Tbio SESN1 Sestrin-1

Protein Summary

Description

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 (PubMed:25263562, PubMed:26449471). This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). 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 (PubMed:23274085). May have an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (By similarity). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (By similarity). This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the cellular response to DNA damage and oxidative stress. The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded protein also plays a critical role in antioxidant defense by regenerating overoxidized peroxiredoxins, and the expression of this gene is a potential marker for exposure to radiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

Uniprot Accession IDs

• Q9Y6P5
• Q2M2B7
• Q5T316
• Q9NV00
• Q9UPD5
• Q9Y6P6

Gene Name

• SESN1

Ensembl ID

• ENST00000302071
• ENSP00000306734
• ENSG00000080546
• ENST00000356644
• ENSP00000349061
• ENST00000436639
• ENSP00000393762

Symbol

• PA26
• SEST1
• PA26
• SEST1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor perturbation	0.97
kinase perturbation	0.88
disease perturbation	0.83
transcription factor binding site profile	0.82
gene perturbation	0.78

Protein Classes

PANTHER Classes

Protein / Oxidoreductase / Peroxidase / Sestrin-1

DTO Classes

Protein / Enzyme / Oxidoreductase / Peroxidase / Sestrin-1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 108.62   (req: < 5)

Gene RIFs: 20   (req: <= 3)

Antibodies: 241   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 108.62   (req: >= 5)

Gene RIFs: 20   (req: > 3)

Antibodies: 241   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 13

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0