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General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Gene namei
Official gene symbol, which is typically a short form of the gene name, according to HGNC.
Assigned HPA protein class(es) for the encoded protein(s).
Enzymes Metabolic proteins
Predicted locationi
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Chromosome
19
Cytoband
p13.3
Chromosome location (bp)
4174109 - 4182566
Number of transcriptsi
Number of protein-coding transcripts from the gene as defined by Ensembl.
Useful information about the protein provided by UniProt.
NAD-dependent protein deacetylase, deacylase and mono-ADP-ribosyltransferase that plays an essential role in DNA damage repair, telomere maintenance, metabolic homeostasis, inflammation, tumorigenesis and aging 1,2,3,4,5,6,7,8,9,10,11,12,13. Displays protein-lysine deacetylase or defatty-acylase (demyristoylase and depalmitoylase) activity, depending on the context 14,15,16. Acts as a key histone deacetylase by catalyzing deacetylation of histone H3 at 'Lys-9', 'Lys-18' and 'Lys-56' (H3K9ac, H3K18ac and H3K56ac, respectively), suppressing target gene expression of several transcription factors, including NF-kappa-B 17,18,19,20,21,22,23,24,25,26,27. Acts as an inhibitor of transcription elongation by mediating deacetylation of H3K9ac and H3K56ac, preventing release of NELFE from chromatin and causing transcriptional pausing (By similarity). Involved in DNA repair by promoting double-strand break (DSB) repair: acts as a DSB sensor by recognizing and binding DSB sites, leading to (1) recruitment of DNA repair proteins, such as SMARCA5/SNF2H, and (2) deacetylation of histone H3K9ac and H3K56ac 28,29,30. SIRT6 participation to DSB repair is probably involved in extension of life span (By similarity). Also promotes DNA repair by deacetylating non-histone proteins, such as DDB2 and p53/TP53 31,32. Specifically deacetylates H3K18ac at pericentric heterochromatin, thereby maintaining pericentric heterochromatin silencing at centromeres and protecting against genomic instability and cellular senescence 33. Involved in telomere maintenance by catalyzing deacetylation of histone H3 in telomeric chromatin, regulating telomere position effect and telomere movement in response to DNA damage 34,35,36. Required for embryonic stem cell differentiation by mediating histone deacetylation of H3K9ac 37,38. Plays a major role in metabolism by regulating processes such as glycolysis, gluconeogenesis, insulin secretion and lipid metabolism 39,40. Inhibits glycolysis via histone deacetylase activity and by acting as a corepressor of the transcription factor HIF1A, thereby controlling the expression of multiple glycolytic genes (By similarity). Has tumor suppressor activity by repressing glycolysis, thereby inhibiting the Warburg effect 41. Also regulates glycolysis and tumorigenesis by mediating deacetylation and nuclear export of non-histone proteins, such as isoform M2 of PKM (PKM2) 42. Acts as a negative regulator of gluconeogenesis by mediating deacetylation of non-histone proteins, such as FOXO1 and KAT2A/GCN5 43,44. Promotes beta-oxidation of fatty acids during fasting by catalyzing deacetylation of NCOA2, inducing coactivation of PPARA (By similarity). Acts as a regulator of lipid catabolism in brown adipocytes, both by catalyzing deacetylation of histones and non-histone proteins, such as FOXO1 (By similarity). Also acts as a regulator of circadian rhythms, both by regulating expression of clock-controlled genes involved in lipid and carbohydrate metabolism, and by catalyzing deacetylation of PER2 (By similarity). The defatty-acylase activity is specifically involved in regulation of protein secretion 45,46,47,48. Has high activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as RRAS2 and TNF, thereby regulating their secretion 49,50. Also acts as a mono-ADP-ribosyltransferase by mediating mono-ADP-ribosylation of PARP1, TRIM28/KAP1 or SMARCC2/BAF170 51,52,53,54. Mono-ADP-ribosyltransferase activity is involved in DNA repair, cellular senescence, repression of LINE-1 retrotransposon elements and regulation of transcription 55,56,57....show less
Molecular function (UniProt)i
Keywords assigned by UniProt to proteins due to their particular molecular function.
Keywords assigned by UniProt to proteins because they are involved in a particular biological process.
DNA damage, DNA repair
Ligand (UniProt)i
Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.
Metal-binding, NAD, Zinc
Gene summary (Entrez)i
Useful information about the gene from Entrez
This gene encodes a member of the sirtuin family of NAD-dependent enzymes that are implicated in cellular stress resistance, genomic stability, aging and energy homeostasis. The encoded protein is localized to the nucleus, exhibits ADP-ribosyl transferase and histone deacetylase activities, and plays a role in DNA repair, maintenance of telomeric chromatin, inflammation, lipid and glucose metabolism. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]...show less
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The ENSP identifier links to the Ensembl website protein summary, while the ENST identifier links to the Ensembl website transcript summary for the selected splice variant. The data in the UniProt column can be expanded to show links to all matching UniProt identifiers for this protein.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The Gene Ontology terms assigned to this protein are listed if expanding the Gene ontology column. The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide (according to a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius) and the number of predicted transmembrane region(s) (according to MDM) are also reported.
Q8N6T7 [Direct mapping] NAD-dependent protein deacylase sirtuin-6
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Enzymes ENZYME proteins Transferases Metabolic proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0000122[negative regulation of transcription by RNA polymerase II] GO:0000781[chromosome, telomeric region] GO:0000785[chromatin] GO:0003677[DNA binding] GO:0003684[damaged DNA binding] GO:0003714[transcription corepressor activity] GO:0003723[RNA binding] GO:0003950[NAD+ ADP-ribosyltransferase activity] GO:0004407[histone deacetylase activity] GO:0005515[protein binding] GO:0005634[nucleus] GO:0005654[nucleoplasm] GO:0005694[chromosome] GO:0005721[pericentric heterochromatin] GO:0005783[endoplasmic reticulum] GO:0006281[DNA repair] GO:0006302[double-strand break repair] GO:0006325[chromatin organization] GO:0006476[protein deacetylation] GO:0006974[cellular response to DNA damage stimulus] GO:0008270[zinc ion binding] GO:0008340[determination of adult lifespan] GO:0009411[response to UV] GO:0010529[negative regulation of transposition] GO:0010569[regulation of double-strand break repair via homologous recombination] GO:0016740[transferase activity] GO:0016746[acyltransferase activity] GO:0016757[glycosyltransferase activity] GO:0016779[nucleotidyltransferase activity] GO:0017136[NAD-dependent histone deacetylase activity] GO:0019213[deacetylase activity] GO:0019216[regulation of lipid metabolic process] GO:0031490[chromatin DNA binding] GO:0031491[nucleosome binding] GO:0031508[pericentric heterochromatin formation] GO:0031509[subtelomeric heterochromatin formation] GO:0031648[protein destabilization] GO:0032024[positive regulation of insulin secretion] GO:0032206[positive regulation of telomere maintenance] GO:0032922[circadian regulation of gene expression] GO:0033558[protein lysine deacetylase activity] GO:0034244[negative regulation of transcription elongation by RNA polymerase II] GO:0034979[NAD-dependent protein deacetylase activity] GO:0035861[site of double-strand break] GO:0042181[ketone biosynthetic process] GO:0042308[negative regulation of protein import into nucleus] GO:0042752[regulation of circadian rhythm] GO:0042803[protein homodimerization activity] GO:0043231[intracellular membrane-bounded organelle] GO:0043687[post-translational protein modification] GO:0045600[positive regulation of fat cell differentiation] GO:0045721[negative regulation of gluconeogenesis] GO:0045814[negative regulation of gene expression, epigenetic] GO:0045820[negative regulation of glycolytic process] GO:0046827[positive regulation of protein export from nucleus] GO:0046872[metal ion binding] GO:0046969[NAD-dependent histone deacetylase activity (H3-K9 specific)] GO:0050994[regulation of lipid catabolic process] GO:0051697[protein delipidation] GO:0055007[cardiac muscle cell differentiation] GO:0070403[NAD+ binding] GO:0070932[histone H3 deacetylation] GO:0090734[site of DNA damage] GO:0097372[NAD-dependent histone deacetylase activity (H3-K18 specific)] GO:0099115[chromosome, subtelomeric region] GO:0106222[lncRNA binding] GO:0106274[NAD+-protein-arginine ADP-ribosyltransferase activity] GO:0120162[positive regulation of cold-induced thermogenesis] GO:0120187[positive regulation of protein localization to chromatin] GO:0140612[DNA damage sensor activity] GO:0140765[NAD-dependent histone deacetylase activity (H3-K56 specific)] GO:0140773[NAD-dependent protein demyristoylase activity] GO:0140774[NAD-dependent protein depalmitoylase activity] GO:0140804[NAD+- protein-lysine ADP-ribosyltransferase activity] GO:1901485[positive regulation of transcription factor catabolic process] GO:1902732[positive regulation of chondrocyte proliferation] GO:1904841[TORC2 complex binding] GO:1905555[positive regulation of blood vessel branching] GO:1905564[positive regulation of vascular endothelial cell proliferation] GO:1990404[NAD+-protein ADP-ribosyltransferase activity] GO:2000738[positive regulation of stem cell differentiation] GO:2000773[negative regulation of cellular senescence] GO:2000781[positive regulation of double-strand break repair]
Q8N6T7 [Direct mapping] NAD-dependent protein deacylase sirtuin-6
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Enzymes ENZYME proteins Transferases Metabolic proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0000122[negative regulation of transcription by RNA polymerase II] GO:0000781[chromosome, telomeric region] GO:0000785[chromatin] GO:0003677[DNA binding] GO:0003682[chromatin binding] GO:0003684[damaged DNA binding] GO:0003714[transcription corepressor activity] GO:0003723[RNA binding] GO:0003950[NAD+ ADP-ribosyltransferase activity] GO:0004407[histone deacetylase activity] GO:0005515[protein binding] GO:0005634[nucleus] GO:0005654[nucleoplasm] GO:0005694[chromosome] GO:0005721[pericentric heterochromatin] GO:0005783[endoplasmic reticulum] GO:0006281[DNA repair] GO:0006284[base-excision repair] GO:0006302[double-strand break repair] GO:0006325[chromatin organization] GO:0006476[protein deacetylation] GO:0006974[cellular response to DNA damage stimulus] GO:0008270[zinc ion binding] GO:0008285[negative regulation of cell population proliferation] GO:0008340[determination of adult lifespan] GO:0009411[response to UV] GO:0010529[negative regulation of transposition] GO:0010569[regulation of double-strand break repair via homologous recombination] GO:0016740[transferase activity] GO:0016746[acyltransferase activity] GO:0016757[glycosyltransferase activity] GO:0016779[nucleotidyltransferase activity] GO:0017136[NAD-dependent histone deacetylase activity] GO:0019213[deacetylase activity] GO:0019216[regulation of lipid metabolic process] GO:0031490[chromatin DNA binding] GO:0031491[nucleosome binding] GO:0031508[pericentric heterochromatin formation] GO:0031509[subtelomeric heterochromatin formation] GO:0031648[protein destabilization] GO:0032024[positive regulation of insulin secretion] GO:0032206[positive regulation of telomere maintenance] GO:0032922[circadian regulation of gene expression] GO:0033558[protein lysine deacetylase activity] GO:0034244[negative regulation of transcription elongation by RNA polymerase II] GO:0034979[NAD-dependent protein deacetylase activity] GO:0035861[site of double-strand break] GO:0042181[ketone biosynthetic process] GO:0042308[negative regulation of protein import into nucleus] GO:0042593[glucose homeostasis] GO:0042752[regulation of circadian rhythm] GO:0042803[protein homodimerization activity] GO:0043231[intracellular membrane-bounded organelle] GO:0043687[post-translational protein modification] GO:0045600[positive regulation of fat cell differentiation] GO:0045721[negative regulation of gluconeogenesis] GO:0045814[negative regulation of gene expression, epigenetic] GO:0045820[negative regulation of glycolytic process] GO:0045892[negative regulation of DNA-templated transcription] GO:0046325[negative regulation of glucose import] GO:0046827[positive regulation of protein export from nucleus] GO:0046872[metal ion binding] GO:0046969[NAD-dependent histone deacetylase activity (H3-K9 specific)] GO:0048146[positive regulation of fibroblast proliferation] GO:0050994[regulation of lipid catabolic process] GO:0051697[protein delipidation] GO:0055007[cardiac muscle cell differentiation] GO:0070403[NAD+ binding] GO:0070932[histone H3 deacetylation] GO:0090734[site of DNA damage] GO:0097372[NAD-dependent histone deacetylase activity (H3-K18 specific)] GO:0099115[chromosome, subtelomeric region] GO:0106222[lncRNA binding] GO:0106274[NAD+-protein-arginine ADP-ribosyltransferase activity] GO:0120162[positive regulation of cold-induced thermogenesis] GO:0120187[positive regulation of protein localization to chromatin] GO:0140612[DNA damage sensor activity] GO:0140765[NAD-dependent histone deacetylase activity (H3-K56 specific)] GO:0140773[NAD-dependent protein demyristoylase activity] GO:0140774[NAD-dependent protein depalmitoylase activity] GO:0140804[NAD+- protein-lysine ADP-ribosyltransferase activity] GO:1901485[positive regulation of transcription factor catabolic process] GO:1902732[positive regulation of chondrocyte proliferation] GO:1904841[TORC2 complex binding] GO:1905555[positive regulation of blood vessel branching] GO:1905564[positive regulation of vascular endothelial cell proliferation] GO:1990404[NAD+-protein ADP-ribosyltransferase activity] GO:2000648[positive regulation of stem cell proliferation] GO:2000738[positive regulation of stem cell differentiation] GO:2000773[negative regulation of cellular senescence] GO:2000781[positive regulation of double-strand break repair]
M0R1N9 [Direct mapping] NAD-dependent protein deacetylase sirtuin-6; Sirtuin (Silent mating type information regulation 2 homolog) 6 (S. cerevisiae), isoform CRA_i
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Metabolic proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Protein evidence (Ezkurdia et al 2014)
M0R1F6 [Direct mapping] NAD-dependent protein deacylase sirtuin-6
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Metabolic proteins SPOCTOPUS predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Protein evidence (Ezkurdia et al 2014)
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