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Aliases for SIRT6 Gene

Aliases for SIRT6 Gene

  • Sirtuin 6 2 3
  • SIR2L6 3 4 6
  • Regulatory Protein SIR2 Homolog 6 3 4
  • SIR2-Like Protein 6 3 4
  • Sirtuin (Silent Mating Type Information Regulation 2, S. Cerevisiae, Homolog) 6 2
  • Sirtuin (Silent Mating Type Information Regulation 2 Homolog) 6 (S. Cerevisiae) 2
  • NAD-Dependent Protein Deacetylase Sirtuin-6 3
  • NAD-Dependent Deacetylase Sirtuin-6 3
  • Sir2-Related Protein Type 6 3
  • Sirtuin Type 6 3
  • EC 3.5.1.- 4

External Ids for SIRT6 Gene

Summaries for SIRT6 Gene

Entrez Gene Summary for SIRT6 Gene

  • 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 IV of the sirtuin family. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jul 2010]

GeneCards Summary for SIRT6 Gene

SIRT6 (Sirtuin 6) is a Protein Coding gene. Among its related pathways are Nicotinate and nicotinamide metabolism and Chromatin Regulation / Acetylation. GO annotations related to this gene include NAD+ ADP-ribosyltransferase activity and NAD+ binding. An important paralog of this gene is SIRT7.

UniProtKB/Swiss-Prot for SIRT6 Gene

  • NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate.

Tocris Summary for SIRT6 Gene

  • Silent information regulator (Sir2)-like family deacetylases (also known as sirtuins) are a group of enzymes closely related to histone deacetylases. These enzymes can be found in the cytoplasm, mitochondria or nucleus and are ubiquitously expressed. Sir2-like family deacetylases catalyze the removal of acetyl groups from lysine residues in histones and non-histone proteins, which is coupled to NAD+ hydrolysis. In general, sirtuins do not act autonomously but as components of large multiprotein complexes, such as pRb-E2F and mSin3A, that mediate important transcription regulatory pathways. Sirtuins have a role in regulation of transcription and apoptosis leading to substantial interest in inhibitors of these enzymes as possible antineoplastic agents. In addition, Sir2-like family deacteylases are involved in the normal ageing process through their role in resistance to cellular stress.

Gene Wiki entry for SIRT6 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SIRT6 Gene

Genomics for SIRT6 Gene

Genomic Location for SIRT6 Gene

Start:
4,174,109 bp from pter
End:
4,182,604 bp from pter
Size:
8,496 bases
Orientation:
Minus strand

Genomic View for SIRT6 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SIRT6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIRT6 Gene

Regulatory Elements for SIRT6 Gene

Proteins for SIRT6 Gene

  • Protein details for SIRT6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N6T7-SIR6_HUMAN
    Recommended name:
    NAD-dependent protein deacetylase sirtuin-6
    Protein Accession:
    Q8N6T7
    Secondary Accessions:
    • B2RCD0
    • O75291
    • Q6IAF5
    • Q6PK99
    • Q8NCD2
    • Q9BSI5
    • Q9BWP3
    • Q9NRC7
    • Q9UQD1

    Protein attributes for SIRT6 Gene

    Size:
    355 amino acids
    Molecular mass:
    39119 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
    Quaternary structure:
    • Interacts with RELA. Interacts with RBBP8; the interaction deacetylates RBBP8.
    Miscellaneous:
    • The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant.
    SequenceCaution:
    • Sequence=AAC34468.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAD15478.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAH04218.1; Type=Erroneous translation; Note=Wrong choice of CCDS.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for SIRT6 Gene

    Alternative splice isoforms for SIRT6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SIRT6 Gene

Proteomics data for SIRT6 Gene at MOPED

Post-translational modifications for SIRT6 Gene

  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys245 and Lys267

No data available for DME Specific Peptides for SIRT6 Gene

Domains for SIRT6 Gene

UniProtKB/Swiss-Prot:

SIR6_HUMAN
Domain:
  • Contains 1 deacetylase sirtuin-type domain.:
    • Q8N6T7
Family:
  • Belongs to the sirtuin family. Class IV subfamily.:
    • Q8N6T7
genes like me logo Genes that share domains with SIRT6: view

No data available for Gene Families for SIRT6 Gene

Function for SIRT6 Gene

Molecular function for SIRT6 Gene

UniProtKB/Swiss-Prot CatalyticActivity: NAD(+) + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.
UniProtKB/Swiss-Prot Function: NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate.

Enzyme Numbers (IUBMB) for SIRT6 Gene

Gene Ontology (GO) - Molecular Function for SIRT6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003682 chromatin binding IEA --
GO:0003950 NAD+ ADP-ribosyltransferase activity TAS 17456799
GO:0003956 NAD(P)+-protein-arginine ADP-ribosyltransferase activity ISS --
GO:0005515 protein binding IPI 19135889
GO:0008270 zinc ion binding ISS --
genes like me logo Genes that share ontologies with SIRT6: view
genes like me logo Genes that share phenotypes with SIRT6: view

Animal Models for SIRT6 Gene

MGI Knock Outs for SIRT6:

No data available for miRNA , Transcription Factor Targeting and HOMER Transcription for SIRT6 Gene

Localization for SIRT6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIRT6 Gene

Nucleus, nucleoplasm. Note=Predominantly nuclear. Associated with telomeric heterochromatin regions.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SIRT6 Gene COMPARTMENTS Subcellular localization image for SIRT6 gene
Compartment Confidence
nucleus 5
cytosol 2
mitochondrion 2

Gene Ontology (GO) - Cellular Components for SIRT6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus ISS --
GO:0005654 nucleoplasm IDA 16079181
GO:0005724 nuclear telomeric heterochromatin IDA 18337721
GO:0005730 NOT nucleolus IDA 16079181
GO:0043231 intracellular membrane-bounded organelle IDA --
genes like me logo Genes that share ontologies with SIRT6: view

Pathways for SIRT6 Gene

genes like me logo Genes that share pathways with SIRT6: view

Pathways by source for SIRT6 Gene

2 GeneGo (Thomson Reuters Life Sciences Research) pathways for SIRT6 Gene
1 Sino Biological pathway for SIRT6 Gene
2 Qiagen pathways for SIRT6 Gene
1 Cell Signaling Technology pathway for SIRT6 Gene

Gene Ontology (GO) - Biological Process for SIRT6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006471 protein ADP-ribosylation TAS 17456799
GO:0010569 regulation of double-strand break repair via homologous recombination IDA 19135889
GO:0016575 histone deacetylation ISS --
GO:0061647 histone H3-K9 modification IDA 18337721
GO:0070932 histone H3 deacetylation --
genes like me logo Genes that share ontologies with SIRT6: view

Compounds for SIRT6 Gene

(6) ApexBio Compounds for SIRT6 Gene

Compound Action Cas Number
EX 527 (SEN0014196) novel, potential, and specific small-molecule inhibitor of SIRT1 [49843-98-3]
Sirtinol specific SIRT1 and SIRT2 inhibitor [410536-97-9]
sirtuin modulator sirtuin modulator. [1093403-33-8]
SRT1720 activating the sirtuin subtype SIRT1 in vitro. [1001645-58-4]
Tenovin-3 Tenovin-3 [1011301-27-1]
Tenovin-6 a potent SIRT1 and SIRT2 inhibitor as well as p53 activator. [1011557-82-6]

(5) Tocris Compounds for SIRT6 Gene

Compound Action Cas Number
AGK 2 Selective SIRT2 inhibitor [304896-28-4]
AK 7 Selective SIRT2 inhibitor; brain penetrant [420831-40-9]
EX 527 Selective SIRT1 inhibitor [49843-98-3]
Sirtinol Selective sirtuin family deacetylase inhibitor [410536-97-9]
Splitomicin Sir2p inhibitor [5690-03-9]

(5) HMDB Compounds for SIRT6 Gene

Compound Synonyms Cas Number PubMed IDs
L-Arginine
  • (S)-2-Amino-5-[(aminoiminomethyl)amino]pentanoate
74-79-3
NAD
  • 3-Carbamoyl-1-D-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate
53-84-9
NADH
  • 1,4-Dihydronicotinamide adenine dinucleotide
58-68-4
NADP
  • Adenine-nicotinamide dinucleotide phosphate
53-59-8
Niacinamide
  • 3-Carbamoylpyridine
98-92-0
genes like me logo Genes that share compounds with SIRT6: view

Transcripts for SIRT6 Gene

Unigene Clusters for SIRT6 Gene

Sirtuin 6:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for SIRT6 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b ^ 3a · 3b · 3c · 3d ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b · 8c · 8d ^ 9a · 9b · 9c · 9d · 9e
SP1: - - - - - - -
SP2: - - - - - - - -
SP3: - - - - - -
SP4: - - - - - - - -
SP5: - - - - - -
SP6: - - - -
SP7: - - - - - - - - - -
SP8: - - - - -
SP9: - - - - - - - -
SP10: - - - - -
SP11: - - - - - - -
SP12: - - - - - - - -
SP13: -
SP14: - -
SP15: - - - - - -
SP16: - - - - - -
SP17: - -

Relevant External Links for SIRT6 Gene

GeneLoc Exon Structure for
SIRT6
ECgene alternative splicing isoforms for
SIRT6

Expression for SIRT6 Gene

mRNA expression in normal human tissues for SIRT6 Gene

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for SIRT6 Gene

SOURCE GeneReport for Unigene cluster for SIRT6 Gene Hs.423756

genes like me logo Genes that share expressions with SIRT6: view

Orthologs for SIRT6 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for SIRT6 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SIRT6 36
  • 99.34 (n)
  • 99.44 (a)
SIRT6 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SIRT6 36
  • 86.1 (n)
  • 89.58 (a)
SIRT6 37
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SIRT6 36
  • 86.85 (n)
  • 90.42 (a)
SIRT6 37
  • 90 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Sirt6 36
  • 82.93 (n)
  • 88.62 (a)
Sirt6 16
Sirt6 37
  • 88 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SIRT6 37
  • 78 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SIRT6 37
  • 74 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Sirt6 36
  • 83.03 (n)
  • 88.48 (a)
chicken
(Gallus gallus)
Aves SIRT6 36
  • 73.54 (n)
  • 77.19 (a)
SIRT6 37
  • 70 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SIRT6 37
  • 66 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.19602 36
tropical clawed frog
(Silurana tropicalis)
Amphibia MGC76070 36
sirt6 36
  • 70.62 (n)
  • 80.94 (a)
zebrafish
(Danio rerio)
Actinopterygii sirt6 36
  • 68.67 (n)
  • 73.14 (a)
sirt6 37
  • 60 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001458 36
  • 58.15 (n)
  • 57.66 (a)
fruit fly
(Drosophila melanogaster)
Insecta Sirt6 36
  • 54.35 (n)
  • 52.54 (a)
Sirt6 37
  • 46 (a)
OneToOne
CG6284 38
  • 51 (a)
worm
(Caenorhabditis elegans)
Secernentea sir-2.4 37
  • 33 (a)
OneToOne
sir-2.4 38
  • 38 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons SRT1 36
  • 51.85 (n)
  • 52.22 (a)
corn
(Zea mays)
Liliopsida Zm.4848 36
rice
(Oryza sativa)
Liliopsida Os.2316 36
Os04g0271000 36
  • 52.96 (n)
  • 53.7 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 59 (a)
OneToOne
Species with no ortholog for SIRT6:
  • 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)
  • 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 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)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SIRT6 Gene

ENSEMBL:
Gene Tree for SIRT6 (if available)
TreeFam:
Gene Tree for SIRT6 (if available)

Paralogs for SIRT6 Gene

Paralogs for SIRT6 Gene

Selected SIMAP similar genes for SIRT6 Gene using alignment to 7 proteins:

genes like me logo Genes that share paralogs with SIRT6: view

Variants for SIRT6 Gene

Sequence variations from dbSNP and Humsavar for SIRT6 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type MAF
rs107251 -- 4,176,088(+) TTCCA(C/T)GAATA intron-variant
rs350843 -- 4,177,334(-) gttgg(G/T)ccact intron-variant
rs350844 -- 4,177,054(+) CCCCC(A/G)CCCCT intron-variant
rs350845 -- 4,174,953(-) GCCCC(A/C/G/T)CGGCA intron-variant
rs350846 -- 4,174,401(+) GCTCA(C/G)CTGTC utr-variant-3-prime, downstream-variant-500B

Structural Variations from Database of Genomic Variants (DGV) for SIRT6 Gene

Variant ID Type Subtype PubMed ID
nsv910783 CNV Loss 21882294
dgv3673n71 CNV Loss 21882294
nsv910816 CNV Loss 21882294
nsv833716 CNV Loss 17160897
nsv910817 CNV Loss 21882294
nsv910818 CNV Loss 21882294

Relevant External Links for SIRT6 Gene

HapMap Linkage Disequilibrium report
SIRT6

Disorders for SIRT6 Gene

Relevant External Links for SIRT6

Human Genome Epidemiology (HuGE) Navigator
SIRT6
genes like me logo Genes that share disorders with SIRT6: view

No data available for UniProtKB/Swiss-Prot for SIRT6 Gene

Publications for SIRT6 Gene

  1. Phylogenetic classification of prokaryotic and eukaryotic Sir-2 like proteins. (PMID: 10873683) Frye R.A. (Biochem. Biophys. Res. Commun. 2000) 2 3 4 23
  2. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. (PMID: 16079181) Michishita E. … Horikawa I. (Mol. Biol. Cell 2005) 3 4 23
  3. SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. (PMID: 19135889) Kawahara T.L.A. … Chua K.F. (Cell 2009) 3 4
  4. Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6. (PMID: 19625767) Michishita E. … Chua K.F. (Cell Cycle 2009) 3 4
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T. … Sugano S. (Nat. Genet. 2004) 3 4

Products for SIRT6 Gene

  • Addgene plasmids for SIRT6

Sources for SIRT6 Gene

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