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Identification
HMDB Protein ID HMDBP00903
Secondary Accession Numbers
  • 6191
Name NAD-dependent protein deacetylase sirtuin-6
Synonyms
  1. SIR2-like protein 6
  2. Regulatory protein SIR2 homolog 6
Gene Name SIRT6
Protein Type Unknown
Biological Properties
General Function Involved in zinc ion binding
Specific 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.
Pathways Not Available
Reactions
NAD + an acetylprotein → Niacinamide + O-acetyl-ADP-ribose + a protein details
GO Classification
Biological Process
protein ADP-ribosylation
regulation of double-strand break repair via homologous recombination
Cellular Component
nuclear telomeric heterochromatin
nucleoplasm
Function
ion binding
cation binding
metal ion binding
binding
nucleotide binding
catalytic activity
hydrolase activity
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
transition metal ion binding
zinc ion binding
nad or nadh binding
nad binding
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
Molecular Function
metal ion binding
NAD(P)+-protein-arginine ADP-ribosyltransferase activity
NAD+ ADP-ribosyltransferase activity
zinc ion binding
NAD+ binding
NAD-dependent histone deacetylase activity (H3-K9 specific)
Process
metabolic process
macromolecule metabolic process
protein amino acid deacetylation
gene silencing
chromatin silencing
cellular process
biological regulation
regulation of biological process
regulation of metabolic process
regulation of macromolecule metabolic process
regulation of gene expression
regulation of transcription
post-translational protein modification
macromolecule modification
protein modification process
Cellular Location
  1. Nucleus
  2. nucleoplasm
Gene Properties
Chromosome Location 19
Locus 19p13.3
SNPs SIRT6
Gene Sequence
>1068 bp
ATGTCGGTGAATTACGCGGCGGGGCTGTCGCCGTACGCGGACAAGGGCAAGTGCGGCCTC
CCGGAGATCTTCGACCCCCCGGAGGAGCTGGAGCGGAAGGTGTGGGAACTGGCGAGGCTG
GTCTGGCAGTCTTCCAGTGTGGTGTTCCACACGGGTGCCGGCATCAGCACTGCCTCTGGC
ATCCCCGACTTCAGGGGTCCCCACGGAGTCTGGACCATGGAGGAGCGAGGTCTGGCCCCC
AAGTTCGACACCACCTTTGAGAGCGCGCGGCCCACGCAGACCCACATGGCGCTGGTGCAG
CTGGAGCGCGTGGGCCTCCTCCGCTTCCTGGTCAGCCAGAACGTGGACGGGCTCCATGTG
CGCTCAGGCTTCCCCAGGGACAAACTGGCAGAGCTCCACGGGAACATGTTTGTGGAAGAA
TGTGCCAAGTGTAAGACGCAGTACGTCCGAGACACAGTCGTGGGCACCATGGGCCTGAAG
GCCACGGGCCGGCTCTGCACCGTGGCTAAGGCAAGGGGGCTGCGAGCCTGCAGGGGAGAG
CTGAGGGACACCATCCTAGACTGGGAGGACTCCCTGCCCGACCGGGACCTGGCACTCGCC
GATGAGGCCAGCAGGAACGCCGACCTGTCCATCACGCTGGGTACATCGCTGCAGATCCGG
CCCAGCGGGAACCTGCCGCTGGCTACCAAGCGCCGGGGAGGCCGCCTGGTCATCGTCAAC
CTGCAGCCCACCAAGCACGACCGCCATGCTGACCTCCGCATCCATGGCTACGTTGACGAG
GTCATGACCCGGCTCATGGAGCACCTGGGGCTGGAGATCCCCGCCTGGGACGGCCCCCGT
GTGCTGGAGAGGGCGCTGCCACCCCTGCCCCGCCCGCCCACCCCCAAGCTGGAGCCCAAG
GAGGAATCTCCCACCCGGATCAACGGCTCTATCCCCGCCGGCCCCAAGCAGGAGCCCTGC
GCCCAGCACAACGGCTCAGAGCCCGCCAGCCCCAAACGGGAGCGGCCCACCAGCCCTGCC
CCCCACAGACCCCCCAAAAGGGTGAAGGCCAAGGCGGTCCCCAGCTGA
Protein Properties
Number of Residues 355
Molecular Weight 36064.295
Theoretical pI 9.743
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>NAD-dependent deacetylase sirtuin-6
MSVNYAAGLSPYADKGKCGLPEIFDPPEELERKVWELARLVWQSSSVVFHTGAGISTASG
IPDFRGPHGVWTMEERGLAPKFDTTFESARPTQTHMALVQLERVGLLRFLVSQNVDGLHV
RSGFPRDKLAELHGNMFVEECAKCKTQYVRDTVVGTMGLKATGRLCTVAKARGLRACRGE
LRDTILDWEDSLPDRDLALADEASRNADLSITLGTSLQIRPSGNLPLATKRRGGRLVIVN
LQPTKHDRHADLRIHGYVDEVMTRLMKHLGLEIPAWDGPRVLERALPPLPRPPTPKLEPK
EESPTRINGSIPAGPKQEPCAQHNGSEPASPKRERPTSPAPHRPPKRVKAKAVPS
GenBank ID Protein 7243749
UniProtKB/Swiss-Prot ID Q8N6T7
UniProtKB/Swiss-Prot Entry Name SIRT6_HUMAN
PDB IDs
GenBank Gene ID AF233396
GeneCard ID SIRT6
GenAtlas ID SIRT6
HGNC ID HGNC:14934
References
General References
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  4. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
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  6. Frye RA: Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun. 2000 Jul 5;273(2):793-8. [PubMed:10873683 ]
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  10. Michishita E, McCord RA, Boxer LD, Barber MF, Hong T, Gozani O, Chua KF: Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6. Cell Cycle. 2009 Aug 15;8(16):2664-6. Epub 2009 Aug 26. [PubMed:19625767 ]