Details of the Target

General Information of Target

Target ID LDTP06371
Target Name GTP-binding protein Rheb (RHEB)
Gene Name RHEB
Gene ID 6009
Synonyms
RHEB2; GTP-binding protein Rheb; Ras homolog enriched in brain; EC 3.6.5.-
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MPQSKSRKIAILGYRSVGKSSLTIQFVEGQFVDSYDPTIENTFTKLITVNGQEYHLQLVD
TAGQDEYSIFPQTYSIDINGYILVYSVTSIKSFEVIKVIHGKLLDMVGKVQIPIMLVGNK
KDLHMERVISYEEGKALAESWNAAFLESSAKENQTAVDVFRRIILEAEKMDGAASQGKSS
CSVM
Target Bioclass
Enzyme
Family
Small GTPase superfamily, Rheb family
Subcellular location
Endomembrane system
Function
Small GTPase that acts as an allosteric activator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth . In response to nutrients, growth factors or amino acids, specifically activates the protein kinase activity of MTOR, the catalytic component of the mTORC1 complex: acts by causing a conformational change that allows the alignment of residues in the active site of MTOR, thereby enhancing the phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1). RHEB is also required for localization of the TSC-TBC complex to lysosomal membranes. In response to starvation, RHEB is inactivated by the TSC-TBC complex, preventing activation of mTORC1. Has low intrinsic GTPase activity.
Uniprot ID
Q15382
Ensemble ID
ENST00000262187.10
HGNC ID
HGNC:10011
ChEMBL ID
CHEMBL3108656

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
TH211
 Probe Info  		Y131(9.22)  LDD0260  [1]
STPyne
 Probe Info  		K120(8.90); K121(5.46)  LDD0277  [2]
ONAyne
 Probe Info  		K121(10.00)  LDD0275  [2]
Jackson_1
 Probe Info  		2.12  LDD0120  [3]
HHS-475
 Probe Info  		Y131(0.57)  LDD0265  [4]
1c-yne
 Probe Info  		N.A.  LDD0228  [5]
PAL-AfBPP Probe
Click To Hide/Show 11 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C094
 Probe Info  		28.64  LDD1785  [6]
C100
 Probe Info  		5.17  LDD1789  [6]
C153
 Probe Info  		17.39  LDD1834  [6]
C158
 Probe Info  		13.83  LDD1838  [6]
C232
 Probe Info  		37.79  LDD1905  [6]
C235
 Probe Info  		22.63  LDD1908  [6]
C293
 Probe Info  		18.25  LDD1963  [6]
C299
 Probe Info  		6.73  LDD1968  [6]
C305
 Probe Info  		11.55  LDD1974  [6]
FFF probe13
 Probe Info  		20.00  LDD0475  [7]
FFF probe3
 Probe Info  		20.00  LDD0464  [7]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0070  Cisar_cp37 MDA-MB-231 2.12  LDD0120  [3]
 LDCM0191  Compound 21 HEK-293T 7.09  LDD0508  [7]
 LDCM0190  Compound 34 HEK-293T 10.47  LDD0510  [7]
 LDCM0192  Compound 35 HEK-293T 6.56  LDD0509  [7]
 LDCM0193  Compound 36 HEK-293T 9.26  LDD0511  [7]
 LDCM0117  HHS-0201 DM93 Y131(0.57)  LDD0265  [4]
 LDCM0118  HHS-0301 DM93 Y131(0.96)  LDD0266  [4]
 LDCM0119  HHS-0401 DM93 Y131(0.89)  LDD0267  [4]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 6 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta (PDE6D) PDE6D/unc-119 family O43924
Caspase-6 (CASP6) Peptidase C14A family P55212
Phospholipase D1 (PLD1) Phospholipase D family Q13393
Serine/threonine-protein kinase mTOR (MTOR) PI3/PI4-kinase family P42345
Fibroblast growth factor receptor 3 (FGFR3) Tyr protein kinase family P22607
GTP-binding nuclear protein Ran (RAN) Ran family P62826
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Glutamate receptor ionotropic, NMDA 2C (GRIN2C) Glutamate-gated ion channel family Q14957
Huntingtin-interacting protein 1 (HIP1) SLA2 family O00291
Other
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cholecystokinin (CCK) Gastrin/cholecystokinin family P06307
Translationally-controlled tumor protein (TPT1) TCTP family P13693
Amyloid protein-binding protein 2 (APPBP2) . Q92624
Ubiquilin-1 (UBQLN1) . Q9UMX0

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Guanosine-5'-diphosphate Small molecular drug DB04315
Guanosine-5'-triphosphate Small molecular drug DB04137

References

1 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
2 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
3 Appendage and Scaffold Diverse Fully Functionalized Small-Molecule Probes via a Minimalist Terminal Alkyne-Aliphatic Diazirine Isocyanide. J Org Chem. 2018 Sep 21;83(18):11245-11253. doi: 10.1021/acs.joc.8b01831. Epub 2018 Aug 31.
4 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
5 Tunable Amine-Reactive Electrophiles for Selective Profiling of Lysine. Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202112107. doi: 10.1002/anie.202112107. Epub 2021 Dec 16.
6 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
7 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.