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    SESN1 sestrin 1 [ Homo sapiens (human) ]

    Gene ID: 27244, updated on 2-Nov-2024

    Summary

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    Official Symbol
    SESN1provided by HGNC
    Official Full Name
    sestrin 1provided by HGNC
    Primary source
    HGNC:HGNC:21595
    See related
    Ensembl:ENSG00000080546 MIM:606103; AllianceGenome:HGNC:21595
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PA26; SEST1
    Summary
    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]
    Expression
    Ubiquitous expression in testis (RPKM 26.4), ovary (RPKM 22.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SESN1 in Genome Data Viewer
    Location:
    6q21
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (108984309..109094846, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (110161725..110272953, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (109305512..109416049, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene armadillo repeat containing 2 Neighboring gene ATP synthase subunit f, mitochondrial-like Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:109241738-109242648 Neighboring gene ARMC2 antisense RNA 1 Neighboring gene ATP synthase membrane subunit f pseudogene 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:109266564-109267120 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:109272427-109272928 Neighboring gene MPRA-validated peak6016 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17456 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24918 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24919 Neighboring gene Sharpr-MPRA regulatory region 5156 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:109367051-109367618 Neighboring gene RNA, U6 small nuclear 653, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24920 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17457 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24921 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:109422661-109423052 Neighboring gene centrosomal protein 57 like 1 Neighboring gene coiled-coil domain containing 162, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:109515122-109515622 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:109562791-109563990 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:109572150-109572928 Neighboring gene uncharacterized LOC124901374

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Gene regulation by temperature-sensitive p53 mutants: identification of p53 response genes. Buckbinder L, et al. Proc Natl Acad Sci U S A, 1994 Oct 25. PMID 7938006, Free PMC Article
    2. Suppressed expression of non-DSB repair genes inhibits gamma-radiation-induced cytogenetic repair and cell cycle arrest. Zhang Y, et al. DNA Repair (Amst), 2008 Nov 1. PMID 18703169
    3. SESN1 attenuates the Ox‑LDL‑induced inflammation, apoptosis and endothelial‑mesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling. Gao F, et al. Mol Med Rep, 2022 May. PMID 35293601, Free PMC Article
    4. Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes. Sanz B, et al. Int J Environ Res Public Health, 2022 Jan 19. PMID 35162104, Free PMC Article
    5. Regulation of protein synthesis by ionizing radiation. Braunstein S, et al. Mol Cell Biol, 2009 Nov. PMID 19704005, Free PMC Article

    See all (40) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. IGF2BP3 stabilizes SESN1 mRNA to mitigate oxidized low-density lipoprotein-induced oxidative stress and endothelial dysfunction in human umbilical vein endothelial cells by activating Nrf2 signaling.
      Title: IGF2BP3 stabilizes SESN1 mRNA to mitigate oxidized low-density lipoprotein-induced oxidative stress and endothelial dysfunction in human umbilical vein endothelial cells by activating Nrf2 signaling.
    2. Metformin Caused Radiosensitivity of Breast Cancer Cells through the Expression Modulation of miR-21-5p/SESN1axis.
      Title: Metformin Caused Radiosensitivity of Breast Cancer Cells through the Expression Modulation of miR-21-5p/SESN1axis.
    3. SESN1 is a FOXO3 effector that counteracts human skeletal muscle ageing.
      Title: SESN1 is a FOXO3 effector that counteracts human skeletal muscle ageing.
    4. SESN1 attenuates the OxLDLinduced inflammation, apoptosis and endothelialmesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling.
      Title: SESN1 attenuates the Ox‑LDL‑induced inflammation, apoptosis and endothelial‑mesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling.
    5. SESN1, negatively regulated by miR-377-3p, suppresses invasive growth of head and neck squamous cell carcinoma by interaction with SMAD3.
      Title: SESN1, negatively regulated by miR-377-3p, suppresses invasive growth of head and neck squamous cell carcinoma by interaction with SMAD3.
    6. The functions and roles of sestrins in regulating human diseases.
      Title: The functions and roles of sestrins in regulating human diseases.
    7. Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes.
      Title: Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes.
    8. Integrating Mouse and Human Genetic Data to Move beyond GWAS and Identify Causal Genes in Cholesterol Metabolism.
      Title: Integrating Mouse and Human Genetic Data to Move beyond GWAS and Identify Causal Genes in Cholesterol Metabolism.
    9. Inhibition of sestrin 1 alleviates polycystic ovary syndrome by decreasing autophagy.
      Title: Inhibition of sestrin 1 alleviates polycystic ovary syndrome by decreasing autophagy.
    10. Circulating Sestrin Levels Are Increased in Hypertension Patients.
      Title: Circulating Sestrin Levels Are Increased in Hypertension Patients.
    Submit: New GeneRIF Correction See all GeneRIFs (21)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC138241, MGC142129

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables L-leucine binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables L-leucine binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables oxidoreductase activity, acting on peroxide as acceptor IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular oxidant detoxification IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to L-leucine IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to amino acid starvation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to glucose starvation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to leucine starvation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of TORC1 signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of TORC1 signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of macroautophagy IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in reactive oxygen species metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of response to reactive oxygen species IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of GATOR2 complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in fibrillar center IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    sestrin-1
    Names
    p53 activated gene 26
    p53 regulated PA26 nuclear protein
    NP_001186862.1
    NP_001186863.1
    NP_055269.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029518.2 RefSeqGene

      Range
      5001..115538
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001199933.2 → NP_001186862.1  sestrin-1 isoform 2

      See identical proteins and their annotated locations for NP_001186862.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AF033120, AL390208, BI549226, BU740021
      Consensus CDS
      CCDS56445.1
      UniProtKB/Swiss-Prot
      Q2M2B7, Q5T316, Q9NV00, Q9UPD5, Q9Y6P5, Q9Y6P6
      UniProtKB/TrEMBL
      A8K3D6
      Related
      ENSP00000349061.7, ENST00000356644.7
      Conserved Domains (1) summary
      pfam04636
      Location:47 → 491
      PA26; PA26 p53-induced protein (sestrin)

    2. NM_001199934.2 → NP_001186863.1  sestrin-1 isoform 3

      See identical proteins and their annotated locations for NP_001186863.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AF033121, AL390208, BU740021
      Consensus CDS
      CCDS56444.1
      UniProtKB/TrEMBL
      A8K3D6
      Related
      ENSP00000306734.2, ENST00000302071.6
      Conserved Domains (1) summary
      pfam04636
      Location:1 → 425
      PA26; PA26 p53-induced protein (sestrin)

    3. NM_014454.3 → NP_055269.1  sestrin-1 isoform 1

      See identical proteins and their annotated locations for NP_055269.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AF033122, AL355305, AL390208
      Consensus CDS
      CCDS5070.1
      UniProtKB/TrEMBL
      A8K292
      Related
      ENSP00000393762.2, ENST00000436639.7
      Conserved Domains (1) summary
      pfam04636
      Location:106 → 550
      PA26; PA26 p53-induced protein (sestrin)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      108984309..109094846 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      110161725..110272953 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y6P5.2 GenPept UniProtKB/Swiss-Prot:Q9Y6P5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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