NAD-dependent protein deacetylase sirtuin-6

An NAD-dependent protein deacylase sirtuin-6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N6T7]

Synonyms

EC 2.3.1.286;
Regulatory protein SIR2 homolog 6;
SIR2-like protein 6

Research

Bioassay Publications (7)

Timeframe	Studies on this Protein(%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	4 (57.14)	24.3611
2020's	3 (42.86)	2.80

Compounds (9)

Drugs with Inhibition Measurements

Drug	Taxonomy	Measurement	Average (mM)	Bioassay(s)	Publication(s)
niacinamide	Homo sapiens (human)	IC50	173.3500	4	4
pyrazinamide	Homo sapiens (human)	IC50	416.9000	1	1
pyrazinoic acid	Homo sapiens (human)	IC50	926.8000	1	1
1-(4-nitrophenyl)piperazine	Homo sapiens (human)	IC50	35.0000	1	1
5-chloropyrazinamide	Homo sapiens (human)	IC50	33.2000	2	2
trichostatin a	Homo sapiens (human)	Ki	226.0000	2	2

Drugs with Activation Measurements

Drug	Taxonomy	Measurement	Average (mM)	Bioassay(s)	Publication(s)
trichostatin a	Homo sapiens (human)	Kd	183.5000	4	4
(3R,5S)-fluvastatin	Homo sapiens (human)	EC50	128.5500	2	2

Drugs with Other Measurements

Drug	Taxonomy	Measurement	Average (mM)	Bioassay(s)	Publication(s)
rubimaillin	Homo sapiens (human)	EC1.5	227.5000	1	1
ly2784544	Homo sapiens (human)	EC1.5	118.2000	1	1

Enables

This protein enables 23 target(s):

Target	Category	Definition
chromatin binding	molecular function	Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase. [GOC:jl, ISBN:0198506732, PMID:20404130]
damaged DNA binding	molecular function	Binding to damaged DNA. [GOC:jl]
NAD+ ADP-ribosyltransferase activity	molecular function	Catalysis of the reaction: NAD+ + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D-ribosyl)(n+1)-acceptor. [EC:2.4.2.30]
protein binding	molecular function	Binding to a protein. [GOC:go_curators]
zinc ion binding	molecular function	Binding to a zinc ion (Zn). [GOC:ai]
nucleotidyltransferase activity	molecular function	Catalysis of the transfer of a nucleotidyl group to a reactant. [ISBN:0198506732]
NAD-dependent histone deacetylase activity	molecular function	Catalysis of the reaction: histone N6-acetyl-L-lysine + H2O = histone L-lysine + acetate. This reaction requires the presence of NAD, and represents the removal of an acetyl group from a histone. [PMID:28450737]
chromatin DNA binding	molecular function	Binding to DNA that is assembled into chromatin. [GOC:mah]
nucleosome binding	molecular function	Binding to a nucleosome, a complex comprised of DNA wound around a multisubunit core and associated proteins, which forms the primary packing unit of DNA into higher order structures. [GOC:mah]
NAD-dependent protein lysine deacetylase activity	molecular function	Catalysis of the reaction: N(6)-acetyl-L-lysyl-[protein] + NAD+ + H2O = L-lysyl-[protein] + 2''-O-acetyl-ADP-D-ribose + nicotinamide. [GOC:BHF, GOC:mah, RHEA:43636]
protein homodimerization activity	molecular function	Binding to an identical protein to form a homodimer. [GOC:jl]
NAD-dependent histone H3K9 deacetylase activity	molecular function	Catalysis of the reaction: histone H3 N6-acetyl-L-lysine (position 9) + H2O = histone H3 L-lysine (position 9) + acetate. This reaction requires the presence of NAD, and represents the removal of an acetyl group from lysine at position 9 of the histone H3 protein. [PMID:28450737]
NAD+ binding	molecular function	Binding to the oxidized form, NAD, of nicotinamide adenine dinucleotide, a coenzyme involved in many redox and biosynthetic reactions. [GOC:mah]
NAD-dependent histone H3K18 deacetylase activity	molecular function	Catalysis of the reaction: histone H3 N6-acetyl-L-lysine (position 18) + H2O = histone H3 L-lysine (position 18) + acetate. This reaction requires the presence of NAD, and represents the removal of an acetyl group from lysine at position 18 of the histone H3 protein. [GOC:sp, PMID:22722849, PMID:28450737]
NAD+-protein-arginine ADP-ribosyltransferase activity	molecular function	Catalysis of the reaction: L-arginyl-[protein] + NAD+ = H+ + (ADP-D-ribosyl)-L-arginyl-[protein] + nicotinamide. [RHEA:19149]
DNA damage sensor activity	molecular function	A molecule that recognises toxic DNA structures, for example, double-strand breaks or collapsed replication forks, and initiates a signaling response. [PMID:31995034]
NAD-dependent histone H3K56 deacetylase activity	molecular function	Catalysis of the reaction: histone H3 N6-acetyl-L-lysine (position 56) + H2O = histone H3 L-lysine (position 56) + acetate. This reaction requires the presence of NAD, and represents the removal of an acetyl group from lysine at position 56 of the histone H3 protein. [PMID:23911928, PMID:30374165]
NAD-dependent protein demyristoylase activity	molecular function	Catalysis of the reaction: N6-tetradecanoyl-L-lysyl-[protein] + NAD+ + H2O = tetradecanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide. [PMID:23552949, RHEA:70567]
NAD-dependent protein depalmitoylase activity	molecular function	Catalysis of the reaction: N6-octadecanoyl-L-lysyl-[protein] + NAD+ + H2O = octadecanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide. [PMID:23552949, RHEA:70563]
NAD+- protein-lysine ADP-ribosyltransferase activity	molecular function	Catalysis of the reaction: L-lysyl-[protein] + NAD+ = H+ + N(6)-(ADP-D-ribosyl)-L-lysyl-[protein] + nicotinamide. [PMID:25043379, RHEA:58220]
TORC2 complex binding	molecular function	Binding to a TORC2 complex. [GOC:TermGenie, PMID:20660630]
NAD+-protein ADP-ribosyltransferase activity	molecular function	Catalysis of the reaction: amino acyl-[protein] + NAD+ = H+ + (ADP-D-ribosyl)-amino acyl-[protein] + nicotinamide. [PMID:1899243]
transcription corepressor activity	molecular function	A transcription coregulator activity that represses or decreases the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Corepressors often act by altering chromatin structure and modifications. For example, one class of transcription corepressors modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators. [GOC:txnOH-2018, PMID:10213677, PMID:16858867]

Located In

This protein is located in 4 target(s):

Target	Category	Definition
nucleus	cellular component	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. [GOC:go_curators]
nucleoplasm	cellular component	That part of the nuclear content other than the chromosomes or the nucleolus. [GOC:ma, ISBN:0124325653]
intracellular membrane-bounded organelle	cellular component	Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane. [GOC:go_curators]
chromosome, subtelomeric region	cellular component	A region of the chromosome, adjacent to the telomere (on the centromeric side) that contains repetitive DNA and sometimes genes. This region is usually heterochromatin. [GOC:mah, PMID:18761674, PMID:22771823, PMID:26205977, PMID:7660126]

Active In

This protein is active in 4 target(s):

Target	Category	Definition
nucleus	cellular component	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. [GOC:go_curators]
endoplasmic reticulum	cellular component	The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). [ISBN:0198506732]
site of double-strand break	cellular component	A region of a chromosome at which a DNA double-strand break has occurred. DNA damage signaling and repair proteins accumulate at the lesion to respond to the damage and repair the DNA to form a continuous DNA helix. [GOC:bf, GOC:mah, GOC:vw, PMID:20096808, PMID:21035408]
site of DNA damage	cellular component	A region of a chromosome at which DNA damage has occurred. DNA damage signaling and repair proteins accumulate at the lesion to respond to the damage and repair the DNA to form a continuous DNA helix. [GOC:pg]

Part Of

This protein is part of 2 target(s):

Target	Category	Definition
pericentric heterochromatin	cellular component	Heterochromatin that is located adjacent to the CENP-A rich centromere 'central core' and characterized by methylated H3 histone at lysine 9 (H3K9me2/H3K9me3). [PMID:12019236, PMID:20206496, PMID:21437270, PMID:22729156, PMID:9413993]
chromatin	cellular component	The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]

Involved In

This protein is involved in 49 target(s):

Target	Category	Definition
negative regulation of transcription by RNA polymerase II	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. [GOC:go_curators, GOC:txnOH]
base-excision repair	biological process	In base excision repair, an altered base is removed by a DNA glycosylase enzyme, followed by excision of the resulting sugar phosphate. The small gap left in the DNA helix is filled in by the sequential action of DNA polymerase and DNA ligase. [ISBN:0815316194]
double-strand break repair	biological process	The repair of double-strand breaks in DNA via homologous and nonhomologous mechanisms to reform a continuous DNA helix. [GOC:elh]
chromatin remodeling	biological process	A dynamic process of chromatin reorganization resulting in changes to chromatin structure. These changes allow DNA metabolic processes such as transcriptional regulation, DNA recombination, DNA repair, and DNA replication. [GOC:jid, GOC:vw, PMID:12042764, PMID:12697820]
protein deacetylation	biological process	The removal of an acetyl group from a protein amino acid. An acetyl group is CH3CO-, derived from acetic [ethanoic] acid. [GOC:ai]
negative regulation of cell population proliferation	biological process	Any process that stops, prevents or reduces the rate or extent of cell proliferation. [GOC:go_curators]
determination of adult lifespan	biological process	The pathways that regulate the duration of the adult phase of the life-cycle of an animal. [PMID:25561524, PMID:273723695, PMID:3424805]
response to UV	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ultraviolet radiation (UV light) stimulus. Ultraviolet radiation is electromagnetic radiation with a wavelength in the range of 10 to 380 nanometers. [GOC:hb]
retrotransposon silencing	biological process	Any process that decreases the frequency, rate or extent of retrotransposition. Retrotransposons are a subset of transposable elements that use an RNA intermediate and reverse transcribe themselves into the genome. [GOC:dph, GOC:tb, PMID:32823517]
regulation of double-strand break repair via homologous recombination	biological process	Any process that modulates the frequency, rate or extent of the error-free repair of a double-strand break in DNA in which the broken DNA molecule is repaired using homologous sequences. [GOC:dph, GOC:jp, GOC:tb]
regulation of lipid metabolic process	biological process	Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving lipids. [GOC:go_curators]
pericentric heterochromatin formation	biological process	The compaction of chromatin located adjacent to the CENP-A rich centromere 'central core' and characterized by methylation of histone H3K9, into heterochromatin, resulting in the repression of transcription at pericentric DNA. [GOC:mah, PMID:14612388, PMID:20206496, PMID:22729156]
subtelomeric heterochromatin formation	biological process	The compaction of chromatin into heterochromatin at the subtelomeric region. [GOC:mah, PMID:10219245, PMID:26205977]
protein destabilization	biological process	Any process that decreases the stability of a protein, making it more vulnerable to degradative processes or aggregation. [GOC:mah]
positive regulation of insulin secretion	biological process	Any process that activates or increases the frequency, rate or extent of the regulated release of insulin. [GOC:mah]
positive regulation of telomere maintenance	biological process	Any process that activates or increases the frequency, rate or extent of a process that affects and monitors the activity of telomeric proteins and the length of telomeric DNA. [GOC:mah]
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	biological process	Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome. [GOC:mah]
circadian regulation of gene expression	biological process	Any process that modulates the frequency, rate or extent of gene expression such that an expression pattern recurs with a regularity of approximately 24 hours. [GOC:mah]
negative regulation of transcription elongation by RNA polymerase II	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription elongation, the extension of an RNA molecule after transcription initiation and promoter clearance by the addition of ribonucleotides, catalyzed by RNA polymerase II. [GOC:mah, GOC:txnOH]
ketone biosynthetic process	biological process	The chemical reactions and pathways resulting in the formation of ketones, a class of organic compounds that contain the carbonyl group, CO, and in which the carbonyl group is bonded only to carbon atoms. The general formula for a ketone is RCOR, where R and R are alkyl or aryl groups. [GOC:go_curators]
negative regulation of protein import into nucleus	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of the movement of proteins from the cytoplasm into the nucleus. [GOC:jl]
glucose homeostasis	biological process	Any process involved in the maintenance of an internal steady state of glucose within an organism or cell. [GOC:go_curators]
regulation of circadian rhythm	biological process	Any process that modulates the frequency, rate or extent of a circadian rhythm. A circadian rhythm is a biological process in an organism that recurs with a regularity of approximately 24 hours. [GOC:dph, GOC:jl, GOC:tb]
post-translational protein modification	biological process	The process of covalently altering one or more amino acids in a protein after the protein has been completely translated and released from the ribosome. [GOC:jsg]
positive regulation of fat cell differentiation	biological process	Any process that activates or increases the frequency, rate or extent of adipocyte differentiation. [GOC:go_curators]
negative regulation of gluconeogenesis	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of gluconeogenesis. [GOC:go_curators]
negative regulation of gene expression, epigenetic	biological process	An epigenetic process that silences gene expression at specific genomic regions through chromatin remodeling either by modifying higher order chromatin fiber structure, nucleosomal histones, or the cytosine DNA methylation. [PMID:22243696]
negative regulation of glycolytic process	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of glycolysis. [GOC:go_curators]
negative regulation of glucose import	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of the import of the hexose monosaccharide glucose into a cell or organelle. [GOC:ai]
positive regulation of protein export from nucleus	biological process	Any process that activates or increases the frequency, rate or extent of directed movement of proteins from the nucleus into the cytoplasm. [GOC:bf]
positive regulation of fibroblast proliferation	biological process	Any process that activates or increases the frequency, rate or extent of multiplication or reproduction of fibroblast cells. [GOC:jid]
regulation of protein secretion	biological process	Any process that modulates the frequency, rate or extent of the controlled release of a protein from a cell. [GOC:ai]
regulation of lipid catabolic process	biological process	Any process that modulates the frequency, rate, or extent of the chemical reactions and pathways resulting in the breakdown of lipids. [GOC:ai]
protein delipidation	biological process	The breakage of covalent bonds to detach lipid groups from a protein. [GOC:ai]
cardiac muscle cell differentiation	biological process	The process in which a cardiac muscle precursor cell acquires specialized features of a cardiac muscle cell. Cardiac muscle cells are striated muscle cells that are responsible for heart contraction. [GOC:devbiol, GOC:mtg_heart]
positive regulation of cold-induced thermogenesis	biological process	Any process that activates or increases the frequency, rate or extent of cold-induced thermogenesis. [PMID:27876809]
negative regulation of protein localization to chromatin	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of protein localization to chromatin. [PMID:20889714, PMID:29899453]
positive regulation of protein localization to chromatin	biological process	Any process that activates or increases the frequency, rate or extent of protein localization to chromatin. [PMID:20889714, PMID:29899453]
DNA repair-dependent chromatin remodeling	biological process	A chromatin remodeling process that allows DNA repair enzyme to access genomic DNA and repair DNA lesions. [PMID:15528408, PMID:28053344, PMID:29095668, PMID:35689883]
positive regulation of stem cell population maintenance	biological process	Any process that activates or increases the frequency, rate or extent of stem cell population maintenance. [GOC:hjd, GOC:TermGenie, PMID:22969033]
positive regulation of chondrocyte proliferation	biological process	Any process that increases the frequency, rate or extent of the multiplication or reproduction of chondrocytes by cell division, resulting in the expansion of their population. A chondrocyte is a polymorphic cell that forms cartilage. [GO_REF:0000058, GOC:TermGenie, PMID:23212449]
regulation of protein localization to plasma membrane	biological process	Any process that modulates the frequency, rate or extent of protein localization to plasma membrane. [GO_REF:0000058, GOC:BHF, GOC:rl, GOC:TermGenie, PMID:11602640]
positive regulation of blood vessel branching	biological process	Any process that activates or increases the frequency, rate or extent of blood vessel branching. [GO_REF:0000058, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:23201774]
positive regulation of vascular endothelial cell proliferation	biological process	Any process that activates or increases the frequency, rate or extent of vascular endothelial cell proliferation. [GO_REF:0000058, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:23201774]
protein localization to site of double-strand break	biological process	Any process in which a protein is transported to, or maintained at, a region of a chromosome at which a DNA double-strand break has occurred. [GOC:mah, PMID:23080121]
positive regulation of stem cell proliferation	biological process	Any process that activates or increases the frequency, rate or extent of stem cell proliferation. [GOC:dph]
positive regulation of stem cell differentiation	biological process	Any process that activates or increases the frequency, rate or extent of stem cell differentiation. [GOC:obol]
negative regulation of cellular senescence	biological process	Any process that stops, prevents or reduces the frequency, rate or extent of cellular senescence. [GOC:BHF]
positive regulation of double-strand break repair	biological process	Any process that activates or increases the frequency, rate or extent of double-strand break repair. [GOC:BHF]