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Protein

Sestrin-3

Gene

SESN3

Organism
Homo sapiens (Human)
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:25263562). May also regulate the insulin-receptor signaling pathway through activation of TORC2 (By similarity). This metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei398Leucine; via carbonyl oxygenBy similarity1
Binding sitei463LeucineBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Enzyme and pathway databases

BioCyciZFISH:ENSG00000149212-MONOMER.
ReactomeiR-HSA-5628897. TP53 Regulates Metabolic Genes.

Names & Taxonomyi

Protein namesi
Recommended name:
Sestrin-3Curated
Gene namesi
Name:SESN3Imported
Synonyms:SEST31 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:23060. SESN3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: InterPro
  • TORC2 complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi143686.
OpenTargetsiENSG00000149212.
PharmGKBiPA134914983.

Polymorphism and mutation databases

DMDMi20141774.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002211831 – 492Sestrin-3Add BLAST492

Proteomic databases

EPDiP58005.
MaxQBiP58005.
PaxDbiP58005.
PeptideAtlasiP58005.
PRIDEiP58005.

PTM databases

iPTMnetiP58005.
PhosphoSitePlusiP58005.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000149212.
CleanExiHS_SESN3.
ExpressionAtlasiP58005. baseline and differential.
GenevisibleiP58005. HS.

Organism-specific databases

HPAiHPA037935.
HPA037936.

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 (PubMed:25263562, PubMed:26449471). 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 (By similarity).By similarity3 Publications

Protein-protein interaction databases

BioGridi126817. 4 interactors.
DIPiDIP-62045N.
STRINGi9606.ENSP00000441927.

Structurei

3D structure databases

ProteinModelPortaliP58005.
SMRiP58005.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni310 – 492C-terminal domain; mediates TORC1 regulationBy similarityAdd BLAST183
Regioni386 – 389Leucine-bindingBy similarity4

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.
InParanoidiP58005.
KOiK10141.
OMAiDPGFGYK.
OrthoDBiEOG091G0IVA.
PhylomeDBiP58005.
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.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P58005-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNRGGGSPSA AANYLLCTNC RKVLRKDKRI RVSQPLTRGP SAFIPEKEVV
60 70 80 90 100
QANTVDERTN FLVEEYSTSG RLDNITQVMS LHTQYLESFL RSQFYMLRMD
110 120 130 140 150
GPLPLPYRHY IAIMAAARHQ CSYLINMHVD EFLKTGGIAE WLNGLEYVPQ
160 170 180 190 200
RLKNLNEINK LLAHRPWLIT KEHIQKLVKT GENNWSLPEL VHAVVLLAHY
210 220 230 240 250
HALASFVFGS GINPERDPEI SNGFRLISVN NFCVCDLAND NNIENASLSG
260 270 280 290 300
SNFGIVDSLS ELEALMERMK RLQEEREDEE ASQEEMSTRF EKEKKESLFV
310 320 330 340 350
VSGDTFHSFP HSDFEDDMII TSDVSRYIED PGFGYEDFAR RGEEHLPTFR
360 370 380 390 400
AQDYTWENHG FSLVNRLYSD IGHLLDEKFR MVYNLTYNTM ATHEDVDTTM
410 420 430 440 450
LRRALFNYVH CMFGIRYDDY DYGEVNQLLE RSLKVYIKTV TCYPERTTKR
460 470 480 490
MYDSYWRQFK HSEKVHVNLL LMEARMQAEL LYALRAITRH LT
Length:492
Mass (Da):57,291
Last modified:January 23, 2002 - v2
Checksum:i0B165C6BAE5A49CF
GO
Isoform 3 (identifier: P58005-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     313-321: DFEDDMIIT → GAFLHFFAF
     322-492: Missing.

Note: No experimental confirmation available.
Show »
Length:321
Mass (Da):36,614
Checksum:i23AECD8BE05E6C0A
GO
Isoform 2 (identifier: P58005-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-78: Missing.
     115-175: Missing.

Note: No experimental confirmation available.
Show »
Length:353
Mass (Da):41,522
Checksum:i736233C2D8B9644D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05195871R → C.Corresponds to variant rs10160385dbSNPEnsembl.1
Natural variantiVAR_051959227I → T.Corresponds to variant rs11021069dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0545631 – 78Missing in isoform 2. 1 PublicationAdd BLAST78
Alternative sequenceiVSP_054564115 – 175Missing in isoform 2. 1 PublicationAdd BLAST61
Alternative sequenceiVSP_006063313 – 321DFEDDMIIT → GAFLHFFAF in isoform 3. 1 Publication9
Alternative sequenceiVSP_006064322 – 492Missing in isoform 3. 1 PublicationAdd BLAST171

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK096300 mRNA. Translation: BAC04754.1.
AK302366 mRNA. Translation: BAH13685.1.
AP000787 Genomic DNA. No translation available.
BC017296 mRNA. Translation: AAH17296.1.
CCDSiCCDS60938.1. [P58005-4]
CCDS8303.1. [P58005-1]
RefSeqiNP_001258523.1. NM_001271594.1. [P58005-4]
NP_653266.2. NM_144665.3. [P58005-1]
UniGeneiHs.120633.

Genome annotation databases

EnsembliENST00000278499; ENSP00000278499; ENSG00000149212. [P58005-4]
ENST00000416495; ENSP00000407008; ENSG00000149212. [P58005-3]
ENST00000536441; ENSP00000441927; ENSG00000149212. [P58005-1]
GeneIDi143686.
KEGGihsa:143686.
UCSCiuc001pfj.5. human. [P58005-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK096300 mRNA. Translation: BAC04754.1.
AK302366 mRNA. Translation: BAH13685.1.
AP000787 Genomic DNA. No translation available.
BC017296 mRNA. Translation: AAH17296.1.
CCDSiCCDS60938.1. [P58005-4]
CCDS8303.1. [P58005-1]
RefSeqiNP_001258523.1. NM_001271594.1. [P58005-4]
NP_653266.2. NM_144665.3. [P58005-1]
UniGeneiHs.120633.

3D structure databases

ProteinModelPortaliP58005.
SMRiP58005.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126817. 4 interactors.
DIPiDIP-62045N.
STRINGi9606.ENSP00000441927.

PTM databases

iPTMnetiP58005.
PhosphoSitePlusiP58005.

Polymorphism and mutation databases

DMDMi20141774.

Proteomic databases

EPDiP58005.
MaxQBiP58005.
PaxDbiP58005.
PeptideAtlasiP58005.
PRIDEiP58005.

Protocols and materials databases

DNASUi143686.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000278499; ENSP00000278499; ENSG00000149212. [P58005-4]
ENST00000416495; ENSP00000407008; ENSG00000149212. [P58005-3]
ENST00000536441; ENSP00000441927; ENSG00000149212. [P58005-1]
GeneIDi143686.
KEGGihsa:143686.
UCSCiuc001pfj.5. human. [P58005-1]

Organism-specific databases

CTDi143686.
DisGeNETi143686.
GeneCardsiSESN3.
HGNCiHGNC:23060. SESN3.
HPAiHPA037935.
HPA037936.
MIMi607768. gene.
neXtProtiNX_P58005.
OpenTargetsiENSG00000149212.
PharmGKBiPA134914983.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3746. Eukaryota.
ENOG410XP7Z. LUCA.
GeneTreeiENSGT00440000040103.
HOGENOMiHOG000232949.
HOVERGENiHBG054648.
InParanoidiP58005.
KOiK10141.
OMAiDPGFGYK.
OrthoDBiEOG091G0IVA.
PhylomeDBiP58005.
TreeFamiTF314230.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000149212-MONOMER.
ReactomeiR-HSA-5628897. TP53 Regulates Metabolic Genes.

Miscellaneous databases

GenomeRNAii143686.
PROiP58005.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149212.
CleanExiHS_SESN3.
ExpressionAtlasiP58005. baseline and differential.
GenevisibleiP58005. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P58005
Secondary accession number(s): B7Z7P9, Q96AD1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: January 23, 2002
Last modified: November 30, 2016
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.