UniProtKB - P49816 (TSC2_RAT)
Tuberin
Tsc2
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 (PubMed:9045618).
By similarity2 PublicationsGO - Molecular functioni
- 14-3-3 protein binding Source: RGD
- GTPase activator activity Source: RGD
- Hsp90 protein binding Source: RGD
- phosphatase binding Source: UniProtKB
- protein-containing complex binding Source: RGD
- protein homodimerization activity Source: RGD
- protein N-terminus binding Source: RGD
- small GTPase binding Source: RGD
GO - Biological processi
- aging Source: RGD
- anoikis Source: RGD
- cell projection organization Source: MGI
- cellular response to insulin stimulus Source: RGD
- establishment of cell polarity Source: RGD
- establishment of protein localization Source: RGD
- glucose import Source: RGD
- heart development Source: RGD
- insulin-like growth factor receptor signaling pathway Source: RGD
- negative regulation of axonogenesis Source: RGD
- negative regulation of cell population proliferation Source: RGD
- negative regulation of cell size Source: MGI
- negative regulation of epithelial cell proliferation Source: RGD
- negative regulation of epithelial to mesenchymal transition Source: RGD
- negative regulation of fibroblast proliferation Source: RGD
- negative regulation of insulin receptor signaling pathway Source: GO_Central
- negative regulation of macroautophagy Source: RGD
- negative regulation of MAP kinase activity Source: RGD
- negative regulation of phosphatidylinositol 3-kinase signaling Source: RGD
- negative regulation of pinocytosis Source: RGD
- negative regulation of protein kinase activity Source: RGD
- negative regulation of protein kinase B signaling Source: RGD
- negative regulation of protein phosphorylation Source: RGD
- negative regulation of TORC1 signaling Source: RGD
- negative regulation of TOR signaling Source: RGD
- negative regulation of vascular endothelial cell proliferation Source: RGD
- negative regulation of Wnt signaling pathway Source: RGD
- neural tube closure Source: RGD
- phosphatidylinositol 3-kinase signaling Source: RGD
- positive chemotaxis Source: RGD
- positive regulation of autophagy Source: RGD
- positive regulation of cell adhesion Source: RGD
- positive regulation of dendritic spine development Source: RGD
- positive regulation of fibroblast migration Source: RGD
- positive regulation of GTPase activity Source: InterPro
- positive regulation of macroautophagy Source: RGD
- positive regulation of neuron projection development Source: RGD
- positive regulation of transcription by RNA polymerase II Source: RGD
- protein import into nucleus Source: RGD
- protein kinase B signaling Source: RGD
- protein localization Source: RGD
- protein localization to cell surface Source: RGD
- protein transport into plasma membrane raft Source: RGD
- regulation of cell cycle Source: GO_Central
- regulation of endocytosis Source: RGD
- regulation of insulin receptor signaling pathway Source: RGD
- regulation of postsynapse organization Source: SynGO
- regulation of small GTPase mediated signal transduction Source: InterPro
- response to hypoxia Source: RGD
- signal transduction Source: RGD
- social behavior Source: RGD
Keywordsi
Molecular function | GTPase activation |
Enzyme and pathway databases
Reactomei | R-RNO-1632852, Macroautophagy R-RNO-165181, Inhibition of TSC complex formation by PKB R-RNO-198323, AKT phosphorylates targets in the cytosol R-RNO-380972, Energy dependent regulation of mTOR by LKB1-AMPK R-RNO-5628897, TP53 Regulates Metabolic Genes R-RNO-8854214, TBC/RABGAPs |
Names & Taxonomyi
Protein namesi | Recommended name: TuberinAlternative name(s): Tuberous sclerosis 2 protein homolog |
Gene namesi | Name:Tsc2 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 3908, Tsc2 |
Subcellular locationi
Cytoskeleton
- cytoskeleton Source: RGD
Cytosol
- cytosol Source: RGD
- TSC1-TSC2 complex Source: RGD
Golgi apparatus
- Golgi apparatus Source: RGD
Lysosome
- lysosome Source: RGD
Nucleus
- nucleus Source: RGD
Plasma Membrane
- caveola Source: RGD
Other locations
- cell projection Source: RGD
- cytoplasm Source: RGD
- dendrite Source: RGD
- glutamatergic synapse Source: SynGO
- growth cone Source: RGD
- intracellular membrane-bounded organelle Source: RGD
- membrane Source: RGD
- membrane raft Source: RGD
- neuron projection Source: RGD
- neuronal cell body Source: RGD
- perinuclear region of cytoplasm Source: RGD
- postsynaptic density Source: RGD
- protein-containing complex Source: RGD
- synapse Source: RGD
Pathology & Biotechi
Involvement in diseasei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 314 | N → S in chemically induced renal carcinoma. 1 Publication | 1 | |
Mutagenesisi | 713 | L → R in chemically induced renal carcinoma. 1 Publication | 1 |
Keywords - Diseasei
Tumor suppressorPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000065656 | 1 – 1809 | TuberinAdd BLAST | 1809 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 540 | PhosphoserineBy similarity | 1 | |
Modified residuei | 664 | PhosphoserineBy similarity | 1 | |
Modified residuei | 927 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 939 | Phosphoserine; by PKB/AKT1By similarity | 1 | |
Modified residuei | 981 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1132 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1155 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1271 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1340 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1341 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1349 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1366 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1389 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1413 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1420 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1422 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1456 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1466 | Phosphothreonine; by PKB/AKT1By similarity | 1 | |
Modified residuei | 1766 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1800 | Phosphoserine; by RPS6KA1By similarity | 1 | |
Modified residuei | 1801 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | P49816 |
PTM databases
iPTMneti | P49816 |
PhosphoSitePlusi | P49816 |
Expressioni
Tissue specificityi
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 (By similarity). 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 (By similarity).
Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex thereby stabilizing TSC2 (By similarity).
Interacts with TSC1 and HERC1; the interaction with TSC1 stabilizes TSC2 and prevents the interaction with HERC1 (By similarity). May also interact with the adapter molecule RABEP1 (PubMed:9045618). The final complex may contain TSC2 and RABEP1 linked to RAB5 (PubMed:9045618).
Interacts with HSPA1 and HSPA8 (By similarity).
Interacts with DAPK1 (By similarity).
Interacts with FBXW5 (By similarity).
Interacts with NAA10 (via C-terminal domain) (By similarity).
Interacts with RRAGA (polyubiquitinated) (By similarity).
Interacts with WDR45B (By similarity).
Interacts with RPAP3 and URI1 (By similarity).
Interacts with YWHAG (By similarity).
By similarity1 PublicationGO - Molecular functioni
- 14-3-3 protein binding Source: RGD
- Hsp90 protein binding Source: RGD
- phosphatase binding Source: UniProtKB
- protein homodimerization activity Source: RGD
- protein N-terminus binding Source: RGD
- small GTPase binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 246972, 9 interactors |
IntActi | P49816, 4 interactors |
MINTi | P49816 |
STRINGi | 10116.ENSRNOP00000016221 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1533 – 1760 | Rap-GAPPROSITE-ProRule annotationAdd BLAST | 228 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1078 – 1136 | DisorderedSequence analysisAdd BLAST | 59 | |
Regioni | 1330 – 1359 | DisorderedSequence analysisAdd BLAST | 30 | |
Regioni | 1373 – 1392 | DisorderedSequence analysisAdd BLAST | 20 | |
Regioni | 1405 – 1492 | DisorderedSequence analysisAdd BLAST | 88 | |
Regioni | 1764 – 1793 | DisorderedSequence analysisAdd BLAST | 30 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1088 – 1102 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 1473 – 1488 | Basic and acidic residuesSequence analysisAdd BLAST | 16 |
Phylogenomic databases
eggNOGi | KOG3687, Eukaryota |
InParanoidi | P49816 |
OrthoDBi | 341431at2759 |
PhylomeDBi | P49816 |
TreeFami | TF324484 |
Family and domain databases
Gene3Di | 1.25.10.10, 1 hit 3.40.50.11210, 1 hit |
InterProi | View protein in InterPro IPR011989, ARM-like IPR016024, ARM-type_fold IPR035974, Rap/Ran-GAP_sf IPR000331, Rap/Ran_GAP_dom IPR003913, Tuberin IPR018515, Tuberin-type_domain IPR027107, Tuberin/Ral-act_asu IPR024584, Tuberin_N |
PANTHERi | PTHR10063, PTHR10063, 3 hits |
Pfami | View protein in Pfam PF11864, DUF3384, 1 hit PF02145, Rap_GAP, 1 hit PF03542, Tuberin, 1 hit |
PRINTSi | PR01431, TUBERIN |
SUPFAMi | SSF111347, SSF111347, 1 hit SSF48371, SSF48371, 1 hit |
PROSITEi | View protein in PROSITE PS50085, RAPGAP, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAKPTSKDSG LKEKFKILLG LGTSRPNPRC AEGKQTEFII TAEILRELSG
60 70 80 90 100
ECGLNNRIRM IGQICDVAKT KKLEEHAVEA LWKAVSDLLQ PERPPEARHA
110 120 130 140 150
VLALLKAIVQ GQGDRLGVLR ALFFKVIKDY PSNEDLHERL EVFKALTDNG
160 170 180 190 200
RHITYLEEEL AEFVLQWMDV GLSSEFLLVL VNLVKFNSCY LDEYIAPMVH
210 220 230 240 250
MICLLCIRTV SSVDIEVSLQ VLDAVVCYNC LPAESLPLFI ITLCRTVNVK
260 270 280 290 300
ELCEPCWKLM RNLLGTHLGH SAIYNMCRIM ENRSYMEDAP LLRGAVFFVG
310 320 330 340 350
MALWGAHRLY SLKNSPTSVL PSFYEAMTCP NEVVSYEIVL SITRLIKKYR
360 370 380 390 400
KELQAVTWDI LLDIIERLLQ QLQNLDSPEL RTIVHDLLTT VEELCDQNEF
410 420 430 440 450
HGSQERYYEL VESYADQRPE SSLLNLITYR AQSIHPAKDG WIQNLQLLME
460 470 480 490 500
RFFRNECRSA VRIKVLDVLS FVLLINRQFY EEELINSVVI SQLSHIPEDK
510 520 530 540 550
DHQVRKLATQ LLVDLAEGCH THHFNSLLDI IEKVMARSLS PPLELEERDL
560 570 580 590 600
AVYSASLEDV KTAVLGLLVI LQTKLYTLPA SHATRVYETL ISHIQLHYKH
610 620 630 640 650
GYSLPIASSI RLQAFDFLLL LRADSLHRLG LPNKDGVVRF SPYCLCDCAE
660 670 680 690 700
LDRASEKKAS GPLSPPTGPP SPVPTGPAVR LGHLPYSLLF RVLLQCLKQE
710 720 730 740 750
TDWKVLKLVL SKLPESLRYK 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 AAEQYASVFA ISLPYTNPSK FNQYIVCLAH HVIAMWFIRC
910 920 930 940 950
RLPFRKDFVP YITKGLRSNV LLSFDDTPEK DKFRARSTSL 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 GSASSSDPGT
1110 1120 1130 1140 1150
HVRQTKEAPA KLESQAGQQV SRGARDRVRS MSGGHGLRVG VLDTSAPYTP
1160 1170 1180 1190 1200
GGPASLGAQA APAARPEKPC AGAQLPAAEK ANLAAYVPLL TQGWAEILVR
1210 1220 1230 1240 1250
RPTGNTSWLM SLENPLSPFS SDINNMPLQE LSNALMAAER FKEHRDTALY
1260 1270 1280 1290 1300
KSLSVPAAGT AKPPTLPRSN TVASFSSLYQ PSCQGQLHRS VSWADSAVVL
1310 1320 1330 1340 1350
EEGSPGEAHV PVEPPELEDF EAALGTDRHC QRPDAYSRSS SASSQEEKSH
1360 1370 1380 1390 1400
LEELAAGGIP IERAISSEGA RPTVDLSFQP SQPLSKSSSS PELQTLQDIL
1410 1420 1430 1440 1450
GDLGDKTDIG RLSPEAKVRS QSGILDGEAA TWSAPGEESR ITVPPEGPLP
1460 1470 1480 1490 1500
SSSPRSPSGL RPRGYTISDS APSRRGKRVE RDNFKSRTAA SSAEKVPGIN
1510 1520 1530 1540 1550
PSFVFLQLYH SPFCGDESNK PILLPNESFE RSVQLLDQIP SYDTHKIAVL
1560 1570 1580 1590 1600
YVGEGQSSSE LAILSNEHGS YRYTEFLTGL GRLIELKDCQ PDKVYLGGLD
1610 1620 1630 1640 1650
VCGEDGQFTY CWHDDIMQAV FHIATLMPTK DVDKHRCDKK RHLGNDFVSI
1660 1670 1680 1690 1700
IYNDSGEDFK LGTIKGQFNF VHVIITPLDY KCNLLTLQCR KDMEGLVDTS
1710 1720 1730 1740 1750
VAKIVSDRNL SFVARQMALH ANMASQVHHR RSNPTDIYPS KWIARLRHIK
1760 1770 1780 1790 1800
RLRQRIREEV HYSNPSLPLM HPPAHTKVPA QAPTEATPTY ETGQRKRLIS
SVDDFTEFV
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD3ZLW4 | D3ZLW4_RAT | Tuberin | Tsc2 | 1,785 | Annotation score: | ||
A0A0G2JSL4 | A0A0G2JSL4_RAT | Tuberin | Tsc2 rCG_33974 | 1,809 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 932 | K → S in BAA08914 (PubMed:7651821).Curated | 1 | |
Sequence conflicti | 1514 | C → F in BAA08914 (PubMed:7651821).Curated | 1 | |
Sequence conflicti | 1730 | R → S in BAA08914 (PubMed:7651821).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_004481 | 947 – 989 | Missing in isoform 2 and isoform 4. 1 PublicationAdd BLAST | 43 | |
Alternative sequenceiVSP_004482 | 1272 – 1294 | Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST | 23 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U24150 mRNA Translation: AAC52289.1 D50413 mRNA Translation: BAA08914.1 |
PIRi | S57329 |
RefSeqi | NP_036812.2, NM_012680.3 [P49816-1] XP_006245971.2, XM_006245909.3 |
Genome annotation databases
GeneIDi | 24855 |
KEGGi | rno:24855 |
UCSCi | RGD:3908, rat [P49816-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U24150 mRNA Translation: AAC52289.1 D50413 mRNA Translation: BAA08914.1 |
PIRi | S57329 |
RefSeqi | NP_036812.2, NM_012680.3 [P49816-1] XP_006245971.2, XM_006245909.3 |
3D structure databases
SMRi | P49816 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 246972, 9 interactors |
IntActi | P49816, 4 interactors |
MINTi | P49816 |
STRINGi | 10116.ENSRNOP00000016221 |
PTM databases
iPTMneti | P49816 |
PhosphoSitePlusi | P49816 |
Proteomic databases
PaxDbi | P49816 |
Genome annotation databases
GeneIDi | 24855 |
KEGGi | rno:24855 |
UCSCi | RGD:3908, rat [P49816-1] |
Organism-specific databases
CTDi | 7249 |
RGDi | 3908, Tsc2 |
Phylogenomic databases
eggNOGi | KOG3687, Eukaryota |
InParanoidi | P49816 |
OrthoDBi | 341431at2759 |
PhylomeDBi | P49816 |
TreeFami | TF324484 |
Enzyme and pathway databases
Reactomei | R-RNO-1632852, Macroautophagy R-RNO-165181, Inhibition of TSC complex formation by PKB R-RNO-198323, AKT phosphorylates targets in the cytosol R-RNO-380972, Energy dependent regulation of mTOR by LKB1-AMPK R-RNO-5628897, TP53 Regulates Metabolic Genes R-RNO-8854214, TBC/RABGAPs |
Miscellaneous databases
PROi | PR:P49816 |
Family and domain databases
Gene3Di | 1.25.10.10, 1 hit 3.40.50.11210, 1 hit |
InterProi | View protein in InterPro IPR011989, ARM-like IPR016024, ARM-type_fold IPR035974, Rap/Ran-GAP_sf IPR000331, Rap/Ran_GAP_dom IPR003913, Tuberin IPR018515, Tuberin-type_domain IPR027107, Tuberin/Ral-act_asu IPR024584, Tuberin_N |
PANTHERi | PTHR10063, PTHR10063, 3 hits |
Pfami | View protein in Pfam PF11864, DUF3384, 1 hit PF02145, Rap_GAP, 1 hit PF03542, Tuberin, 1 hit |
PRINTSi | PR01431, TUBERIN |
SUPFAMi | SSF111347, SSF111347, 1 hit SSF48371, SSF48371, 1 hit |
PROSITEi | View protein in PROSITE PS50085, RAPGAP, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TSC2_RAT | |
Accessioni | P49816Primary (citable) accession number: P49816 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 1, 1996 | |
Last modified: | February 23, 2022 | |
This is version 178 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |