 1419 1419 Phosphoserine (By similarity).
 MOD_RES 1421 1421 Phosphoserine.
 MOD_RES 1451 1451 Phosphoserine; by AMPK (By similarity).
 MOD_RES 1455 1455 Phosphoserine (By similarity).
 MOD_RES 1465 1465 Phosphothreonine; by PKB/AKT1 (By
 MOD_RES 1805 1805 Phosphoserine; by RPS6KA1 (By  
Keyword
 Alternative splicing; Complete proteome; Cytoplasm; GTPase activation; Membrane; Phosphoprotein; Reference proteome; Tumor suppressor; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1814 AA 
Protein Sequence
MAKPTSKDSG LKEKFKILLG LGTSRPNPRC AEGKQTEFII TSEILRELSG ECGLNNRIRM 60
IGQICDVAKT KKLEEHAVEA LWKAVSDLLQ PERPPEARHA VLTLLKAIVQ GQGDRLGVLR 120
ALFFKVIKDY PSNEDLHERL EVFKALTDNG RHITYLEEEL AEFVLQWMDV GLSSEFLLVL 180
VNLVKFNSCY LDEYIASMVH MICLLCIRTV SSVDIEVSLQ VLDAVVCYNC LPAESLPLFI 240
ITLCRTINVK ELCEPCWKLM RNLLGTHLGH SAIYNMCRIM EDRSYMEDAP LLRGAVFFVG 300
MALWGAHRLY SLKNSPTSVL PSFYEAMTCP NEVVSYEIVL SITRLIKKYR KELQAVTWDI 360
LLDIIERLLQ QLQNLDSPEL KTIVHDLLTT VEELCDQNEF HGSQERYYEL VESYADQRPE 420
SSLLNLISYR AQSIHPAKDG WIQNLQLLME RFFRNECRSA VAIKVLDVLS FVLLIIRQFY 480
EEELINSVVI SQLSHIPEDK DHQVRKLATQ LLVDLAEGCH THHFNSLLDI IEKVMARSLS 540
PPPELEERDL AVHSASLEDV KTAVLGLLVI LQTKLYTLPA SHATRVYESL ISHIQLHYKH 600
GYSLPIASSI RLQAFDFLLL LRADSLHRLG LPNKDGVVRF SPYCLCDCME LDRASEKKAS 660
GPLSPPTGPP SPVPMGPAVR LGYLPYSLLF RVLLQCLKQE SDWKVLKLVL SRLPESLRYK 720
VLIFTSPCSV DQLSSALCSM LSAPKTLERL RGTPEGFSRT DLHLAVVPVL TALISYHNYL 780
DKTRQREMVY CLEQGLIYRC ASQCVVALAI CSVEMPDIII KALPVLVVKL THISATASMA 840
IPLLEFLSTL ARLPHLYRNF VPEQYASVFA ISLPYTNPSK FNQYIVCLAH HVIAMWFIRC 900
RLPFRKDFVP YITKGLRSNV LLSFDDTPEK DSFRARSTSL NERPKSLRIA RAPKQGLNNS 960
PPVKEFKESC AAEAFRCRSI SVSEHVVRSR IQTSLTSASL GSADENSMAQ ADDNLKNLHL 1020
ELTETCLDMM ARYVFSNFTA VPKRSPVGEF LLAGGRTKTW LVGNKLVTVT TSVGTGTRSL 1080
LGLDSGDLQG GSDSSSDPST HVRQTKEAPA KLESQAGQQV SRGARDRVRS MSGGHGLRVG 1140
VLDTSAPYSP GGSASLGPQT AVAAKPEKPP AGAQLPTAEK TNLAAYVPLL TQGWAEILVR 1200
RPTGNTSWLM SLENPLSPFS SDINNMPLQE LSNALMAAER FKEHGHAPVQ VIVSATGCTA 1260
KPPTLPRSNT VASFSSLYQP SCQGQLHRSV SWADSAMVLE EGSPGETQVP VEPPELEDFE 1320
AALGTDRHCQ RPDTYSRSSS ASSQEEKSHL EELAAGGIPI ERAISSEGAR PAVDLSFQPS 1380
QPLSKSSSSP ELQTLQDILG DLGDKIDIGR LSPEAKVRSQ SGILDGEAAT WSATGEESRI 1440
TVPPEGPLPS SSPRSPSGLR PRGYTISDSA PSRRGKRVER DNFKSRAAAS SAEKVPGINP 1500
SFVFLQLYHS PFFGDESNKP ILLPNESFER SVQLLDQIPS YDTHKIAVLY VGEGQSSSEL 1560
AILSNEHGSY RYTEFLTGLG RLIELKDCQP DKVYLGGLDV CGEDGQFTYC WHDDIMQAVF 1620
HIATLMPTKD VDKHRCDKKR HLGNDFVSII YNDSGEDFKL GTIKQGQFNF VHVIITPLDY 1680
KCNLLTLQCR KDGPACKCEW WRQPGEIVVW ALPVVMELTV TILLCHLQMA SQVHHSRSNP 1740
TDIYPSKWIA RLRHIKRLRQ RIREEVHYSN PSLPLMHPPA HTKAPAQAPE ATPTYETGQR 1800
KRLISSVDDF TEFV 1814 
Gene Ontology
 GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IBA:RefGenome.
 GO:0033596; C:TSC1-TSC2 complex; IBA:RefGenome.
 GO:0071889; F:14-3-3 protein binding; IDA:MGI.
 GO:0005096; F:GTPase activator activity; IBA:RefGenome.
 GO:0019902; F:phosphatase binding; ISS:UniProtKB.
 GO:0030030; P:cell projection organization; ISO:MGI.
 GO:0007507; P:heart development; IMP:MGI.
 GO:0048009; P:insulin-like growth factor receptor signaling pathway; IMP:MGI.
 GO:0008285; P:negative regulation of cell proliferation; IMP:MGI.
 GO:0045792; P:negative regulation of cell size; ISO:MGI.
 GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase cascade; IMP:MGI.
 GO:0006469; P:negative regulation of protein kinase activity; IMP:MGI.
 GO:0051898; P:negative regulation of protein kinase B signaling cascade; IMP:MGI.
 GO:0032007; P:negative regulation of TOR signaling cascade; IMP:MGI.
 GO:0030178; P:negative regulation of Wnt receptor signaling pathway; IBA:RefGenome.
 GO:0001843; P:neural tube closure; IMP:MGI.
 GO:0014065; P:phosphatidylinositol 3-kinase cascade; IMP:MGI.
 GO:0050918; P:positive chemotaxis; IMP:MGI.
 GO:0006606; P:protein import into nucleus; IMP:MGI.
 GO:0043491; P:protein kinase B signaling cascade; IMP:MGI.
 GO:0051726; P:regulation of cell cycle; IBA:RefGenome.
 GO:0030100; P:regulation of endocytosis; IMP:MGI.
 GO:0046626; P:regulation of insulin receptor signaling pathway; IMP:MGI.
 GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
 GO:0001666; P:response to hypoxia; IMP:MGI. 
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.