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Aliases for SESN1 Gene

Aliases for SESN1 Gene

  • Sestrin 1 2 3 5
  • SEST1 3 4
  • PA26 3 4
  • P53 Regulated PA26 Nuclear Protein 3
  • P53-Regulated Protein PA26 4
  • P53 Activated Gene 26 3
  • EC 1.11.1.15 4
  • Sestrin-1 3

External Ids for SESN1 Gene

Previous GeneCards Identifiers for SESN1 Gene

  • GC06M109307
  • GC06M109353
  • GC06M109414
  • GC06M106874

Summaries for SESN1 Gene

Entrez Gene Summary for SESN1 Gene

  • This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the cellular response to DNA damage and oxidative stress. The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded protein also plays a critical role in antioxidant defense by regenerating overoxidized peroxiredoxins, and the expression of this gene is a potential marker for exposure to radiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

GeneCards Summary for SESN1 Gene

SESN1 (Sestrin 1) is a Protein Coding gene. Among its related pathways are Gene Expression and Direct p53 effectors. An important paralog of this gene is SESN3.

UniProtKB/Swiss-Prot for SESN1 Gene

  • 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:25263562, PubMed:26449471). This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). 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 (PubMed:23274085). May have an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (By similarity). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (By similarity).

Gene Wiki entry for SESN1 Gene

Additional gene information for SESN1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SESN1 Gene

Genomics for SESN1 Gene

GeneHancer (GH) Regulatory Elements for SESN1 Gene

Promoters and enhancers for SESN1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J109092 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 650.7 +0.3 284 5.1 PKNOX1 SMAD1 FOXA2 ARNT ARID4B SIN3A FEZF1 DMAP1 ZNF2 ZBTB7B SESN1 CEP57L1 ZBTB24 ENSG00000271730 GC06M109088
GH06J109006 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 650.2 +85.7 85727 5 PKNOX1 FOXA2 ARID4B SIN3A FEZF1 ZNF2 IRF4 YY1 POLR2B ZNF213 GC06P109009 SESN1 RNU6-653P ARMC2-AS1 ENSG00000271730
GH06J108555 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 4 +533.2 533157 11.9 FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 ZNF143 ZNF548 SP3 NFYC FOXO3 PIR59886 ZBTB24 SMPD2 ENSG00000227072 LOC100506224 ENSG00000230248 ENSG00000233908 CD164 RNU6-653P
GH06J109481 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 2.2 -388.6 -388587 3.1 ATF1 ARID4B SIN3A DMAP1 YY1 ETS1 GLIS2 ZNF213 ELK1 ZNF207 ZBTB24 LOC105377935 SMPD2 ENSG00000260273 PPIL6 MICAL1 SESN1 AK9
GH06J108871 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 2.1 +221.1 221113 4.1 BMI1 BATF ZIC2 IRF4 NFATC1 ATF7 ETV6 BCLAF1 IKZF2 RUNX3 ARMC2 RNU6-653P ARMC2-AS1 ZBTB24 SESN1 RPS12P13 ATP5MFP2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SESN1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SESN1 gene promoter:
  • Sp1
  • POU3F2 (N-Oct-5b)
  • POU3F2 (N-Oct-5a)
  • POU3F2
  • Pax-4a
  • Sox5
  • FOXO4
  • Pax-5
  • POU2F1a

Genomic Locations for SESN1 Gene

Genomic Locations for SESN1 Gene
chr6:108,986,437-109,094,819
(GRCh38/hg38)
Size:
108,383 bases
Orientation:
Minus strand
chr6:109,307,640-109,416,022
(GRCh37/hg19)
Size:
108,383 bases
Orientation:
Minus strand

Genomic View for SESN1 Gene

Genes around SESN1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SESN1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SESN1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SESN1 Gene

Proteins for SESN1 Gene

  • Protein details for SESN1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6P5-SESN1_HUMAN
    Recommended name:
    Sestrin-1
    Protein Accession:
    Q9Y6P5
    Secondary Accessions:
    • Q2M2B7
    • Q5T316
    • Q9NV00
    • Q9UPD5
    • Q9Y6P6

    Protein attributes for SESN1 Gene

    Size:
    492 amino acids
    Molecular mass:
    56557 Da
    Quaternary structure:
    • Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively 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 KEAP1, RBX1 and SQSTM1; in the SQSTM1-dependent autophagic degradation of KEAP1 (PubMed:23274085). May interact with PRDX1 (PubMed:15105503).

    Alternative splice isoforms for SESN1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SESN1 Gene

Post-translational modifications for SESN1 Gene

  • Ubiquitination at isoforms=2, 3337
  • Modification sites at PhosphoSitePlus

Other Protein References for SESN1 Gene

No data available for DME Specific Peptides for SESN1 Gene

Domains & Families for SESN1 Gene

Gene Families for SESN1 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for SESN1 Gene

Suggested Antigen Peptide Sequences for SESN1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9Y6P5

UniProtKB/Swiss-Prot:

SESN1_HUMAN :
  • 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.
  • Belongs to the sestrin family.
Domain:
  • 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.
Family:
  • Belongs to the sestrin family.
genes like me logo Genes that share domains with SESN1: view

Function for SESN1 Gene

Molecular function for SESN1 Gene

UniProtKB/Swiss-Prot Function:
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:25263562, PubMed:26449471). This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). 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 (PubMed:23274085). May have an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (By similarity). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
2 R-SH + ROOH = R-S-S-R + H(2)O + ROH.
UniProtKB/Swiss-Prot Induction:
Isoform T2 and isoform T3 are induced by genotoxic stress (UV, gamma-irradiation and cytotoxic drugs) in a p53/TP53-dependent manner. Isoform T1 is not induced by p53/TP53.

Enzyme Numbers (IUBMB) for SESN1 Gene

Phenotypes From GWAS Catalog for SESN1 Gene

Gene Ontology (GO) - Molecular Function for SESN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15105503
GO:0016491 oxidoreductase activity IEA --
GO:0016684 oxidoreductase activity, acting on peroxide as acceptor IBA --
GO:0051920 peroxiredoxin activity IEA --
GO:0070728 leucine binding IDA 26449471
genes like me logo Genes that share ontologies with SESN1: view
genes like me logo Genes that share phenotypes with SESN1: view

Animal Models for SESN1 Gene

MGI Knock Outs for SESN1:
  • Sesn1 Sesn1<tm1a(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for SESN1 Gene

miRTarBase miRNAs that target SESN1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SESN1

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SESN1 Gene

Localization for SESN1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SESN1 Gene

Nucleus. 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 SESN1 gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoli fibrillar center (3)
  • Nucleus (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SESN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001650 fibrillar center IDA --
GO:0005634 nucleus IDA 9926927
GO:0005737 cytoplasm IEA,IDA 15105503
GO:0005829 cytosol TAS --
GO:0031932 COLOCALIZES_WITH TORC2 complex IBA --
genes like me logo Genes that share ontologies with SESN1: view

Pathways & Interactions for SESN1 Gene

genes like me logo Genes that share pathways with SESN1: view

Gene Ontology (GO) - Biological Process for SESN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016239 positive regulation of macroautophagy IBA --
GO:0034198 cellular response to amino acid starvation IMP 25263562
GO:0042149 cellular response to glucose starvation IMP 25263562
GO:0055114 oxidation-reduction process IEA --
GO:0071230 cellular response to amino acid stimulus IBA --
genes like me logo Genes that share ontologies with SESN1: view

No data available for SIGNOR curated interactions for SESN1 Gene

Drugs & Compounds for SESN1 Gene

No Compound Related Data Available

Transcripts for SESN1 Gene

mRNA/cDNA for SESN1 Gene

Unigene Clusters for SESN1 Gene

Sestrin 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SESN1

Alternative Splicing Database (ASD) splice patterns (SP) for SESN1 Gene

No ASD Table

Relevant External Links for SESN1 Gene

GeneLoc Exon Structure for
SESN1
ECgene alternative splicing isoforms for
SESN1

Expression for SESN1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SESN1 Gene

mRNA differential expression in normal tissues according to GTEx for SESN1 Gene

This gene is overexpressed in Muscle - Skeletal (x5.5).

Protein differential expression in normal tissues from HIPED for SESN1 Gene

This gene is overexpressed in Testis (35.9) and Serum (13.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SESN1 Gene



NURSA nuclear receptor signaling pathways regulating expression of SESN1 Gene:

SESN1

SOURCE GeneReport for Unigene cluster for SESN1 Gene:

Hs.591336

mRNA Expression by UniProt/SwissProt for SESN1 Gene:

Q9Y6P5-SESN1_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for SESN1 Gene

  • Lung(4.3)
  • Nervous system(3.9)
  • Muscle(2.7)
  • Intestine(2.2)
genes like me logo Genes that share expression patterns with SESN1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SESN1 Gene

Orthologs for SESN1 Gene

This gene was present in the common ancestor of animals.

Orthologs for SESN1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SESN1 34 33
  • 99.76 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SESN1 34 33
  • 95.72 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SESN1 34 33
  • 93.28 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SESN1 34
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Sesn1 16 34 33
  • 88.87 (n)
rat
(Rattus norvegicus)
Mammalia Sesn1 33
  • 86.67 (n)
oppossum
(Monodelphis domestica)
Mammalia SESN1 34
  • 85 (a)
OneToOne
chicken
(Gallus gallus)
Aves SESN1 34 33
  • 77.05 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SESN1 34
  • 80 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sesn1 33
  • 76.34 (n)
African clawed frog
(Xenopus laevis)
Amphibia sesn1-A 33
zebrafish
(Danio rerio)
Actinopterygii sesn1 34 33
  • 70.82 (n)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.10916 33
fruit fly
(Drosophila melanogaster)
Insecta Sesn 34
  • 41 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sesn-1 34
  • 24 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3472 34
  • 33 (a)
OneToMany
Species where no ortholog for SESN1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • 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 SESN1 Gene

ENSEMBL:
Gene Tree for SESN1 (if available)
TreeFam:
Gene Tree for SESN1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SESN1: view image

Paralogs for SESN1 Gene

Paralogs for SESN1 Gene

(2) SIMAP similar genes for SESN1 Gene using alignment to 1 proteins:

  • SESN1_HUMAN

Pseudogenes.org Pseudogenes for SESN1 Gene

genes like me logo Genes that share paralogs with SESN1: view

Variants for SESN1 Gene

Sequence variations from dbSNP and Humsavar for SESN1 Gene

SNP ID Clin Chr 06 pos Variation AA Info Type
rs1000007652 -- 109,066,651(-) A/G genic_upstream_transcript_variant, intron_variant
rs1000024959 -- 109,020,925(-) A/C genic_upstream_transcript_variant, intron_variant
rs1000166344 -- 109,042,763(-) GG/GGG genic_upstream_transcript_variant, intron_variant
rs1000166896 -- 109,051,822(-) A/G genic_upstream_transcript_variant, intron_variant
rs1000167234 -- 109,090,434(-) A/G genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for SESN1 Gene

Variant ID Type Subtype PubMed ID
nsv1017230 CNV gain 25217958
nsv1117662 CNV deletion 24896259
nsv830768 CNV gain 17160897
nsv950492 CNV duplication 24416366

Variation tolerance for SESN1 Gene

Residual Variation Intolerance Score: 5.83% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.22; 69.96% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SESN1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SESN1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SESN1 Gene

Disorders for SESN1 Gene

Additional Disease Information for SESN1

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

No disorders were found for SESN1 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for SESN1 Gene

Publications for SESN1 Gene

  1. PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes. (PMID: 9926927) Velasco-Miguel S … Kley N (Oncogene 1999) 2 3 4 22 58
  2. 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) 3 4 22 58
  3. Sestrin2 is a leucine sensor for the mTORC1 pathway. (PMID: 26449471) Wolfson RL … Sabatini DM (Science (New York, N.Y.) 2016) 3 4 58
  4. 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 58
  5. Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. (PMID: 23274085) Bae SH … Rhee SG (Cell metabolism 2013) 3 4 58

Products for SESN1 Gene

Sources for SESN1 Gene

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