Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Sestrin-1

Gene

Sesn1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. May have an 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).By similarity1 Publication

Catalytic activityi

2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei130 – 1301Cysteine sulfenic acid (-SOH) intermediateBy similarity
Binding sitei398 – 3981Leucine; via carbonyl oxygenBy similarity
Binding sitei463 – 4631LeucineBy similarity

GO - Biological processi

  • cellular response to amino acid stimulus Source: UniProtKB
  • negative regulation of TORC1 signaling Source: UniProtKB
  • regulation of protein kinase B signaling Source: MGI
  • regulation of response to reactive oxygen species Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Enzyme and pathway databases

ReactomeiR-MMU-5628897. TP53 Regulates Metabolic Genes.

Names & Taxonomyi

Protein namesi
Recommended name:
Sestrin-1Curated (EC:1.11.1.15By similarity)
Gene namesi
Name:Sesn1Imported
Synonyms:Pa261 Publication, Sest11 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:2155278. Sesn1.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 492492Sestrin-1PRO_0000221179Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei293 – 2931PhosphoserineBy similarity
Modified residuei314 – 3141PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP58006.
MaxQBiP58006.
PaxDbiP58006.
PRIDEiP58006.

PTM databases

iPTMnetiP58006.
PhosphoSiteiP58006.

Expressioni

Tissue specificityi

Highly expressed in heart and also detected in liver and skeletal muscles (at protein level).1 Publication

Gene expression databases

BgeeiP58006.
CleanExiMM_SESN1.
ExpressionAtlasiP58006. baseline and differential.
GenevisibleiP58006. MM.

Interactioni

Subunit structurei

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).By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000097515.

Structurei

3D structure databases

ProteinModelPortaliP58006.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni71 – 252182N-terminal domain; mediates the alkylhydroperoxide reductase activityBy similarityAdd
BLAST
Regioni321 – 492172C-terminal domain; mediates TORC1 regulationBy similarityAdd
BLAST
Regioni386 – 3894Leucine-bindingBy similarity

Domaini

Composed of an N-terminal domain that has an alkylhydroperoxide reductase activity and a C-terminal domain that mediates interaction with GATOR2 through which it regulates TORC1 signaling.By similarity

Sequence similaritiesi

Belongs to the sestrin family.Curated

Phylogenomic databases

eggNOGiKOG3746. Eukaryota.
ENOG410XP7Z. LUCA.
GeneTreeiENSGT00440000040103.
HOGENOMiHOG000232949.
HOVERGENiHBG054648.
InParanoidiP58006.
KOiK10141.

Family and domain databases

Gene3Di1.20.1290.10. 1 hit.
InterProiIPR029032. AhpD-like.
IPR006730. Sestrin.
[Graphical view]
PfamiPF04636. PA26. 1 hit.
[Graphical view]
SUPFAMiSSF69118. SSF69118. 1 hit.

Sequencei

Sequence statusi: Complete.

P58006-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRLAAASNEA YAASLAVSEL LSCHQCGGDR GQDEELGIRI PRPLGHGPSR
60 70 80 90 100
FIPEKEMLQV GSEDAQMHAL FADSFAALGR LDNITLVMVF HPQYLESFLK
110 120 130 140 150
TQHYLLQMDG PLPLHYRHYI GIMAAARHQC SYLVNLHVSD FLHVGGDPKW
160 170 180 190 200
LNGLENAPQK LQNLGELNKV LAHRPWLITK EHIEGLLKAE EHSWSLAELV
210 220 230 240 250
HAVVLLTHYH SLASFTFGCG ISPEIHCDGG HTFRPPSVSN YCICDITNGN
260 270 280 290 300
HSVDEMQVNS AGNASVSDSF FEVEALMEKM RQLQECREEE EASQEEMASR
310 320 330 340 350
FEMEKRESMF VFSSDDDEVT PARDVSRHFE DTSYGYKDFS RHGMHVPTFR
360 370 380 390 400
VQDYCWEDHG YSLVNRLYPD VGQLIDEKFH IAYNLTYNTM AMHKDVDTSM
410 420 430 440 450
LRRAIWNYIH CMFGIRYDDY DYGEINQLLD RSFKVYIKTV VCTPEKVTKR
460 470 480 490
MYDSFWRQFK HSEKVHVNLL LIEARMQAEL LYALRAITRY MT
Length:492
Mass (Da):56,637
Last modified:July 27, 2011 - v3
Checksum:i1DF5CF63A45F52F2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti382 – 3821A → P in AAH55753 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC115297 Genomic DNA. No translation available.
AC165442 Genomic DNA. No translation available.
BC055753 mRNA. Translation: AAH55753.1.
CCDSiCCDS23809.1.
RefSeqiNP_001013388.2. NM_001013370.2.
UniGeneiMm.139418.

Genome annotation databases

EnsembliENSMUST00000041438; ENSMUSP00000043034; ENSMUSG00000038332.
GeneIDi140742.
KEGGimmu:140742.
UCSCiuc007eyf.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC115297 Genomic DNA. No translation available.
AC165442 Genomic DNA. No translation available.
BC055753 mRNA. Translation: AAH55753.1.
CCDSiCCDS23809.1.
RefSeqiNP_001013388.2. NM_001013370.2.
UniGeneiMm.139418.

3D structure databases

ProteinModelPortaliP58006.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000097515.

PTM databases

iPTMnetiP58006.
PhosphoSiteiP58006.

Proteomic databases

EPDiP58006.
MaxQBiP58006.
PaxDbiP58006.
PRIDEiP58006.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000041438; ENSMUSP00000043034; ENSMUSG00000038332.
GeneIDi140742.
KEGGimmu:140742.
UCSCiuc007eyf.2. mouse.

Organism-specific databases

CTDi27244.
MGIiMGI:2155278. Sesn1.

Phylogenomic databases

eggNOGiKOG3746. Eukaryota.
ENOG410XP7Z. LUCA.
GeneTreeiENSGT00440000040103.
HOGENOMiHOG000232949.
HOVERGENiHBG054648.
InParanoidiP58006.
KOiK10141.

Enzyme and pathway databases

ReactomeiR-MMU-5628897. TP53 Regulates Metabolic Genes.

Miscellaneous databases

ChiTaRSiSesn1. mouse.
PROiP58006.
SOURCEiSearch...

Gene expression databases

BgeeiP58006.
CleanExiMM_SESN1.
ExpressionAtlasiP58006. baseline and differential.
GenevisibleiP58006. MM.

Family and domain databases

Gene3Di1.20.1290.10. 1 hit.
InterProiIPR029032. AhpD-like.
IPR006730. Sestrin.
[Graphical view]
PfamiPF04636. PA26. 1 hit.
[Graphical view]
SUPFAMiSSF69118. SSF69118. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain.
  3. "PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse."
    Peeters H., Debeer P., Bairoch A., Wilquet V., Huysmans C., Parthoens E., Fryns J.-P., Gewillig M., Nakamura Y., Niikawa N., Van De Ven W., Devriendt K.
    Hum. Genet. 112:573-580(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: RECONSTRUCTION FROM ESTS.
  4. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney.
  5. "Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling."
    Peng M., Yin N., Li M.O.
    Cell 159:122-133(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RRAGA; RRAGB; RRAGC AND RRAGD, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiSESN1_MOUSE
AccessioniPrimary (citable) accession number: P58006
Secondary accession number(s): E9QPK0, Q7TNF3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 27, 2011
Last modified: July 6, 2016
This is version 93 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.