Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tuberin

Gene

Tsc2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (PubMed:16707451). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

  • anoikis Source: ParkinsonsUK-UCL
  • cell projection organization Source: MGI
  • cellular response to insulin stimulus Source: MGI
  • glucose import Source: MGI
  • heart development Source: MGI
  • insulin-like growth factor receptor signaling pathway Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of cell size Source: MGI
  • negative regulation of insulin receptor signaling pathway Source: GO_Central
  • negative regulation of phosphatidylinositol 3-kinase signaling Source: MGI
  • negative regulation of protein kinase activity Source: MGI
  • negative regulation of protein kinase B signaling Source: MGI
  • negative regulation of TORC1 signaling Source: ParkinsonsUK-UCL
  • negative regulation of TOR signaling Source: MGI
  • negative regulation of Wnt signaling pathway Source: GO_Central
  • neural tube closure Source: MGI
  • phosphatidylinositol 3-kinase signaling Source: MGI
  • positive chemotaxis Source: MGI
  • positive regulation of autophagy Source: ParkinsonsUK-UCL
  • positive regulation of macroautophagy Source: ParkinsonsUK-UCL
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • protein import into nucleus Source: MGI
  • protein kinase B signaling Source: MGI
  • protein localization Source: MGI
  • protein transport into plasma membrane raft Source: MGI
  • regulation of cell cycle Source: GO_Central
  • regulation of endocytosis Source: MGI
  • regulation of insulin receptor signaling pathway Source: MGI
  • regulation of small GTPase mediated signal transduction Source: InterPro
  • response to hypoxia Source: MGI

Keywordsi

Molecular functionGTPase activation

Names & Taxonomyi

Protein namesi
Recommended name:
Tuberin
Alternative name(s):
Tuberous sclerosis 2 protein homolog
Gene namesi
Name:Tsc2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:102548 Tsc2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000656551 – 1814TuberinAdd BLAST1814

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei540PhosphoserineBy similarity1
Modified residuei664PhosphoserineBy similarity1
Modified residuei927PhosphothreonineBy similarity1
Modified residuei939Phosphoserine; by PKB/AKT1By similarity1
Modified residuei981PhosphoserineBy similarity1
Modified residuei1132PhosphoserineCombined sources1
Modified residuei1155PhosphoserineBy similarity1
Modified residuei1339PhosphoserineBy similarity1
Modified residuei1340PhosphoserineBy similarity1
Modified residuei1348PhosphoserineBy similarity1
Modified residuei1365PhosphoserineBy similarity1
Modified residuei1388PhosphoserineBy similarity1
Modified residuei1412PhosphoserineBy similarity1
Modified residuei1419PhosphoserineBy similarity1
Modified residuei1421PhosphoserineBy similarity1
Modified residuei1451Phosphoserine; by AMPKBy similarity1
Modified residuei1455PhosphoserineBy similarity1
Modified residuei1465Phosphothreonine; by PKB/AKT1By similarity1
Modified residuei1772PhosphoserineCombined sources1
Modified residuei1805Phosphoserine; by RPS6KA1By similarity1
Modified residuei1806PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-1388, Ser-1419 or Ser-1421 does not affect interaction with TSC1. Phosphorylation at Ser-939 and Thr-1465 by PKB/AKT1 is induced by growth factor stimulation. Phosphorylation by AMPK activates it and leads to negatively regulates the mTORC1 complex. Phosphorylated at Ser-1805 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling. Phosphorylated by DAPK1.By similarity
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.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PeptideAtlasiQ61037
PRIDEiQ61037

PTM databases

iPTMnetiQ61037
PhosphoSitePlusiQ61037

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

CleanExiMM_TSC2

Interactioni

Subunit structurei

Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2. Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23. Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex thereby stabilizing TSC2. Interacts with TSC1 and HERC1; the interaction with TSC1 stabilizes TSC2 and prevents the interaction with HERC1. May also interact with the adapter molecule RABEP1. The final complex may contain TSC2 and RABEP1 linked to RAB5. Interacts with HSPA1 and HSPA8. Interacts with DAPK1. Interacts with FBXW5. Interacts with NAA10 (via C-terminal domain). Interacts with RRAGA (polyubiquitinated).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Tsc1Q9EP536EBI-7924402,EBI-1202690

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ61037, 5 interactors
MINTiQ61037

Structurei

3D structure databases

ProteinModelPortaliQ61037
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1532 – 1766Rap-GAPPROSITE-ProRule annotationAdd BLAST235

Phylogenomic databases

HOVERGENiHBG018005
InParanoidiQ61037
PhylomeDBiQ61037

Family and domain databases

Gene3Di3.40.50.11210, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR035974 Rap/Ran-GAP_sf
IPR000331 Rap_GAP_dom
IPR003913 Tuberin
IPR018515 Tuberin-type_domain
IPR027107 Tuberin/Ral-act_asu
IPR024584 Tuberin_N
PANTHERiPTHR10063 PTHR10063, 1 hit
PfamiView protein in Pfam
PF11864 DUF3384, 1 hit
PF02145 Rap_GAP, 1 hit
PF03542 Tuberin, 1 hit
PRINTSiPR01431 TUBERIN
SUPFAMiSSF111347 SSF111347, 1 hit
SSF48371 SSF48371, 1 hit
PROSITEiView protein in PROSITE
PS50085 RAPGAP, 1 hit

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform G (identifier: Q61037-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAKPTSKDSG LKEKFKILLG LGTSRPNPRC AEGKQTEFII TSEILRELSG
60 70 80 90 100
ECGLNNRIRM IGQICDVAKT KKLEEHAVEA LWKAVSDLLQ PERPPEARHA
110 120 130 140 150
VLTLLKAIVQ GQGDRLGVLR ALFFKVIKDY PSNEDLHERL EVFKALTDNG
160 170 180 190 200
RHITYLEEEL AEFVLQWMDV GLSSEFLLVL VNLVKFNSCY LDEYIASMVH
210 220 230 240 250
MICLLCIRTV SSVDIEVSLQ VLDAVVCYNC LPAESLPLFI ITLCRTINVK
260 270 280 290 300
ELCEPCWKLM RNLLGTHLGH SAIYNMCRIM EDRSYMEDAP LLRGAVFFVG
310 320 330 340 350
MALWGAHRLY SLKNSPTSVL PSFYEAMTCP NEVVSYEIVL SITRLIKKYR
360 370 380 390 400
KELQAVTWDI LLDIIERLLQ QLQNLDSPEL KTIVHDLLTT VEELCDQNEF
410 420 430 440 450
HGSQERYYEL VESYADQRPE SSLLNLISYR AQSIHPAKDG WIQNLQLLME
460 470 480 490 500
RFFRNECRSA VAIKVLDVLS FVLLIIRQFY EEELINSVVI SQLSHIPEDK
510 520 530 540 550
DHQVRKLATQ LLVDLAEGCH THHFNSLLDI IEKVMARSLS PPPELEERDL
560 570 580 590 600
AVHSASLEDV KTAVLGLLVI LQTKLYTLPA SHATRVYESL ISHIQLHYKH
610 620 630 640 650
GYSLPIASSI RLQAFDFLLL LRADSLHRLG LPNKDGVVRF SPYCLCDCME
660 670 680 690 700
LDRASEKKAS GPLSPPTGPP SPVPMGPAVR LGYLPYSLLF RVLLQCLKQE
710 720 730 740 750
SDWKVLKLVL SRLPESLRYK VLIFTSPCSV DQLSSALCSM LSAPKTLERL
760 770 780 790 800
RGTPEGFSRT DLHLAVVPVL TALISYHNYL DKTRQREMVY CLEQGLIYRC
810 820 830 840 850
ASQCVVALAI CSVEMPDIII KALPVLVVKL THISATASMA IPLLEFLSTL
860 870 880 890 900
ARLPHLYRNF VPEQYASVFA ISLPYTNPSK FNQYIVCLAH HVIAMWFIRC
910 920 930 940 950
RLPFRKDFVP YITKGLRSNV LLSFDDTPEK DSFRARSTSL NERPKSLRIA
960 970 980 990 1000
RAPKQGLNNS PPVKEFKESC AAEAFRCRSI SVSEHVVRSR IQTSLTSASL
1010 1020 1030 1040 1050
GSADENSMAQ ADDNLKNLHL ELTETCLDMM ARYVFSNFTA VPKRSPVGEF
1060 1070 1080 1090 1100
LLAGGRTKTW LVGNKLVTVT TSVGTGTRSL LGLDSGDLQG GSDSSSDPST
1110 1120 1130 1140 1150
HVRQTKEAPA KLESQAGQQV SRGARDRVRS MSGGHGLRVG VLDTSAPYSP
1160 1170 1180 1190 1200
GGSASLGPQT AVAAKPEKPP AGAQLPTAEK TNLAAYVPLL TQGWAEILVR
1210 1220 1230 1240 1250
RPTGNTSWLM SLENPLSPFS SDINNMPLQE LSNALMAAER FKEHGHAPVQ
1260 1270 1280 1290 1300
VIVSATGCTA KPPTLPRSNT VASFSSLYQP SCQGQLHRSV SWADSAMVLE
1310 1320 1330 1340 1350
EGSPGETQVP VEPPELEDFE AALGTDRHCQ RPDTYSRSSS ASSQEEKSHL
1360 1370 1380 1390 1400
EELAAGGIPI ERAISSEGAR PAVDLSFQPS QPLSKSSSSP ELQTLQDILG
1410 1420 1430 1440 1450
DLGDKIDIGR LSPEAKVRSQ SGILDGEAAT WSATGEESRI TVPPEGPLPS
1460 1470 1480 1490 1500
SSPRSPSGLR PRGYTISDSA PSRRGKRVER DNFKSRAAAS SAEKVPGINP
1510 1520 1530 1540 1550
SFVFLQLYHS PFFGDESNKP ILLPNESFER SVQLLDQIPS YDTHKIAVLY
1560 1570 1580 1590 1600
VGEGQSSSEL AILSNEHGSY RYTEFLTGLG RLIELKDCQP DKVYLGGLDV
1610 1620 1630 1640 1650
CGEDGQFTYC WHDDIMQAVF HIATLMPTKD VDKHRCDKKR HLGNDFVSII
1660 1670 1680 1690 1700
YNDSGEDFKL GTIKQGQFNF VHVIITPLDY KCNLLTLQCR KDGPACKCEW
1710 1720 1730 1740 1750
WRQPGEIVVW ALPVVMELTV TILLCHLQMA SQVHHSRSNP TDIYPSKWIA
1760 1770 1780 1790 1800
RLRHIKRLRQ RIREEVHYSN PSLPLMHPPA HTKAPAQAPE ATPTYETGQR
1810
KRLISSVDDF TEFV
Length:1,814
Mass (Da):202,071
Last modified:November 1, 1996 - v1
Checksum:i913AB87194AADA5B
GO
Isoform A (identifier: Q61037-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     79-115: Missing.

Show »
Length:1,777
Mass (Da):197,982
Checksum:iEC1013448D7CECCE
GO
Isoform B (identifier: Q61037-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     534-572: Missing.

Show »
Length:1,775
Mass (Da):197,891
Checksum:i9D54C4EF90B89C4E
GO
Isoform C (identifier: Q61037-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     947-990: Missing.

Show »
Length:1,770
Mass (Da):197,163
Checksum:i6BA34A440D4378C6
GO
Isoform D (identifier: Q61037-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1271-1293: Missing.

Show »
Length:1,791
Mass (Da):199,550
Checksum:iE616D6579FAF310F
GO
Isoform E (identifier: Q61037-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1245-1258: GHAPVQVIVSATGC → RDTALYKSLSVPAAG
     1271-1293: Missing.
     1693-1728: GPACKCEWWRQPGEIVVWALPVVMELTVTILLCHLQ → MEGLVDTSVAKIVSDRNLSFVARQMALHAN

Show »
Length:1,786
Mass (Da):198,914
Checksum:iEDC8768C66FBFE76
GO
Isoform F (identifier: Q61037-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     947-989: Missing.
     1245-1258: GHAPVQVIVSATGC → RDTALYKSLSVPAAG
     1271-1293: Missing.
     1693-1728: GPACKCEWWRQPGEIVVWALPVVMELTVTILLCHLQ → MEGLVDTSVAKIVSDRNLSFVARQMALHAN
     1776-1814: Missing.

Show »
Length:1,704
Mass (Da):189,855
Checksum:iF6A528C77739AE59
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti161Missing in AAA86902 (PubMed:8833243).Curated1
Sequence conflicti161Missing in AAA86901 (PubMed:8833243).Curated1
Sequence conflicti269G → S in AAA86902 (PubMed:8833243).Curated1
Sequence conflicti269G → S in AAA86901 (PubMed:8833243).Curated1
Sequence conflicti462A → R in AAA86902 (PubMed:8833243).Curated1
Sequence conflicti462A → R in AAA86901 (PubMed:8833243).Curated1
Sequence conflicti476I → N in AAA86902 (PubMed:8833243).Curated1
Sequence conflicti476I → N in AAA86901 (PubMed:8833243).Curated1
Sequence conflicti549D → N in AAA86902 (PubMed:8833243).Curated1
Sequence conflicti549D → N in AAA86901 (PubMed:8833243).Curated1
Sequence conflicti707K → N in AAD27867 (PubMed:10584558).Curated1
Sequence conflicti861 – 862VP → AA in AAA86902 (PubMed:8833243).Curated2
Sequence conflicti861 – 862VP → AA in AAA86901 (PubMed:8833243).Curated2
Sequence conflicti1127R → P in AAA86902 (PubMed:8833243).Curated1
Sequence conflicti1127R → P in AAA86901 (PubMed:8833243).Curated1
Sequence conflicti1665Missing in AAA86902 (PubMed:8833243).Curated1
Sequence conflicti1665Missing in AAA86901 (PubMed:8833243).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00447379 – 115Missing in isoform A. CuratedAdd BLAST37
Alternative sequenceiVSP_004474534 – 572Missing in isoform B. CuratedAdd BLAST39
Alternative sequenceiVSP_004476947 – 990Missing in isoform C. CuratedAdd BLAST44
Alternative sequenceiVSP_004475947 – 989Missing in isoform F. CuratedAdd BLAST43
Alternative sequenceiVSP_0044771245 – 1258GHAPV…SATGC → RDTALYKSLSVPAAG in isoform E and isoform F. CuratedAdd BLAST14
Alternative sequenceiVSP_0044781271 – 1293Missing in isoform D, isoform E and isoform F. CuratedAdd BLAST23
Alternative sequenceiVSP_0044791693 – 1728GPACK…LCHLQ → MEGLVDTSVAKIVSDRNLSF VARQMALHAN in isoform E and isoform F. CuratedAdd BLAST36
Alternative sequenceiVSP_0044801776 – 1814Missing in isoform F. CuratedAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37775 mRNA Translation: AAA86902.1
U37775 mRNA Translation: AAA86901.1
U39818 mRNA Translation: AAB18754.1
AB009371 Genomic DNA Translation: BAA28845.1
AF132986 mRNA Translation: AAD27867.1
UniGeneiMm.30435

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTSC2_MOUSE
AccessioniPrimary (citable) accession number: Q61037
Secondary accession number(s): P97723
, P97724, P97725, P97727, Q61007, Q61008, Q9WUF6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: April 25, 2018
This is version 157 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health