This gene encodes a member of the sestrin family of stress-induced proteins. The encoded protein reduces the levels of intracellular reactive oxygen species induced by activated Ras downstream of RAC-alpha serine/threonine-protein kinase (Akt) and FoxO transcription factor. The protein is required for normal regulation of blood glucose, insulin resistance and plays a role in li... See more...

Aliases for SESN3 Gene

Aliases for SESN3 Gene

  • Sestrin 3 2 3 5
  • Sestrin-3 3 4
  • SEST3 3 4

External Ids for SESN3 Gene

Previous GeneCards Identifiers for SESN3 Gene

  • GC11M095090
  • GC11M094594
  • GC11M094545
  • GC11M094906
  • GC11M090971

Summaries for SESN3 Gene

Entrez Gene Summary for SESN3 Gene

  • This gene encodes a member of the sestrin family of stress-induced proteins. The encoded protein reduces the levels of intracellular reactive oxygen species induced by activated Ras downstream of RAC-alpha serine/threonine-protein kinase (Akt) and FoxO transcription factor. The protein is required for normal regulation of blood glucose, insulin resistance and plays a role in lipid storage in obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

GeneCards Summary for SESN3 Gene

SESN3 (Sestrin 3) is a Protein Coding gene. Among its related pathways are Regulation of TP53 Activity and DNA Damage Response. An important paralog of this gene is SESN1.

UniProtKB/Swiss-Prot Summary for SESN3 Gene

  • 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).

Additional gene information for SESN3 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SESN3 Gene

Genomics for SESN3 Gene

GeneHancer (GH) Regulatory Elements for SESN3 Gene

Promoters and enhancers for SESN3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SESN3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SESN3 gene promoter:
  • CBF(2)
  • CBF-A
  • CBF-B
  • CP1A
  • NF-Y
  • NF-YA
  • NF-YB
  • SREBP-1c
  • USF-1
  • USF1

Genomic Locations for SESN3 Gene

Genomic Locations for SESN3 Gene
chr11:95,165,513-95,232,541
(GRCh38/hg38)
Size:
67,029 bases
Orientation:
Minus strand
chr11:94,898,704-94,965,705
(GRCh37/hg19)
Size:
67,002 bases
Orientation:
Minus strand

Genomic View for SESN3 Gene

Genes around SESN3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SESN3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SESN3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SESN3 Gene

Proteins for SESN3 Gene

  • Protein details for SESN3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P58005-SESN3_HUMAN
    Recommended name:
    Sestrin-3
    Protein Accession:
    P58005
    Secondary Accessions:
    • B7Z7P9
    • Q96AD1

    Protein attributes for SESN3 Gene

    Size:
    492 amino acids
    Molecular mass:
    57291 Da
    Quaternary structure:
    • 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).

    Alternative splice isoforms for SESN3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SESN3 Gene

Post-translational modifications for SESN3 Gene

  • Ubiquitination at Lys378
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for SESN3 Gene

Domains & Families for SESN3 Gene

Gene Families for SESN3 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for SESN3 Gene

Suggested Antigen Peptide Sequences for SESN3 Gene

GenScript: Design optimal peptide antigens:
  • Sestrin-3 (SESN3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P58005

UniProtKB/Swiss-Prot:

SESN3_HUMAN :
  • The C-terminal domain may mediate interaction with GATOR2 and regulation of TORC1 signaling.
  • Belongs to the sestrin family.
Domain:
  • The C-terminal domain may mediate interaction with GATOR2 and regulation of TORC1 signaling.
Family:
  • Belongs to the sestrin family.
genes like me logo Genes that share domains with SESN3: view

Function for SESN3 Gene

Molecular function for SESN3 Gene

UniProtKB/Swiss-Prot Function:
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).

Phenotypes From GWAS Catalog for SESN3 Gene

Gene Ontology (GO) - Molecular Function for SESN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 25263562
GO:0016491 oxidoreductase activity IEA --
GO:0016684 oxidoreductase activity, acting on peroxide as acceptor IBA 21873635
GO:0070728 leucine binding IBA 21873635
genes like me logo Genes that share ontologies with SESN3: view
genes like me logo Genes that share phenotypes with SESN3: view

Animal Models for SESN3 Gene

MGI Knock Outs for SESN3:
  • Sesn3 Sesn3<tm1a(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for SESN3 Gene

miRTarBase miRNAs that target SESN3

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SESN3

Clone Products

  • Addgene plasmids for SESN3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SESN3 Gene

Localization for SESN3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SESN3 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SESN3 gene
Compartment Confidence
mitochondrion 3
nucleus 2
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SESN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IDA,IBA 25263562
GO:0031932 colocalizes_with TORC2 complex IBA 21873635
GO:0061700 colocalizes_with GATOR2 complex IDA 25263562
genes like me logo Genes that share ontologies with SESN3: view

Pathways & Interactions for SESN3 Gene

genes like me logo Genes that share pathways with SESN3: view

Pathways by source for SESN3 Gene

Gene Ontology (GO) - Biological Process for SESN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016239 positive regulation of macroautophagy IBA 21873635
GO:0032868 response to insulin IEA --
GO:0034198 cellular response to amino acid starvation IMP 25263562
GO:0038203 TORC2 signaling IEA --
GO:0042149 cellular response to glucose starvation IMP 25263562
genes like me logo Genes that share ontologies with SESN3: view

No data available for SIGNOR curated interactions for SESN3 Gene

Drugs & Compounds for SESN3 Gene

No Compound Related Data Available

Transcripts for SESN3 Gene

mRNA/cDNA for SESN3 Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SESN3

Clone Products

  • Addgene plasmids for SESN3

Alternative Splicing Database (ASD) splice patterns (SP) for SESN3 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13
SP1: - -
SP2: - -
SP3: - - -
SP4: -

Relevant External Links for SESN3 Gene

GeneLoc Exon Structure for
SESN3
ECgene alternative splicing isoforms for
SESN3

Expression for SESN3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SESN3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SESN3 Gene

This gene is overexpressed in Liver, secretome (49.9) and Gallbladder (7.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SESN3 Gene



NURSA nuclear receptor signaling pathways regulating expression of SESN3 Gene:

SESN3

SOURCE GeneReport for Unigene cluster for SESN3 Gene:

Hs.120633

mRNA Expression by UniProt/SwissProt for SESN3 Gene:

P58005-SESN3_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for SESN3 Gene

  • Lung(4.3)
  • Nervous system(4)
genes like me logo Genes that share expression patterns with SESN3: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SESN3 Gene

Orthologs for SESN3 Gene

This gene was present in the common ancestor of animals.

Orthologs for SESN3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SESN3 33 32
  • 99.12 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SESN3 33 32
  • 94.85 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SESN3 33 32
  • 94.04 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SESN3 33
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Sesn3 17 33 32
  • 88.48 (n)
rat
(Rattus norvegicus)
Mammalia Sesn3 32
  • 87.53 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SESN3 33
  • 85 (a)
OneToOne
chicken
(Gallus gallus)
Aves SESN3 33 32
  • 84.43 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SESN3 33
  • 87 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sesn3 32
  • 75.9 (n)
Str.2876 32
African clawed frog
(Xenopus laevis)
Amphibia Xl.12344 32
zebrafish
(Danio rerio)
Actinopterygii sesn3 33 32
  • 67.18 (n)
OneToOne
Dr.5129 32
fruit fly
(Drosophila melanogaster)
Insecta Sesn 33 32
  • 54.79 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007169 32
  • 52.67 (n)
worm
(Caenorhabditis elegans)
Secernentea sesn-1 33 32
  • 45.84 (n)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3472 33
  • 30 (a)
OneToMany
Species where no ortholog for SESN3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SESN3 Gene

ENSEMBL:
Gene Tree for SESN3 (if available)
TreeFam:
Gene Tree for SESN3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SESN3: view image

Paralogs for SESN3 Gene

Paralogs for SESN3 Gene

(2) SIMAP similar genes for SESN3 Gene using alignment to 3 proteins:

  • SESN3_HUMAN
  • B7Z7P9_HUMAN
  • F5H1K7_HUMAN
genes like me logo Genes that share paralogs with SESN3: view

Variants for SESN3 Gene

Sequence variations from dbSNP and Humsavar for SESN3 Gene

SNP ID Clin Chr 11 pos Variation AA Info Type
rs1320887348 uncertain-significance, not provided 95,191,585(-) G/A/C 5_prime_UTR_variant, coding_sequence_variant, missense_variant
rs1000054643 -- 95,188,979(-) A/G intron_variant
rs1000092960 -- 95,208,295(-) C/G/T intron_variant
rs1000118201 -- 95,186,321(-) AAAACAAAACAAAACAAAACAAAA/AAAACAAAACAAAA/AAAACAAAACAAAACAAAA/AAAACAAAACAAAACAAAACAAAACAAAA intron_variant
rs1000146597 -- 95,234,281(-) C/T upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for SESN3 Gene

Variant ID Type Subtype PubMed ID
esv2677596 CNV deletion 23128226
esv3548184 CNV deletion 23714750
esv3627339 CNV loss 21293372
esv3627341 CNV loss 21293372
esv989063 CNV deletion 20482838
esv994857 CNV loss 20482838
nsv1044269 CNV gain 25217958
nsv1050445 CNV gain 25217958
nsv447 CNV deletion 18451855

Variation tolerance for SESN3 Gene

Residual Variation Intolerance Score: 22.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.02; 20.98% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SESN3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SESN3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SESN3 Gene

Disorders for SESN3 Gene

Additional Disease Information for SESN3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for SESN3 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for SESN3 Gene

Publications for SESN3 Gene

  1. PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse. (PMID: 12607115) Peeters H … Devriendt K (Human genetics 2003) 2 3 4 56
  2. Sestrin2 is a leucine sensor for the mTORC1 pathway. (PMID: 26449471) Wolfson RL … Sabatini DM (Science (New York, N.Y.) 2016) 3 4 56
  3. The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. (PMID: 25263562) Chantranupong L … Sabatini DM (Cell reports 2014) 3 4 56
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 43 56
  5. Repression of sestrin family genes contributes to oncogenic Ras-induced reactive oxygen species up-regulation and genetic instability. (PMID: 17510393) Kopnin PB … Chumakov PM (Cancer research 2007) 3 23 56

Products for SESN3 Gene

Sources for SESN3 Gene