P58006 · SESN1_MOUSE
- ProteinSestrin-1
- GeneSesn1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids492 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (PubMed:25259925).
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 (By similarity).
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 (By similarity).
Catalytic activity
- a hydroperoxide + L-cysteinyl-[protein] = an alcohol + S-hydroxy-L-cysteinyl-[protein]This reaction proceeds in the forward direction.
Features
Showing features for active site, binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | nucleus | |
Molecular Function | L-leucine binding | |
Molecular Function | oxidoreductase activity, acting on peroxide as acceptor | |
Biological Process | cellular oxidant detoxification | |
Biological Process | cellular response to amino acid starvation | |
Biological Process | cellular response to amino acid stimulus | |
Biological Process | cellular response to L-leucine | |
Biological Process | cellular response to leucine starvation | |
Biological Process | negative regulation of cell growth | |
Biological Process | negative regulation of TORC1 signaling | |
Biological Process | positive regulation of macroautophagy | |
Biological Process | reactive oxygen species metabolic process | |
Biological Process | regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | |
Biological Process | regulation of response to reactive oxygen species |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSestrin-1
- EC number
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP58006
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Disruption phenotype
Triple knockout mice lacking Sesn1, Sesn2 and Sesn3 do not display an embryonic lethal phenotype since they are born at an expected Mendelian ratio. Moreover, they are not distinguishable from their wild-type littermates. However, their survival at 10 days is dramatically affected. This is associated with a constitutive activation of TORC1 signaling in the liver, heart and skeletal muscle during postnatal fasting, that occurs between birth and suckling.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 15 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000221179 | 1-492 | Sestrin-1 | |||
Sequence: MRLAAASNEAYAASLAVSELLSCHQCGGDRGQDEELGIRIPRPLGHGPSRFIPEKEMLQVGSEDAQMHALFADSFAALGRLDNITLVMVFHPQYLESFLKTQHYLLQMDGPLPLHYRHYIGIMAAARHQCSYLVNLHVSDFLHVGGDPKWLNGLENAPQKLQNLGELNKVLAHRPWLITKEHIEGLLKAEEHSWSLAELVHAVVLLTHYHSLASFTFGCGISPEIHCDGGHTFRPPSVSNYCICDITNGNHSVDEMQVNSAGNASVSDSFFEVEALMEKMRQLQECREEEEASQEEMASRFEMEKRESMFVFSSDDDEVTPARDVSRHFEDTSYGYKDFSRHGMHVPTFRVQDYCWEDHGYSLVNRLYPDVGQLIDEKFHIAYNLTYNTMAMHKDVDTSMLRRAIWNYIHCMFGIRYDDYDYGEINQLLDRSFKVYIKTVVCTPEKVTKRMYDSFWRQFKHSEKVHVNLLLIEARMQAELLYALRAITRYMT | ||||||
Modified residue | 293 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 314 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in heart and also detected in liver and skeletal muscles (at protein level).
Gene expression databases
Interaction
Subunit
Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by leucine (By similarity).
Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925).
Interacts with KEAP1, RBX1 and SQSTM1; in the SQSTM1-dependent autophagic degradation of KEAP1. May interact with PRDX1 (By similarity).
Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925).
Interacts with KEAP1, RBX1 and SQSTM1; in the SQSTM1-dependent autophagic degradation of KEAP1. May interact with PRDX1 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 71-252 | N-terminal domain; may mediate the alkylhydroperoxide reductase activity | ||||
Sequence: FADSFAALGRLDNITLVMVFHPQYLESFLKTQHYLLQMDGPLPLHYRHYIGIMAAARHQCSYLVNLHVSDFLHVGGDPKWLNGLENAPQKLQNLGELNKVLAHRPWLITKEHIEGLLKAEEHSWSLAELVHAVVLLTHYHSLASFTFGCGISPEIHCDGGHTFRPPSVSNYCICDITNGNHS | ||||||
Region | 321-492 | C-terminal domain; mediates TORC1 regulation | ||||
Sequence: PARDVSRHFEDTSYGYKDFSRHGMHVPTFRVQDYCWEDHGYSLVNRLYPDVGQLIDEKFHIAYNLTYNTMAMHKDVDTSMLRRAIWNYIHCMFGIRYDDYDYGEINQLLDRSFKVYIKTVVCTPEKVTKRMYDSFWRQFKHSEKVHVNLLLIEARMQAELLYALRAITRYMT |
Domain
The N-terminal domain may have an alkylhydroperoxide reductase activity.
The C-terminal domain mediates interaction with GATOR2 through which it regulates TORC1 signaling.
Sequence similarities
Belongs to the sestrin family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length492
- Mass (Da)56,637
- Last updated2011-07-27 v3
- Checksum1DF5CF63A45F52F2
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E9PXR3 | E9PXR3_MOUSE | Sesn1 | 551 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 382 | in Ref. 2; AAH55753 | ||||
Sequence: A → P |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AC115297 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC165442 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC055753 EMBL· GenBank· DDBJ | AAH55753.1 EMBL· GenBank· DDBJ | mRNA |