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Protein

Sestrin-3

Gene

Sesn3

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

Functioni

May function as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway (PubMed:25259925). May also regulate the insulin-receptor signaling pathway through activation of TORC2 (PubMed:25377878). This metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity).By similarity2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei398 – 3981Leucine; via carbonyl oxygenBy similarity
Binding sitei463 – 4631LeucineBy similarity

GO - Molecular functioni

GO - Biological processi

  • cellular response to amino acid stimulus Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • negative regulation of TORC1 signaling Source: UniProtKB
  • regulation of insulin receptor signaling pathway Source: UniProtKB
  • regulation of protein kinase B signaling Source: MGI
  • regulation of response to reactive oxygen species Source: InterPro
  • response to insulin Source: UniProtKB
  • TORC2 signaling Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Names & Taxonomyi

Protein namesi
Recommended name:
Sestrin-3Curated
Gene namesi
Name:Sesn3Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1922997. Sesn3.

Subcellular locationi

  • Cytoplasm 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Liver-specific Sesn3 knockout mice display insulin resistance and glucose intolerance (PubMed:25377878). Sesn2 and Sesn3 double knockout mice display insulin resistance and glucose intolerance (PubMed:22958918). 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 littermate. 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 (PubMed:25259925).3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 492492Sestrin-3PRO_0000221184Add
BLAST

Proteomic databases

MaxQBiQ9CYP7.
PaxDbiQ9CYP7.
PRIDEiQ9CYP7.

PTM databases

iPTMnetiQ9CYP7.
PhosphoSiteiQ9CYP7.

Expressioni

Tissue specificityi

Detected in liver and skeletal muscles.1 Publication

Gene expression databases

BgeeiENSMUSG00000032009.
CleanExiMM_SESN3.
ExpressionAtlasiQ9CYP7. baseline and differential.
GenevisibleiQ9CYP7. MM.

Interactioni

Subunit structurei

Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is not 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 the TORC2 complex; through RICTOR (PubMed:25377878).By similarity2 Publications

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000034507.

Structurei

3D structure databases

ProteinModelPortaliQ9CYP7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni310 – 492183C-terminal domain; mediates TORC1 regulationBy similarityAdd
BLAST
Regioni386 – 3894Leucine-bindingBy similarity

Domaini

The C-terminal domain may mediate interaction with GATOR2 and regulation of TORC1 signaling.By similarity

Sequence similaritiesi

Belongs to the sestrin family.Curated

Phylogenomic databases

eggNOGiKOG3746. Eukaryota.
ENOG410XP7Z. LUCA.
GeneTreeiENSGT00440000040103.
HOGENOMiHOG000232949.
HOVERGENiHBG054648.
InParanoidiQ9CYP7.
KOiK10141.
OMAiDPGFGYK.
OrthoDBiEOG091G0IVA.
PhylomeDBiQ9CYP7.
TreeFamiTF314230.

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.

Q9CYP7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNRGGSSASA SANYLLCTNC RKVLRKDKRI RVSQPLTRGP SAFIPEKEVV
60 70 80 90 100
QANTADERTN FLVEEYSTSG RLDNITQVMS LHTQYLESFL RSQFYMLRMD
110 120 130 140 150
GPLPLPDRHY IAIMAAARHQ CSYLINMHVD EFLKTGGIAE WLNGLEYVPQ
160 170 180 190 200
RLRNLNEINK LLAHRPWLIT KEHIQKLVKT GENNWSLPEL VHAVVLLAHY
210 220 230 240 250
HALASFVFGS GINPERDPGI ANGFRLISVS SFCVCDLAND NSIENTSLAG
260 270 280 290 300
SNFGIVDSLG ELEALMERMK RLQEDREDDE TTREEMTTRF EKEKKESLFV
310 320 330 340 350
VPGETLHAFP HSDFEDDVIV TADVSRYIED PSFGYEDFAR RGEEHLPTFR
360 370 380 390 400
AQDYTWENHG FSLVNRLYSD IGHLLDEKFR MVYNLTYNTM ATHEDVDTTT
410 420 430 440 450
LRRALFNYVH CMFGIRYDDY DYGEVNQLLE RSLKVYIKTV TCYPERTTKR
460 470 480 490
MYDSYWRQFT HSEKVHVNLL LMEARMQAEL LYALRAITRH LT
Length:492
Mass (Da):57,021
Last modified:April 27, 2001 - v1
Checksum:i8E8AD9CB45656827
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK017464 mRNA. Translation: BAB30755.1.
AK155398 mRNA. Translation: BAE33242.1.
CCDSiCCDS22820.1.
RefSeqiNP_084537.2. NM_030261.4.
UniGeneiMm.325126.
Mm.439776.

Genome annotation databases

EnsembliENSMUST00000208222; ENSMUSP00000146362; ENSMUSG00000032009.
GeneIDi75747.
KEGGimmu:75747.
UCSCiuc009oej.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK017464 mRNA. Translation: BAB30755.1.
AK155398 mRNA. Translation: BAE33242.1.
CCDSiCCDS22820.1.
RefSeqiNP_084537.2. NM_030261.4.
UniGeneiMm.325126.
Mm.439776.

3D structure databases

ProteinModelPortaliQ9CYP7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000034507.

PTM databases

iPTMnetiQ9CYP7.
PhosphoSiteiQ9CYP7.

Proteomic databases

MaxQBiQ9CYP7.
PaxDbiQ9CYP7.
PRIDEiQ9CYP7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000208222; ENSMUSP00000146362; ENSMUSG00000032009.
GeneIDi75747.
KEGGimmu:75747.
UCSCiuc009oej.1. mouse.

Organism-specific databases

CTDi143686.
MGIiMGI:1922997. Sesn3.

Phylogenomic databases

eggNOGiKOG3746. Eukaryota.
ENOG410XP7Z. LUCA.
GeneTreeiENSGT00440000040103.
HOGENOMiHOG000232949.
HOVERGENiHBG054648.
InParanoidiQ9CYP7.
KOiK10141.
OMAiDPGFGYK.
OrthoDBiEOG091G0IVA.
PhylomeDBiQ9CYP7.
TreeFamiTF314230.

Miscellaneous databases

ChiTaRSiSesn3. mouse.
PROiQ9CYP7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032009.
CleanExiMM_SESN3.
ExpressionAtlasiQ9CYP7. baseline and differential.
GenevisibleiQ9CYP7. 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...

Entry informationi

Entry nameiSESN3_MOUSE
AccessioniPrimary (citable) accession number: Q9CYP7
Secondary accession number(s): Q3U2A0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 27, 2001
Last modified: September 7, 2016
This is version 96 of the entry and version 1 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.