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Protein

Sestrin-1

Gene

Sesn1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Active sitei130Cysteine sulfenic acid (-SOH) intermediateBy similarity1
Binding sitei398Leucine; via carbonyl oxygenBy similarity1
Binding sitei463LeucineBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cellular oxidant detoxification Source: UniProtKB
  • cellular response to amino acid starvation Source: UniProtKB
  • cellular response to amino acid stimulus Source: UniProtKB
  • cellular response to glucose starvation Source: MGI
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of TORC1 signaling Source: UniProtKB
  • reactive oxygen species metabolic process Source: UniProtKB
  • regulation of protein kinase B signaling Source: MGI
  • regulation of response to reactive oxygen species Source: InterPro

Keywordsi

Molecular functionOxidoreductase

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi

Organism-specific databases

MGIiMGI:2155278 Sesn1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
ChainiPRO_00002211791 – 492Sestrin-1Add BLAST492

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei293PhosphoserineBy similarity1
Modified residuei314PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP58006
MaxQBiP58006
PaxDbiP58006
PRIDEiP58006

PTM databases

iPTMnetiP58006
PhosphoSitePlusiP58006

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000038332
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
SMRiP58006
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni71 – 252N-terminal domain; mediates the alkylhydroperoxide reductase activityBy similarityAdd BLAST182
Regioni321 – 492C-terminal domain; mediates TORC1 regulationBy similarityAdd BLAST172
Regioni386 – 389Leucine-bindingBy similarity4

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
InterProiView protein in InterPro
IPR029032 AhpD-like
IPR006730 Sestrin
PANTHERiPTHR12474 PTHR12474, 1 hit
PfamiView protein in Pfam
PF04636 PA26, 1 hit
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)DescriptionActionsGraphical viewLength
Sequence conflicti382A → P in AAH55753 (PubMed:15489334).Curated1

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

Similar proteinsi

Entry informationi

Entry nameiSESN1_MOUSE
AccessioniPrimary (citable) accession number: P58006
Secondary accession number(s): E9QPK0, Q7TNF3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 27, 2011
Last modified: April 25, 2018
This is version 103 of the entry and version 3 of the sequence. See 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

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