General Information of Target

Target ID LDTP14283
Target Name Sestrin-1 (SESN1)
Gene Name SESN1
Gene ID 27244
Synonyms
PA26; SEST1; Sestrin-1; EC 1.11.1.-; p53-regulated protein PA26
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDRKVAREFRHKVDFLIENDAEKDYLYDVLRMYHQTMDVAVLVGDLKLVINEPSRLPLFD
AIRPLIPLKHQVEYDQLTPRRSRKLKEVRLDRLHPEGLGLSVRGGLEFGCGLFISHLIKG
GQADSVGLQVGDEIVRINGYSISSCTHEEVINLIRTKKTVSIKVRHIGLIPVKSSPDEPL
TWQYVDQFVSESGGVRGSLGSPGNRENKEKKVFISLVGSRGLGCSISSGPIQKPGIFISH
VKPGSLSAEVGLEIGDQIVEVNGVDFSNLDHKEAVNVLKSSRSLTISIVAAAGRELFMTD
RERLAEARQRELQRQELLMQKRLAMESNKILQEQQEMERQRRKEIAQKAAEENERYRKEM
EQIVEEEEKFKKQWEEDWGSKEQLLLPKTITAEVHPVPLRKPKYDQGVEPELEPADDLDG
GTEEQGEQDFRKYEEGFDPYSMFTPEQIMGKDVRLLRIKKEGSLDLALEGGVDSPIGKVV
VSAVYERGAAERHGGIVKGDEIMAINGKIVTDYTLAEAEAALQKAWNQGGDWIDLVVAVC
PPKEYDDELTFF
Target Bioclass
Enzyme
Family
Sestrin family
Subcellular location
Nucleus
Function
Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway. This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses. May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1. Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein. Was originally reported to contribute to oxidative stress resistance by reducing PRDX1. However, this could not be confirmed.
Uniprot ID
Q9Y6P5
Ensemble ID
ENST00000302071.6
HGNC ID
HGNC:21595

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C470(2.41); C345(2.48); C414(1.75)  LDD3377  [1]
AHL-Pu-1
 Probe Info 
C442(2.16)  LDD0169  [2]
IA-alkyne
 Probe Info 
N.A.  LDD0165  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0026  4SU-RNA+native RNA HEK-293T C442(2.16)  LDD0169  [2]
 LDCM0625  F8 Ramos C442(1.14); C355(1.04)  LDD2187  [4]
 LDCM0572  Fragment10 Ramos C442(1.16)  LDD2189  [4]
 LDCM0573  Fragment11 Ramos C442(0.74); C355(0.73)  LDD2190  [4]
 LDCM0574  Fragment12 Ramos C442(1.57)  LDD2191  [4]
 LDCM0575  Fragment13 Ramos C442(0.88); C355(0.71)  LDD2192  [4]
 LDCM0576  Fragment14 Ramos C355(0.52)  LDD2193  [4]
 LDCM0580  Fragment21 Ramos C442(0.88); C355(1.16)  LDD2195  [4]
 LDCM0582  Fragment23 Ramos C442(1.08); C355(0.81)  LDD2196  [4]
 LDCM0578  Fragment27 Ramos C442(0.76); C355(0.64)  LDD2197  [4]
 LDCM0586  Fragment28 Ramos C442(0.73); C355(1.03)  LDD2198  [4]
 LDCM0588  Fragment30 Ramos C442(1.06); C355(0.88)  LDD2199  [4]
 LDCM0589  Fragment31 Ramos C442(1.04); C355(0.79)  LDD2200  [4]
 LDCM0590  Fragment32 Ramos C442(1.02)  LDD2201  [4]
 LDCM0468  Fragment33 Ramos C442(0.90); C355(0.74)  LDD2202  [4]
 LDCM0596  Fragment38 Ramos C442(0.95); C355(0.73)  LDD2203  [4]
 LDCM0566  Fragment4 Ramos C442(1.22); C355(1.15)  LDD2184  [4]
 LDCM0610  Fragment52 Ramos C442(1.27); C355(0.72)  LDD2204  [4]
 LDCM0614  Fragment56 Ramos C442(1.51); C355(0.95)  LDD2205  [4]
 LDCM0569  Fragment7 Ramos C442(1.13)  LDD2186  [4]
 LDCM0022  KB02 Ramos C442(1.76)  LDD2182  [4]
 LDCM0023  KB03 Ramos C442(1.61); C355(1.15)  LDD2183  [4]
 LDCM0024  KB05 OPM-2 C470(2.41); C345(2.48); C414(1.75)  LDD3377  [1]

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
3 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
4 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578