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    SIRT1 sirtuin 1 [ Homo sapiens (human) ]

    Gene ID: 23411, updated on 10-Dec-2024

    Summary

    Official Symbol
    SIRT1provided by HGNC
    Official Full Name
    sirtuin 1provided by HGNC
    Primary source
    HGNC:HGNC:14929
    See related
    Ensembl:ENSG00000096717 MIM:604479; AllianceGenome:HGNC:14929
    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
    SIR2; SIR2L1; SIR2alpha
    Summary
    This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]
    Expression
    Ubiquitous expression in adrenal (RPKM 17.4), testis (RPKM 16.6) and 25 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See SIRT1 in Genome Data Viewer
    Location:
    10q21.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (67884656..67918390)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (68753401..68787131)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (69644414..69678147)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:69620921-69621442 Neighboring gene RNA, U6 small nuclear 523, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr10:69628867-69628993 Neighboring gene SIRT1 promoter region Neighboring gene Sharpr-MPRA regulatory region 7890 Neighboring gene ribosomal protein L12 pseudogene 8 Neighboring gene HECT and RLD domain containing E3 ubiquitin protein ligase 4 Neighboring gene RPS3A pseudogene 38 Neighboring gene RNA, 7SL, cytoplasmic 220, pseudogene

    Genomic regions, transcripts, and products

    Expression

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of SIRT1 by shRNA enhances HIV-1 transactivation in HIV latency condition, suggesting the direct involvement of SIRT1 to HIV latency PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat The gene expression of SIRT1 is significantly upregulated in both clade B and clade C Tat treated SK-N-MC neuroblastoma cells PubMed
    tat HIV-1 Tat-induced inhibition of SIRT1 activity in TZM-bl cells is reversed by tanshinone II A (a main lipid-soluble monomer derivative from the root of Salvia miltiorrhiza) PubMed
    tat HIV-1 Tat modulates SIRT1 expression in neuron cells PubMed
    tat HIV-1 Tat upregulates miR-182 in TZM-bl cells, which results in downregulation of SIRT1 protein expression and activity by MiR-182 PubMed
    tat HIV-1 Tat inhibits SIRT1 and increases acetylation of p53, which leads to activation of p21 and BAX in HeLa-CD4+ cells PubMed
    tat HIV-1 Tat upregulates miR-34a in TZM-bl cells, which results in downregulation of SIRT1 protein expression and activity and induction of NFkappaB p65 acetylation by MiR-34a PubMed
    tat HIV-1 Tat-induced expression of miR-217 downregulates SIRT1 and promotes HIV-1 LTR transactivation in MAGI cells PubMed
    tat HIV-1 Tat is identified to have a physical interaction with sirtuin 1 (SIRT1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    tat Tat causes NAD(+) depletion and inhibits Nicotinamide phosphoribosyltransferase (Nampt) mRNA and protein expression in cells. Nampt is critical in the regulation of Tat-induced inhibition of sirtuin 1 (SIRT1) activity and LTR transactivation PubMed
    tat HIV-1 Tat binds the deacetylase domain (amino acids 341-512) of SIRT1 and inhibits SIRT1 deacetylase activity, which results in the induction of NF-kappaB hyperacetylation PubMed
    tat Overexpression of SIRT1 attenuates Tat-induced HIV-1 transcription in MAGI cells PubMed
    tat Knockdown of SIRT1 by its inhibitor or siRNA results in Tat-mediated reduction of phosphorylation of AMP-activated protein kinase (AMPK) and downstream acetyl-CoA carboxylase (ACC) PubMed
    tat Deacetylation of HIV-1 Tat by human sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent class III protein deacetylase, regulates Tat transactivation of the HIV-1 promoter PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    General gene information

    Gene Ontology Provided by GOA

    Items 1 - 25 of 47
    Function Evidence Code Pubs
    enables DNA-binding transcription factor binding PubMed 
    enables HLH domain binding PubMed 
    enables NAD+ binding  
    NOT enables NAD+-protein ADP-ribosyltransferase activity PubMed 
    NOT enables NAD+-protein poly-ADP-ribosyltransferase activity PubMed 
    enables NAD-dependent histone decrotonylase activity PubMed 
    enables NAD-dependent protein lysine deacetylase activity PubMed 
    enables NAD-dependent protein lysine deacetylase activity PubMed 
    enables NAD-dependent protein lysine deacetylase activity  
    enables NAD-dependent protein lysine delactylase activity PubMed 
    enables NAD-dependent protein-lysine depropionylase activity  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding  
    enables bHLH transcription factor binding PubMed 
    enables deacetylase activity PubMed 
    enables enzyme activator activity PubMed 
    enables enzyme binding PubMed 
    enables histone H3K deacetylase activity PubMed 
    enables histone H3K14 deacetylase activity, NAD-dependent PubMed 
    enables histone H3K18 deacetylase activity, NAD-dependent  
    enables histone H3K18 decrotonylase activity  
    enables histone H3K4 deacetylase activity, NAD-dependent  
    enables histone H3K56 deacetylase activity, NAD-dependent  
    enables histone H3K9 deacetylase activity, NAD-dependent PubMed 
    enables histone H3K9 deacetylase activity, NAD-dependent  
    enables histone H4K12 deacetylase activity, hydrolytic mechanism PubMed 
    enables histone H4K16 deacetylase activity, NAD-dependent PubMed 
    enables histone binding PubMed 
    enables histone deacetylase activity PubMed 
    enables histone deacetylase activity, NAD-dependent  
    enables histone deacetylase activity, NAD-dependent PubMed 
    enables identical protein binding PubMed 
    enables keratin filament binding PubMed 
    enables metal ion binding  
    enables mitogen-activated protein kinase binding PubMed 
    enables nuclear receptor binding PubMed 
    enables p53 binding  
    enables p53 binding PubMed 
    enables promoter-specific chromatin binding  
    enables protein binding PubMed 
    enables protein lysine deacetylase activity PubMed 
    enables protein lysine deacetylase activity PubMed 
    enables protein lysine deacetylase activity  
    enables transcription coactivator activity  
    enables transcription corepressor activity  
    enables transcription corepressor activity PubMed 
    enables transcription corepressor activity PubMed 
    enables transcription corepressor activity  
    Items 1 - 25 of 47
    Items 1 - 25 of 122
    Process Evidence Code Pubs
    involved_in DNA damage response PubMed 
    involved_in DNA methylation-dependent constitutive heterochromatin formation PubMed 
    involved_in DNA repair-dependent chromatin remodeling PubMed 
    involved_in DNA synthesis involved in DNA repair  
    involved_in UV-damage excision repair PubMed 
    involved_in angiogenesis PubMed 
    involved_in behavioral response to starvation  
    involved_in cellular response to glucose starvation PubMed 
    involved_in cellular response to hydrogen peroxide PubMed 
    involved_in cellular response to hypoxia PubMed 
    involved_in cellular response to ionizing radiation  
    involved_in cellular response to leukemia inhibitory factor  
    involved_in cellular response to starvation  
    involved_in cellular response to tumor necrosis factor PubMed 
    involved_in cholesterol homeostasis  
    involved_in chromatin organization PubMed 
    involved_in circadian regulation of gene expression PubMed 
    involved_in circadian regulation of gene expression  
    involved_in energy homeostasis PubMed 
    involved_in fatty acid homeostasis  
    involved_in heterochromatin formation  
    involved_in heterochromatin formation PubMed 
    involved_in intracellular glucose homeostasis  
    involved_in intracellular triglyceride homeostasis  
    involved_in intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator PubMed 
    involved_in leptin-mediated signaling pathway  
    involved_in macrophage differentiation  
    involved_in maintenance of nucleus location PubMed 
    involved_in muscle organ development  
    involved_in negative regulation of DNA damage response, signal transduction by p53 class mediator PubMed 
    involved_in negative regulation of DNA-binding transcription factor activity PubMed 
    involved_in negative regulation of DNA-templated transcription  
    involved_in negative regulation of DNA-templated transcription PubMed 
    involved_in negative regulation of DNA-templated transcription PubMed 
    involved_in negative regulation of NF-kappaB transcription factor activity PubMed 
    involved_in negative regulation of TOR signaling PubMed 
    involved_in negative regulation of androgen receptor signaling pathway PubMed 
    involved_in negative regulation of apoptotic process PubMed 
    involved_in negative regulation of attachment of mitotic spindle microtubules to kinetochore PubMed 
    involved_in negative regulation of canonical NF-kappaB signal transduction PubMed 
    involved_in negative regulation of cell cycle PubMed 
    involved_in negative regulation of cellular response to testosterone stimulus PubMed 
    involved_in negative regulation of cellular senescence PubMed 
    involved_in negative regulation of cellular senescence PubMed 
    involved_in negative regulation of fat cell differentiation  
    involved_in negative regulation of gene expression PubMed 
    involved_in negative regulation of hippo signaling PubMed 
    involved_in negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator PubMed 
    involved_in negative regulation of neuron apoptotic process  
    involved_in negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway PubMed 
    involved_in negative regulation of peptidyl-lysine acetylation PubMed 
    involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction PubMed 
    involved_in negative regulation of phosphorylation PubMed 
    involved_in negative regulation of prostaglandin biosynthetic process  
    involved_in negative regulation of protein acetylation PubMed 
    involved_in negative regulation of signal transduction by p53 class mediator PubMed 
    involved_in negative regulation of transcription by RNA polymerase II PubMed 
    involved_in negative regulation of transcription by RNA polymerase II PubMed 
    involved_in negative regulation of transforming growth factor beta receptor signaling pathway  
    involved_in negative regulation of triglyceride biosynthetic process PubMed 
    involved_in ovulation from ovarian follicle  
    involved_in peptidyl-lysine acetylation PubMed 
    involved_in positive regulation of DNA repair PubMed 
    involved_in positive regulation of MHC class II biosynthetic process PubMed 
    involved_in positive regulation of adaptive immune response PubMed 
    involved_in positive regulation of adipose tissue development  
    involved_in positive regulation of angiogenesis PubMed 
    involved_in positive regulation of angiogenesis PubMed 
    involved_in positive regulation of apoptotic process PubMed 
    involved_in positive regulation of apoptotic process PubMed 
    involved_in positive regulation of blood vessel endothelial cell migration PubMed 
    involved_in positive regulation of cAMP-dependent protein kinase activity PubMed 
    involved_in positive regulation of cell population proliferation PubMed 
    involved_in positive regulation of cellular senescence PubMed 
    involved_in positive regulation of cholesterol efflux  
    involved_in positive regulation of cysteine-type endopeptidase activity PubMed 
    involved_in positive regulation of double-strand break repair PubMed 
    involved_in positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway  
    involved_in positive regulation of endothelial cell proliferation PubMed 
    involved_in positive regulation of gluconeogenesis PubMed 
    involved_in positive regulation of insulin receptor signaling pathway PubMed 
    involved_in positive regulation of macroautophagy PubMed 
    involved_in positive regulation of macrophage apoptotic process  
    involved_in positive regulation of macrophage cytokine production  
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction  
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process PubMed 
    involved_in positive regulation of protein phosphorylation  
    involved_in positive regulation of smooth muscle cell differentiation  
    involved_in positive regulation of transcription by RNA polymerase II PubMed 
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process PubMed 
    involved_in protein deacetylation PubMed 
    involved_in protein deacetylation PubMed 
    involved_in protein depropionylation  
    involved_in protein destabilization  
    involved_in protein ubiquitination PubMed 
    involved_in pyrimidine dimer repair by nucleotide-excision repair PubMed 
    involved_in rDNA heterochromatin formation PubMed 
    involved_in rDNA heterochromatin formation PubMed 
    involved_in rDNA heterochromatin formation  
    involved_in regulation of apoptotic process PubMed 
    involved_in regulation of bile acid biosynthetic process  
    involved_in regulation of brown fat cell differentiation  
    involved_in regulation of cell population proliferation PubMed 
    involved_in regulation of cellular response to heat  
    involved_in regulation of centrosome duplication PubMed 
    involved_in regulation of endodeoxyribonuclease activity PubMed 
    involved_in regulation of glucose metabolic process  
    involved_in regulation of lipid storage  
    involved_in regulation of mitotic cell cycle PubMed 
    involved_in regulation of peroxisome proliferator activated receptor signaling pathway  
    involved_in regulation of smooth muscle cell apoptotic process  
    involved_in regulation of transcription by glucose PubMed 
    involved_in response to hydrogen peroxide PubMed 
    involved_in response to insulin  
    involved_in response to leptin  
    involved_in response to oxidative stress PubMed 
    involved_in single strand break repair PubMed 
    involved_in spermatogenesis  
    involved_in stress-induced premature senescence PubMed 
    involved_in transforming growth factor beta receptor signaling pathway PubMed 
    involved_in triglyceride mobilization  
    involved_in white fat cell differentiation  
    Items 1 - 25 of 122
    Items 1 - 20 of 25
    Component Evidence Code Pubs
    part_of ESC/E(Z) complex PubMed 
    located_in PML body PubMed 
    located_in chromatin PubMed 
    part_of chromatin silencing complex PubMed 
    NOT located_in cytoplasm PubMed 
    located_in cytoplasm PubMed 
    is_active_in cytosol PubMed 
    located_in cytosol  
    part_of eNoSc complex PubMed 
    located_in euchromatin PubMed 
    located_in fibrillar center  
    located_in heterochromatin PubMed 
    located_in mitochondrion  
    located_in nuclear envelope PubMed 
    is_active_in nuclear inner membrane  
    located_in nuclear inner membrane PubMed 
    NOT located_in nucleolus PubMed 
    located_in nucleolus PubMed 
    is_active_in nucleoplasm  
    located_in nucleoplasm PubMed 
    located_in nucleoplasm  
    is_active_in nucleus  
    located_in nucleus PubMed 
    located_in rDNA heterochromatin  
    located_in rDNA heterochromatin PubMed 
    Items 1 - 20 of 25

    General protein information

    Preferred Names
    NAD-dependent protein deacetylase sirtuin-1
    Names
    NAD-dependent protein deacylase sirtuin-1
    SIR2-like protein 1
    regulatory protein SIR2 homolog 1
    sirtuin type 1
    NP_001135970.1
    NP_001300978.1
    NP_036370.2

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_050664.2 RefSeqGene

      Range
      5002..38736
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001142498.2 → NP_001135970.1  NAD-dependent protein deacetylase sirtuin-1 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternate in-frame exon in the 5' coding region and uses a downstream start codon, compared to variant 1. Isoform b has a shorter N-terminus, compared to isoform a.
      Source sequence(s)
      AL133551
      Consensus CDS
      CCDS44412.1
      UniProtKB/TrEMBL
      A8K128, E9PC49
      Related
      ENSP00000409208.1, ENST00000432464.5
      Conserved Domains (1) summary
      cl00195
      Location:1 → 194
      SIR2; SIR2 superfamily of proteins includes silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+, ...
    2. NM_001314049.2 → NP_001300978.1  NAD-dependent protein deacetylase sirtuin-1 isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and uses an alternate translation start site compared to variant 1. The encoded isoform (c) is shorter and has a distinct N-terminus compared to isoform a.
      Source sequence(s)
      AL133551
      Consensus CDS
      CCDS81469.1
      UniProtKB/TrEMBL
      B0QZ35
      Related
      ENSP00000384508.1, ENST00000406900.5
      Conserved Domains (1) summary
      cl00195
      Location:12 → 186
      SIR2; SIR2 superfamily of proteins includes silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+, ...
    3. NM_012238.5 → NP_036370.2  NAD-dependent protein deacetylase sirtuin-1 isoform a

      See identical proteins and their annotated locations for NP_036370.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AL133551
      Consensus CDS
      CCDS7273.1
      UniProtKB/Swiss-Prot
      Q2XNF6, Q5JVQ0, Q96EB6, Q9GZR9, Q9Y6F0
      Related
      ENSP00000212015.6, ENST00000212015.11
      Conserved Domains (1) summary
      cd01408
      Location:254 → 489
      SIRT1; SIRT1: Eukaryotic group (class1) which includes human sirtuins SIRT1-3 and yeast Hst1-4; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. Sir2 ...

    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_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      67884656..67918390
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      68753401..68787131
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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