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Protein

Sestrin-3

Gene

SESN3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • leucine binding Source: GO_Central
  • oxidoreductase activity, acting on peroxide as acceptor Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase

Enzyme and pathway databases

ReactomeiR-HSA-5628897 TP53 Regulates Metabolic Genes
SIGNORiP58005

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

EuPathDBiHostDB:ENSG00000149212.11
HGNCiHGNC:23060 SESN3
MIMi607768 gene
neXtProtiNX_P58005

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

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
ProteomicsDBi57044
57046 [P58005-3]

PTM databases

iPTMnetiP58005
PhosphoSitePlusiP58005

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000149212 Expressed in 210 organ(s), highest expression level in sperm
CleanExiHS_SESN3
ExpressionAtlasiP58005 baseline and differential
GenevisibleiP58005 HS

Organism-specific databases

HPAiHPA037935

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

Binary interactionsi

WithEntry#Exp.IntActNotes
WDR24Q96S153EBI-16179942,EBI-746424

Protein-protein interaction databases

BioGridi126817, 4 interactors
DIPiDIP-62045N
IntActiP58005, 3 interactors
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
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

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H1K7F5H1K7_HUMAN
Sestrin-3
SESN3
70Annotation score:
A0A0U1RR17A0A0U1RR17_HUMAN
Sestrin-3
SESN3
83Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05195871R → C. Corresponds to variant dbSNP:rs10160385Ensembl.1
Natural variantiVAR_051959227I → T. Corresponds to variant dbSNP:rs11021069Ensembl.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

Similar proteinsi

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
IntActiP58005, 3 interactors
STRINGi9606.ENSP00000441927

PTM databases

iPTMnetiP58005
PhosphoSitePlusiP58005

Polymorphism and mutation databases

DMDMi20141774

Proteomic databases

EPDiP58005
MaxQBiP58005
PaxDbiP58005
PeptideAtlasiP58005
PRIDEiP58005
ProteomicsDBi57044
57046 [P58005-3]

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
EuPathDBiHostDB:ENSG00000149212.11
GeneCardsiSESN3
HGNCiHGNC:23060 SESN3
HPAiHPA037935
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

ReactomeiR-HSA-5628897 TP53 Regulates Metabolic Genes
SIGNORiP58005

Miscellaneous databases

ChiTaRSiSESN3 human
GenomeRNAii143686
PROiPR:P58005
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149212 Expressed in 210 organ(s), highest expression level in sperm
CleanExiHS_SESN3
ExpressionAtlasiP58005 baseline and differential
GenevisibleiP58005 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiSESN3_HUMAN
AccessioniPrimary (citable) accession number: P58005
Secondary accession number(s): B7Z7P9, Q96AD1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: January 23, 2002
Last modified: November 7, 2018
This is version 132 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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