Tbio SESN1 Sestrin-1

Protein Classes

PANTHER Classes

Protein / Oxidoreductase / Peroxidase / Sestrin-1

DTO Classes

Protein / Enzyme / Oxidoreductase / Peroxidase / 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

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: 86.81   (req: < 5)

Gene RIFs: 8   (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: 86.81   (req: >= 5)

Gene RIFs: 8   (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

Pathways (12)

Reactome (5)

KEGG (2)

PathwayCommons (1)

WikiPathways (4)

Gene expression (Transcription) (R-HSA-74160)

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Items per page:

5

1 – 5 of 5

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436
Reactome	RNA Polymerase II Transcription	1314 targets	R-HSA-73857
Reactome	TP53 Regulates Metabolic Genes	86 targets	R-HSA-5628897
Reactome	Transcriptional Regulation by TP53	365 targets	R-HSA-3700989

Name	Explore in Pharos	Explore in Source
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436
RNA Polymerase II Transcription	1314 targets	R-HSA-73857
TP53 Regulates Metabolic Genes	86 targets	R-HSA-5628897
Transcriptional Regulation by TP53	365 targets	R-HSA-3700989

Gene Ontology Terms (17)

Functions (3)

Components (4)

Processes (10)

Items per page:

10

1 – 3 of 3

GO Term	Evidence	Assigned by
leucine binding	Inferred from Direct Assay (IDA)	UniProtKB
oxidoreductase activity, acting on peroxide as acceptor	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
peroxiredoxin activity	Inferred from Electronic Annotation (IEA)	UniProtKB-EC

Protein-Protein Interactions (78)

Explore Interacting Targets

1 – 10 of 78

• See Interactions on String-DB

SESN2

Tbio

Novelty: 0.00594978

Score: 0.807

Data Source: STRINGDB

SESN3

Tbio

Novelty: 0.05189758

Score: 0.806

Data Source: STRINGDB

CACNA2D2

Tclin

Family: IC

Novelty: 0.0236407

Score: 0.801

Data Source: STRINGDB

PRKAB1

Tchem

Family: Kinase

Novelty: 0.027886

Score: 0.752

Data Source: Reactome,STRINGDB

WDR59

Tdark

Novelty: 0.27755881

Score: 0.747

Data Source: STRINGDB

TP53

Tchem

Family: TF

Novelty: 0.00002203

Score: 0.745

Data Source: STRINGDB

MIOS

Tdark

Novelty: 0.03378873

Score: 0.745

Data Source: STRINGDB

PRKAB2

Tchem

Family: Enzyme

Novelty: 0.05936112

Score: 0.737

Data Source: Reactome,STRINGDB

WDR24

Tdark

Novelty: 1.44736842

Score: 0.719

Data Source: STRINGDB

TSC2

Tbio

Novelty: 0.00092908

Score: 0.677

Data Source: STRINGDB

Publication Statistics

PubMed Score  86.81

PubMed score by year

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PubTator Score  29.82

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MRLAAAANEAYTAPLAVSGLLGCKQCGGGRDQDEELGIRIPRPLGQGPSRFIPEKEILQVGSEDAQMHAL

1-70

FADSFAALGRLDNITLVMVFHPQYLESFLKTQHYLLQMDGPLPLHYRHYIGIMAAARHQCSYLVNLHVND

70-140

FLHVGGDPKWLNGLENAPQKLQNLGELNKVLAHRPWLITKEHIEGLLKAEEHSWSLAELVHAVVLLTHYH

140-210

SLASFTFGCGISPEIHCDGGHTFRPPSVSNYCICDITNGNHSVDEMPVNSAENVSVSDSFFEVEALMEKM

210-280

RQLQECRDEEEASQEEMASRFEIEKRESMFVFSSDDEEVTPARAVSRHFEDTSYGYKDFSRHGMHVPTFR

280-350

VQDYCWEDHGYSLVNRLYPDVGQLIDEKFHIAYNLTYNTMAMHKDVDTSMLRRAIWNYIHCMFGIRYDDY

350-420

DYGEINQLLDRSFKVYIKTVVCTPEKVTKRMYDSFWRQFKHSEKVHVNLLLIEARMQAELLYALRAITRY

420-490

MT

490-492

MRLAAAANEAYTAPLAVSGLLGCKQCGGGRDQDEELGIRIPRPLGQGPSRFIPEKEILQVGSEDAQMHALFADSFAALGRLDNITLVMVFHPQYLESFLKTQHYLLQMDGPLPLHYRHYIGIMAAARHQCSYLVNLHVNDFLHVGGDPKWLNGLENAPQKLQNLGELNKVLAHRPWLITKEHIEGLLKAEEHSWSLAELVHAVVLLTHYHSLASFTFGCGISPEIHCDGGHTFRPPSVSNYCICDITNGNHSVDEMPVNSAENVSVSDSFFEVEALMEKMRQLQECRDEEEASQEEMASRFEIEKRESMFVFSSDDEEVTPARAVSRHFEDTSYGYKDFSRHGMHVPTFRVQDYCWEDHGYSLVNRLYPDVGQLIDEKFHIAYNLTYNTMAMHKDVDTSMLRRAIWNYIHCMFGIRYDDYDYGEINQLLDRSFKVYIKTVVCTPEKVTKRMYDSFWRQFKHSEKVHVNLLLIEARMQAELLYALRAITRYMT

Find similar targets by:

Uniprot Keyword

Alternative splicing
Complete proteome
Cytoplasm
Nucleus
Oxidoreductase
Phosphoprotein
Polymorphism
Reference proteome